Lasers in

Dermatology
and Medicine
Dermatologic Applications
Keyvan Nouri
Editor
Second Edition

123
Lasers in Dermatology and Medicine
Keyvan Nouri
Editor

Lasers in Dermatology
and Medicine
Dermatologic Applications

Second Edition
Editor
Keyvan Nouri
Leonard M. Miller School of Medicine
University of Miami
Miami, FL
USA

ISBN 978-3-319-76116-9    ISBN 978-3-319-76118-3 (eBook)

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Foreword—And Forward!

This, Nouri’s book, is a thorough, recent, practical, and refreshing one that
puts “laser dermatology” into a broader perspective; it is a pleasure to update
my brief contribution for this edition. Almost immediately after the first laser
was created in 1960, a handful of visionary physicians recognized the poten-
tial for surgical applications, starting with the organ systems readily accessi-
ble to light. Lasers in laryngology, ophthalmology, and dermatology are so
fully adopted now that the standards of care have forever been changed. Now,
light is marching inside the body. Laser lithotripsy is widely practiced all over
the world. Know-how about lasers and biomedical optics is jumping between
medical specialties. Optical coherence tomography, a rapid form of live
microscopy invented for retinal imaging, is starting to impact dermatology
while making a larger splash for upper GI tract and coronary artery diagnostic
imaging. Dermatology was the first to figure out how to target individual
pigmented cells with laser pulses, a capability later adopted into ophthalmol-
ogy for glaucoma treatment. Recently, the various optical nanoparticles
developed for laser photo-thermal cancer therapy are being used in dermatol-
ogy for acne treatment.
How did we get such a wide, almost dazzling, variety of treatment lasers
in dermatology? (Because, we need them for different uses in various practice
settings; lasers are the most tissue-specific surgical tools in existence.) Do we
really need so many? (Well, we need most all of them. Only a few are inter-
changeable.) Are the mechanistic, clinical, safety, ethical, and practice-related
chapters of this book worthy of study? (Yes.) Can’t we just learn which but-
tons to push, in courses provided by the more reputable device manufacturers
just after a laser is purchased? (This approach is foolish beyond words, yet
such fools exist). Even more foolish are those who purchase a used laser and
start using it without any training whatsoever.
A great asset of this book is the breadth of its practical, clinical discus-
sions. There is no substitute for hands-on training, which cannot be obtained
even from this practical book. If you use lasers in practice, talk with your
colleagues and attend medical laser conferences in which you are free to ask
questions to faculty who are not trying to sell something. Many laser compa-
nies provide useful information, but are inherently biased. Laser companies
are restricted from discussing off-label indications. FDA clearance of a device
for a particular indication cannot be taken as assurance that it will work safely
and effectively enough to satisfy you and your patients, while lack of FDA
clearance for a specific indication cannot be taken as assurance that it will not

v
vi Foreword—And Forward!

work safely and effectively. Some of the best uses for dermatological lasers
are not FDA-labeled indications, and probably never will be.
It is remarkable what lasers already can do for our patients, yet this field is
clearly still in its youth. What comes next? With the advent of fiber laser
technology, various industries and telecommunications now have extremely
powerful, efficient, wavelength-versatile lasers that operate reliably for
decades with little or no maintenance. Those have begun to make their way
into dermatology, and may ultimately do better what we do now, plus add
wholly new capabilities. Fractional lasers have taught us how amazingly tol-
erant skin is, to a large volume of micro-injury. Up to 30% of skin can be
killed or removed in random, full-thickness wounds that heal rapidly without
scarring. The caveat is that every little wound must be less than about 0.4 mm
wide. Given that, is it possible to “target” anything in the skin that can be
localized, regardless of its optical or thermal properties? If we knew where
various things are in the skin, can’t we just aim at them? Yes, we could!
Image-guided smart fractional lasers will be used to selectively treat struc-
tures and lesions not now addressed with lasers—and with that, we will have
software-programmable laser targeting. For example, all three cutaneous
glands—eccrine, sebaceous, and apocrine—are reasonable targets, as well as
nerves, lymphatics, sensory end organs, mast cells, antigen-presenting cells,
and other components of normal skin. Microscopy-driven ablative lasers may
even rival conventional microscopic margin-controlled tumor surgery, some
day. When laser microscopy and laser tissue ablation are finally married, sur-
gical oncology in general may be impacted. This new era is coming sooner
than you think.
I have been fortunate to play a role in launching many aspects of laser
dermatology, starting with some fundamental understanding of skin optics,
the concept of selective photothermolysis, lasers specifically designed for
dermatological use, permanent laser hair removal, scanning confocal laser
microscopy, and “fractional” laser treatments. Each of these arose from try-
ing to understand or solve one clinical problem, but now the panoply of clini-
cal laser applications far exceeds the initial effort. For example, fractional
lasers arose as a safer alternative to fully ablative laser skin resurfacing, a
safer way to induce skin remodeling. We had no idea that tissue so grossly
abnormal as a hypertrophic wound scar could be stimulated to normalize
itself this way. Fractional ablative lasers also offer a new way for delivery of
topical agents, including very high molecular weight macromolecules, parti-
cles, and even cells. The current widespread and diverse use of lasers in der-
matology attests not so much to new technology, as to the extreme value of
astute clinical observations made by dedicated dermatologists. Nouri’s text is
aimed exactly at achieving that. So please be a gourmet laser chef, not a
short-order cook. Contribute to an amazing and evolving part of
dermatology.
Thank you, Dr. Nouri and the many authors involved in this text, for your
excellent contribution.

R. Rox Anderson
Preface

Laser technology is quickly evolving with the presence of newer lasers, along
with new indications, that are constantly being introduced. The use of lasers
has become a major discipline and is currently practiced in a variety of fields
of medicine today. This book specifically offers a comprehensive literature
covering the different ways lasers are being used in the field of dermatology.
The authors of Lasers in Dermatology and Medicine are well known in their
respective fields and have attempted to cover each topic in the most compre-
hensive, readable, and understandable format. Each chapter consists of an
introduction and summary boxes in bulleted formats with up-to-date informa-
tion highlighting the importance of each respective section, enabling the
reader to have an easy approach towards reading and understanding the vari-
ous topics on lasers. This book has been written with the sincere hope of the
editors and the authors to serve as a cornerstone of laser usage in dermatol-
ogy, ultimately leading to better patient care and treatments. Lasers in derma-
tology have clearly expanded. The areas or laser treatments include port wine
stains, vascular anomalies and lesions, pigmented lesions and tattoos, hair
removal and hair re-growth, acne, facial rejuvenation, psoriasis, hypopig-
mented lesions and vitiligo, and treatment of fat and cellulites, among others.
The lasers are also being used for treatment and diagnosis of skin cancers.
We anticipate that this book will be of interest to all the physicians in the
field of dermatology who use or are interested in using lasers in their practice.
We are extremely grateful to our contributing authors. This book will serve as
a potential study source for physicians that would like to expand their knowl-
edge in lasers and light devices.

Miami, FL, USA Keyvan Nouri

vii
Acknowledgements

I would like to sincerely thank my family for their support and encourage-
ment throughout my life. Special thanks to Dr. William H.  Eaglestein, Dr.
Lawrence A. Schachner (former Chairman of Dermatology at the University
of Miami School of Medicine), and Dr. Robert Kirsner (Chairman of the
Department of Dermatology and Cutaneous Surgery at the University of
Miami Miller School of Medicine). They have given me great support and
have served as mentors throughout my professional career. Their guidance
and encouragement over the years has been greatly appreciated. Dr. Dr. Perry
Robins, Dr. Robin Ashinoff, Dr. Vicki Levine, Dr. Seth Orlow, the late Dr.
Irvin Freedberg, Dr. Hideko Kamino, and the entire faculty and staff at
New  York University School of Medicine Department of Dermatology:
Thank you all for the wonderful learning and friendship during my surgery
fellowship.
I would like to thank the faculty and dermatology residents, and the staff
of the Department of Dermatology and Cutaneous Surgery at the University
of Miami Miller School of Medicine, for their teaching, expertise, and friend-
ship. Special acknowledgements to the Mohs and Laser Center staff at the
Sylvester Cancer Center for their dedication, hard work, and support on a
daily basis. I would also like to thank Dr. Ali Rajabi-Estarabadi, my research
fellow, for his diligence and hard work and the rest of the Mohs staff, includ-
ing Cathy Mamas, Juana Alonso, Gladys Quintero, Destini M. Adkins, and
Ileana P. Reyes.
Special thanks to my clinical research fellows in dermatologic surgery,
Sofia Iglesia, Ariel Eva Eber, Sebastian H.  Verne, Marina Perper, Robert
Magno, Alaleh Dormishian, and Samuel C. Smith, for all their hard work and
contributions to this book.
I would also like to acknowledge the publishing staff Mr. Grant Weston,
Ms. Tracy Marton, Mr. Leo Johnson, and the entire Springer Publishing team
for having done a superb job with the publication. It has been a pleasure
working with them and this excellent project to compile the textbook.
Lastly, I would like to sincerely thank all the authors of this textbook.
These individuals are world-renowned in their respective specialties and
without their time and energy, writing this book would have not been possi-
ble. These individuals have made this a comprehensive, up-to-date, and reli-
able source on Lasers in Dermatology and Medicine. I truly appreciate their
hard work and thank them for their contributions.
Keyvan Nouri

ix
Contents

1 Laser-Tissue Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .    1

Amanda Abramson Lloyd, Michael S. Graves, and Edward
Victor Ross
2 Laser Safety: Regulations, Standards
and Practice Guidelines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   37
Brienne D. Cressey, Ashley Keyes, and Murad Alam
3 Lasers for Treatment of Vascular Lesions . . . . . . . . . . . . . . . . .   49
Jayne Joo, Daniel Michael, and Suzanne Kilmer
4 Laser for Scars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .   63
Voraphol Vejjabhinanta, Shalu S. Patel, and Keyvan Nouri
5 Laser Treatment of Leg Veins . . . . . . . . . . . . . . . . . . . . . . . . . . .   73
Julie K. Karen and Shields Callahan
6 Lasers and Lights for Treating Pigmented Lesions. . . . . . . . . .   83
Emmy M. Graber and Jeffrey S. Dover
7 Laser Treatment of Tattoos . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  109
Voraphol Vejjabhinanta, Caroline V. Caperton,
Christopher Wong, Rawat Charoensawad, and Keyvan Nouri
8 Laser for Hair Removal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  121
Voraphol Vejjabhinanta, Keyvan Nouri, Anita Singh,
Ran Huo, Rawat Charoensawad, Isabella Camacho, and Ali
Rajabi-Estarabadi
9 Lasers for Resurfacing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  137
Rungsima Wanitphakdeedecha and Tina S. Alster
10 Fractional Photothermolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . .  165
Dieter Manstein, Hans-Joachim Laubac, Sofia Iglesia,
Alaleh Dormishian, Ali Rajabi-­Estarabadi, and Keyvan Nouri
11 Sub-surfacing Lasers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  197
Michael Howard Gold
12 Non-invasive Rejuvenation/Skin Tightening:
Light-Based Devices. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  213
Marina Perper, John Tsatalis, Ariel E. Eber, and Keyvan Nouri

xi
xii Contents

13 Laser and Light Therapies for Acne. . . . . . . . . . . . . . . . . . . . . .  227

Ali Rajabi-Estarabadi, Ariel E. Eber, and Keyvan Nouri
14 Lasers for Psoriasis and Hypopigmentation. . . . . . . . . . . . . . . .  237
Laura Jordan, Summer Moon, and James M. Spencer
15 Lasers for Adipose Tissue and Cellulite . . . . . . . . . . . . . . . . . . .  247
Molly Wanner and Mathew M. Avram
16 Photodynamic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  261
Ariel E. Eber, Marina Perper, Sebastian H. Verne,
Robert Magno, Ibrahim Abdullah Omair ALOmair,
Mana ALHarbi, and Keyvan Nouri
17 Intense Pulsed Light (IPL). . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  275
Sanjana Iyengar, Keyvan Nouri, Peter Bjerring,
Kåre Christiansen, Robert A. Weiss, Girish S. Munavalli,
Sonal Choudhary, and Angel Leiva
18 Current Status of Light-Emitting Diode Phototherapy
in Dermatological Practice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  285
R. Glen Calderhead
19 Laser and Light for Wound Healing Stimulation . . . . . . . . . . .  339
Ehsan Azimi, Navid Bouzari, and Keyvan Nouri
20 Lasers in Hair Growth and Hair Transplantation. . . . . . . . . . .  351
Nicole E. Rogers, Marc R. Avram, Isabella Camacho,
and Ali Rajabi-Estarabadi
21 Photobiomodulation and Hair Growth. . . . . . . . . . . . . . . . . . . .  367
Molly B. Hirt and Ronda S. Farah
22 Reflectance Confocal Microscopy
in Oncological Dermatology. . . . . . . . . . . . . . . . . . . . . . . . . . . . .  375
Pablo Fernández-Crehuet Serrano,
Gonzalo Segurado-Miravalles, and Salvador González
23 Laser Clinical and Practice Pearls . . . . . . . . . . . . . . . . . . . . . . .  401
Hana Jeon, Lori A. Brightman, and Roy G. Geronemus
24 The Selection and Education of Laser Patients. . . . . . . . . . . . .  415
Murad Alam and Meghan Dubina
25 Anesthesia for Laser Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . .  427
Marina Perper, Ali Rajabi-Estarabadi, Ariel E. Eber,
Voraphol Vejjabhinanta, Ran Huo, Keyvan Nouri,
and John Tsatalis
26 Lasers in Skin of Color. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  437
Heather Woolery-Lloyd and Nkanyezi Ferguson
27 Laser Applications in Children. . . . . . . . . . . . . . . . . . . . . . . . . .  449
Jessica Cervantes, Sebastian H. Verne,
and Mercedes E. Gonzalez
Contents xiii

28 Dressing/Wound Care for Laser Treatment. . . . . . . . . . . . . . . .  467

Ariel E. Eber, Vincent M. Hsu, Stephen C. Davis,
and Keyvan Nouri
29 Prevention and Treatment of Laser Complications. . . . . . . . . .  475
Rachael L. Moore, Juan-Carlos Martinez, Ken K. Lee,
Yun Ehrlich, Brian Simmons, and Keyvan Nouri
30 Ethical Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  493
Abel Torres, Tejas Desai, Alpesh Desai, William T. Kirby,
and Maren C. Locke
31 Medicolegal Issues (Documentation/Informed
Consent/Non-physician Operators). . . . . . . . . . . . . . . . . . . . . . .  499
Abel Torres, Tejas Desai, Sailesh Konda, Alpesh Desai,
and William T. Kirby
32 Photography of Dermatological Laser Treatment. . . . . . . . . . .  505
Shraddha Desai and Ashish C. Bhatia
33 Online Resources of Dermatologic Laser Therapies. . . . . . . . .  517
Shraddha Desai, Elizabeth Uhlenhake, and Ashish C. Bhatia
34 Starting a Laser Practice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  523
Vic A. Narurkar
35 Research and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . .  527
Yakir S. Levin, Fernanda Hidemi Sakamoto,
and R. Rox Anderson

Index��������������������������������������������������������������������������������������������������������  541
Contributors

Murad  Alam Department of Dermatology, Otolaryngology, and Surgery,

Northwestern University, Chicago, IL, USA
Department of Dermatology, Northwestern University, Chicago, IL, USA
Mana  ALHarbi Department of Dermatology, College of Medicine, Al
Imam Muhammad Ibn Saud Islamic University (IMSIU), Riyadh, Kingdom
of Saudi Arabia
Ibrahim Abdullah Omair ALOmair  Department of Dermatology, College
of Medicine, Al Imam Muhammad Ibn Saud Islamic University (IMSIU),
Riyadh, Kingdom of Saudi Arabia
Tina S. Alster  Georgetown University Medical Center, Washington Institute
of Dermatologic Laser Surgery, Washington, DC, USA
Marc  R.  Avram Department of Dermatology, Massachusetts General
Hospital, Harvard Medical School, Boston, MA, USA
Mathew  M.  Avram Department of Dermatology, Massachusetts General
Hospital, Harvard Medical School, Boston, MA, USA
Ehsan  Azimi Department of Dermatology, Cutaneous Biology Research
Center, Massachusetts General Hospital, Charlestown, MA, USA
Ashish C. Bhatia  Department of Dermatology, Northwestern University –
Feinberg School of Medicine, Chicago, IL, USA
Oak Dermatology, Schaumburg, IL, USA
Peter Bjerring  Department of Dermatology, Swansea University, Swansea,
Wales, UK
Navid Bouzari  South Shore Skin Center, Plymouth, MA, USA
Lori A. Brightman  Laser & Skin Surgery Center of New York, New York,
NY, USA
R.  Glen  Calderhead Research Division, VP Medicoscientific Affairs,
Clinique L, Goyang-shi, Gyeonggi-Do, South Korea
Shields  Callahan Department of Dermatology, Virginia Commonwealth
University School of Medicine, Richmond, VA, USA

xv
xvi Contributors

Isabella Camacho  School of Medicine, Georgetown University, Washington,

DC, USA
Caroline  V.  Caperton Miller School of Medicine, University of Miami,
Miami, FL, USA
Jessica Cervantes  Department of Dermatology, University of Miami Miller
School of Medicine, Miami, FL, USA
Rawat Charoensawad  Rawat Clinic, Bangkok, Thailand
Biophile Training Center, Bangkok, Thailand
Sonal  Choudhary Department of Dermatology and Cutaneous Surgery,
Miller School of Medicine, University of Miami, Miami, FL, USA
Kåre Christiansen  Molholm Research, Molholm Hospital, Vejle, Denmark
Brienne D. Cressey  Department of Dermatology, New York Presbyterian-
Weill Cornell Hospital, New York, NY, USA
Stephen  C.  Davis Department of Dermatology and Cutaneous Surgery,
University of Miami, Miami, FL, USA
Alpesh  Desai Heights Dermatology and Aesthetic Center, Houston,
TX, USA
Shraddha Desai  Dermatology Institute, DuPage Medical Group, Naperville,
IL, USA
Tejas Desai  Heights Dermatology and Aesthetic Center, Houston, TX, USA
Roberto  Diaz  Department of Neurosurgery, University of Miami, Miami,
FL, USA
Alaleh  Dormishian Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, Miami, FL, USA
Jeffrey  S.  Dover Department of Dermatology, Yale University School of
Medicine and Brown University, Chestnut Hill, MA, USA
Meghan  Dubina Department of Dermatology, Northwestern University,
Chicago, IL, USA
Ariel  E.  Eber Department of Dermatology and Cutaneous Surgery,
University of Miami, Miller School of Medicine, Miami, FL, USA
Yun Ehrlich  Department of Dermatology and Cutaneous Surgery, University
of Miami, Miami, FL, USA
Ronda  S.  Farah Department of Dermatology, University of Minnesota,
Minneapolis, MN, USA
Nkanyezi  Ferguson Department of Dermatology, University of Iowa
Hospital and Clinics, Iowa City, IA, USA
Elizabeth A. M. Frost  Mount Sinai Medical Center, New York, NY, USA
Julie A. Gayle  Department of Anesthesiology, LSUHSC School of Medicine,
New Orleans, LA, USA
Contributors xvii

Roy G. Geronemus  Laser & Skin Surgery Center of New York, New York,

NY, USA
Department of Dermatology, New York University Medical Center,
New York, NY, USA
Michael  C.  Giovingo  Department of Ophthalmology, Stroger Hospital of
Cook County, Chicago, IL, USA
Michael  Howard  Gold Gold Skin Care Center and Tennessee Clinical
Research Center, Nashville, TN, USA
Mercedes  E.  Gonzalez  Department of Dermatology, University of Miami
Miller School of Medicine, Miami, FL, USA
Salvador  González Department of Medicine and Medical Specialities,
Alcalá University, Madrid, Spain
Department of Dermatology, Memorial Sloan-Kettering Cancer Center, New
York, NY, USA
Hospital Ramón y Cajal, Alcala University, Madrid, Spain
Emmy M. Graber  Dermatology Institute of Boston, PC, Boston, MA, USA
Michael S. Graves  Southwest Skin Cancer & Vein Clinic, Austin, TX, USA
Ramez  I.  Haddadin Department of Ophthalmology, Feinberg School of
Medicine, Northwestern University, Chicago, IL, USA
Molly  B.  Hirt Department of Dermatology, University of Minnesota,
Minneapolis, MN, USA
Vincent  M.  Hsu Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, Miami, FL, USA
Ran Huo  Broward Dermatology Clinic, Pembroke Pines, FL, USA
Sofia Iglesia  Department of Dermatology and Cutaneous Surgery, University
of Miami Miller School of Medicine, Miami, FL, USA
Viacheslav  Iremashvili Department of Urology, Jackson Memorial
Hospital, Miami, FL, USA
Michael E. Ivan  Department of Neurological Surgery, University of Miami
Hospital, Jackson Memorial Hospital, and Jackson South Hospital, Miami,
FL, USA
Sanjana Iyengar  Department of Dermatology, Feinberg School of Medicine,
Northwestern University, Chicago, IL, USA
Hana Jeon  Laser & Skin Surgery Center of New York, New York, NY, USA
Jayne Joo  Department of Dermatology, Davis and Sacramento VA Medical
Center, University of California, Sacramento, CA, USA
Laura Jordan  Kansas City University Consortium, Tri-County Dermatology
Residency Program, Cuyahoga Falls, OH, USA
xviii Contributors

Julie  K.  Karen Department of Dermatology, CompleteSkinMD, NYU

Langone Medical Center, New York, NY, USA
Alan David Kaye  Department of Anesthesiology, Louisiana Health Sciences
Center, School of Medicine, New Orleans, LA, USA
Ashley Keyes  Department of Dermatology, Weill Cornell Medicine, Lincoln
Medical Center, Bronx, NY, USA
Suzanne  Kilmer Laser & Skin Surgery Center of Northern California,
Sacramento, CA, USA
Department of Dermatology, Davis Medical Center, University of California,
Sacramento, CA, USA
William T. Kirby  Laseraway Hermosa Beach, Hermosa Beach, CA, USA
Ricardo  J.  Komotar Department of Neurosurgery, University of Miami,
Miami, FL, USA
Sailesh Konda  Department of Dermatology, University of Florida College
of Medicine, Gainesville, FL, USA
Raymond  J.  Lanzafame Raymond J.  Lanzafame, MD PLLC, Buffalo,
NY, USA
School of Dental Medicine, State University of New York at Buffalo, Buffalo,
NY, USA
Hans-Joachim  Laubac Dermatologische Abteilung, Universitäre
Krankenhäuser von Gen, Genf, Schweiz
Ken K. Lee  Dermatologic and Laser Surgery, Oregon Health and Sciences
University, Portland, OR, USA
Angel  Leiva Department of Dermatology and Cutaneous Surgery, Miller
School of Medicine, University of Miami, Miami, FL, USA
Yakir  S.  Levin Department of Dermatology, Massachusetts General
Hospital, Boston, MA, USA
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston,
MA, USA
Amanda Abramson Lloyd  Skin and Vein Institute, Encinitas, CA, USA
Maren  C.  Locke Department of Dermatology, MetroHealth System,
Cleveland, OH, USA
Robert  Magno Department of Dermatology, University of Miami, Toms
River, NJ, USA
Dieter  Manstein Wellman Center for Photomedicine, Massachusetts
General Hospital, Harvard Medical School, Boston, MA, USA
Robert  Marcovich  Department of Urology, University of Miami, Miami,
FL, USA
Juan-Carlos  Martinez Dermatologic and Laser Surgery, Oregon Health
and Sciences University, Portland, OR, USA
Contributors xix

Daniel Michael  Department of Dermatology, Laser and Skin Surgery Center

of Northern California, University of California, Davis, Medical Center,
Sacramento, CA, USA
Summer Moon  Dermatology Specialists of West Florida, FL, USA
Rachael L. Moore  Dermatology Specialists of West Florida, Oregon Health
and Sciences University, Portland, OR, USA
Girish  S.  Munavalli Dermatology, Laser, and Vein Specialists of the
Carolinas, Charlotte, NC, USA
Timothy  G.  Murray Department of Ophthalmology/Ocular Oncology,
Retina Vitreous Diseases/Pediatric Ophthalmology, Medical Arts Surgery
Center Baptist, Nicklaus Children’s Hospital, Miami, FL, USA
Vic A. Narurkar  Bay Area Laser Institute, San Francisco, CA, USA
Keyvan Nouri  Dermatology, University of Miami, Miami, FL, USA
Ophthalmology, University of Miami, Miami, FL, USA
Otolaryngology, University of Miami, Miami, FL, USA
Dermatologic Surgery, University of Miami, Miami, FL, USA
Department of Dermatology and Cutaneous Surgery, University of Miami
Medical Group, University of Miami, Miami, FL, USA
Dermatology Services at Sylvester Comprehensive Cancer Center, University
of Miami Hospital and Clinics, Miami, FL, USA
MOHS, Dermatologic and Laser Surgery, University of Miami, Miami, FL,
USA
Surgical Training, University of Miami, Miami, FL, USA
Mahnaz Nouri  Boston Eye Group, Brookline, MA, USA
Peter  O’Kane Dorset Heart Centre, Royal Bournemouth Hospital,
Bournemouth, Dorset, UK
Carolyn  Orgain  Department of Otolaryngology, University of California,
Irvine, Orange, CA, USA
Steven Parker  , Harrogate, North Yorkshire, UK
Krishna B. Patel  Department of Ophthalmology, John H. Stroger Hospital
of Cook County, Lombard, IL, USA
Shalu S. Patel  Department of Dermatology and Cutaneous Surgery, Miller
School of Medicine, University of Miami, Miami, FL, USA
Robert Perez  Department of Dermatology and Cutaneous Surgery, Miller
School of Medicine, University of Miami, Miami, FL, USA
Marina  Perper Department of Dermatology and Cutaneous Surgery,
University of Miami Hospital, Miller School of Medicine, Miami, FL, USA
xx Contributors

Roberto Pineda  Department of Ophthalmology, Massachusetts Ear and Eye

Hospital, Boston, MA, USA
Ali Rajabi-Estarabadi  Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, Miami, FL, USA
John  Rawlins Dorset Heart Centre, Royal Bournemouth Hospital,
Bournemouth, UK
Douglas  J.  Rhee Department of Ophthalmology and Visual Science,
University Hospitals, Cleveland, OH, USA
Department of Ophthalmology and Visual Sciences, Case Western Reserve
University School of Medicine, Cleveland, OH, USA
Cornelia Selma de Riese  Department of Obstetrics and Gynecology, Texas
Tech University Health Sciences Center, Lubbock, TX, USA
Nicole E. Rogers  Hair Restoration of the South, Metairie, LA, USA
Edward  Victor  Ross Department of Dermatology, Scripps Clinic, San
Diego, CA, USA
Vanessa  Rothholtz Pacific Coast Ear Nose and Throat, Beverly Hills,
CA, USA
R.  Rox  Anderson Department of Dermatology, Massachusetts General
Hospital, Harvard Medical School, Boston, MA, USA
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard
Medical School, Boston, MA, USA
Ryan  Rubin Department of Anesthesiology, Louisiana Health Sciences
Center, New Orleans, LA, USA
Fernanda Hidemi Sakamoto  Department of Dermatology, Massachusetts
General Hospital, Harvard Medical School, Boston, MA, USA
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard
Medical School, Boston, MA, USA
Amy  C.  Schefler Department of Ophthalmology, Bascom Palmer Eye
Institute, Miami, FL, USA
Gonzalo  Segurado-Miravalles Department of Dermatology, Ramón y
Cajal Hospital, Madrid, Spain
Pablo  Fernández-Crehuet  Serrano Department of Dermatology, Alto
Guadalquivir de Andújar, Andújar, Jaén, Spain
Brian  Simmons Department of Dermatology and Cutaneous Surgery,
University of Miami, Miami, FL, USA
Anita  Singh Montefiore Medical Center, Albert Einstein College of
Medicine, Bronx, NY, USA
James M. Spencer  Spencer Dermatology and Skin Surgery Center (Spencer
Dermatology, Carillon Outpatient Center), St. Petersburg, FL, USA
Contributors xxi

Joseph  Stuto  Department of Dermatology, Weill Cornell Medical Center,

New York, NY, USA
Amit  Todani Department of Ophthalmology, Goodman Eye Medical &
Surgical Center, Milford, MA, USA
Allyne  Topaz Hackensack University Medical Center, Hackensack,
NJ, USA
On Topaz  Asheville VA Medical Center, Asheville, NC, USA
Abel Torres  Department of Dermatology, Loma Linda University School of
Medicine, Loma linda, CA, USA
John  Tsatalis Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, Miami, FL, USA
Elizabeth Uhlenhake  The Dermatology Group, Mason, OH, USA
Voraphol  Vejjabhinanta Department of Dermatology and Cutaneous
Surgery, Leonard M. Miller School of Medicine, University of Miami, Miami,
FL, USA
Department of Dermatology, Siriraj Hospital, Mahidol University, Bangkok,
Thailand
Sebastian  H.  Verne  Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, Miami, FL, USA
Victor M. Villegas  Bascom Palmer Eye Institute, Miami, FL, USA
Rungsima  Wanitphakdeedecha Department of Dermatology, Faculty of
Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Molly  Wanner Department of Dermatology, Massachusetts General
Hospital, Harvard Medical School, Boston, MA, USA
Robert  A.  Weiss Department of Dermatology, Maryland Dermatology
Laser Skin and Vein Institute, University of Maryland School of Medicine,
Hunt Valley, MD, USA
Andrew Whittaker  Department of Cardiology, Dorset Heart Centre, Royal
Bournemouth Hospital, Bournemouth, Dorset, UK
Heather  Woolery-Lloyd Department of Dermatology and Cutaneous
Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
Brian J. F. Wong  Department of Otolaryngology, University of California,
Irvine, Orange, CA, USA
Christopher Wong  Miller School of Medicine, University of Miami, Miami,
FL, USA
Charles  C.  Wykoff Department of Ophthalmology, Bascom Palmer Eye
Institute, Miller School of Medicine, University of Miami, Miami, FL, USA
Roger  B.  Yandell  Department of Obstetrics and Gynecology, Texas Tech
University Health Sciences Center, Lubbock, TX, USA
 Laser-Tissue Interactions
1
Amanda Abramson Lloyd, Michael S. Graves,
and Edward Victor Ross

Abstract driving a car (where the operator may have no

The best gauge of laser interactions is the tis- idea about nature of the drive train compo-
sue response, and experiment is the most real- nents), successful laser operation does not
istic manner to address medical treatment demand a complete understanding of the
challenges. However, theoretical models are machine or the details of the light-tissue inter-
helpful in planning treatment approaches and action. However, a comprehension of first
laser parameters. In this chapter we discuss principles allows for a logical analysis of final
basics of lasers, their non laser counterparts, clinical outcomes—furthermore, more cre-
and laser-tissue interactions. ative uses of equipment should follow. For
Many physicians choose laser settings out example, with an education in laser tissue
of habit (or reading it off of a label attached to interactions (LTIs) and tissue cooling, one can
the side of the machine—a “cheat” sheet with deploy the alexandrite (long pulse) laser either
skin-type specific parameters), using tissue as a hair removal device, vascular laser, or to
endpoints to confirm the appropriateness of remove lentigines.
the parameters. For example, when treating a The reader should note that although the
tattoo with a Q-switched laser, the operator title of this chapter is “Laser Tissue
looks for immediate frosty whitening. Like Interactions”, the introduction of many new
and diverse technologies make the term some-
what obsolete. We will continue to use the
term, but a more appropriate term is “energy–
A. A. Lloyd tissue interactions.” As both radiofrequency
Skin and Vein Institute, and ultrasound are increasingly applied in
Encinitas, CA, USA
medicine. We will use both terms interchange-
M. S. Graves ably in the remainder of the text.
Southwest Skin Cancer and Vein Clinic,
Austin, TX, USA
Keywords
E. V. Ross (*)
Laser · Radiofrequency · Ultrasound · Skin ·
Laser and Cosmetic Dermatology, Scripps Clinic,
San Diego, CA, USA Lentigines · Hair removal · Vascular ·
e-mail: [email protected] Dermatology

© Springer International Publishing AG, part of Springer Nature 2018 1

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_1
2 A. A. Lloyd et al.

Introduction with an education in laser tissue interactions

(LTIs) and tissue cooling, one can deploy the
1. Light represents one portion of a broader elec- alexandrite (long pulse) laser either as a hair
tromagnetic spectrum. removal device, vascular laser, or to remove len-
2. Light-tissue interactions involve the complex tigines [2].
topics of tissue optics, absorption, heat gen- The reader should note that although the title
eration, and heat diffusion of this chapter is “Laser Tissue Interactions”, the
3. Lasers are a special type of light with the char- introduction of many new and diverse technolo-
acteristics of monochromaticity, directional- gies make the term somewhat obsolete. We will
ity, and coherence. continue to use the term, but a more appropriate
4. Coagulation/denaturation is time and temper- term is “energy–tissue interactions.” As both
ature dependent radiofrequency and ultrasound are increasingly
5. Proper selection of light parameters is based applied in medicine. We will use both terms
on the color, size, and geometry of the target interchangeably in the remainder of the text.
6. Wound healing is the final but not least impor-
tant part of the laser tissue sequence (the
epilogue) Light
7. Laser-tissue interactions are fluid—the opera-
Light represents one portion of a much broader
tor should closely examine the skin surface
during all aspects of the procedure electromagnetic spectrum. Light can be divided
into the UV (200–400 nm), VIS (400–700 nm),
8. Pulse duration and light doses are often as
NIR “I” (755–810 nm), NIR “II” (940–1064 nm),
important as wavelength in predicting tissue
responses to laser to irradiation MIR (1.3–3 μm), and Far IR (3 μm and beyond).
On a macroscopic level, light is adequately char-
The best gauge of laser interactions is the tis- acterized as waves. The amplitude of the wave is
sue response, and experiment is the most realistic perpendicular to the propagation direction. Light
manner to address medical treatment challenges. waves behave according to our “eyeball” obser-
However, theoretical models are helpful in plan- vations in day-to-day life. For example, we are
ning treatment approaches and laser parameters. familiar with refraction and reflection. The sur-
In this chapter we discuss basics of lasers, their face of a pond is a partial mirror (reflection); a
non-laser counterparts, and laser-tissue interac- fish seen in the pond is actually deeper than it
tions [1]. appears (refraction) [3]. Normally, the percent-
Many physicians choose laser settings out of age of incident light reflected from the skin sur-
habit (or reading it off of a label attached to the face is determined by the index of refraction
side of the machine—a “cheat” sheet with skin-­ difference between the skin surface (stratum cor-
type specific parameters), using tissue endpoints neum n = 1.55) and air (n = 1) [4]. This regular
to confirm the appropriateness of the parameters. reflectance is about 4–7% for light incident at
For example, when treating a tattoo with a right angles to the skin [3, 5]. The angle between
Q-switched laser, the operator looks for immedi- the light beam and the skin surface determines
ate frosty whitening. Like driving a car (where the % of reflected light. More light is reflected at
the operator may have no idea about nature of the “grazing” angles of incidence. It follows that, to
drive train components), successful laser opera- minimize surface losses, in most laser applica-
tion does not demand a complete understanding tions, one should deliver light approximately per-
of the machine or the details of the light-tissue pendicular to the skin [3, 6]. One can deliberately
interaction. However, a comprehension of first angle the beam, on the other hand, to decrease
principles allows for a logical analysis of final penetration depth and also attenuate the surface
clinical outcomes—furthermore, more creative fluence by “spreading” the beam. One can reduce
uses of equipment should follow. For example, interface losses by applying an alcohol solution
1  Laser-Tissue Interactions 3

(n = 1.4), water (n = 1.33), or a sapphire crystal are controlling the device–tissue interaction time
(n = 1.55 μm). This allows for optical coupling to allow for precise heating (vide infra).
(vide infra). On the other hand, the surface of dry Lasers are useful because they allow for pre-
skin reflects more light because of multiple skin– cise control of where and how much one heats
air interfaces (hence the white appearance of a [10]. There are four properties that are common
psoriasis plaque). to all laser types (1) Beam directionality (colli-
Light penetrates into the epidermis according mation), (2) Monochromaticity, (3) Spatial and
to wavelength dependent absorption and scatter- temporal coherence of the beam, and (4) High
ing (vide infra) [1, 6–8]. Because of scattering, intensity of the beam [11]. The intensity, direc-
much incident light is remitted (remittance refers tionality, and monochromaticity of laser light
to the total light returned to the environment due allow the beam to be expanded, or focused quite
to multiple scattering in the epidermis and der- easily. With non-laser sources like flashlamps
mis, as well as the regular reflection from the sur- directed toward the skin surface, the light inten-
face). In laser surgery, light reflected from the sity at the skin surface cannot exceed the bright-
surface is typically “wasted”. This “lost” energy ness of the source lamp. With many lasers, a lamp
varies from 15% to as much as 70% depending similar to the intense pulsed light (IPL) flashlamp
on wavelength and skin type. For example, for pumps the laser cavity [12]. The amplification of
1064 nm, 60% of an incident laser beam may be light within the laser cavity sets laser light apart
remitted. One can easily verify this by holding a from other sources.
finger just adjacent to the beam near the skin sur- For most visible light applications, laser rep-
face. Warmth can be felt from the remitted por- resents a conversion from lamplight to an ampli-
tion of the beam. fied monochromatic form [13]. The high power
To describe laser tissue interactions at the possible with lasers (especially peak power) is
molecular/microscopic level, light is considered achieved through resonance in the laser cavity.
as a stream of “particles” called photons, where For many dermatology applications requiring ms
the photon energy depends on the wavelength of or longer pulses delivered to large skin areas,
light. IPLs are either adequate or preferable to lasers.
The scientific principle on which lasers are based
E photon = hc / l (1.1)
is stimulated emission. With spontaneous emis-
Where h is Plank’s constant (6.6 × 10−34 J -s), sion, electrons transition to the lower level in a
and c is the speed of light (3 × 1010 cm/s) [9]. random process. With stimulated emission, the
emission occurs only in the presence of photons
of a certain energy. The critical point is maintain-
Types of Light Devices ing a condition where the population of photons
in a higher state is larger than that in the lower
In principle, many non-laser devices could be state. To create this population inversion, a pump-
used for heating skin [9]. Most properties of laser ing energy must be directed either with electric-
light (i.e., coherence) are unimportant insofar as ity, light, or chemical energy.
the way light interacts with tissue in therapeutic All lasers contain four main components, the
applications. And although collimation (lack of lasing medium, the excitation source, feedback
divergence) of the incident beam might increase apparatus, and an output coupler. With respect to
the % of transmitted light with laser versus IPL, lasing media, there are diode lasers, solid-state
the increasing use of filtered flash lamps in der- lasers, dye, and gas lasers. Most solid state and
matology suggests that losses from IPL beam dye lasers use optical exciters (lamps), whereas
divergence are not critical. In lieu of lasers, some gas and diode lasers use electrical excitation (i.e.,
thermal sources can be used in skin surgery (i.e., CO2 and RF). The feedback mechanism consists
nitrogen plasma device) for resurfacing (Portrait, of mirrors where one mirror reflects 100% and
Rhytec, MA). The critical features of any device the other transmits a small fraction of light [14].
4 A. A. Lloyd et al.

An example of a solid-state laser is the alexan-

drite laser. A solid-state laser consists of a rod
that is pumped by a flashlamp. The lamp pumps
the rod for stimulated emission. The rod and
lamp assembly must also be designed for ade-
quate cooling. Lasers typically are finicky
because all of the components are driven near
their damage thresholds (like redlining your car
all the time). As an example of this concept, con-
sider the pulsed dye laser (PDL). As the dye
degrades, the lamps must work harder to generate
higher pulse energies from the dye. Also, mirrors Fig. 1.1 A red LED (OmniLux, Phototherapeutics, Inc.)
become contaminated over time such that the
lamps must work harder and harder. These is no oscillation and the semiconductor LASER
demands stress the power supply. Thus, eventu- acts like an LED. This emission is very similar to
ally, the dye kit, the power supply, lamps, and dye the visible emission of light emitting diodes. If
are all working at their maximal output. Often one adds mirrors it operates as a tiny laser instead
people speak of a tunable dye laser. In fact many of an LED. The overall efficiency of semiconduc-
dye lasers are tunable; the manufacturers have tor lasers is quite high, approximately 30% and
simply chosen one wavelength. An example of a among the highest available  for any laser types.
tunable laser was the Sclero-plus pulsed dye laser Most semiconductor (diode) lasers are operated in
(tunable from 585 to 600 nm in 5 nm increments) CW mode but can be pulsed. New visible
from Candela (Candela, Wayland, MA). light semiconductor lasers are available, and also
Laser systems differ with regard to duration laser diode arrays are available where scientists
and power of the emitted laser radiation. In con- have created large numbers of semiconductor
tinuous wave lasers (CW mode) with power out- lasers on one substrate. Some diode lasers are
puts of up to 103 W, the lasing medium is excited housed separate from the handpiece and delivered
continuously. With pulsed lasers, excitation is by fiber optics. Others are configured with the
effected in a single pulse or in on-line pulses laser diodes in the handpiece as arrays. Modern
(free-running mode). Peak powers of 105 W can diode lasers achieve higher powers than in the
be developed for a duration of 100  μs–10  ms. past, but their peak powers are still lag behind
Storing the excitation energy and releasing it sud- most pulsed solidstate lasers [14].
denly (Q-switch mode or mode-locking) leads to Excimer lasers emit UV light and are used for
a peak power increase of up to 1010–1012 W, and a photomodulation of the immune system. They
pulse duration of 10 ps–100 ns [13]. have also been used in surgery. The possible muta-
Light emitting diodes (LEDs) are becoming genicity of these lasers has not been well studied.
commonplace in dermatology (Fig. 1.1). Primarily Materials such as the KTP crystal can be used to
used as a PDT light source, they are also used in generate harmonics with lasers. The KTP crystal is
biostimulation. LEDs are similar to semiconduc- used to convert 1064  nm radiation to 532 green
tor (aka diode) lasers in that they use electrical light. Also quality (Q) switching is used for gener-
current placed between two types of semiconduc- ating short pulses. Much of the electrical energy
tors. However, they lack an amplification process used to create laser emissions is wasted as heat,
(no mirrors). LEDs do not produce coherent which is why water is used for cooling most lasers.
beams but can produce monochromatic light. Air cooling is used for some high-powered flash
Semiconductor (diode) lasers contain an LED as lamps and many diode lasers. In the future, free
the active gain medium. A current passes through electron lasers might be useful but presently they
a sandwich of two layers consisting of compounds are too cumbersome and only generate small
(called p type and n type). Below threshold, there amounts of energy per unit wavelength.
1  Laser-Tissue Interactions 5

Intense pulsed light devices are becoming cost of both laser and flashlamp technology are
increasingly comparable to lasers that emit ms steadily decreasing.
domain pulses [15]. Absorption spectra of skin
chromophores show multiple peaks (HgB) or can
be broad (melanin) [16], and therefore a broad- Light Device Terminology
band light source is a logical alternative to lasers.
Proper filtration of a xenon lamp tailors the out- Basic parameters for light sources are power,
put spectrum for a particular application. Some time, and spot size for continuous wave lasers,
concessions are made with direct use of lamp- and for pulsed sources, the energy per pulse,
light. For example, rapid beam divergence pulse duration, spot size, fluence, repetition rate,
obliges that the lamp source be near the skin sur- and the total number of pulses [17]. Energy is
face. This subsequent requirement makes for a measured in joules (J). The amount of energy
typically heavier handpiece compared with most delivered per unit area is the fluence, sometimes
lasers (Fig. 1.2) (the exception being some diode called the dose or radiant exposure, given in
arrays where the light source is also housed in the J/cm2. The rate of energy delivery is called power,
handpiece-(i.e., Light Sheer, Lumenis, CA)). measured in watts (W). One watt is one joule per
Also IPL cannot be adapted to fibers for subsur- second (W = J/s). The power delivered per unit
face delivery. High energy short pulses area is called the irradiance or power density,
(Q-switched ns pulses) are not possible with usually given in W/cm2. Laser exposure duration
flashlamps. They can, however, be used to pump (called pulse width for pulsed lasers) is the time
a laser, and some modern IPLs feature a laser over which energy is delivered. Fluence is equal
attachment where the flashlamp and laser rod are to the irradiance times the exposure duration
in the handpiece. In general, the size, weight, and [10]. Power density is a critical parameter, for it

Fig. 1.2  IPL and green light laser—note smaller size of laser handpiece
6 A. A. Lloyd et al.

often determines the action mechanism in cuta- physician can control spot size and tissue effects
neous applications. For example, a very low irra- simply by moving the handpiece tip toward or
diance emission (typical range of 2–10 mW/cm2) away from the skin. The subsequent rapid
does not heat tissue and is associated with diag- changes in power density offer “on the fly” flexi-
nostic applications, photochemical processes, bility and control.
and biostimulation. On the other extreme, a very A thorough knowledge of a specific laser’s
short ns pulse can generate high peak power den- operation and quirks is imperative for optimal and
sities associated with shock waves and even “safe” lasering. Vendors are creating lasers that
plasma formation [18]. Plasma is a “spark” due are more intuitive to operate. Increasingly, manu-
to ionization of matter. facturers have added touch screen interfaces with
Another factor is the laser exposure spot size application-driven menus and skin-­type specific
(which can greatly affect the beam strength inside preset parameters. Some devices permit patient
the skin). Other characteristics of importance are laser parameters to be stored for future reference.
whether the incident light is convergent, diver- Most lasers are designed such that the handpiece
gent, or diffuse, and the uniformity of irradiance and instrument panels are electronically inter-
over the exposure area (spatial beam profile). The faced. It follows that the laser control module
pulse profile, that is, the character of the pulse “knows” what spot size is being used. Typically
shapes in time (instantaneous power versus time) this “handshake” occurs when one inserts the
also affects the tissue response [19]. handpiece into the calibration port, or through a
Many lasers in dermatology are pulsed, and control cable from the handpiece to the laser
the user interface shows pulse duration, fluence, “main frame”. With others, one selects the spot-
spot size and fluence. Some multi-wavelength size on the display, and the laser calculates the flu-
lasers also allow for wavelength selection. Some ence accordingly. For example, one of our erbium
older lasers, for example a popular CO2 laser, YAG lasers possesses interchangeable lenses for
showed only the pulse energy on the instrument 1, 3, 5, and 7 mm spots. However, there is no feed-
panel, or in continuous wave (CW) mode, the back from the handpiece to the laser control
number of watts. In these cases one uses the board. The user “tells” the laser which lens cell is
exposure area and exposure time to calculate the inserted, and the laser calculates the fluence based
total light dose (fluence). on the selected spot and selected pulse energy. In
this case, if one changes the spot size (for exam-
Power ´ time
Fluence = (1.2) ple, by exchanging the 7 mm for the 3 mm lens
area cell), the laser still “thinks” the 7 mm spot is being
With the exception of PDT sources and CW used, and the actual surface fluence is now ~5×
CO2 lasers, most aesthetic lasers create pulsed the fluence on the panel. The resulting impact on
light. In many CW applications (i.e., wart treat- the skin surface (the wound depth and diameter)
ment with a CO2 laser), the fluence is not of great should alert the enlightened user to reassess his
importance in characterizing the overall tissue parameter selection.
effect. A more important parameter is power den- Most lasers calibrate through a system where
sity (where higher power densities achieve abla- the end of the handpiece is placed in a portal on
tion and lower power densities cause charring), the base unit (Fig. 1.3). This configuration allows
and the physician stops the procedure when an for interrogation of the entire system, from the
appropriate endpoint is reached. On the other “pumping” lamps to the fiber/articulated arm to
hand, in PDT applications with CW light where the handpiece optics. For example, if a fiber is
the clinical endpoint might be delayed, the total damaged, the laser will fail calibration, and an
fluence and power density are important predic- error message appears. Other systems measure
tors of the tissue response. the output within the distal end of the handpiece
In CW mode, CO2 lasers are used with a using a small calibration module that “picks off”
focusing (noncollimated) handpiece such that the a portion of the beam.
1  Laser-Tissue Interactions 7

a b

Calibration port
Handpiece
tip

Fig. 1.3  Figures show handpiece before and during insertion into calibration port of a Q switched alexandrite laser

There are some simple ways to interrogate for damental optimized “mode” of the laser. This
system integrity. One can examine the aiming shape is usually observed when the beam has
beam as it illuminates a piece of white paper, been delivered through an articulated arm. For
checking that the beam edges are sharp—this some wavelengths, this is an effective way to
suggests that the treatment beam is also sharp and deliver energy (CO2 and erbium). The disadvan-
the profile is according to the manufacturer’s tage of the rigid arm is limited flexibility, the
specifications. Also, burn paper can be used— typically short arm length, the possibility of mis-
here the laser is used with a low energy and the alignment from even minor impact, and a ten-
spot is checked for uniformity from beam edge to dency for non-­uniform heating across the spot
edge. By checking the impact pattern, one can [20]. For example, in treating a lentigo with a
uncover damaged mirrors in the knuckle of the Q-switched alexandrite laser equipped with a
articulated arm, or a damaged focusing lens that rigid articulated arm, one may observe complete
renders the laser unstable or unsafe. Likewise, for ablation of the epidermis at the center of the
scanners, one can ensure that skin coverage will “spot”, but only whitening at the periphery. On
be uniform. the other hand, sometimes a bell-shaped profile
is desirable, for example, when applying a small
1. LEDs are becoming commonplace in biomed- spot FIR beam with a scanner. In this scenario,
ical applications the wings of the beam allows for some overlap
2. Solid state lasers generally achieve the largest without delivering “too much” energy at points
peak powers among laser types of overlap.
3. The laser operator should know every nook The Gaussian profile can be modified outside
and cranny of a laser’s features to optimize the cavity, which is desirable in many applica-
patient outcomes and safety tions. With a fiber equipped delivery system, the
4. Power density determines the mechanism for beam is mixed within the fiber and can be shaped
many LTIs to be more flat-topped. The lentigo then is more
likely to be uniformly heated (so long as the
lesion itself if uniformly colored!). Although
 eam Profiles: Top Hat Versus
B fiber delivery systems are usually preferred by
Gaussian physicians, some laser beams are difficult to
deliver through a fiber. Examples include far IR
Laser beam profiles vary based on intercavity wavelengths and very short pulses (i.e., few ns
design, lasing medium, and the delivery system. with typical Q switched Nd YAG lasers whose
A common profile is Gaussian or bell-shaped. high peak power exceeds the damage threshold
For many lasers, this profile represents the fun- of most fibers).
8 A. A. Lloyd et al.

Palomar smooth pulse technology Competing system

30 30
Skin temperature
25 25

Power, au; ∆ Tepi, °C

Power, au; ∆ Tepi, °C

Skin safety level Skin safety level

20 20
Skin temperature
15 15

10 10

5 5

0 0
–5 0 5 10 15 20 25 –5 0 5 10 15 20 25
Time, ms Time, ms

Fig. 1.4  Figure shows spiky versus smooth pulse and effect on epidermal temperature

Pulse Profiles: Square Versus Spiky 193 nm have been used for skin and corneal
ablation.
The pulse profile is the temporal shape of the 2. Violet IPL emissions, low power 410  nm

laser pulse (Fig. 1.4) [21]. In many pulsed laser LED, and fluorescent lamps are used either
applications, the “macro pulse” is comprised of alone or with ALA.  Alone, the devices take
several shorter micropulses [22]. Depending on advantage of endogenous porphyrins and kill
the application, the temporal pulse profile may P. acnes [24]. After application, of ALA, this
impact the tissue effect. For example, simply by wavelength range is highly effective in creat-
increasing the pulse number from four to six ing singlet O2 after absorption by PpIX. Uses
pulselets, the purpura threshold is increased with include treatment of actinic keratoses, actinic
the PDL.  Also, highly energetic spikes tend to cheilitis, and basal cell carcinomas [25].
increase the epidermal to dermal damage ratio in 3. Visible light (green yellow) - VIS (GY). These
applications such as laser hair reduction. This is wavelengths are highly absorbed by HgB and
especially true with green-yellow light in vascu- melanin and are especially useful in treating
lar applications. epidermal pigmented lesions and superficial
vessels [26–28]. Their relatively poor penetra-
tion in skin (and the even poorer penetration
Summary of Wavelength Ranges in blood—see Table  1.1) make them poor
choices for treatment of deeper pigmented
In this section we examine wavelength ranges lesions or deeper larger vessels. Their shallow
that are useful for cutaneous surgery. penetration depths preclude their use in per-
manent hair reduction (with the possible
1. UV laser and light sources have been used pri- exception of very large spots (i.e., IPL) that
marily for treatment of inflammatory skin dis- enhance light depth). The effective portions of
eases and/or vitiligo, as well as striae. The many IPL spectra include the GY range.
presumed action is immunomodulatory. The By the proper manipulation a laser delivery
XeCl excimer laser emits at 308 nm, near the device, one can optimize parameters for selec-
peak action spectrum for psoriasis. Other UV tive heating of pigmented versus vascular
non-laser sources have also been used for lesions. For example, by applying a compres-
hypopigmentation, striae, and various inflam- sion handpiece without cooling with 595 nm,
matory diseases [22, 23]. Excimer lasers at blood is depleted as a target and pigment is
1  Laser-Tissue Interactions 9

Table 1.1  Absorption coefficients (cm−1) for various chromophores

Wavelength (nm) 410 532 595 694 755 810 940 1064
Oxy HgB (40% Hct) 1990 187 35 1.2 2.3 3.6 5.2 2.2
Deoxy HgB 1296 138 96 6.6 5.2 2.7 3.0 0.6
Melanina 140 56 38 23 17 13 7 5.7
Water 6.7 × 10−5 0.00044 0.0017 0.005 0.03 0.02 0.27 0.15
Bloodless dermis 10 3 2 1.2 0.8 0.6 0.5 0.4
OPD in skin (μm) 100 350 550 750 1000 1200 1500 1700
(net epidermis) for moderately pigmented adult—10% mel. volume fraction in epidermis [7, 29]
a

a b In “sun” mode T
is increased

Fig. 1.5  Figure shows user controllable temperature change with an IPL. By increasing the handpiece tip temperature,
pigmented lesion heating is favored over vascular heating

preferentially heated [30]. Also, by (see lime- lengths useful for PDT (i.e., sodium lamp,
light desert mode—Fig. 1.5), one can increase IPL, frequency doubled Nd YAG, or PDL)
or decrease the sapphire window temperature [31, 32]. On the other hand, all visible light
to enhance epidermal versus vascular heating. can be used for PDT, as the Soret band and
By reducing the pulsewidth into the nanosec- smaller “Q-bands” can all create singlet O2 on
ond range, melanosomes are preferentially irradiation of PpIX.  Therefore the 532, 595,
heated over vessels. For example, extremely and IPL devices, when used adjunctively with
short Q-switched 532  nm pulses will cause ALA, can all augment the cosmetic result
fine vessels to rupture, but inadequate heat dif- through both photothermal and photochemi-
fusion to the vessel wall precludes long term cal effects.
vessel destruction. On the other hand, melano- 4. Red and Near IR (I) (630, 694, 755, 810 nm).
somes are sufficiently heated for single-­ Deeply penetrating red light (630 nm) contin-
session lentigo destruction. By choosing uous wave devices are efficient activators of
specific wavelengths with respect to HgB and PpIX after topical application of ALA.  The
melanin, one can achieve some degree of 694 nm (ruby) laser is optimized for pigment
selective melanin or HgB heating. For exam- reduction and hair reduction in lighter skin
ple, if one wanted to avoid HgB in heating a types. The 810 nm diode and 755 nm alexan-
lentigo, 694  nm (ruby) represents a better drite laser, depending on spot size, cooling,
choice than 532 or 595 nm. This choice might pulse duration, and fluence can be configured
decrease inflammation by unintended heating to optimize outcomes for hair reduction, len-
of normal vessels in the dermis. tigines, or blood vessels [33]. They are posi-
There are absorption peaks for PpIX in the tioned in the absorption spectrum for blood
green–yellow range, making these wave- and melanin between the GY wavelengths and
10 A. A. Lloyd et al.

1064 nm. They will penetrate deeply enough

in blood to coagulate vessels up to 2 mm [34–
36]; also, they are reasonably tolerant of epi-
dermal pigment in hair reduction (with surface
cooling) so long as very dark skin is not
treated [37]. By decreasing the pulsewidth
into the nanosecond range, the alexandrite
laser is a first line treatment for many tattoo
colors.
5 . Near IR (II). 940 and Nd YAG (1064  nm).
These two wavelengths have been used for a
broad range of vessel sizes on the leg and face
[38]. They occupy a unique place in the
absorption spectrum of our “big 3” chromo-
phores, that is blood, melanin, and water.
Because of the depth of penetration (on the
order of mm), they are especially useful for
hair reduction and coagulation of deeper
blood vessels. By varying fluence and spot
size, reticular ectatic veins, as well as those
associated with nodular port wine stains or
hemangiomas, can be safely targeted. On the Fig. 1.6  Note scar after 1064 nm irradiation of a nodule
other hand, they are not well suited for within a port wine stain
epidermal-­pigmented lesions. Also, although
water absorption is poor, it exceeds that of the
VIS and near VIS wavelengths. The result is absorbing wavelengths. Without surface cool-
that 940 and 1064  nm achieve large volume ing, unless very small fluences are applied, a
temperature elevation in the skin, and with top to bottom thermal injury occurs. The
repeated laser impacts, because of the slow absorption coefficients for the 1320  nm,
cooling of this volume (large τ–vide infra), 1450 nm, and 1540 nm systems are ~3 cm−1,
catastrophic pan-cutaneous thermal damage is 20  cm−1, and 8  cm−1 respectively [39], while
possible. This wavelength (1064  nm) repre- the effective scattering coefficients are about
sents the extreme example of a “what you 14, 12, and 11 cm−1. The corresponding pene-
don’t see can hurt you laser” [18] (Fig. 1.6). tration depths are ~1500, 300, and 700 μm. It
The Q-switched YAG laser plays an expand- follows that for equal surface cooling and
ing role in the treatment of tattoos, nevus of equal fluences, the most superficial heating
Ota, and even melasma. will occur with the 1450 nm laser, followed by
6. MIR-lasers and deeply penetrating halogen the 1540 and 1320  nm lasers. Newer deeply
lamps. These lasers and lamps heat tissue penetrating lamps have been introduced (Titan,
water. With macrowounding (>1  mm) spot Cutera, Brisbane, CA). They emit light over a
sizes, depending on where we want to heat, we 1–2  μm wavelength band with relatively low
can “choreograph” our laser and/or cooling power densities and long exposures (several
settings to maximize the skin temperature in seconds). In a typical scenario, the irradiation
certain skin layers. In general, with more begins after a roughly 2 s period of cooling. At
deeply penetrating wavelengths, larger vol- this point, a band of tissue from roughly 700–
umes are heated. On the other hand, achieving 1.5 μm deep in the skin is heated. By varying
temperature elevations in the volume will the fluence, this relatively large volume can be
require higher fluences than with highly heated to different peak temperatures. As part
1  Laser-Tissue Interactions 11

of each iteration, post pulse cooling is impera-  eam Propagation: How the Laser
B
tive because such a large volume of skin is Energy Gets to the Target
heated that a “thermal wake” advances toward
the skin surface. If one removes the handpiece Skin optical properties determine the penetration,
prematurely, heat accumulates near the skin absorption, and internal dosimetry of laser light.
surface with the risks of pain, dermal thermal The laser surgeon can divide the skin into two
injury, and scarring [40]. The 1320  nm components, (1) the epidermis (primarily an
Nd:YAG has been used in the endovenous absorber of visible light due to melanin) and (2)
ablation of the deep saphenous venous system The dermis (which can be envisioned as a carton
as well as laser liposculpture. Recently the of milk with red dots in it). Light tissue interac-
MIR spectral subset has become the mainstay tions can be broken down into A. The transport of
for fractional non-ablative technologies. light in tissue, B.  Absorption of light and heat
7 . Far infrared systems. The major lasers are the generation in tissue, C.  Localized temperature
CO2, erbium YAG, and erbium YSGG elevation in the target tissue (and denaturation of
(chromium:yttrium-scandiumgallium-garnet) proteins), and D. Heat diffusion away from the
lasers. Overall, the ratio of ablation to heating target [17, 45].
is much higher with the erbium YAG laser. The optical properties of the skin mimic a tur-
However, one can enhance the thermal effects bid medium intermixed with focal discrete visi-
of the Er YAG laser by extending the pulse or ble and infrared light absorbers (blood, melanin,
increasing the repetition rate, and likewise one bilirubin, and dry collagen) [46]. The thermal or
can decrease residual thermal damage (RTD) photochemical effects depend on the local energy
of the CO2 laser by decreasing pw [41, 42]. density at the target. Once the light penetrates the
Where precision is required in ablation, Er surface, it undergoes a series of absorbing and
YAG is preferred. On the other hand, depend- scattering events. Photons statistically are either
ing on settings, the CO2 laser enjoys a desir- scattered or absorbed in a wavelength dependent
able blend of ablation and heating. The fashion [1, 47]. Scattering is affected by the shape
thresholds for ablation for CO2 and erbium or size of the particle and the index of refraction
lasers vary inversely with their optical pene- mismatch between the particle and medium. For
tration depths in tissue (20  μm and 1  μm most tissues, for λ > 2.5 μm or < 250 nm, absorp-
respectively). This assumes thermal confine- tion dominates over scattering. For the remainder
ment. It follows that less surface fluence is of the EM spectrum, scattering is the primary
required for ablation with the erbium laser. attenuator of light in tissue with the exception of
The CO2 laser at typical operating “pulsed” focal discrete absorbers (melanosome, HgB, etc.)
parameters performs self-limited controlled The probabilities of absorption or scattering
heating of the skin [43, 44], whereas the (designated μa and μs respectively, Table 1.1) are
erbium laser operates in an almost purely determined by experiment. For example, for a μa
ablative regime. The erbium YSGG (2.79 μm) of 0.3 cm−1, the mean free path before absorption
laser has recently been applied to LSR and its is 1/μa or 3.3 cm. Generally, light is attenuated as
absorption coefficient makes it a kind of it propagates through tissue. In turbid tissue (i.e.,
hybrid between CO2 and erbium YAG insofar the dermis, where collagen acts as the major scat-
as the ratios of heating to ablation. All three terer), the fluence attenuation can be described
wavelengths (2.79, 2.94, and 10.6  μm) have by:
recently been integrated into fractional deliv-
I ( z ) = I o ke (
-z /d )
ery systems. (1.3)

There are four key components in the sequence where I(z) is the local subsurface fluence at
of most photothermal laser-tissue interactions some depth z, k is a constant that accounts for
(Sects. 7.1–7.4). backscattered light and δ is the wavelength
12 A. A. Lloyd et al.

dependent optical penetration depth of light, or most tissues [10]. Various skin pigments can play
the depth at which there is attenuation to 37% of optical “tricks” on the cutaneous surgeon. For
the surface value (37% = l/e, where e = 2.7, the example, poikiloderma appears to be a mix of
base of the natural logarithm). This depth is hyperpigmentation and hypervascularity. In fact,
determined by absorption and scattering coeffi- although there is some melanin influence in the
cients, as related by the simple equation below red-brown appearance, the dyschromia is by far
[1, 47]: more a disorder of matted telangiectasia. This is
confirmed by the good response of the condition
1
d= (1.4) to the PDL, even with aggressive surface cooling
3m a ( ma + m s (1 - g ) ) that should preclude any impact on superficial

cutaneous hyperpigmentation. Additionally, with
Where g is the anisotropy coefficient (a mea- diascopy, “poikilodermatous” skin often appears
sure of the “mean” direction of the scattered pho- no browner than the surrounding apparently nor-
tons). g = 0.9 for the skin. As μa and μs increase, δ mal skin. The explanation is that deoxy-Hb con-
decreases accordingly. For example, for hair tributes to a “pigmented skin appearance”. This
removal, based solely on depth of penetration, finding follows from the absorption spectrum of
longer wavelengths such as 800 and 1064  nm deoxy-Hb in the 630–700  nm range, which is
should be preferable to 694 and 755 nm. In the very similar to the absorption spectrum of epider-
visible light range, this is why red light can pen- mal melanin. The size of the vessels in the super-
etrate one’s hand when shining a flash light on ficial venous plexus is such that the transmitted
the surface. Scattering decreases roughly propor- light through these vessels is approximately 50%
tional to λ3/2, so that, for example, an 800-nm lower than the incident intensity. These vessels
photon will on average travel about 1.3 times as therefore appear dark [49].
far in tissue as a 700-nm photon without being In most biological systems, tissue constituents
scattered. It follows that for “more” scattering show broad absorption bands with only a few dis-
wavelengths, there will be greater accumulation tinct absorption peaks. From 200 to 290  nm
of photons near the surface. In addition to scatter- (UVC), all biological objects (cells and tissue)
ing, this superficial convergence of photons is absorb energy very strongly. From 290 to 320
based on index of refraction mismatches between (UVB) nm, only a limited number of biomole-
air and tissue [1]. Accordingly, light must be cules show absorption (aromatic amino acids and
deposited more slowly with shorter wavelengths nucleic acids). For UVA 320–400  nm, light is
to avoid overheating the superficial tissue. weakly absorbed by colorless skin parts. From
There is backscattered light that can yield a 400 to 1000  nm mainly pigments—bilirubin,
higher fluence beneath the tissue than at the tis- blood, and melanin absorb light. The heterogene-
sue surface [48]. This paradox of tissue optics is ity of the skin allows for discrete heating over
that the internal fluence can actually exceed that this range, and therefore selective photothermol-
at the surface, as below: ysis (SPT) is exploited in this band. For
>1100 nm, all biomolecules have specific strong
I = I o (1 + 6 R ) (1.5)
vibrational absorption bands. Tissue water is the
primary determiner of the response to laser in this
Where I is the subsurface energy density, Io is wavelength range [9].
the surface fluence, R  =  the surface remittance The absorption coefficient (μa) is the relative
(0.3, 0.6, and 0.7 for 585  nm, 694  nm, and “probability” per unit path length that a photon at
1064 nm respectively). (personal communication a particular wavelength will be absorbed. It is
from RR Anderson, 1994) therefore measured in units of 1/distance and is
Since neither macromolecules nor water typically designated μa, given as cm−1. The
strongly absorb in the red light and near IR (600– absorption coefficient is chromophore and wave-
1200 nm) this range allows deeper penetration in length dependent. For larger heterogeneous vol-
1  Laser-Tissue Interactions 13

umes, μa can be weighted according to the Melanin: Most pigmented lesions result from
fraction of a specific chromophore. For example, excessive melanin in the epidermis. By choosing
for a dermis a typical blood fraction (f.blood) is almost any wavelength (<800 nm), one can pref-
0.2%, assuming that the blood is uniformly dis- erentially heat epidermal melanin. Shorter wave-
tributed in the skin [7]. lengths will create very high superficial epidermal
Following the descriptive convention of temperatures, whereas longer wavelengths tend
describing an equivalent average homogeneous to bypass epidermal melanin (i.e., 1064 nm).
f.blood, the net absorption of the dermis, μa.derm, Fat: Fat shows strong absorption at 1200 and
is calculated: 1700 nm [51]. Although the ratios of fat to water
absorption are small, the small differences are
ma .derm = ( f .blood )( m a .blood )
(1.6) exploited with the proper choice of parameters.
+ (1 - f .blood )( m a .skinbaseline ) 1200 nm might represent the best choice due to

decreased overall water absorption and therefore
Scattering is responsible for much of light’s increased penetration. Sebum is similar to fat but
behavior in skin (beam dispersion, spot size also is comprised of wax esters and squalene.
effects, etc.). The dermis appears white because Carbon: Carbon is a product of prolonged
of light scatter. The main scattering wavelengths skin heating. Once carbon is formed at the skin
(relative to absorption) are between 400 and surface, the skin becomes “opaque” to most laser
1200 nm. Absorption occurs where the laser fre- wavelengths (that is, most energy will be
quency equals the natural frequency of the free absorbed very superficially). It follows that the
vibrations of the particles (absorption is associ- dynamics of surface heating changes immedi-
ated with resonance) [50]. Scattering occurs at ately once carbon is formed. This can be used
frequencies not corresponding to those natural creatively as an advantage. For example, one can
frequencies of particles. Scattering is decreased convert a deeply penetrating laser to one that
as wavelength increases [7]. would only affect the surface by using a carbon
There are four major chromophores (water, dye. This has been accomplished with a laser peel
blood, tattoo ink, and melanin) in cutaneous laser using a Q Switched Nd YAG laser.
medicine [50]. Water makes up about 65% of the Collagen: Dry collagen has absorption peaks
dermis and lower epidermis. There is some water near 6 and 7 μm. With a free electron laser oper-
absorption in the UV. Between 400 and 800 nm, ating at these wavelengths, collagen can be
water absorption is quite small (which is consis- directly heated. Ellis et  al. found that this
tent with our real world experience that light approach might allow for less tissue irradiation
propagates quite readily through a glass of water). and less thermal damage than CO2 laser [52].
Beyond 800 nm, there is a small peak at 980 nm,
followed by larger peaks at 1480 and 10,600 nm.
The water absorption maximum is 2940  nm Heat Generation
(erbium YAG).
Hemoglobin: There is a large HgBO2 (oxyhe-  elective Photothermolysis (SPT)
S
moglobin) peak at 415 nm, followed by smaller Non-bulk skin heating is based on selective
peaks at 540 and 577 nm. An even smaller peak is absorption by discrete chromophores of rela-
at 940  nm. For deoxyhemoglobin (HgB), the tively low concentration (i.e., melanin, hemoglo-
peaks are at 430 and 555 nm. The discrete peaks bin). Dr. Leon Goldman showed that color
of hemoglobin absorption allow for selective ves- contrast allowed for selective damage of dermal
sel heating. Although the 410 nm peak achieves targets as early as 1963 [53]. However, it was Dr.
the greatest theoretical vascular to pigment dam- RR Anderson who elegantly described the con-
age ratio among the other peaks, scattering is too cept of selective photothermolysis [26]. Selective
strong for violet light to be a viable option for photothermolysis offered a mathematically rigor-
vascular applications. ous rationale for tissue-selective lasers. As
14 A. A. Lloyd et al.

described by Dr. Anderson, extreme localized assume instantaneous heating of the target, so
heating relies on: (1) a wavelength that reaches that τ is the time for cooling after the pulse. If the
and is preferentially absorbed by the desired tar- pulse is too long, the target cools during the
get structures; (2) an exposure duration less than pulse, akin to one pouring water slowly into a
or equal to the time necessary for cooling of the leaky bucket. If the water represents heat, one
target structures; and (3) sufficient energy to observes that the bucket never fills (akin to a tar-
damage the target. The heterogeneity of the skin get never becoming very hot). If one wants to
allows for selective injury in microscopic targets. spatially confine heating one chooses a short
The focal nature of the heating decreases the like- pulse less than τ of the chromophore. For the
lihood of catastrophic pancutaneous thermal same volume, a sphere will cool faster than a cyl-
damage. For example, one can apply a 4  mm inder, which will cool faster than a slab. When
laser beam and observe only a 1 mm wide tattoo defining thermal relaxation time, the target size
line “whiten” with Q switched Nd YAG laser and geometry are important. Normally, τ is
with a larger round spot (Fig. 1.7)—the skin out- defined by:
side the tattoo but within the spot will appear nor-
d 2 / gk (1.7)
mal. Also, a darker lentigo will become white but
a lighter lentigo will remain unchanged. The pri- where δ is the optical penetration depth for
mary areas where SPT is helpful in dermatology homogeneously absorbing layers (such as tissue
is in the treatment of vascular lesions, tattoos, water for IR applications), and κ is the thermal
and pigmented lesions. However, even in applica- diffusivity (a measure of heat capacity and con-
tions where water is the chromophore, the prin- ductivity—for tissue, κ ~ 1.3 × 10−3 cm2/s). For
ciples of SPT are useful, as one can design precise discrete absorbers, i.e., the melanosome or a
heating and ablation protocols based on wave- blood vessel, τ is defined in terms of the particle
length and pulse duration [54]. size, and δ represents the diameter of the particle.
κ is the thermal diffusivity, a quantity based on
Thermal Relaxation Time the thermal conductivity and specific heat of the
The thermal relaxation time (τ) is the interval medium, and “g” is a constant based on the
necessary for a target to cool to a certain percent- geometry of the target (slab, cylinder, or sphere)
age of its peak temperature [28]. Larger objects [26]. See Table 1.2 for sample thermal relaxation
require longer times than smaller volumes to times for common targets in skin.
cool. For example, a tubful of warm bathwater The often-used term “thermal relaxation time
requires much longer than a thimbleful to cool to of the skin” is meaningful only when used for
room temperature. With laser irradiation, we specific wavelengths (or specific skin structures,
i.e., the epidermis). With a ubiquitous absorber
such as tissue water, τ should be considered
within the context of  the wavelength dependent
optical penetration depth (δ) and the laser source,
not the dimensions of the skin constituents. For

Table 1.2  Thermal relaxation time of some potential

targets
Erythrocyte—2 μs
200 μm hair follicle—40 ms
Melanosome (0.5 μm)—0.25 μs
Nevus cell (10 μm)—0.1 ms
0.1 mm diameter vessel—10 ms
Fig. 1.7  Tattoo treated with 4 mm spot Q YAG laser; note
0.4 mm diameter vessel—80 ms
only 1 mm linear tattoo is heated (indicated by immediate
frosty whitening)  0.8 mm diameter vessel—300 ms
1  Laser-Tissue Interactions 15

example, if one uses the 1540 nm laser, the entire wave of heat diffuses from this cylinder, the tem-
epidermis and large portions of the dermis are perature decreases.
heated, and τ is on the order of seconds, because Spatially selective temperature elevation is
δ is several hundred micrometer. So even though possible when (1) the absorption coefficient of
τ of the epidermis is about 10  ms based on its the target exceeds that of collateral tissue (selec-
thickness, a thicker slab of skin is heated at tive photothermolysis), or (2) when the “innocent
1540 nm, the epidermis will take several seconds bystander” tissues are cooled so their peak tem-
to cool because there is little temperature gradi- peratures do not exceed some damage threshold
ent between it and that of the dermis. or (3) with very small microwounds (fractional).
For most targets a simple rule can be used: the Localized heating, for example, in telangiectasia
thermal relaxation time in seconds is about equal and lentigines, follows from the concentrations
to the square of the target dimension in millime- of blood and melanin there, respectively, such
ters. Thus a 0.5 μm melanosome (5 × 10−4 mm) that μa is focally increased. Verification of the
should cool in about 25  ×  10−8  s, or 250  ns, models can be made by real-time measurements,
whereas a 0.1  mm PWS vessel should cool in thermocouple needles, thermal cameras, etc.
about 10−2  s, or 10  ms. Recall that τ is derived The geometry (and therefore the microscopic
from a solution of a differential equation and characteristics) of lesions is important—for
does not represent an absolute cooling time, but example in the treatment for a nevus versus a len-
rather provides approximate pulsewidths for tigo, the nevus is composed of melanocytes in
varying degrees of thermal confinement [13]. aggregates as nodules (collectively the nodules
Once the local subsurface energy density has are often several hundred micrometer in diame-
been determined (Eq. 3), heat generation can be ter) whereas the lentigo is a mere sheet of mela-
predicted by energy balance (conservation of nocytes some 10  μm thick. For example, in
energy), pulse duration, thermal relaxation time, treating nevus with a long pulsed alexandrite
and the wavelength specific absorption for that laser with a high fluence, the TRT will approach
target. a second. From the above equation, it follows that
The temperature increase of a desired target thermal confinement will be high, and the peak
can be roughly calculated by knowing the absorp- temperature will rise accordingly. More impor-
tion and scattering coefficients, surface light tantly, the thick slab of melanocytes will take
dose, size of the target, and the length of the long to cool, such that the will be considerable
pulse, as follows: heat diffusion away from the target. On the other
g/2 hand, the lentigo represents a slab only tens of
Fm æ tr ö microns thick; there will be heat diffusion during
DT = z a çç ÷÷ (1.8)
rc ètr +t p ø the long pulse and rapid cooling after the pulse.
Thus, with ms-domain fluences, the nevus case
where Fz is the local subsurface fluence, ρ is might result in scarring, and a lighter lentigo
the density, c is the specific heat “g” is a geomet- might not become hot enough for clearance. If
ric factor (“1” for planes, “2” for cylinders, and one applies ns pulses to the two lesion types, the
“3” for spheres), τp is the laser pulse duration, lentigo shows a good response with possibly
and τr is the thermal relaxation time of the target complete clearing, whereas the nevus will require
(time for target to cool to 37% of peak tempera- multiple sessions, as each laser application will
ture), defined by Eq. 1.7. Thus one can perform result in heat confined to the most superficial part
some quick algebraic calculations to estimate the of the lesion.
peak temperatures of local targets in the skin. The Two “offshoots” of SPT are the concepts of
temperature generally decays as a function of thermal damage time and thermokinetic selectiv-
diameter and time from the target. For ex, in hair ity (TKS).
removal the shaft and bulb, heavily invested with Thermal damage time. In some applications
melanin, reach high temperatures, and as the the immediate absorber and the intended target
16 A. A. Lloyd et al.

are not collocated (i.e., hair shaft and hair bulb/ state, followed by a complete relaxation into
bulge). Thermal damage time is defined as the vibrational modes (internal conversion).
pulsewidth that achieves irreversible target dam- However, NIR wavelengths and beyond are
age with sparing of the surrounding tissue. The absorbed via rotational and vibrational excita-
thermal damage time represents the interval tions in biomolecules (all of which are hydrocar-
when the outermost part of the target reaches the bons with the exception of pigments). These
target damage temperature through heat diffusion reactions can be considered a two-step process.
from the heater. In this case the eventual target In the first the molecule is “pumped” to an excited
and the heater (for example, hair shaft) are differ- state. Then, through a process known as non-­
ent and at a considerable distance from each radiative decay, there are inelastic collisions with
other [55]. Using this model, the thermal damage nearby molecules [50]. The temperature rise
time can be many times longer than the thermal results from the transfer of photon energy to
relaxation time. For example, for laser hair kinetic energy.
removal, with a 100 μm shaft and 30 μm follicle, For thermal reactions to occur, the energy
the TDT can approach several hundred millisec- must be randomized with a large ensemble of
onds [55]. molecules through statistical processes. With
Thermokinetic selectivity: Along the same HgB, the electronic excited state gives way to
lines is the concept of thermal kinetic selectivity vibrational modes. With longer wavelengths, the
(TKS). Using this principle, one selects larger or quantized energy packets correlate with vibra-
smaller targets for heating based on pulse dura- tional transitions from NIR and MIR.
tion. For example, if one wants to damage larger
targets while sparing relatively smaller ones, the
pulse duration is extended beyond the thermal Reaction Types and Effects of Heating
relaxation time of the smaller target. In this man-
ner, i.e., a melanosome will be heated to a lower • Photochemical effects (usually 10–1000  s;
temperature than the subjacent vessel. 10−3–10 W/cm2)
• Photothermal effects (1  ms–100  s; 1–106  W/
 olecular Basis of LTI
M cm2)
Most devices for cosmetic rejuvenation are based • Photomechanical and photoionizing effects
on photothermal or “electrothermal” mecha- (10 ps–100 ns; 108–1012 W/cm2)
nisms, that is, the conversion of light or electrical
energy to heat. Two fundamental processes gov- Photothermal Effects
ern all interactions of light with matter: absorp- Photothermal processes depend on type and
tion and scattering. Absorption and excitation are degree of heating, from coagulation to vaporiza-
necessary for all photobiologic effects and laser-­ tion. With a very short pulsewidths (pw), lasers
tissue interactions. Energy is proportional to fre- vaporize targets. For example, in treating blood
quency and inversely proportional to wavelength. vessels, rapid heating results in acute vessel wall
Thus a 532  nm photon (532  nm is the distance damage and petechial hemorrhage (with Q
between two of the transverse waves in a stream switched 532  nm) [56–58]. With intermediate
of light) is twice as energetic as a 1064  nm length pulses (0.1–1.5  ms), one can gently heat
photon. targets without immediate rupture of the vessels.
Macroscopically, the atomic events in LTIs Still intravascular thrombosis can create purpura
are not identifiable, but on the molecular level, and delayed hemorrhage. With still longer pulses
EMR exchanges energy only in discrete quanti- (6–100 ms), the ratio of contraction to thrombo-
ties (photons). The molecular basis of LTIs is sis increases and side effects are less likely. On
based on electronic transitions for the ultraviolet the other hand, too long pulses with very small
(UV) and visible (VIS) wavelengths. For exam- targets can create two problems. With highly
ple, hemoglobin is excited to a higher electronic absorbing targets, (i.e., tattoo inks)—the heat
1  Laser-Tissue Interactions 17

shorter wavelengths and are therefore preferable

for treatment. In fact, as the blood temperature
rises during laser irradiation, 532 nm light trans-
mission increases and longer wavelength (i.e.
595 nm) transmission decreases [29, 60].
Even after the heating source is removed,
whole blood optical properties change. A macro-
scopic coagulum emerges comprised of dena-
tured HgB, cell membranes of erythrocytes and
plasma proteins. Met HgB formation is also
important, with absorption peaks near 630–
635  nm. With increasing met HgB and deoxy
production, 755–1064  nm lasers penetrate less
Fig. 1.8 Figure shows extensive damage from long
pulsed 1064 nm irradiation of tattoo particle and will generate more heat in vessels. This is
one argument for sequential pulses with 1064 nm
lasers. One potential downside of this is that an
generation is so great and long-lived that signifi- abrupt increase in absorption, particularly with
cant diffusion occurs to the surrounding dermis 940–1064  nm, causes too much collateral
(Fig. 1.8). On the other hand, using a long pulse damage.
YAG for a nevus of Ota results in an insufficient
temperature rise as the pigmented nevus cells Thermal Injury to Cells
cool off too fast during the delivery of the pulses There is a range of measurable effects on skin
(also melanin absorption is much weaker than based on temperature. Below 43  °C, the skin
black ink). remains intact, even for very long exposures [45,
A mild–moderate temperature increase results 61]. The first change is a conformational change
in denaturation of enzymes and function. If the in the molecular structure that occurs at tempera-
heating is very fast, a phase change occurs [50, tures from 43 to 50  °C.  After several minutes,
59]. Depending on the rate of energy delivery, there will be tissue necrosis as described by the
photovaporization occurs with or without inertial Arrhenius equation (an equation that quantita-
confinement (vide infra), where time is short tively describes conversion of tissue from a native
compared to the time for pressure relaxation. to denatured state). Thermal denaturation is a rate
Here the laser induced pressure causes compres- process: temperature increases the rate at which
sive stresses in tissue. Microcracks in the tissue molecules denature, depending on the specific
are the result of these large stress gradients [13]. molecule. For example, at 45 °C, cultured human
Whitening after ns irradiation is thought be gas fibroblasts die after about 20 min. However, the
vacuoles with scattering that resolve as the as the same cells can withstand over 100 °C for 10−3 s.
“spaces” are refilled with interstitial fluid. In general, a temperature of >60° lasting for at
Hemoglobin undergoes a complex set of reac- least 6 s leads to irreversible damage.
tions when heated. Formation of met HgB and
deoxy HgB occur during irradiation on the order Coagulation
of ms, representing a real-time change in tissue Temperature, directly related to the average
optics. During the heating phase, hemoglobin kinetic energy of molecules, is a critical factor in
absorption undergoes a bathochromic (red) shift tissue coagulation. Denaturation depends on time
of the 580 nm absorption peak (the 540 nm peak and temperature, and at least for exposures >1 s,
does not shift). This has important implications conforms to a rate process as described by the
for designing optimal blood vessel protocols. For Arrhenius equation. The characteristic behavior
example, it has been suggested that 585  nm of the Arrhenius-type kinetic damage model is
though 600  nm should penetrate deeper than that, below a threshold temperature, the rate of
18 A. A. Lloyd et al.

damage accumulation is negligible; and it away from the skin. The evaporation of tissue
increases precipitously when this value is water acts as a sort of buffer, reducing the peak T
exceeded. An example of coagulation is the cook- to just over 100 °C. When there is vaporization
ing of an egg white. Thermal denaturation is both there is also increasing pressure as the water tries
temperature and time dependent, yet it usually to expand in volume. The expansion leads to
shows an all or none like behavior. Most denatur- localized microexplosions. At the surface, parti-
ation reactions follow first order rate kinetics. For cles are ejected at supersonic velocities. At tem-
a given heating time there is usually a narrow peratures beyond 100  °C (without further
temperature region above which complete dena- vaporization), carbonization takes place, which is
turation occurs. As a rule, for denaturation of obvious by blackening of adjacent tissue and the
most proteins, one must increase the temperature escape of smoke. Carbon is the ultimate end
by about 10 °C for every decade of decrease in product of all living tissues being heated and car-
the heating time to achieve the same amount of bon temperatures often reach up to 300 °C. When
thermal coagulation [13]. treating a wart at low power densities with the
An absolute temperature for coagulation-­ CO2 laser, one can observe almost simultane-
denaturation does not exist. For very short times, ously incandescence and combustion. In water
higher temperatures than the oft-quoted “62– free structures, such as char, temperatures can
65 °C” should be required. Early signs of micro- reach 1000  °C, and incandescence can be
scopic damage are vacuolization, nuclear observed with continued irradiation of char at
hyperchromasia and protein denaturation (recog- long pulse cw CO2 lasers. Normally, this should
nized as a birefringence loss for collagen). be avoided, because the depth of tissue injury
Moderate temperature-induced damage phenom- will extend well beyond the blackened skin sur-
ena in tissue are difficult to assess with conven- face [50]. This is particularly true, for example,
tional light microscopy. In fact, histology when treating a rhinophyma or performing laser
represents and conveys the overall reactions of a skin resurfacing.
complex system and cannot be related to molecu-
lar species. Specimens obtained 24 h after irradi- Photomechanical Effects
ation tend to be more sensitive than those obtained With very short pulses, there is insufficient time
immediately after treatment, as often a day is for pressure relaxation. Mechanical damage is
required to show sign of necrosis; also, an inflam- observed with high-energy, submicrosecond
matory response might be the most sensitive indi- lasers for tattoo and pigmented lesion removal.
cator of injury. Particularly in light of newer large The time threshold for inertial confinement is
volume low intensity heating devices for rejuve- predicted by the relation [1]:
nation, more sensitive tools might be required to d /v (1.9)
characterize subtle thermal effects. Beckham
et al. [62]. found that over a narrow temperature where δ is the target diameter and v is the
range, heat shock protein (HSP) expression cor- velocity of sound in tissue.
related with laser induced heat stress, and that the Inertially confined ablation occurs when there
HSP production followed the Arrhenius integral. is high-pressure at constant volume. In a very
Thus HSP expression (in addition to tissue ultra- short pulse, the energy is invested so quickly one
structure, i.e., EM) might be an excellent tool to that there is no time for the pressure to be relieved.
examine low intensity high volume heat injury. Under these conditions of inertial confinement,
there’s not enough time for material to move—
Vaporization this can lead to the generation of tremendous
At a certain threshold power density, coagulation pressures and relief through shock waves. For
gives way to photovaporization (ablation). Water example, one can feel the recoil during laser tat-
expands as it is converted to steam. Vaporization too treatment if one touches the skin surface near
is beneficial in that much of the heat is carried the impact site.
1  Laser-Tissue Interactions 19

Photochemical Effects light (DUSA, Vahalla, NY) or Omni Lux

The absorption of light in tissue does not always (Phototherapeutics, CA, USA) will outperform a
generate heat. A term luminescence describes pulsed source (IPL, KTP, or PDL) for AKs with
cases where absorbed light causes emission of one treatment. However, largely because most
light of a different color. This occurs after elec- practitioners posses at least one pulsed visible
trons are excited from some lower (ground) state, light source, they have been widely used in PDT
to an upper level, excited state. If the process is and shown to be useful in a range of PDT-­
fast, fluorescence occurs. If the is an intermediary responsive skin disorders [64, 65]. Because
reaction and longer decay time, phosphorescence pulsed light sources in dermatology do not meet
occurs. Most photochemical reactions occur in the theoretical PDT saturation threshold
the UV and violet portion of the spectrum as the (4  ×  108  W/m2) [66], in theory there should be
electronic transitions demand highly energetic significant PDT activity [67].
photons. Most photochemical activity is observed
Photochemical reactions are governed by spe- between 320 and 630  nm. The main absorption
cific reaction pathways, whereas thermal reac- peaks for PpIX are 415, 504, 538, 576, and
tions tend to be non specific. Photochemical 630  nm. Beyond 800  nm, photochemistry, even
reactions include fluorescence, phosphorescence with exogenous photosensitizers or pro-drugs, is
and photodynamic action. The former two unlikely. PDT reactions are complex; for exam-
involve the reemission of light after absorption at ple, with ALA, optimization require an under-
lesser wavelengths. Fluorescence spectra are standing of skin pharmacokinetics, conversion
increasingly used in diagnostic applications. An kinetics of ALA to PpIX, and proper delivery of
example is PpIX fluorescence to determine the light dose (including power density, wavelength,
amount of photosensitizer (PS) in the skin after etc.). A new development is a possible role for
application of ALA.  Fluorescence spectra can vascular specific therapy with PDT.  Both with
also be used to assess collagen content in the hematoporphyrin and benzoporphyrin deriva-
skin. Also, keratin fluoresces such that a milium tives, this approach is being investigated for
will display a bright yellow color during irradia- refractory deeper vascular lesions [68].
tion with a green light laser. We have occasion-
ally used this technique to distinguish a Photodisruption or Photodecomposition
deep-seated milium from a small pearly This reaction type is usually observed at 107–
BCC. Endogenous fluorescence applications are 108 W/cm2 in the UV range. Usually there is little
increasing and have included assays of NADH, residual thermal damage (RTD).
collagen, and amino acids [63]. Rather than heating water directly as their FIR
In photodynamic reactions, a photosensitizer counterparts, these lasers can exceed the bond
(acting as a catalyst) is excited by a certain wave- energies of many organic compounds. Among the
length of light. The PS then undergoes several available wavelengths (193, 241 and 308  nm)
sequential decays, forming singlet O2. In the XeCl (308 nm) is more likely to be more thermal
presence of oxygen, oxygen is transformed from because of the lowered energy per photon.
its triplet state, which is its normal ground state,
to an excited singlet state. The excited singlet Excimer Laser (308 nm)
state oxygen reacts with biological molecules The mechanism of action for the excimer laser
and attacks plasma and intracellular membranes (XeCl) is thought to be the same as narrow band
(type II PDT reactions). The most common pho- UV therapy. A reduction in cellular proliferation
tosensitizer (PS) in dermatology is PpIX. This PS most likely plays a role in epidermal cellular
is formed by skin cells by the pro-drug, ami- DNA synthesis and mitosis. In Parrish’s original
nolevulinic acid (ALA). Most photochemical study in 1981, he showed that wavelengths
reactions proceed more efficiently with lower between 300 and 313  nm were most effective
power densities, such that for example, the Blu-U [69]. It appears that the excimer laser works
20 A. A. Lloyd et al.

through in an immunomodulatory way much like  eat Conduction Away

H
standard non coherent UVB “light boxes”. There from the Chromophore
may be a thermal component as well at fluences
>800 mJ/cm2. This final “physical” step in LTIs in important in
characterizing collateral damage. Once heat is
Biostimulation generated, heat losses are based on heat conduc-
Biostimulation belongs to the group of photo- tion, heat convection, or radiation. Radiation can
chemical interactions. Increasingly this field is be neglected in most types of laser applications.
validated by the number of well-executed investi- A good example of heat convection is transfer
gations. Typical fluences are in the range of from blood flow. Heat conduction is the primary
1–10 J/cm2, and temperature elevation is absent. mechanism by which heat is transferred to unex-
Potentially positive reactions include (1) Increase posed tissue structures.
in phagocytic activity (2) Depression in rate of
bacteria replication (3) Increase in repair of skin, Cooling
and (4) Stimulation of wound healing. We should Surface cooling enhances efficacy and safety in
not debunk these applications—certainly they are skin laser surgery, especially for visible light tech-
being studied more and we are witnessing a tran- nologies, (i.e., green–yellow light sources such
sition from lab to bedside. One example of a “bio- as IPL, KTP laser, and PDL) that are popular in
stimulation” device is the Gentlewaves LED cutaneous laser surgery. They are also the wave-
Photomodulation unit (Light BioScience, LLC, length ranges where epidermal damage is most
Virginia Beach, VA). This device uses 590  nm likely. The epidermis is an innocent bystander in
light in a high repetition rate and low power den- cutaneous laser applications where the intended
sity to increase collagen synthesis and enhance targets, such as hair follicles or blood vessels, are
facial tone. Cell culture work supports this con- located in the dermis. Specifically, absorption of
cept [70]. Newer LED devices (800 nm) also sup- light by epidermal melanin causes skin surface
port a role for photorejuvenation and even hair heating.
growth. It is unknown if any special features of The first goal is of surface cooling is preserva-
laser light are relevant for biostimulation, although tion of the epidermis. The second and related
at least one study supports coherence as a possible goal of surface cooling permits higher fluences to
factor in photomodulation. Some investigators the intended target (i.e., the hair bulb and/or
have shown that laser showed the best effect while bulge or a subsurface blood vessel). Another ben-
the non-coherent LED light showed the poorest. efit of surface cooling is analgesia, as almost all
Coherence does not influence the transmission; cooling strategies will provide some pain relief
rather, because of interference in the scattered [71–79].
light field, coherency influences the microscopic The timing of the cooling relative to the
light distribution into tissue. laser pulse is important. Cooling can be pre,
during the pulse (parallel), or after the pulse
Plasma Induced Ablation (post) [79]. Post cooling may prevent retro-
With very high power densities exceeding 108 W/ grade heating (i.e., from the vessel back to the
cm2, optical breakdown occurs. Plasma removes epidermis) from damaging the skin surface. A
skin without evidence of mechanical or thermal cooling protection factor (CPF) has been pro-
damage when choosing appropriate parameters. posed by Dr. Rox Anderson. The cooling pro-
Plasmas are sometimes produced by laser tattoo tection factor is the ratio of fluence, with and
removal, where one can observe a spark [13]. without surface cooling, that spares the epider-
There is a new resurfacing system that uses mis. It is defined by:
plasma created by an RF excited N2 gas. Unlike Tc - Tic
laser-induced plasma, this flame heats tissue by CPF = (1.10)
Tc - Ti
direct heat transfer from the plasma edge.
1  Laser-Tissue Interactions 21

In the above equation, Tic and Ti are basal layer in macrophages of the dermis—the combination
temperatures before laser irradiation with and of gold and Q-switched lasers produces a
without cooling, respectively. Tc is the critical photothermal-­ photochemical conversion such
temperature at which thermal injury occurs. The that the gold darkens to a light blue or grey color
detailed calculations described later indicate that (Fig. 1.9). This reaction is a good teaching tool in
if the initial skin temperature is 30  °C, contact that it points out the role of pulse duration on the
cooling reduces the temperature of the basal layer laser tissue interaction [80, 81]. As noted earlier,
to about 20 °C. If Tc is assumed to be 60 °C (it is some reactions are dependent on power den-
actually somewhat higher for the brief laser sity—with higher power densities, multi-photon
exposure times in this analysis), this would give interactions are possible, that is, the energy is
the CPF as (60–20)/(60–30) or 1.33. Similarly, condensed into such a short duration, that simul-
cryogen cooling reduces the temperature to about taneous “arrival” of two photons at the same
0 °C, thus giving a CPF value as (60–0)/(60–30) locale can result in two-photon absorption. In the
or 2.0. Finally, there is convective air cooling, case of gold, the chemical compound structure
where cold air is commonly used in skin chilling. can be changed (from crystalline to elemental).
The Zimmer (Cyro5, Zimmer Medizin Systeme, Once the reaction occurs, one can apply longer
Ulm, Germany) directs −10 °C air at the skin at a pulses to diminish the dyspigmentation (even
rapid rate (1000 L/min). This system proves for with the same wavelength!). This reaction also
good bulk cooling but spatial localization of the underscores the importance of beam scattering,
cooling is poor. The CPF, depending on the air as the “gold” Q-switched laser reaction extends
temperature and nozzle velocity, is near that of beyond the diameter of the beam with each pulse.
contact cooling.

 ome Interesting Concepts

S
and Ideas in Laser Tissue
Interactions

With Q switched lasers, one might hear a loud

“pop” accompanied by a spark-like emission at
the skin surface. Normally this is the result of
inorganic compounds (make-up) remaining in
the skin during irradiation. Thorough cleaning of
the skin will remove this distraction. One should
ensure that any dark markers are off the skin,
especially when using long pulsed visible light
technologies. For example, one of our trainees
placed a black marking pen to outline an area for
a test spot for laser hair removal. During irradia-
tion, the beam was absorbed almost completely
by the ink—the hot ink cooled at the expense of
the skin surface, such that a very superficial burn
occurred.
Also, one should consider oral medications
both in the genesis of treatable lesions (i.e.,
­minocycline hyperpigmentation), and in the cau-
sation of pigmentation disturbances (i.e., gold).
In the case of gold, the medication is sequestered Fig. 1.9 Note blue macules
22 A. A. Lloyd et al.

Focusing the laser beam: A trick to increase with similar microvolumes of injury, that is, even
the dermal to epidermal damage ratio is use of a when the same total volume is observed, wound
convergent lens. This tool increases the local healing proceeds differently.
radiant exposure in the dermis (targeting the hair In the most common approach, 75–150  μm
bulb, a blood vessel, or dermal water). wide microwounds are created in the skin
Theoretically, one should be able to use smaller (Fig.  1.10) with densities ranging from 100 to
incident fluences, therefore achieving some pro- 1500  microwounds/cm2. By spatially confining
tection of the epidermis.
Vacuuming the target in the laser beam: A
company (Aesthera, Livermore, CA) has created
a pneumatic device whereby the skin is vacu-
umed into the light path such that the light pene-
tration in skin is enhanced. In this way more
energetic high frequency photons can be deliv-
ered, for example, to the hair follicle, with rela-
tive epidermal sparing. By applying suction, the
absorption coefficient of the epidermis can be
reduced by up to 25%. The technologies have
also been used for acne and pain reduction.
By proper timing of the suction with respect to
irradiation, selective targeting of various chromo-
phores can be achieved, for example, to increase
the dermal blood fraction in pale PWS (and
increase the blood vessel diameter). The very
small vessels in paler PWS have too small vessel
diameters for thermal confinement—that is, the
vessels cool too quickly to reach a critical tem-
perature. By applying suction, the blood volume
fraction increases, not simply a result of the
mechanical force but a physiologic response as
well [82, 83].
Pixilated Injury (aka fractional photothermol-
ysis): One can use a “pixilated” injury with water
as a chromophore in what is called fractional
photothermolysis. Roughly 100  μm spots have
been used with 250–500  μm spacing [84]. The
tissue can recover from this fractional injury
without the widespread epidermal loss observed
after traditional resurfacing applications. A num-
ber of technologies have been introduced. Despite
a wide range of devices, the pitch, wound diam-
eter, wound depth, and other wound features have
not been optimized. Ideally one would design
devices that maximize downtime while maximiz-
ing cosmetic enhancement. One can consider
ablative and non ablative approaches. Early evi-
dence suggests that there is a difference between
ablative and non ablative wound healing even Fig. 1.10  Note damage pattern with 1540 nm microbeam
1  Laser-Tissue Interactions 23

the micro-lesions, deeper wounds can be created ers on routine histology. Particularly for the erbium
than with a “slab-like” approach, while still man- YAG laser, there is immediate water loss through
aging a larger measure of safety. There are both these portals of entry [85], and postoperative dis-
ablative and nonablative approaches. Ablative comfort is often severe for an hour after the proce-
devices include the Profractional laser (Sciton), dure. Pinpoint bleeding is sometime observed,
equipped with a scanned microbeam, the Pixel particularly with higher-­pulse energies and shorter
erbium YAG laser from Alma (Alma lasers, pulsed erbium YAG applications.
Buffalo Grove, IL), and a newly introduced Optical damping: Replacing air (n = 1.0) with a
2940  nm technology from Palomar. Reliant higherindex medium at the skin surface such as
Technologies manufactures a fractional CO2 laser glass (n = 1.5) or sapphire (n = 1.7) tends to spare
system (Re Pair) that creates 125  μm diameter the epidermis. This effect has nothing to do with
“ablative” wounds as deep as 1 mm. Early inves- heat transfer, but rather is a consequence of optical
tigations have shown immediate superficial skin scattering behavior. At wavelengths from about
tightening. 600–1200 nm, most light in Caucasian epidermis is
“Macrowound” fractional technologies create back- and multiply-scattered light. By providing a
wounds >300 μm in diameter. These include the match to the skin’s refractive index, internal reflec-
KTP laser with a scanner (with approximately tion of the back-scattered light is greatly reduced,
700 μm wounds) as well as the active FX CO2 sys- decreasing the natural convergence of photons at
tem (Lumenis, Santa Clara, CA), which creates an the skin surface. This version of optical epidermal
array of 1.3  mm wounds and covers approxi- sparing requires a physically thick external medium
mately 60% of the surface area per session. such as a sapphire window or heavy layer of gel.
Wound depths range from 80 to 150 μm depend-
ing on pulse energy. Fluences with these
approaches range from 5 to 15 J/cm2. The applied Compacting the Dermis
fluences are another means (besides wound diam-
eter) to differentiate microwound injuries from One can decrease the depth photons must propa-
macrowound injuries. With ablative micro- gate by applying pressure over the treated area.
wounds, fluences tends to exceed 30× the ablation This maneuver may, for example, decrease the
threshold, whereas with traditional resurfacing relative depth of the bulb and bulge of the hair
laser applications (CO2 and erbium) fluences follicle up to 30% relative to the skin surface.
range from 0.8 to 10× ablation threshold per pass. Disadvantages include variability in the amount
The original non ablative fractional laser was of pressure, such that adjacent treatment areas are
(Reliant Technologies, Mountain View, CA), exposed to different subsurface fluences. Also, it
deploying a 1550  nm scanned microbeam that is unclear if compacting the dermis might alter its
required a surface blue dye for proper tracking scattering properties. In theory compression
along the skin. The newer Fraxel  technology should decrease water content and improve der-
achieves deeper wounds and does not require the mal transmission [86].
dye. Palomar introduced a fractional 1540-nm sys- Spot diameter: In general the spot size should
tem. This device uses a “stamping” approach, be 3–4×  >  δ  (for wavelengths where scattering
where each 10  mm macro-spot is comprised of dominates absorption), as larger spots make it
100 beamlets. With progressive passes, an increas- more likely that photons will be scattered back
ing skin surface area is covered. Another nonabla- into the incident collimated beam [13]. Photons
tive example is a 1440-nm/1320-nm Nd YAG laser scattered out of the beam are essentially wasted.
(Affirm, Cynosure, Chelmsford, MA) that delivers Traveling “alone”, they carry insufficient energy
hundreds of beamlets interspersed with a relatively to cause macroscopic thermal responses. The
uniform low-fluence background irradiation. consequences of spot size can be explained best
After high-fluence fractional CO2 and erbium on surface to volume arguments. Larger beams
YAG laser (50–200 J/cm2), one observes microcrat- (with the same surface fluence as smaller beams)
24 A. A. Lloyd et al.

create deeper subsurface cylinders of injury ple, can increase local blood flow, as can applying
because there is less surface versus volume for heating pad or simply placing a patient in
photons to escape. Basically, for small beams Trendelenburg position. One of our patients actu-
(narrow), scattered photons are carried out of the ally performs jumping jacks prior to her rosacea
beam path after only a few scattering events. As a laser therapy to increase the response [87].
clinical example of the effect of spot size, we Most laser tissue interactions are threshold-­
have found for 3  mm vs. 6  mm spots with the based, that is, a certain amount of energy must be
YAG laser that roughly ½ the fluence is required invested over a specific time to achieve the
with the larger spot for leg vein clearance. For desired efficacy. For example, to lighten a lentigo
shallow penetrating lasers such as CO2 and on the nose, even ten very–low-fluence passes, so
erbium where the δ ≪ spotsize (all cases except long as the interval between passes is long enough
for fractional devices), the diameter of the beam to preclude cumulative heating, will not result in
does not affect the tissue response. That is why clearance. The analogy is a smallish man trying
equivalent results can be obtained for skin resur- to push a car up a hill. Even if the man were to
facing using pulsed CO2 lasers versus scanned, arrive every day at 6 AM to push the heavy car,
tightly focused cw CO2 lasers [44]. Although the vehicle will remain stationary. There is no
studies suggest that large spots increase the ratio incremental car movement each day. One “laser”
of dermal to epidermal damage (usually desir- exception to this analogy is perhaps tissue tight-
able, for example, when treating a hair bulb), ening and protein denaturation over large vol-
there are instances where small spots are desir- umes with complex molecules (i.e., collagen),
able. For example, when treating a smaller vessel where repeated low impact low fluence passes
with an Nd YAG laser, a small spot with higher have been shown to increase the percentage of
fluence will result in a higher percentage of the denatured collagen fibers recruited in to the tight-
energy being invested in vessel heating versus ening process. Part of this phenomenon might be
larger spots. For any turbid medium, even if the secondary to differential denaturation tempera-
spot is “top hat”, there will be an accumulation of tures of older versus younger fibers.
photons near the center of the beam such that a When treating vascular lesions, multiple
greater clinical effect will often be noted at the “low” fluence passes can achieve cumulative
center of the spot. improvement. For example, a second pass even
Changing optical properties in real-time: seconds after an initial pass with the YAG laser or
Chromophore concentrations can change during a PDL will achieve additional bluing of an angi-
treatment session. One should never consider each oma. The dynamics of vascular heating is some-
laser tissue interaction as an independent event, but what different than for water and melanin. In
rather a cumulative process where visual endpoints vascular applications, dynamic changes in blood
are the most important ally for the physician. properties play a role. Met-Hg is produced by
Optical properties of the skin are like the weather one pass so that additional passes can result in an
[3], and one must accommodate the changes in increase in absorption. Also the partial clot
real-time. For example, the dermal blood fraction enhances absorption venous red blood.
increases after one pass of the PDL, such that for a With pigment lesions, repeated laser pulses
second pass, the skin temperature will increase due delivered over short periods (0.25–1 s) intervals
to the higher μa. The phenomenon will, for exam- results in progressive graying or darkening of the
ple, lower the purpura threshold on a second pass. lesions. On the other hand, repeated passes (after
On the other hand, general anesthesia can decrease >1 min) will result in cumulative extent.
the blood flow in PWS and require a higher light Both immediate and delayed pigmented dark-
dose. A failure to respond to these real-time ening (seconds to minute after irradiation) after
changes accounts for many laser treatment short- application is most likely due to optical property
comings. In treating a PWS, tetracaine, for exam- changes in melanin as well as erythema deep to
1  Laser-Tissue Interactions 25

the lesions that might add to the darkening per- a more superficially penetrating laser by having a
ception of (Fig. 1.11). fine carbon layer at the surface. For example, one
Optical clearing with hyperosmolar solutions: can “convert” a 694  nm ruby laser into a laser
Transparency of the skin is enhanced by topical with CO2 laser like effects by applying a fine
application or intradermal injection of solutions layer of graphite from a copy machine to the skin
such as glycerin [88]. Water and collagen become surface. In this way the 694  nm laser energy is
less bound such that the effective scattering coef- confined to the surface by the almost 100%
ficient of the dermis is reduced. Already this con- absorption by carbon. This fine layer of heated
cept has been applied to increase the visibility of materiel then cools much like a superficial layer
blood vessels from the surface. Possible applica- of tissue heated by a CO2 laser alone.
tions include tattoo removal, where particles Photon recycling: The remittance of human
often are found several mm deep in tissue. More skin is wavelength dependent (vide supra). These
recently Perfluorodecalin has been applied topi- reflected photons are scattered into the environ-
cally to accelerate the clearing of the immediate ment and “wasted” in surgical laser applications.
tissue whitening response after tattoo removal. One can design a simple hemispherical reflector
Once the whitening response has diminished to return reflected light to the incident spot on the
(usually about 5 min after the application), a sec- skin. In theory the gain in total energy available
ond treatment can be applied in the same session 1
to skin is a factor of , where RS is the
without the tissue scattering created by the first (1 - R S R M )
pass [89].
“Carbonization” at the surface: Carbon will skin reflectance, and RM is that of a hemispherical
cause all wavelengths to increase absorption such
that one can convert a deeply penetrating laser to mirror. For example, if RS is 0.7, and RM is 0.9, a
1
gain of , or almost threefold, can be
(1 - 0.63)
Darkening
after IPL achieved.
Photothermal responses in individual cells.
Most of our characterization of laser-tissue
responses is based on “macroscopic” responses.
That is, individual cells are rarely examined dur-
ing and after laser irradiation. When focal cell
damage has been examined, the following consid-
erations are made. (1) Heterogeneity of cell struc-
ture can lead to extreme localized light absorption
and temperature elevation different from that of a
homogenous medium. (2) Localized overheating
may cause cell damage, even in the absence of
average thermal effects over larger volumes [90].
After absorption of a laser pulse, non-radia-
tive relaxation of optical energy occurs within
10−11 s. Thus heating at the site of absorption is
Whitening instantaneous. On the other hand, heat diffusion
after Q alex is much slower and characterized by the TRT. In
experiment, not unexpectedly, it was found that
Fig. 1.11  Figure shows immediate pigment response that temperature fields in cells were more uni-
after IPL and Q switched alexandrite laser form with longer pulses. It follows that short
26 A. A. Lloyd et al.

pulses have smaller thermal fields but higher 1. LTIs are usually based on varying degrees of
localized T elevations. The shorter the laser light absorption by tissue HgB, melanin, and
pulse, the more the final tissue response will water.
depend on the properties of the local absorbing 2. Wavelength ranges should be chosen to

components. One interesting phenomenon is that achieve as much specificity as possible in tis-
on a localized level, an initial thermal field does sue heating
not provide the maximum amplitude of the inte-
gral photothermal response inside a cell. Rather,
the T response reaches its maximum as a result Radiofrequency (RF) Technology
of the multiple secondary thermal fields as they
emerge. With R  radiofrequency energy, local heat gener-
Using a polarizing lamp to enhance illumina- ation depends on the local electrical resistance
tion. Laser treatment can be enhanced by using a and current density. The distribution of the cur-
polarizing lamp during procedures to treat vascu- rent density is determined by the configuration of
lar and pigmented lesions. This is particularly the electrodes with respect to the skin anatomy.
helpful, for ex. when treating PWS in kids using There are multiple types of electrode deploy-
general anesthetic, the lamp is [91] helpful to ments [94–97].
delineate the edges of the PWS prior to treat-
ment. Also, the visual enhancement tends to
result in more complete elimination of vessels, Monopolar vs. Bipolar
therefore patients are more satisfied.
Selective cell targeting. A process called Radiofrequency energy induces tissue heating in
selected cell targeting has been examined as a multiple ways, one by creating bulk heating of
way to destroy selected cells. This precise energy the dermis while sparing the epidermis via cool-
deposition is achieved by using laser pulses and ing mechanisms, and alternatively, micro needles
light absorbing immunoconjugates tagged to the can be placed in the skin to deliver small coagula-
respective cells. The investigators in one study tive injuries [98, 99].
showed, for example, that lymphocytes could be Since radiofrequency energy stimulates the
selectively damaged by attaching iron oxide mic- generation of new collagen and elastin, most
roparticles absorbing 565  nm radiation at those devices require at least three treatments and
sites [92]. One can imagine, in the future, using effects are not typically fully seen until 1–3 months
this type of modality to treat T-cell mediated dis- after the last treatment. One benefit to using radio-
eases such as atopic dermatitis or psoriasis. In frequency devices is that the energy is colorblind
this way, one makes the “bad guy” more notice- and passes through the melanin and hemoglobin
able to the laser. present in the tissue; therefore, all skin types can
Scatter limited therapy—using small micro- be treated. One should note that there is attenua-
beams. Reinisch [93] proposed the use of beam tion of the electrical field as a function of depth
diameter to titrate the depth of penetration, For (like light and lasers); however, the specific equa-
example, we have studied a fractional 1064  nm tions that guide the specifics of the attenuation are
ms laser (100  μm diameter microbeam and beyond the scope of this chapter.
100  mb/cm2) technology to achieve superficial There are four broad types of RF interventions
vessel heating with relative epidermal sparing in the skin. One is a monopolar system where
with just such a device to limit penetration into a capacitive coupling device is placed on the
the dermis. By using the aforementioned spot surface and heat is delivered for a few ­seconds.
size arguments, one can exploit the properties of Simultaneously and just after the “pulse”, the
small spots to change the way particular wave- surface is cooled. The second is a bipolar sys-
lengths behave in the skin. For example, one can tem comprised of metal rails on the skin surface
tailor a 1064 nm laser to heat progressively larger where the current is alternated in a rapid manner
depths of skin by increasing the spot size. (300  kHz–1  MHz) between the superficial skin
1  Laser-Tissue Interactions 27

layers. Generally, in this configuration, the depth [99]. The theory predicts that once the selectively
of the heating is roughly ½ the distance between targeted chromophores are heated by the visible
the electrodes. In the third type of intervention, light, their impedance decreases and the subse-
an array of needle or pin electrodes is placed in quent RF energy will preferentially heat those tar-
the skin such that very focal heating zones are geted tissues (i.e. hair and vessels). A purported
created at predetermined depths. A final type advantage of the treatment is that lower optical
of RF heating is capacitive far field heating, energies can be used to selectively heat sub-sur-
where a system of electrodes delivers energy at face targets than if a light source were used alone
27.12 MHz to create apoptosis in fat. (thus enhancing epidermal preservation).
For monopolar radiofrequency, the delivery In microneedling fractional radiofrequency
electrode is in the hand piece and the return elec- devices, the needles become the delivery and return
trode is placed elsewhere on the patient’s body electrodes and the electric power and current is
whereas with bipolar radiofrequency, the deliv- divided among the needles. In this configuration,
ery and return electrodes are both incorporated the device fractionates the radiofrequency energy
into the hand piece. Therefore, with monopolar among several delivery and return ­electrodes. With
radiofrequency the area of heating is a column/ uninsulated needles as electrodes, the entire needle
cylinder extending from the epidermis towards conducts heat, and wounds are created along the
the subcutaneous tissue. The electrical energy is entire length of the needle. Insulated needles only
most concentrated near the tip of the delivery allow the tip of the needle to heat and therefore
electrode and decreases rapidly with distance, the epidermis is preserved. There are also devices
with the penetration depth about half the size of where the needles (or “pins”) are deployed very
the delivery electrode. However, the behavior of superficially (only down to 100–300  μm) where
the current as it passes through the body to the both fine lines and pigment can be reduced with
return electrode is somewhat unpredictable. multiple treatment sessions.
Monopolar skin rejuvenation systems create
large-volume heating. Electrical energy is distrib-
uted uniformly over the electrode surface through How RF Creates Dermal Heating
“capacitive coupling”. This type of coupling
reduces the natural accumulation of electrical Skin has inherent impedance, which is the resis-
energy at the electrode edge [100]. The first non-­ tance to electric current, and when an electric
ablative RF device (Therma Cool TC, Solta current meets resistance it generates heat in
Medical, Hayward, CA) uses cryogen spray cool- accordance with Joule’s law,
ing (CSC), where the spray is started before the
RF current. Interestingly, if an electric field is Q = I2Rt
induced perpendicular to the skin-fat interface, a
monopolar device can selectively heat large areas where Q is the heat generated in joules, I is the
of fat while sparing the skin and muscle [98]. electric current, R is the resistance and t is the
With bipolar radiofrequency, a U shaped area time of application. Ohm’s law is V = IR where V
of heating is created between the delivery and is the voltage, I is the electric current and R is the
return electrodes in the hand piece and thus the resistance. Ultimately, it is the local current dis-
current travels a fixed distance. The depth of the tribution, time, and resistance (impedance) that
“U” is limited to one half of the fixed distance determine the local heat generation.
between the electrodes. Therefore, the distribution One can envision local RF effects as P = GV2
of, as well as the location of the radiofrequency where P is the power loss in the tissue, G is the
current, is controlled and predictable within the local conductivity of the tissue, and V is the voltage
tissue. In one scenario, cooled bipolar electrodes drop across the target. If one examines Fig. 1.12,
are combined with a diode laser, halogen lamp, or the local heat generation can always be determined
intense pulsed light device. In this configuration, if one knows the microenvironment of the electrical
there is synergy between the two energy sources system. Oftentimes, we must simplify the a­ nalysis
28 A. A. Lloyd et al.

Fig. 1.12 Heating I
homogeneous tissue a c
with direct-contact,
conducting plates C
J
V δ
d J ~

δ
Physical E
Configuration δ
I
b
Id Ic

jB V
G ~

Equivalent Elemental
Circuit Volume

Where
I = Current
G = Admittance
J = Current density
V = Rms voltage
C = Capacitance
Id = Displacement current
B = Susceptance

by characterizing the interaction in terms of macro the muscle. This observation only holds true for
scale electrical equivalent circuits. this particular electrode configuration and can-
For example, if we consider a non-contact not be extrapolated to other dissimilar electrode
capacitive electrode system, where we have a deployments.
“series circuit” comprised of capacitive and Blood has the highest electrical conductivity
resistive parallel parts (Fig. 1.13), the fat will be among most body components. At 1 MHz, blood
preferentially heated according to Joules law. In conductivity is 0.7  siemens/meter (S/m), where
this particular capacitive electrode application 1 S is equal to the reciprocal of 1 Ω. Wet skin is
(i.e. Vanquish, BTL Aesthetics, Prague, Czech at 0.25  S/m and finally dry skin, fat, and bone
Republic), spacing of the plates is important. The have the lowest conductivity at around 0.02–
spacing should prevent too close positioning to 0.03  S/m [99]. Additionally, tissue conductivity
the skin surface, or the superficial skin might be is significantly correlated with tissue tempera-
overloaded with current. On the other hand, if ture, where every 1 °C of increase in temperature
sweating occurs under the spacer, local current lowers skin impedance by 2% [101]. Thus, sur-
on the skin can produce thermal injury. face cooling drives the electrical current deeper
If we look at the scenario in Fig.  1.14, one into the tissue which allows for selective dermal
sees the highest T will be achieved in the sub- heating by the radiofrequency current and pro-
cutaneous fat under the electrodes, where the vides epidermal protection. This electrothermal
tissues are modeled as a “series” circuit. On the reaction results in selective heating of the dermis,
other hand, between the electrodes, the superfi- and when the temperature reaches 65 °C for 1 s,
cial muscles will be heated more. If one examines tissue is coagulated. It should be noted that for
the accompanying equations above Fig. 1.14, one most RF applications (save the needle configura-
can see that the power delivery in the fat will be tions), the peak temperatures are much lower
roughly an order of magnitude larger than that in (38–42 °C) but delivered over much longer times.
1  Laser-Tissue Interactions 29

I Monopolar Devices

For the monopolar devices, the radiofrequency

E0
Air energy can be delivered by a stamped mode, a
Fat
d Muscle continuously gliding movement, or via a fiber
V
Fat ~ that is placed internally.
E0 Thermage (Comfort pulsed technology, Solta
Medical Hayward, CA)
Thermage (Comfort pulsed technology, Solta
Medical Hayward, CA) is a monopolar radiofre-
Physical Configuration quency device where the radiofrequency is deliv-
ered via a stamped method. For each “stamp”
Y0 pulse, the hand piece is held in place and within a
C0
short 3–4 s sequence; the hand piece tip releases a
Yt cooling cryogen spray simultaneously with the
Gf delivery of the radiofrequency energy. The cryogen
Ct
cooling spray provides epidermal protection and
the device continuously monitors the epidermal
Ym temperature with each pulse so that it does not
V
Cm G m ~ exceed 45  °C.  The peak heating depth is most
likely around 1–4  mm and the intention is (1)
immediate tissue tightening and (2) delayed colla-
Yt gen production. There is minimal downtime from
Gf the procedure as the post treatment redness resolves
Ct
in a few hours and bruising and discomfort are very
Y0 rare. With the initial protocol of a single pass with
Equivalent Circuit
C0 a high fluence, there was intense pain during the
procedure, and on occasion scars and surface irreg-
Where ularities were seen, therefore the protocol was
Y = The admittanace for Fat,
revised to multiple passes with lower fluence [102].
Muscle, and Air layers
E0 = Electric Field strength The new protocol has no reports of scarring, fat
I = Current atrophy, and the treatment is much less painful.
V = Voltage Exilis system (BLT Aesthetics, Prague, Czech
E = The Conductance
C = Capacitance Republic)
Exilis (BLT Aesthetics, Prague, Czech
Fig. 1.13  Heating multiple layers of tissue with non-­ Republic) is a monopolar radiofrequency device
contacting capacitor plates
that delivers its radiofrequency via a continuous
motion hand piece which has a cooled gliding
electrode ball tip with an integrated “energy flow
SKIN
control system” which senses if contact is lost,
FAT
therefore eliminating peaks of energy that could
MUSCLE arc and burn the skin [102]. In combination with
the hand piece, a bipolar grounding pad is used to
allow for real time monitoring of impedance to
Due to electrical and thermal properties of eliminate spikes of radiofrequency and increase
Fat Vs. Muscle, there is a tendency for greater
Fat Vs. Muscle, heating in this electrode patient comfort [102]. As the hand piece is con-
Configuration.
tinuously moved over the patient’s skin, it deliv-
Fig. 1.14  Cross-sectional sketch showing fields in lay- ers its radiofrequency energy; the goal of therapy
ered tissue exposed to shortwave diathermy capacitor-­ is to maintain the skin at 40–43 °C for 10–15 min
type electrodes
30 A. A. Lloyd et al.

for each region treated. It is indicated for skin used off label to treat areas of unwanted local-
tightening and body contouring. Side effects ized fat and/or loose skin of the arms, abdomen,
include redness and edema. love handles, thighs or knees. Side effects
Pelleve (Ellman International, Inc., Oceanside, include erythema and edema which typically
NY) resolve in 24  h. The procedure does require
Pelleve (Ellman International, Inc., Oceanside, injections with local anesthetic.
NY) is a monopolar radiofrequency device that TrueSculpt (Cutera, Inc., Brisbane, CA)
delivers its radiofrequency via a continuous TrueSculpt (Cutera, Inc., Brisbane, CA) is a
motion hand piece. The epidermis is cooled in monopolar radiofrequency device that creates an
this system via two mechanisms, first with the gel electric field perpendicular to the skin-­
that is applied to the skin and second by convec- subcutaneous interface and results in bulk heat-
tion to the surrounding air created by the continu- ing of the adipose layer. During a treatment, the
ous motion use of the device. During the treatment area is treated with a stamping delivery technique
an infrared laser thermometer is used to fre- and with each individual iteration the fat is heated
quently monitor the epidermal temperature and to 43–45 °C for 15 min, which results in a delayed
ensure the epidermal temperature is maintained adipocyte cellular death response at about day 9
between 41 and 43  °C for the duration of the post treatment [98]. The operational frequency
treatment. It is FDA indicated for treatment of can be adjusted to match the anatomic site of
mild to moderate facial wrinkles. The patient treatment, using high frequencies in areas that
experiences minimal pain during the procedure have a thin layer of adipose and low frequencies
and there is little to no down time. Side effects in areas with thicker adipose layers [98]. The
are minimal and include erythema and edema. device has target depths of 7–14  mm and has a
ThermiTight (ThermiTight; Thermi­Aesthetics, 16 cm2 and a 40 cm2 hand piece. It is indicated for
Southlake, TX) noninvasive body contouring. There is minimal
ThermiTight (ThermiTight; Thermi­Aesthetics, downtime. Reported side effects include redness,
Southlake, TX) is a minimally invasive monopolar swelling and mild tenderness in treated areas
radiofrequency device that delivers its radiofre- which typically resolve in a few hours.
quency via a 600 μm electrode enclosed in a 1 mm Vanquish (BLT Aesthetics, Prague, Czech
cannula that is inserted into the subcutaneous Republic)
layer in order to completely spare the epidermis Vanquish (BLT Aesthetics, Prague, Czech
and to more directly heat the dermal hypoder- Republic) is a non-invasive and non-contact,
mal interface. The target temperature is set to hands free body contouring device. It uses radio-
the optimal temperature for the target; the skin frequency energy to selectively heat the adipose
surface T should not exceed about 42  °C, tissue to the point of adipocyte apoptosis while
whereas the T to shrink fibrous septae is sparing the epidermis. The device uses a capaci-
55–65 °C and to melt fat it is 70 °C. The device tive coupling far field configuration and automat-
features dual T monitoring, where the internal T ically adjusts its energy output based on the
is measured firm the probe tip and the skin T is resistance of adipose tissue to maintain homoge-
monitored from an external thermal camera. neous heating of the tissue [103, 104]. The adi-
This configuration optimizes safety and effi- pose tissue is heated to 40–45  °C and the
cacy. If the temperature exceeds the set temper- surrounding tissue only experiences temperatures
ature by 7 °C, the system is automatically turned of 40–41 °C [103, 104]. There is minimal down-
off [102]. Additionally, a forward looking infra- time from the procedure as the device never con-
red camera (FLIR) (FLIR E40; FLIR Systems, tacts the patient. Side effects include transient
Inc., Wilsonville, OR) provides infrared video erythema, warmth and tenderness which last at
streaming of the entire epidermis in the treat- most 1 h post treatment.
ment field so epidermal temperature is simulta- Infini (Lutronic, Inc., Fremont, CA)
neously visually monitored. It has its FDA The Infini (Lutronic, Inc., Fremont, CA) is
indication to treat glabellar lines; however, it is an insulated microneedle fractional rejuvenation
1  Laser-Tissue Interactions 31

device with a 49 needle tip and a 16 needle tip. not be colorblind. Any superficial needle based
The microneedles are made of surgical stainless RF systems can create hyperpigmentation (PIH)
steel, are coated with gold for increased conduc- like their laser counterparts.
tivity, and then double coated with an insulating EndyMed Intensif (EndyMed Medical,
silicone compound except for the 300  μm clos- Cesarea, Israel)
est to the point of the needle. Therefore, only the The EndyMed intensif (EndyMed Medical,
tip of each needle is active and there is no elec- Cesarea, Israel) is a fractionated radiofrequency
trothermal damage to the epidermis. The needles device with gold plated, sharp tapered noninsu-
are each 200 μm in diameter and a point diameter lated needles. The needles are 300 μm in diame-
of 20 μm. The maximum power for the device is ter and the tips are tapered. The needles can
50 W at level 20 and the exposure times can range achieves dermal heating up to 3.5 mm deep with
from 10 to 1000 ms. It is the exposure time that minimal epidermal damage using a fractionated
provides the user with the most control over the tis- pulse mode which enables uniform distribution
sue damage as the exposure time can be decreased of the energy. There is built in constant energy
for the higher power levels. The maximum cur- delivery circuitry. It is indicated for treatment of
rent density is near the electrodes. At 1 MHz, the acne scarring, deep wrinkles, atrophic scars and
current flows rapidly to and fro between the alter- stretch marks. After treatment, there is minimal
nating rows of electrodes and creates small ~0.5– micro-crusting and erythema lasts <24 h. There is
0.7 mm diameter subsurface microthermal zones. no risk for hypopigmentation, and only a mini-
In these applications we model the micro-currents mal risk for hyperpigmentation.
as purely resistive and would find the greatest cur- InMode Fractora (InMode MD Ltd.
rent density at the needle tip; as heating proceeds, Yokneam, Israel)
the tissue impedance (Z) will decrease so long as The InMode Fractora (InMode MD Ltd.
the tissue is not vaporized neat her needle surface. Yokneam, Israel) is a bipolar fractional radiofre-
As we proceed to the midpoints between the quency resurfacing device which uses either a 24
electrode arrays, the absorbed power density (or needle, a 60 needle and a 126 high density tip.
heat generation) drops off to a very small value. The 24 pin tip can be coated to create an insulated
By manipulating the applied voltage to the elec- needle option. The needles penetrate up to 3 mm
trode and “on” times, one can optimize localized in depth and when used with ablative settings,
heating around the electrodes. In our application they create a zone of coagulation up to 100 μm
with microneedles, the time scales are short around the ablated area. It is indicated for fine
enough such that blood flow is irrelevant in the lines, deep wrinkles, scars and discolored red and
calculations. brown skin tone. The downtime involves moder-
The needles can penetrate from a depth of ate redness and swelling for the first 3–5  days,
0.5–3.5  mm, which allows the user to set treat however, the redness can last up to a week.
multiple layers of the dermis. It is currently indi-
cated for the treatment of wrinkles. There is mini-
mal downtime and moderate intra-treatment Ultrasound Tissue Interaction
discomfort. Side effects include mild edema can
occur for 12–48 h post procedure and erythema Ultrasound waves can travel several millimeters
can last 3–5 days post procedure. There typically deep through tissue. Their propagation results in
is no persistent erythema. Mild crusting as well vibration at the molecular level that can lead to
as pin point bleeding can occur and typically tissue heating in a dose-dependent fashion.
resolves spontaneously in 3–5 days. Mild PIH is Unlike EMR waves, US is comprised of com-
possible at the needle insertion points. This pressive and refracted longitudinal waves that
observation brings up an important point. As behave like a “slinky” toy. Generally, as the fre-
noted earlier, the RF immediate tissue interaction quency and the focusing increase, the injuries
is colorblind; however, depending on where and become smaller in volume. Different physical
how intense the injury is, the skin response might processes are operative in US interactions, such
32 A. A. Lloyd et al.

as cavitation in lower frequency, lower power tissue and cadaveric human skin have revealed
density, non focused applications. With very low predictable, reproducible and dose-dependent
power density applications, gentle diffuse waves creation of thermal injury zones at the level of
can be delivered as a physical therapy tool for the subcutaneous fat down to the superficial
heating muscles after injuries (US diathermy). musculoaponeurtoic system [106]. Increased
By utilizing a specialized hand piece to focus energy levels results in thicker thermal injury
ultrasound waves tightly at a controlled depth zones. The epidermis is spared from injury by
and using much higher fluences than needed for focusing the beam several millimeters below the
imaging, selective zones of thermal injury can be surface of the skin, although with increased
created. The result is collagen denaturation and injury the thermal injury zones extend more
coagulative necrosis [105]. superficially [106]. A limited degree of direct
One advantage of US over light is the capacity collagen contraction has been observed.
to deliver energy deeper in the tissues. For exam- Ulthera (Ulthera, Inc, Mesa, AZ) is currently
ple, even with relatively deeply penetrating light the only microfocused ultrasound device on the
(1064 nm), the surface intensity will diminish by market. It is FDA approved for lifting of the eye-
a factor of over 60% over a depth of 2 mm in the brow, neck and submental areas as well as for
skin. If follows that in the absence of cooling and improvement of décolletage lines and wrinkles.
very long exposures (>1 s), very deep tissue heat- The device allows one to with visualize the skin
ing with laser is challenging, particularly where with the same ultrasound probe as the treatment
water is the target. The only viable way to create transducer. There is no downtime with treatment
focal deep heating in the tissue is with the assis- and it is safe for use in all skin types. Potential
tance of a cannula or other conduit that allows the side effects tend to be transient and can include
laser beam to bypass the highly scattering dermis erythema, edema, temporary pain, bruising,
and fat tissues. numbness and scarring. It is contraindicated in
Two other focused US technologies are avail- patients with open wounds, severe acne or active
able in the USA and target fat. One targets fat implants in the treated area.
about 1–2  cm deep in the tissue and the other
(Ultra shape) about 2–4  cm deep in the tissue.
The volumes of damage (although focused) are Summary
larger than the Ulthera device.
Overall, lower frequencies will result in An understanding of the scientific principles in
deeper penetration and larger volumes of injury. laser applications empowers the physician to
For example, an US system (ultrashape) uses a optimize the use of this very expensive equip-
200 KHz transducer and cavitation to target fat. ment. At every patient encounter, the physician
Another system (Liposonix, Solta Medical) should craft an approach based on the logical
uses HIFU but at a lower frequency (2 MHz ver- sequence of laser tissue interactions outlined in
sus 4–7 MHz for Ulthera) and targets tissue in a this chapter. By appropriate choreographing of
plane down to about 1–2 cm. cooling and heating, the physician can be con-
If one looks at the total amount of tissue fidant in predicting the immediate tissue
affected, the lower frequency devices create response. However, all approaches should be
larger wounds deeper in the tissue, such that after undertaken within the context of an under-
an Ulthera procedure only about a tsp of tissue is standing of wound healing. The physical
damaged, whereas the for the deeper heating fat aspects of the interaction are typically more
destruction US devices, a few hundred milliliter predictable than the subsequent healing
(size of soda can) are damaged. response. If in doubt, test spots are always an
In the case of HIFU (specifically Ulthera), option and should be considered for the anx-
studies of this technology on both porcine soft ious patient (or physician).
1  Laser-Tissue Interactions 33

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 Laser Safety: Regulations,
Standards and Practice Guidelines 2
Brienne D. Cressey, Ashley Keyes,
and Murad Alam

Abstract Laser Safety

The use of lasers is routine in many medical
specialties. In some cases, the particular ben- The use of lasers is routine in many medical spe-
efit of lasers has made them desirable alterna- cialties. In some cases, the particular benefit of
tives to conventional surgical instruments lasers has made them desirable alternatives to con-
such as scalpels, electrosurgical units, cryo- ventional surgical instruments such as scalpels,
surgery probes, or microwave devices. electrosurgical units, cryosurgery probes, or micro-
wave devices. The American Society for Laser
Keywords Medicine and Surgery (ASLMS) outlines several
Laser · Laser safety · Laser regulations advantages of laser use in clinical practice [1]:
Laser standards · Laser guidelines Lasers allow the surgeon to accomplish more com-
Dermatologic lasers · Medical lasers plex tasks, reduce blood loss, decrease postopera-
tive discomfort, reduce the chance of wound
infection, decrease the spread of some cancers,
minimize the extent of surgery in selected circum-
stances and result in better wound healing, if used
appropriately by a skilled and properly trained
surgeon.

Despite these benefits, when misused, lasers

can injure both patients and operator. To ensure
safety and quality care, guidelines for laser safety
B. D. Cressey have been developed.
Department of Dermatology, New York Presbyterian-­
Weill Cornell Hospital, New York, NY, USA
A. Keyes (*)
Department of Dermatology, Weill Cornell Medicine,
Lincoln Medical Center, Bronx, NY, USA
e-mail: [email protected]
M. Alam
Section of Cutaneous and Aesthetic Surgery,
Department of Dermatology, Otolaryngology-Head
and Neck Surgery, and Surgery, Feinberg School of
Medicine, Northwestern University,
Chicago, IL, USA
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 37

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_2
38 B. D. Cressey et al.

 overning Bodies and Professional

G and other health professionals, is an umbrella
Organizations organization for all specialties whose clinical
care involves lasers. In addition to formulating
standards and guidelines for implementing safe
Many regulatory and professional organi- and effective laser practices, ASLMS also makes
zations provide recommendations and recommendations to medical laser training pro-
guidelines for laser safety. While the grams regarding procedural skills for individuals
American National Standards Institute operating lasers.
(ANSI) publishes consensus standards The American Academy of Dermatology
considered to be the standard in laser (AAD), the primary professional organization for
safety, these standards are recommended practicing dermatologists in the United States,
practices only. The positions of profes- encourages the safe practice of medicine and
sional organizations are important to con- acknowledges that medical laser is subsumed
sider in addition to those of ANSI to ensure under the practice of medicine. “The Academy
comprehensive safety standards for laser endorses the concept that use of properly trained
use are practiced. non-physician office personnel under appropriate
supervision allows certain procedures to be per-
formed safely and effectively” [2].
The American Society for Dermatologic
A number of regulatory and professional Surgery (ASDS), the main professional organiza-
organizations have promulgated and dissemi- tion within dermatology for proceduralists, is
nated recommendations for safe laser use. committed to the development of safe in-office
Though there is considerable agreement among procedures. The ASDS maintains that medical
professional organizations and regulatory laser use constitutes the practice of medicine, and
agencies regarding laser safety guidelines, that non-physicians should use lasers only when
variation among patients, facilities, and state delegated do so by physicians who are appropri-
laws ultimately affects how these rules are ately supervising them.
implemented. Medical laser use is also subject to regulation
The American National Standards Institute by the relevant state and by the U.S.  Food and
(ANSI) creates and publishes consensus stan- Drug Administration (FDA). Laser devices, such
dards for the conduct of business in almost all as those used for medical application require
sectors, including medicine. This chapter will clearance or premarket approval by the FDA
refer to the ANSI Z 136.3, the American National Center for Devices and Radiological Health
Standard for Safe Use of Lasers in Health Care (CDRH) prior to distribution for commercial use
Facilities, with specific attention to control mea- in the United States. The Radiation Control for
sures, as it is widely regarded as the standard for Health and Safety Act (RCHSA), a standard sim-
laser use. It is important to clarify that these stan- ilar to that of ANSI, is intended to prevent unnec-
dards are recommended practices rather than essary or inappropriate access to laser equipment,
rules subject to enforcement, and compliance is and to minimize exposure to collateral radiation.
both voluntary and dependent on individual orga- Additionally, RCHSA ensures the appropriate
nization’s specifications. performance features and labels are provided by
In addition to the standards set forth by ANSI, the manufacturer [2]. With respect to laser
medical organizations also set professional stan- devices, the FDA is responsible for classifying
dards for their membership. The American laser devices based on levels of laser emission.
Society for Laser Medicine and Surgery For medical use, lasers are defined as Class III
(ASLMS), with its multidisciplinary member- and IV, which require the highest level of regula-
ship, including physicians and surgeons, nurses, tion for safe use.
2  Laser Safety: Regulations, Standards and Practice Guidelines 39

Practice Guidelines observed. It is valuable for the novice to perform

the laser procedures with supervision by the expert,
however, for a variety of reasons, such as hospital
privileges, status of patients and insurance cover-
The first tenet to laser safety is the training age of physicians, this is not always possible.
of physicians, healthcare professionals,
and personnel. The American Society for In addition to training recommendations for
Laser Medicine and Surgery (ASLMS) physicians, ANSI also suggests standards for gen-
outlines recommendations for training and eral laser safety and training programs, with specific
credentialing, which are referenced by the attention to nurses and other non-­medical person-
ANSI standards nel. The following summarizes this position [3]:
Laser safety training for perioperative nursing and
support personnel must be compatible with that
taught to physicians. A smoothly functioning laser
Procedural Skills team depends on this, and every effort must be
made to eliminate any discrepancies in training
materials. Content of this program should stress
The ASLMS outlines recommendations for the overall understanding of operation characteristics
safe use of laser technology, specifically training of equipment, biologic and physical properties of
and credentialing benchmarks, to be used in con- the laser tissue interaction, potential hazards asso-
ciated with laser use, and procedures and equip-
junction with the ANSI Z 136.3 guidelines. ment required to ensure a safe laser environment.
Training and credentialing represent distinct issues
for laser safety, especially given the escalating ANSI maintains that training in laser safety
debate regarding laser use by non-physicians. practices for physicians and non-physicians
The ANSI Z 136.3 refers to the ASLMS pol- should be distinguished from training of methods
icy “Standards of Training for Physicians for the and techniques of laser procedures.
Use of Lasers in Medicine and Surgery”, which Though the need for operators to be trained
was approved by the board of directors on April in laser use is universally accepted, the process
3 of 2008, regarding the recommendation for of credentialing physician and/or non-physician
appropriate training for laser privileges. The spe- operators as competent in laser use is more sub-
cific suggestions for training are as follows [3]: ject to debate and interpretation. Often strict
The initial program should include clinical applica- and multiple criteria must be simultaneously
tions of various wavelengths in the particular specialty met to satisfy credentialing rules. In its paper
field and hands-on practical sessions with lasers and entitled “Procedural Skills for Using Lasers in
their appropriate surgical or therapeutic delivery sys- General Surgery,” which was revised on August
tems. A minimum of 8–10 hours is suggested by the
ANSI standards. A further 40% of the time should be 2, 2012 by the ASLMS board of directors, the
allocated to the practical sessions. However, more criteria for granting laser privileges are summa-
time may be required to complete the basic course rized [4]:
contents. Usually, basic training is concentrated on
one or more wavelengths. Subsequent programs cov- A. The physician (attending) must be a diplo-
ering different wavelengths or substantially different mat of or be admissible to a specialty
applications or delivery instruments may require more Board such as the American Board of
hours of training of which 50% of the time is allocated Surgery; Orthopedics; Otolaryngology;
to hands-on sessions. A small faculty-student ratio in Ophthalmology; Urology; Dermatology;
the range of 1 to 3-5 is optimal. Plastic Surgery; Cardiovascular Surgery;
It is recommended that an applicant for privi- Neurosurgery; or other medical specialty.
leges spend time after the basic training course in a B. The physician must first have been granted
clinical setting with an experienced operator (such appropriate privileges by the facility
programs are often called “preceptorship” training through the designated certification and
programs or “observation”) when appropriate and facility process. The physician must have
practical. Several brief visits or a more prolonged privileges to perform requested procedures
period suffices provided that a variety of cases is in the absence of laser use.
40 B. D. Cressey et al.

C. The physician must have been trained to use • Possession of an appropriate medical degree or
laser(s) in a recognized and approved resi- its equivalent. Candidates must be a Doctor of
dency program or must have obtained train- Medicine (MD) or Doctor of Osteopathy (DO)
ing through an appropriate CME course. and complete an ACGME accredited residency
D. Physicians using a laser adapted to an oper- in their specialty areas.
ating microscope or other optical device • Must possess primary specialty certification
must demonstrate proficiency in the use of from the American Board of Dermatology.
the optical equipment in addition to the • For a specified period of time (5 years) there
laser technology. The physician must will be a practice category for eligibility.
already have hospital privileges for the use Specific criteria for qualifying under this cate-
of these instruments in the performance of gory will be determined and approved by an
procedures with conventional techniques. independent certifying body. Suggested
E. The user of the laser must be cognizant of requirements for this category may include the
the safety hazards of lasers. This knowledge following:
must be obtained either through a residency
program or an appropriate CME course. a) Completion of at least 150 hours of Category 1
Proof of this training must be supplied in
writing to the Laser Usage Committee at
CME including laser safety and physics. At least
the time privileges are requested. 20 hours of the 150 hours must entail hands on
F. Initial approval or use of laser will be provi- workshops proctored by an experienced physi-
sional until the physician has demonstrated cian in laser medicine and surgery and a mini-
the ability to use lasers to a member of the
Medical Staff who has been designated by
mum of 50 hours in programming approved by
the facility as being qualified and must have the American Society for Laser Medicine and
achieved the required standards as previ- Surgery (ASLMS), American Academy of
ously listed. The criteria for recertification Dermatology (AAD) or the American Society
shall be set forth and a yearly review of cases
and their outcomes shall be performed.
for Dermatological Surgery (ASDS).
G. If the applicant requests the use of the laser b) Submission of 100 cases with a minimum of
for investigational purposes, the request 15 sets of before and after photos or video-
must receive approval by the facility’s tapes representative of at least 4 of the 9 man-
Clinical Investigation Committee (IRB/
CIC) as is required for all other research
agement areas.
purposes. An appropriate investigational c) Mastery of Standards of Training must be
protocol and informed consent process demonstrated by obtaining a passing grade on
must be in place. an examination the content of which will be
H. Residents involved in the use of lasers may
not perform procedures with these instru-
determined by an independent certifying body.
ments until such time as they have attended d) Letters of recommendation attesting to char-
an in-depth training program or an appro- acter from at least three practicing physicians
priate CME course recognized to be ade- in the same specialty.
quate by the Laser Usage Committee. In
addition, residents must be supervised by a
laser-certified attending physician during It is the widely accepted belief of the aforemen-
actual utilization of laser technology at all tioned organizations that a necessary precondition for
times. patient safety is the proper training and credentialing
Similarly, ASLMS outlines physician qualifica- of healthcare professionals. As such, despite differ-
tions for proficiency in laser techniques in its policy ences in details, there is minimal, significant varia-
statement entitled “Procedural Skill and Technique tion in the standards by which physicians are assessed
Proficiency for Surgery and Other Energy-Based with regard to their competence to utilize medical
Therapies in Dermatology”. Approved and revised laser devices. Discrepancies arise when considering
on August 2, 2012, by the board of directors, the credentialing of alternative allied health providers,
following requirements are relevant to laser use in which will be addressed later in this chapter in the
dermatology [5]. section on delegation and regulation by the state.
2  Laser Safety: Regulations, Standards and Practice Guidelines 41

Administrative Controls (3) Maintaining a list of authorized laser users and Health
Care Personnel (HCP)
(4) Requiring storage or disabling (removal of key) of the
HCLS where unauthorized operation is of concern.
Administrative controls are essential for (5) Assuring that operators know the location and opera-
tion of the emergency stop control provided with each
the safe operation of lasers within a health- HCLS.
care facility. These control measures mini- (6) Assuring that the ready function is enabled only when
mize the potential for hazards to operator the user is ready to treat the target tissue.
and patient during laser use. A Laser Safety (7) Using of only diffuse reflective materials or instru-
ments with low reflectance in or near the beam path,
Officer (LSO) is appointed to ensure the where feasible.
appropriate standards are followed. (8) Taking steps to avoid confusion encountered during
surgical procedures when operating with more than
one floor pedal.

The ANSI Z 136.3 is accepted as the standard The specific administrative controls imple-
for guidelines regarding the safe use of laser in mented in a health care facility may vary. It is
health care facilities. Specifically, this document the LSO’s responsibility to ensure the appropri-
details control measures to minimize the poten- ate safety measures are in place to accommo-
tial hazards of laser use. Though each facility and date the specific needs of the patient and
patient engenders unique safety considerations, facility.
the following guidelines address unintended haz- Figure 2.1 illustrates an overview of practice
ards to both patients and personnel. guidelines and to whom they are relevant.
To ensure administrative control within the
health care facility, a Laser Safety Officer (LSO)
is appointed to implement the following stan- Protective Equipment
dards [3].
4.2.1 Policies and Procedures (Class 3B and Class 4).
The health care facility (HCF) shall establish policies Protective equipment includes warning
and procedures (P&Ps). The P&Ps should include, for signs and labels, eye and skin protection,
example, perioperative checklists for use by operating
and smoke evacuation systems to reduce
personnel. The LSO shall require approved written
operating and maintenance P&Ps for Class 3B and non-beam hazards. Used properly during
Class 4 Hospital Care Laser Systems (HCLS). These laser procedures, protective equipment
operating and maintenance P&Ps shall be maintained reduces the risk of injury to operator and
and readily available. The LSO shall require that
patient, as well as increases the overall
safety SOPs exist for servicing of the HCLS.
4.2.3 Authorized Personnel-Laser Users. Class 3B safety of healthcare facilities in which laser
and Class 4 HCLSs shall be operated by facility-­ equipment resides.
authorized personnel appropriately trained in the
safe use of the HCLS.
4.2.5 Procedural Controls. Procedural controls, as
determined, by the LSO, shall be used where pos-
sible to avoid potential hazards associated with Warning Signs and Labels
Class 3B and Class 4 HCLSs. These include con-
trols such as: The Nominal Hazard Zone (NHZ) is the physical
space in which levels of radiation, direct,
( 1) Adhering to written P&Ps reflected, or scattered, exceed the Maximum
(2) Assigning a dedicated person to operate the controls, Permissible Exposure (MPE), which may be
if applicable, when appropriate for the procedure and
practice setting.
determined by the safety information provided
42 B. D. Cressey et al.

Fig. 2.1  Three key

Administrative Controls The Laser Perioperative Safety
components of a laser
safety program include
understanding of
administrative controls,
knowledge of laser
function and use, and Training Program
guidelines for
perioperative safety.
Despite variation in
responsibilities among
physicians, healthcare
professionals and the Physician Allied LSO
LSO, consensus among Health Professional
practice guidelines is
essential to the safe use
of medical lasers

Responsible Responsible Responsible

for the safe for for the laser
and effective understanding safety
performance the standards program in
of laser and the health
procedures administrative care facility
infrastructure

by the manufacturer. While a Class III or Class a. For Class 2 lasers and laser systems, “Laser
IV laser is in operation, appropriate warning Radiation—Do Not Stare into Beam”
signs and labels, as well as protective equipment b. For Class 3 lasers and laser systems where
is administratively required for all individuals the accessible irradiance does not exceed
within the NHZ. Warning signs and labels are the appropriate MPE based on a 0.25 s
provided by the ANSI Z 136.3 in accordance with exposure, “Laser Radiation—Do Not Stare
the Federal Laser Product Performance Standard, into Beam or View with Optical Instruments”
including the following [3]: c. For all other Class 3R lasers and laser sys-
4.7.1 Display of Warning Signs. Warning signs
tems, “Laser Radiation—Avoid Direct
shall be conspicuously displayed on all doors Exposure to Beam”
entering the Laser Treatment Controlled Area d. For all Class 3B lasers and laser systems,
(LTCA), so as to warn those entering the area of “Laser Radiation—Avoid Direct Exposure
laser use. Warning signs should be covered or
removed when the laser is not in use.
to Beam”
4.7.3 Inclusion of Pertinent Information. Signs and e. For Class 4 laser and laser systems, “Laser
Labels shall conform to the following Radiation—Avoid Eye or Skin Exposure to
specifications. Direct or Scattered Radiation”
4.7.3.1 The appropriate signal word (Caution or (2) At position 1 above the tail of the sunburst, special pre-
Danger) shall be located in the upper panel. cautionary instructions or protective action such as:
4.7.3.2 Adequate space shall be left on all signs “Laser Surgery in Process—Eye Protection Required”
and labels to allow the inclusion of pertinent infor- (3) At position 2 below the tail of the sunburst, type of
mation. Such information may be included during laser (Nd: YAG, CO2, etc.) or the emitted wavelength,
the printing of the sign or label or may be hand- pulse duration (if appropriate), and maximum
written in a legible manner, and shall include the output.
following. (4) At position 3, the class of the laser or laser system.
(1) At position 1 above the tail of the sunburst, special
precautionary instructions or protection action such
as “Laser Surgery in Process—Eye Protection Figure 2.2 shows the appropriate warning signs
Required” for (a) Class 2 lasers and (b) Class 3 and 4 lasers.
2  Laser Safety: Regulations, Standards and Practice Guidelines 43

POSITION 1 POSITION 1
BOLD BLACK LETTERING BOLD BLACK LETTERING

POSITION 2 POSITION 2
BOLD BLACK LETTERING BOLD BLACK LETTERING
POSITION 3 POSITION 3
a BLACK LETTERING b BLACK LETTERING

Fig. 2.2  The distinction between appropriate laser warning signs for (a) Class 2 and (b) Class 3 and 4 lasers

4.6.3 Laser Protective Barriers and Curtains (Class

Eye and Skin Protection 3B and Class 4). Facility windows (exterior or inte-
rior) or entry ways that are located within the NHZ
of a Class 3B or Class 4 laser system, shall be pro-
Additional protective measures must be followed vided with an appropriate filter or barrier which
to ensure the safety of patients, staff, and opera- reduces any transmissible radiation to levels below
tor while in the NHZ. The following recommen- the applicable MPE level.
dations are relevant to eye and skin safety [3]: 4.6.3.1 Drapes. Use only wet or nonflammable
drapes in the operative field.
4.6.2 Laser Protective Eyewear (Class 3B and 4.6.4 Skin Protection (Class 3B and Class 4). The
Class 4). Laser protective eyewear may include but manufacturer of the HCLS or the LSO shall spec-
not be limited to goggles, face shields, spectacles ify the appropriate laser protective equipment by
or prescription eyewear using special filter materi- make and model or performance specifications
als or reflective coatings (or a combination of and the locations and conditions for use of the
both), which are selected to reduce the potential skin protective equipment. Skin protection shall
ocular exposure below the applicable MPE level. be used whenever there is a potential hazard to
Eyewear shall be accompanied by the following HCP.
information:
Though protective equipment is required for
( 1) Optical density at appropriate wavelengths.
(2) Manufacturer’s recommendations on shelf life,
all individuals within the NHZ, depending on the
storage conditions, and appropriate cleaning nature of the procedure, the protocol for patient
methods. eye protection may be different for operator and
staff protection. The following specifications are
4.6.2.4 Cleaning and Inspection. Periodic cleaning
important to consider, especially for procedures
and inspection of protective eyewear shall be made
to ensure the maintenance of satisfactory condition. performed on the face:
The lenses should be cleaned carefully to avoid 4.4.4 Patient Eye Protection. When the patient’s
damage to the absorbing and reflecting surfaces. eyes are potentially within the NHZ, they shall be
This shall include: protected from inadvertent exposure by a method
approved by the LSO. The suitability of patient eye
(1) Inspection of the attenuation material for pitting,
protection methods and equipment shall be deter-
crazing, cracking, discoloration, etc. mined based on the intended procedure, target
(2) Inspection of the frame for mechanical integrity. ­tissue site, wavelength and delivery system of the
(3) Inspection of straps or other retaining devices to
HCLS, positioning of the patient, and type of
ensure that they are not excessively worn or anesthesia.
damaged. When facial areas, particularly around the eyes
(4) Inspection for light leaks and coating damage that are being treated, e.g., for port wine stains or neo-
would permit hazardous intrabeam viewing. plasia, protective glasses may not be appropriate
44 B. D. Cressey et al.

for shielding the eyes. For treatments on or near the of about 100 to 150 feet per minute at the inlet
eyelids, appropriate corneal shields are usually nozzle is generally recommended. It is also impor-
required, and the shield shall have appropriate tant to choose a filter that is effective in collecting
optical properties to reduce exposure below the the contaminants. A High Efficiency Particulate
applicable MPE. Additionally, patient eye protec- Air (HEPA) filter or equivalent is recommended
tion is not intended to restrict or limit in any way for trapping particulates. Various filtering and
the use of laser radiation intentionally adminis- cleaning processes also exist which remove or
tered for therapeutic or diagnostic purposes. inactivate airborne gases and vapors. The various
filters and absorbers used in smoke evacuators
There is a consensus among professional require monitoring and replacement on a regular
organizations that laser protective equipment basis and are considered a possible biohazard
requiring proper disposal.
should not only be in good working order, but Room suction systems can pull at a much lower
also meet both local and ANSI standards for pro- rate and were designed primarily to capture liquids
tective equipment. Figure 2.3 shows a variety of rather than particulate or gases. If these systems
eye protection for both patient and operator. are used to capture generated smoke, users must
install appropriate filters in the line, ensure that the
line is cleared, and that filters are disposed prop-
erly. Generally speaking, the use of smoke evacua-
Non-beam Hazards tors is more effective than room suction systems to
control the generated smoke from nonendoscopic
Besides direct hazards to the eyes and skin due to laser/electric surgical procedures.
laser beam exposure, concerns associated with
non-beam hazards present unique laser safety In a statement entitled “Smoking Guns”,
considerations. According to a publication by the approved by the Board of Directors of the
National Institute for Occupational Safety and ASLMS, the aforementioned NIOSH guidelines
Health (NIOSH), the plume (smoke byproduct) are referenced; however, the statement highlights
produced by thermal destruction of tissue can that these guidelines stop short of requiring per-
contain toxic gases or vapors, dead or living cel- sonal respirators for personnel within the operat-
lular material, or even viruses. As a result, control ing room. The ANSI Z 136.3 states that currently
of smoke is essential to minimize health risks to a suitable half-mask respirator (fitting over the
health care personnel, as well as visual interfer- nose and mouth) to exclude laser-generated
ence to the individual performing the procedure. plume does not exist. As such, the recommenda-
NIOSH recommends the two following methods tion is that health care facilities rely on appropri-
of ventilation for the management of airborne ate ventilation techniques to protect against laser
contaminants [6]: generated airborne contaminants [3]. It is the
Smoke evacuators contain a suction unit (vacuum unanimous opinion of the aforementioned
pump), filter, hose, and an inlet nozzle. The smoke ­regulatory organizations that a smoke evacuation
evacuator should have high efficiency in airborne
apparatus be utilized to protect patient and per-
particle reduction and should be used in accor-
dance with the manufacturer’s recommendations sonnel and to control smoke levels in the operat-
to achieve maximum efficiency. A capture velocity ing room.

Fig. 2.3  A selection of

eyewear suitable for
patient and operator
safety. Care should be
taken to select the
appropriate lenses to
protect against various
levels of laser emission
2  Laser Safety: Regulations, Standards and Practice Guidelines 45

Delegation of Use of Lasers In a position statement approved by the

Board of Directors on February 22, 2002, the
AAD expressed a similar opinion regarding
Non-physician use of lasers has been sub- medical laser use by non-physicians with an
ject to debate in recent years leading to additional requirement: “The non-physician
calls for increased regulation regarding office personnel should also be appropriately
delegation of medical procedures to alter- trained by the delegating physician in cutaneous
native healthcare professionals. While pro- medicine” [2].
fessional organizations maintain their own Though the positions of the ASDS and AAD
positions on delegation of medical proce- appear clear, delegation remains a controver-
dures, state legislature plays a significant sial issue, especially due to the potential ambi-
role in this determination as well. guity that arises from differences in state
Regardless of the differences between legislation.
organizations and states, the consensus is In addition to adhering to the standards set
that the physician is ultimately responsible forth by their professional organization, physi-
for patient safety. cians must comply with state laws regarding laser
use. In this chapter, legislation in California,
Florida, Illinois, New  York, and Texas will be
addressed. The Federation of State Medical
In recent years, there has been increasing con- Boards last summarized the following regula-
cern regarding frequency and severity of reported tions for each state in May 2012.
adverse events associated with the use of lasers In California, laser regulation adheres
by non-physicians. This has led to calls for closely to the position of the ASDS, with addi-
increased regulation regarding delegation of tional stipulations regarding written documen-
medical procedures to non-physicians. Guidelines tation of supervision protocols and procedures.
have been created by professional organizations California also defines which non-physician
as well as state medical boards and legislature to health professionals may perform laser hair
delineate who is qualified to safely practice med- removal [8]:
icine involving lasers. The Business and Professions Code includes the
The ASDS and AAD maintain the position that use of laser devices in the definition of the practice
only active and properly licensed doctors of medi- of medicine. Only physicians, dentists, physician
cine and osteopathy shall conduct the practice of assistants and nurses may use laser devices, includ-
ing intense pulse light devices, with physician
medicine. But, a physician may delegate certain supervision within their legal scope of practice.
medical procedures to certified or licensed allied The law requires written protocols and procedures
health professionals under the appropriate circum- relating to supervision. Laser hair removal may be
stances. The ASDS Board of Directors approved performed only by a nurse physician or, when
working with a physician, registered nurse or phy-
the following statement in May of 2008 [7]. sician assistants.
The physician must directly supervise the allied
health professionals to protect the best interests In Florida, however, specifications requiring
and welfare of each patient. The supervising physi- registration of laser systems with the Department
cian shall be physically present on-site, immedi- of Health set an additional standard for safety [8].
ately available, and able to respond promptly to
any question or problem that may occur while the The Board of medicine considers the use of high-­
procedure is being performed. It is the responsible powered lasers (all Class IIIa, IIIb, and IV lasers as
physician’s obligation to ensure that, with respect designated by the FDA) to be the practice of medi-
to each procedure performed, the allied health pro- cine. These may be used only by physicians, or by
fessionals possess knowledge of cutaneous medi- those exempt from the Medical Practice Act (such
cine, documented training in the procedure, the as nurses) while acting under the direct supervision
indications for the procedure, and the pre- and of a physician. Florida also requires all high-­
post-operative care involved. powered laser systems to be registered with the
46 B. D. Cressey et al.

Department of Health. Failure to do so may be In the position statements on laser regulation, on-­
grounds for disciplinary action against a physician
site supervision is defined as continuous supervi-
and may result in a criminal penalty.
sion with the individual in the same building [8].
Additionally, Florida mandates specialty-­ Further, the State Board explicitly distinguishes
specific requirements relating to supervision [8]. practice guidelines for ablative and non-ablative
procedures [8]:
In office setting where supervision not onsite, pri-
mary health practitioners limited to supervising 4
offices in addition to the primary office location; (2) The use of lasers/pulsed light devices for
specialty practitioners limited to 2; dermatologists non-ablative procedures cannot be dele-
limited to 1. gated to nonphysicians delegates, other
than an advanced health care practitioner
In Illinois, the state legislature issued the fol- without the delegating physician being on
site and immediately available.
lowing statement regarding the use of lasers for
(3) The use of lasers/pulsed light devices for
non-physician users: ablative procedures may only be performed
“Laser equipment, which affects living layers of by a physician.
skin, is a medical device and must only be used
with the direct supervision by a physician. While In the latest 2012 publication, the Texas Board
the physician may delegate performance of laser has updated its position on the delegation of medi-
procedures to appropriately educated, trained, and
experienced nurses or other personnel, the physi- cal services from 2008. As of 2012, “a physician has
cian must provide proper supervision, including the authority to delegate a medical act to qualified
initial assessment, on-site availability and ultimate and properly trained persons if the physician deter-
responsibility.” mines that the act can be properly and safely per-
formed by that person and such delegation does not
The Board of Medicine in New York regulates violate any other statute. The delegating physician
the use of lasers for hair removal in a similar remains responsible for delegated medical acts.”
manner as California and Illinois [8]: A 2011 survey study of state medical boards
In August 2002, the NY State Board of Medicine showed a wide variability in the regulation of
passed a resolution recommending that the use of how responsibilities related to minimally inva-
lasers and intense pulsed light for hair removal to sive cosmetic procedures are regulated [9].
be considered the practice of medicine and thus be Despite this variability, the consensus remains
performed by a physician or under direct physician
supervision. that ultimate responsibility for performing any
medical procedure resides with the physician.
To ensure compliance with these regulations,
the New York Education Law defines the follow- Conclusion
ing two statutes as professional misconduct [8]: Guidelines and regulations for medical lasers
24) Practicing beyond the scope of practice permit- are essential for their safe and effective use.
ted by state law and performing professional As previously noted, there is no single, finite
responsibilities a licensee knows he/she is not standard of practice, therefore consultation
competent to perform. with the appropriate governing bodies and
25) Delegating professional responsibilities to a
person when the licensee delegating such responsi- professional organizations is necessary to
bilities knows or has reason to know that such per- ensure the quality of care provided and the
son is not qualified, by training, experience or by safety of the laser patient, staff and
licensure to perform. operator.
Though New  York law does not address new
issues, it strengthens the responsibility of the phy-
sician by including regulations on delegation
prominently within its code of professional References
misconduct.
1. The laser revolution – laser skin surgery. Approved by
In Texas, the State Board provides a few the Board of Directors, American Society for Laser
detailed clarifications the previous states do not. Medicine and Surgery, Inc., October 1, 2007.
2  Laser Safety: Regulations, Standards and Practice Guidelines 47

2. The use of lasers, pulsed light, radio frequency, Society for Laser Medicine and Surgery, Inc., August
and microwave devices. American Academy of 2, 2012.
Dermatology, Approved by the Board of Directors, 6. Control of smoke from laser/electric surgical pro-
February 22, 2002. cedures. Hazards controls. HC 11. DHHS (NIOSH)
3. American National Standards Institute. American Publication 96–128, 1996.
National Standard for Safe use of lasers in health care 7. Position statement on non-physician practice of
facilities: ANSI Z 136.3. Orlando, FL: Laser Institute medicine and use of non-physician office person-
of America; 2011. nel. Approved by the Board of Directors, American
4. Lanzafame RJ.  Procedural skills for using lasers in Society for Dermatologic Surgery, May 2008.
general surgery. American Society for Laser Medicine 8. Use of lasers/delegation of medical functions regu-
and Surgery, Approved by the Board Directors, lation by state. Federation of State Medical Boards,
August 2, 2012. May 2012.
5. Procedural skill and technique proficiency for sur- 9. Choudhry S, et al. State medical board regulation of
gery and other energy-based therapies in dermatol- minimally invasive cosmetic procedures. J Am Acad
ogy. Approved by the Board of Directors, American Dermatol. 2012;66:86.
 Lasers for Treatment of Vascular
Lesions 3
Jayne Joo, Daniel Michael, and Suzanne Kilmer

Abstract Nd:YAG (Potassium-Titanyl-Phosphate

Lasers for the treatment of vascular lesions are [KTP]) · Pulsed dye lasers (PDL)
continually improving using the principles of Alexandrite laser · Neodymium:Yttrium–
selective photothermolysis. Aluminum–Garnet (Nd:YAG)
Important variables to consider in the treat- Dual wavelength combination lasers
ment of vascular lesions are size, depth, and
composition.
Effective treatment of vascular lesions Introduction
requires tailoring the light wavelength, flu-
ence, and pulse duration to the specifics of the A large number of lasers and intense non-­
targeted lesion. coherent pulsed light devices are available for the
treatment of vascular lesions. New devices have
Keywords been developed, and existing devices are continu-
Lasers · Vascular lesions · Selective ally being improved to increase their ability to
photothermolysis · Pulse duration · Epidermal specifically target vessels while decreasing risk
temperature control · Frequency-doubled of potential complication such as scarring. Here
we review lasers that are utilized for the treat-
ment of commonly encountered vascular lesions.

J. Joo
Department of Dermatology, University of California,
Davis, CA, USA Principles of Laser Treatment
for Vascular Lasers
Sacramento VA Medical Center, Sacramento, CA, USA
e-mail: [email protected]
Selective Photothermolysis
D. Michael
Department of Mohs Surgery, Kaiser Permanente,
Walnut Creek, CA, USA In 1983, Richard Rox Anderson and John Parrish
e-mail: [email protected] proposed the theory of selective photothermoly-
S. Kilmer (*) sis, whereby laser energy can be used to create
Department of Dermatology, University of California, targeted damage to cutaneous structures while
Davis, CA, USA minimizing damage to surrounding tissue [1].
Laser and Skin Surgery Center of Northern The selective destruction of vascular lesions with
California, Sacramento, CA, USA light is based on the following tenets:
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 49

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_3
50 J. Joo et al.

• The wavelength of light has to penetrate to at The major chromophores competing for
least the depth of the target absorption in the skin are melanin, water, and fat.
• The energy is absorbed selectively by the target Melanin is primarily present in the epidermis and
• The heated target must cool quickly enough so may absorb incident laser light. This may reduce
that it does not cause thermal damage to the the effective energy delivered to the vascular tar-
surrounding tissue. get and possibly cause direct thermal damage to
the epidermis. Melanin absorption spectrum
The target (chromophore) for vascular lasers decreases with longer wavelengths from ultravio-
is hemoglobin. Choosing the appropriate laser let (<400 nm) through the visible (400–760 nm)
involves selecting a wavelength with deep enough spectrum (Fig.  3.1). Longer visible and near
penetration that is primarily absorbed by the vas- infrared wavelengths are absorbed less by epider-
cular target. There are commercially available mal melanin and penetrate deeper into the dermis
lasers ranging from 532 to 1064 nm for the treat- than the shorter visible and ultraviolet wave-
ment of vascular lesions with non-coherent lengths [2].
pulsed light sources spanning an even broader
spectrum. Within this range, shorter wavelengths
scatter more quickly and penetrate less deeply Pulse Duration
than longer wavelengths which can reach several
millimeters into the dermis before scattering ren- Based on the principle of selective photothermol-
ders it useless. ysis described by Anderson and Parrish, the size
The wavelength of light that is preferentially of the chromophore determines optimal pulse
absorbed depends on whether it is bound to oxy- duration. The thermal relaxation time is defined as
gen. Oxygenated hemoglobin (oxyhemoglobin) is the time it takes for a target structure to dissipate
normally the most abundant form of hemoglobin 50% of the absorbed energy into surrounding tis-
and has three peaks of absorption (418, 542 and sue. This can be approximated by the square of
577 nm) with decreasing absorption in the near- the diameter of the target structure. The ideal set-
infrared range [1]. Deoxygenated hemoglobin ting would have high enough fluences with pulse
(deoxyhemoglobin) has an absorption peak of durations that are short enough to limit diffusion
755 nm that is well targeted by the 755 nm wave- of heat from target vessels while still causing pho-
length alexandrite laser. The absorption of light tocoagulation [3]. Excessively long pulse dura-
energy by intravascular oxyhemoglobin results in tions that exceed the thermal relaxation time can
healing and destruction of vascular lesion. lead to diffusion of heat to surrounding tissue and

20,000 Tabulated molar extinction coefficient for hemoglobin in water

10,000 1,000,000
hbo2 cm-1/m
Hb hb cm-1/m
1000 100,000
Water
Absorbance (cm-1)

100
Melanin 10,000

10
HbO2
1000
1

0.1 100
200 1000 5000 250 350 450 550 650 750 850 950
a Wavelength (nm) b Wavelength nm

Fig. 3.1  Absorption curve for (a) hemoglobin, melanin, and water, and (b) oxygenated (red) and deoxygenated (blue)
hemoglobin
3  Lasers for Treatment of Vascular Lesions 51

thermal damage. In contrast, excessively short Pulsed Dye Lasers (PDL)

durations can cause focal boiling of the blood
which may lead to cavitation-­induced vessel dis- The flash lamp-pumped pulsed dye laser (PDL)
ruption which in turn can produce excessive pur- was the first laser developed for selective photo-
pura without necessarily causing elimination of thermolysis of vascular lesions [1, 4]. It was ini-
the vessel. tially designed to produce 577  nm light to
correspond with one of the oxyhemoglobin peaks
[5] (Fig. 3.1). The wavelength was increased to
Epidermal Temperature Control 585  nm to increase the depth of penetration,
improving efficacy for the treatment of deeper
Heat transfer to the epidermis during laser ther- vessels. The original pulsed dye lasers had short
apy can cause untoward thermal damage. This pulse widths of 0.45 ms, whereas the next gener-
can occur by several mechanisms: direct ation of PDLs could deliver high frequency
absorption of light energy, back scatter of light pulses that could be combined into longer com-
from deeper tissue, and conduction of heat pro- bined pulse widths of 1.5  ms. The longer pulse
duced in the dermis. Selective cooling of the widths allow treatment of larger vessels with less
epidermis is therefore very important before, extravasation of blood and therefore less purpura.
during, and after treatment and allows for Although longer wavelengths allow deeper pen-
higher temperatures to occur in the target struc- etration, hemoglobin absorption begins to drop
tures without damage to the epidermis. Current off rapidly as the wavelength increases. The next
methods for epidermal cooling include: direct generation of PDLs is also able to produce light
contact (conduction), forced cold air (convec- with wavelengths of 585, 590, 595, or 600  nm.
tion), and cryogen spray (conduction and The most recent versions of pulsed dye lasers
evaporation). have only the 595 nm wavelength but have adjust-
able pulse widths ranging from 0.45 to 40 ms to
provide optimal treatment parameters for various
 asers for Treatment of Vascular
L vessel sizes.
Lesions

Frequency-Doubled Nd:YAG Alexandrite Laser

(Potassium-Titanyl-Phosphate [KTP])
Bluish vascular lesions often extend deeper and
Frequency-doubled neodymium:yttrium-­ contain more deoxyhemoglobin. PDLs are not
aluminum-­ garnet (Nd:YAG) lasers use very effective against these lesions because their
potassium-­ titanyl-phosphate (KTP) crystals to wavelengths often do not penetrate deeply
double the frequency, which halves the wave- enough and are not absorbed by deoxyhemoglo-
length from 1064 to 532  nm. Oxyhemoglobin bin as well as they are by oxyhemoglobin.
absorbs the light of this wavelength about as well Initially, the long pulsed alexandrite laser was
as it absorbs the light of 585  nm wavelength used for hair removal, but was found to be effec-
(Fig. 3.1). This shorter wavelength is effective for tive against violaceous deeper vascular lesions.
destruction of more superficial vessels whereas The long pulsed alexandrite laser utilizes the
longer wavelengths penetrate deeper and are bet- deoxyhemoglobin absorption peak at 755 nm to
ter suited for vessels that are located deeper in the target certain vascular lesions [6]. In addition to
skin. Melanin also absorbs this wavelength well. being well absorbed by deoxyhemoglobin, the
Therefore, efficient epidermal cooling is neces- longer wavelength of the long pulsed alexandrite
sary when using these devices, especially in lasers produced over longer pulse widths allows
darker skin types that have higher epidermal mel- the light energy to penetrate deeper into the der-
anin content. mis and to target larger vessels.
52 J. Joo et al.

Neodymium:Yttrium–Aluminum– an Nd:YAG laser [9]. In addition, the thrombus

Garnet (Nd:YAG) that can be formed by PDL energy also is a better
target for the 1064 nm light [9, 10]. Because of
Neodymium:yttrium-aluminum-garnet (Nd:YAG) the increased absorption of 1064  nm by methe-
lasers produce light at 1064 nm which penetrates moglobin and thrombus, lower fluences of the
deeper than shorter wavelengths. However, at Nd:YAG can produce vessel specific damage
this wavelength, oxyhemoglobin no longer while decreasing risk of thermal damage to sur-
absorbs the energy better than the surrounding rounding tissue.
dermis. These lasers can be effective, but the risk PDL light only penetrates approximately
of scarring is significant at fluences high enough 0.75  mm into the skin. For lesions with deeper
to effect vascular damage, so these lasers are less components, it is necessary to allow the PDL
often used [7]. Fluences and pulse width used at formed products time to flow deeper into the
this wavelength are dependent on vessel size, lesion before illumination with the deeper pene-
location, and the oxygenation of hemoglobin. trating Nd:YAG laser. The combination PDL/
Vessels with larger diameters require longer Nd:YAG therapy works best for superficial dis-
pulse widths (Fig.  3.2). Conversely, small ves- crete telangiectasias with vessels in the 0.2–
sels need shorter pulse widths but require higher 1.2 mm diameter range. Although PDL remains
fluences as there is less chromophore (i.e., hemo- the treatment of choice for vascular birthmarks,
globin) present. the dual wavelength combination KTP/Nd:YAG
and PDL/Nd:YAG lasers may be helpful for
lesions that resistant to PDL alone [11, 12].
Dual Wavelength Combination Lasers

Methemoglobin is hemoglobin in which the fer- Intense Pulsed Light (IPL)

rous iron of the heme group has oxidized to ferric
iron. Unlike oxyhemoglobin and melanin, methe- Intense Pulsed Light (IPL) devices produce high-­
moglobin has higher absorption with increasing energy, non-coherent light. Their output covers a
wavelength from 700 to 1000 nm [8] and can be broad range of the light spectrum, often ranging
targeted by Nd:YAG laser light. It has been from near 500 nm to around 1200 nm with pulse
shown that pulsed dye lasers are able to induce widths of several milliseconds. Cut-off filters are
the transformation of oxyhemoglobin to methe- used to limit the spectrum of the incident light to
moglobin resulting in a more selective target for the desired wavelengths. For treatment of vascular

a b

Fig. 3.2  Blue facial veins (a) before and (b) after treatment with long-pulsed Nd:YAG 1064 nm laser [Excel V (5 mm,
110 J/cm2, 40 ms, 5 °C cooling with sapphire tip)]
3  Lasers for Treatment of Vascular Lesions 53

lesions, wavelengths shorter than 580–590 nm are well by PDLs. For these reasons, PWSs are gen-
generally filtered out [13]. Newer devices filter out erally best treated with PDLs earlier in the pink
the longer infrared wavelengths, reducing many of macular stage, as often seen in infants. More
the adverse effects of earlier devices [13]. These mature hypertrophic bluish PWSs often require
devices usually have larger application tips which longer pulse widths and even longer wavelengths
cover larger surface areas and are well suited to [19]. Successful treatment generally requires
broader treatment areas. repeated treatments, especially for larger lesions
Output varies by wavelength and by device, so and those on the distal extremities. As discussed
parameters tend to be device-specific. IPL devices above, longer wavelengths can treat deeper ves-
can be effective against capillary malformations, sels in the lesion and may show improved rates of
telangiectasias, and small cherry angiomas [14]. clearance, although the decreased absorption by
Adverse effects include postinflammatory hyper- hemoglobin necessitates higher fluences which
or hypopigmentation, blistering, and scarring. may be more likely to produce post-inflammatory
pigment changes.
Most patients see significant improvement but
 ascular Lesions and Laser
V complete clearance of the lesion is often not pos-
Treatment Options sible. Lesions in newborns tend to respond faster
and more completely than those in older patients.
 apillary Malformations (e.g., Port
C There is much less melanin in neonatal skin com-
Wine Stains or Nevus Flammeus) peting as a chromophore for the absorption of the
laser, and the lesions tend to be smaller and thinner
Capillary malformations are the most common than in adults. All of these features render earlier
type of vascular malformation. Port wine stains lesions more responsive to PDL than later lesions.
(PWS), also called nevus flammeus, are congen- Pink macular PWSs are best treated using
ital developmental malformations of the superfi- 585–595  nm wavelengths with a short pulse
cial dermal capillaries. They are present at birth, width in the 0.45–1.5  ms range (Fig.  3.3). The
grow as the child grows, and do not involute. best spot size and energy used is dependent on
Treatment of PWSs was initially performed the specific PDL used, but for 10 mm spot size,
with the continuous wave 488–514  nm argon 7.5 J/cm2 is often effective and for 12 mm spot
laser [15, 16]. One of the main problems with size, 7 J/cm2 is often needed, which may be the
the argon laser was that the pulse width could maximum output available. For more resistant
not be controlled. This often led to scarring PWSs, when higher energies are needed, we
from excess heat deposition. A laser with a lon- found that the 7 mm spot size may be needed to
ger wavelength and a controllable pulse width deliver 8–10  J/cm2. As higher energy levels are
was needed. To overcome the inadequacies of used, the risk of purpura or ulceration increases
the argon laser for treating these lesions, Richard and these settings should be used with caution.
Rox Anderson and John Parrish developed the For PWS composed of larger vessels, the pulse
theory of selective photothermolysis. This led to width may need to be lengthened. With longer
the PDL becoming the treatment of choice for pulse widths, it becomes very important not to
these lesions. PDL selectively targets hemoglo- exceed the ability of the cooling to protect the
bin and the pulse width more closely matches to epidermis. As with all lasers, appropriate cooling
the thermal relaxation time of the target vessels is important to protect the epidermis while deliv-
in PWSs [17]. ering sufficient heat to effectively destroy the
Most PWSs start as pink macules with tiny target.
vessels, but with time these lesions become Frequency-doubled Nd:YAG (Nd:YAG/KTP)
larger, thicker, and tortuous [18]. In addition, lasers produce sequential nanosecond length
more of the hemoglobin in larger, older lesions pulses at a high frequency (>20,000 Hz) to pro-
tend to be deoxygenated and are not targeted as duce semi-continuous pulses in the 2–20  ms
54 J. Joo et al.

a b

Fig. 3.3  Young boy with pink macular PWS (a) before and (b) after ten PDL treatments

range. The 532 nm wavelength does not penetrate a 10–12 mm spot size and 3 ms pulse width have
deeply but has been shown to be effective against improved resolution in those recalcitrant to
the superficial components of PWSs [20–22]. previous treatments.
For hypertrophic PWSs, the PDL can be used More recently, the 595  nm wavelengths has
at 595  nm with similar settings as above; how- been used in combination with the 1064  nm
ever, increasing the pulse width may improve wavelength to take advantage of the improved
outcome. In addition, hypertrophic bluish PWSs absorption of 1064 nm by methylated hemoglo-
have more tortuous dilated vessels and slower bin so that less energy at 1064 nm is needed mak-
blood flow resulting in more deoxygenated ing it safer. PDL and Nd:YAG lasers, when used
hemoglobin. Therefore, they may be better tar- in combination, are generally set lower than
geted by the 755  nm wavelength of alexandrite either would be if used alone. Fluences generally
lasers, which utilizes the absorption peak of used ­range between 6 and 10 J/cm2 for the PDL
deoxyhemoglobin near 755  nm (Fig.  3.4). We and between 40 and 80  J/cm2 for the
often find settings of 35–40  J/cm2 with 12  mm Nd:YAG.  However, appropriate sample starting
spot size and 3  ms pulse width with 50  ms of settings for PDL is 7–8 J/cm2 and 10 ms, and for
spray cooling safe and effective. Care must be Nd:YAG is 40 J/cm2 and 15 ms.
taken to not overlap these pulses. Multiple factors influence the effectiveness of
Nd:YAG lasers have also been shown to be treatment, including thickness, patient age, and
effective against capillary malformations. location of the lesion. Treatment response
However, because this laser has a greater risk of decreases with age and thickness of the lesion
scarring, we rarely use this laser in infants or young [23]. The earlier these lesions are treated, the bet-
children. In a more mature PWS, 60–70 J/cm2 with ter the results [24–26]. Not only do they clear
3  Lasers for Treatment of Vascular Lesions 55

a b

Fig. 3.4  Middle aged Hispanic women with mixed (mac- and alexandrite 755 nm laser (40 J/cm2, 3 ms, 12 mm spot
ular and hypertrophic) PWS (a) before and (b) after three size)
treatments with PDL (7.5 J/cm2, 1.5 ms, 10 mm spot size)

better, but the treatments are better tolerated. It is Hemangiomas

often possible to achieve effective treatment
before 6 months of age. Treatment intervals are In contrast to vascular malformations, infantile
typically 4–6 weeks apart though there is little hemangiomas (IH) are true neoplasms composed
documentation establishing the optimal interval. of endothelial cells. They usually develop soon
In fact, for resistant PWSs, 2 week intervals have after birth, but almost a third are present at birth
resulted in dramatic improvement without [30]. They are more common in Caucasians
increasing complication rates [27]. This may be (~10% of births) and are more likely in infants
because more frequent treatments may prevent that are premature, of very low birth weight
neovascularization that would otherwise occur (<1.5  kg), born to mothers who had chorionic
before the next treatment. In addition, lesions ­villus sampling, or those with a first-degree rela-
involving V2 distribution of the trigeminal nerve tive who have a vascular anomaly [31].
as well as those in the V1 distribution over the Although IHs can undergo a proliferative
nose respond less well than those superior or phase during which they grow rapidly in size,
inferior to these regions [28, 29]. many involute as suggested by the mnemonic
The most common adverse effect of PDL often taught medical students, “50% resolve by
treatment is purpura, though this is becoming less 5 years, 70% resolve by 7 years, 90% resolve by
common with newer lasers. It used to be thought 9 years.” However, end-stage or involuted hem-
that production of purpura is necessary for suc- angiomas often have residual superficial telangi-
cessful treatment. and therefore the lowest energy ectasias with saggy, atrophic skin.
settings that produce purpura were used. More When IHs as located in cosmetically sensitive
recently, we and others have found that these areas or impinge on normal form and function, it
lesions can be successfully treated without induc- necessitates early intervention before permanent
ing purpura [26]. damage results. For example, periocular lesions
56 J. Joo et al.

may obstruct vision and can impair visual cortex

a
development leading to permanent blindness.
Perioral lesions may frequently hemorrhage and
impair feeding ability, possibly leading to failure-­
to-­thrive. Perineal lesions often ulcerate and can
be very painful. Until recently, problematic IHs
were treated with systemic corticosteroids with
variable response [32, 33]. In 2008, Léauté-­
Labréze et al. made the serendipitous discovery
that propranolol given to infants with IHs for
treatment of cardiac problems also resulted in
dramatic regression of their IHs [34]. Propranolol
b
is now widely regarded as first line treatment for
problematic IHs [35]. Recently, topical timolol
has shown promise for the treatment of superfi-
cial IHs [36]. Timolol is hydrophilic and does not
permeate skin easily. Fractional CO2 laser-
assisted transdermal delivery of topical timolol
has shown promising results for deep IHs [37].
Both PDL and Nd:YAG lasers have been suc-
cessfully used to treat IHs [38, 39]. Hemangiomas
frequently have a stronger response to laser treat-
ment and need to be handled more carefully to
c
avoid iatrogenic ulceration. Though deep compo-
nents of the hemangioma will not be treated by
the 595 nm lasers (which have a limited depth of
penetration up to 1.2 mm), selective elimination
of the more superficial component of the heman-
gioma will preserve superficial skin architecture.
Because the Nd:YAG lasers can penetrate up to
6 mm, it has been proposed that sequential dual
wavelength modality of treatment is ideal for
mixed hemangiomas that have a superficial and
deep component [40]. In comparison to treatment
of PWSs, we typically start more conservatively Fig. 3.5  Ulcerated congenital hemangioma (a) at presen-
tation, (b) after PDL treatment, and (c) resolved lesion
using settings approximately 1  J/cm2 lower and
then evaluate the response. In addition, these
lesions require more frequent monitoring with regresses, a more normal appearing epidermis is
shorter treatment intervals and careful adjust- more likely to remain (Fig. 3.6).
ments made to treatment settings based on evalu-
ation of the response from the previous visits.
Systemic and topical treatment options may be Spider Angiomas
combined with laser therapy to improve results. In
fact, when the IH has deep dermal ­vessels, lasers Spider angiomas consist of a central arteriole
may provide better results than topical timolol directly supplying a radiating network of dilated
alone because of a better depth of penetration [40]. superficial capillaries. Spider angiomas are com-
Laser treatment can accelerate re-­epithelialization, mon among people with lighter skin and are often
prevent hemorrhage, and restore skin integrity localized to areas of sun exposure, such as the
and comfort (Fig. 3.5). Once the deep component face, neck, and upper chest. They are also associ-
3  Lasers for Treatment of Vascular Lesions 57

a b

Fig. 3.6  Scrotal hemangioma (a) at presentation and (b) after six treatments with PDL

ated with portal hypertension and hereditary PDL continues to be the most effective treat-
hemorrhagic telangiectasia (HHT) [18]. PDLs are ment option. This laser used to be associated with
the laser of choice for the treatment of spider high rates of purpura [41]. However current ­opinion
angiomas. Treatment is aimed at the destruction is that telangiectasias can be treated with longer
of the central “feeder” vessel which can then be pulse widths in the 6–10 ms range utilizing pulse
followed by destruction of the peripheral capillar- stacking where two to four pulses are “stacked”
ies. Diascopy can be used to target the feeder ves- immediately one on top of the other until vessel
sel by blanching the draining capillaries. Fluences clearing is noted without inducing purpura [42, 43]
of 7–10  J/cm2 using a 5–10  mm spot size are (Fig. 3.7). In fact, even longer pulse widths in the
often effective after just one or two treatments. 20–40 ms range may be effective. Treatment using
fluences between 7 and 10 J/cm2 and spot sizes of
5–10  mm are often effective with pulse widths
Telangiectasias ranging from 6 to 10 ms (Fig. 3.8). For the com-
bined Cynosure Cynergy device, the PDL at
Facial telangiectasias are one of the most com- 7–8 J/cm2 with a pulse width of 10–20 ms and with
mon complaints encountered by the cosmetic a short or medium delay followed by Nd:YAG at
dermatologist. They are more common in peo- 30–40 ms with pulse width of 15 ms is often effec-
ple with lighter skin types and are associated tive (Fig. 3.9). Immediate coagulation/graying that
with a history of sun exposure and rosacea. quickly clears is the desired endpoint. Purpura may
They represent dilated capillaries and post-cap- be more likely to develop in patients taking anti-­
illary venules with thickened walls. They are coagulants (e.g., ASA, Coumadin, vitamin E, etc.).
superficial (200–250  μm deep) and have small IPLs have also been shown to be effective
cross-sections (200–500 μm in diameter) [41]. against telangiectasias. They induce mild
58 J. Joo et al.

a b

Fig. 3.7  Fifty-two year old woman with rosacea (a) before and (b) after two PDL treatments (7.5 J/cm2, 6 ms, and
10 mm spot size)

a b c d

Fig. 3.8  Facial and nasal telangiectasias (a, b) before and (c, d) after two treatments with PDL (7.5 J/cm2, 6 ms, and
10 mm spot size)

a b

Fig. 3.9  Sixty-one year old woman with facial telangiec- telangiectasias, followed by a second pass with 10  mm
tasias (a) before and (b) after treatment with PDL spot size, 7.5 J/cm2, 6 ms)
(3 × 10 mm spot size, 17 J/cm2, 40 ms over linear, discrete
3  Lasers for Treatment of Vascular Lesions 59

erythema and have a lower risk of inducing pur- the longer pulse widths which makes post-laser
pura. Effective fluences range from 32 to 40 J/cm2 cooling an important consideration.
with pulse widths of around 20  ms [41]. While The aim with a PDL is to produce mild pur-
PDLs continue to be the treatment of choice for pura and edema. With diode and Nd:YAG lasers,
focal telangiectasias, IPLs may be more tolerable the goal is reduction in lesion thickness and
for some patients with larger ­ matted clearance of the ectatic vessel. For the larger and
telangiectasias and the diffuse erythema associ- deeper lesions, Nd:YAG with a spot size of 3 mm,
ated with rosacea. pulse widths of 30–100 ms, and fluences of up to
150 J/cm2 may be needed [41] (Fig. 3.10).

Venous Lakes
Other Vascular Anomalies
Venous lakes are vascular ectasias that usually
develop after the age of 50 and may enlarge over In addition to the above mentioned vascular
time [18]. Their size and depth can vary greatly. lesions, there are a variety of other less common
As with most vascular lesions, laser therapy is vascular anomalies for which surgery used to be
often effective and needs to be tailored to the the mainstay of treatment. These lesions can
depth of the target. PDL is usually effective for now be treated successfully with laser therapy.
superficial venous lakes but longer wavelength For example, the lesions of blue rubber bleb
lasers, such as the diode (800–900 nm), alexan- nevus syndrome, which are typically cutaneous
drite (755 nm), or Nd:YAG (1064 nm), are neces- venous malformations of varying sizes that
sary for thicker or deeper lesions. Fluences of enlarge with age, respond well to long pulse
80 J/cm2, pulse durations of 60 ms or longer, and alexandrite laser with a fluence of 40 J/cm2, spot
10–12 mm spot sizes are often required; however, size of 12 mm, and efficient cooling (Fig. 3.11).
such settings may put the epidermis at risk of The long pulse Nd:YAG laser can also be uti-
being thermally damaged. Therefore, appropriate lized with settings starting at 80 J/cm2 at 60 ms.
cooling is very important. In addition, there can Again, appropriate cooling is extremely impor-
be significant heat return to the epidermis with tant to minimize epidermal injury and scarring.

a b

Fig. 3.10  Venous lake (a) before and (b) after single pulse with Nd:YAG 1064 nm laser (110 J/cm2, 30 ms, 5 mm spot
size)
60 J. Joo et al.

a b

Fig. 3.11  Blue rubber bleb nevus of the tongue (a) before ing). Care must be taken to assure proper cooling and to
and (b) after treatment with alexandrite 755  nm laser not over-treat as this may cause tongue swelling and air-
(40 J/cm2, 3 ms, 12 mm spot, 50 ms cryogen spray cool- way occlusion

Lymphangioma can also be targeted by vascular diameter: implications for port wine stain laser ther-
apy. Lasers Surg Med. 2002;30(2):160–9.
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enough to provide a sufficient target for these selectively damaged using dye lasers: a basic theory
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44. Railan D, Parlette EC, Uebelhoer NS, Rohrer

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1993;129(2):182–8.
 Laser for Scars
4
Voraphol Vejjabhinanta, Shalu S. Patel,
and Keyvan Nouri

Abstract Outline
Introduction of scar pathogenesis, epidemiol-
ogy, and classifications.
• Introduction of scar pathogenesis,
Indications and contraindications for laser
epidemiology, and classifications
scar treatment.
• Indications and contraindications for
Appropriate management of scars, includ-
laser scar treatment
ing pre- and post-operative techniques.
• Appropriate management of scars,
including pre- and post-operative
Keywords
techniques
Scar pathogenesis · Scar epidemiology · Scar
• Potential adverse side effects of laser
classification · Scar treatment · Atrophic scars
scar treatment
• The use of laser therapy for atrophic
scars, including ablative, nonablative
and fractional resurfacing
• Future directions of laser scar therapy

V. Vejjabhinanta, MD (*)
Dermatologic Surgery and Lasers Unit, Department
of Medical Services Ministry of Public Health,
Institute of Dermatology, Bangkok, Thailand
S. S. Patel, MD
The Permanente Medical Group, Redwood City,
CA, USA
e-mail: [email protected]
K. Nouri
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 63

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_4
64 V. Vejjabhinanta et al.

Introduction brane. Revascularization occurs with endothe-

lial cells and angiogenic factors such as
fibroblast growth factor (FGF). As maturation
• The skin’s normal wound healing ensues, the collagen network and proteoglycans
process involves coagulation, inflam- are also remodeled. While both collagen types I
mation, proliferation and and III increase during the beginning of the
remodeling. wound healing process, the contribution of col-
• Hypertrophic scars and keloids occur lagen type III decreases as remodeling takes
when the skin’s normal wound heal- place.
ing process goes awry. Further, they An abnormal response to the wound healing
more commonly occur in ethnic skin. process results in hypertrophic scars (Fig. 4.1)
• There are multiple techniques used to and keloids (Fig.  4.2). These are essentially
treat these scars, and recent advances excess scar tissues that form at the site of
in laser therapy have made lasers a injury. Fibroblasts from keloids abnormally
practical alternative. respond by producing high levels of collagen,
particularly type I. In contrast, fibroblasts from
hypertrophic scars respond normally, with a
The skin is a primary barrier for protection and is slight increase in collagen. The collagen fibers
often submitted to damage from surgical proce- in hypertrophic scars are more organized,
dures, burns, trauma or inflammation. The skin while those in keloids are arranged in whorled,
has an incredible capacity to renew and repair
itself through a process called wound healing, in
which a cascade of mechanisms result in
scarring.
The normal wound healing process, which
results in a flat and flexible scar, can be divided
into four stages: coagulation, inflammation,
proliferation, and remodeling. Once the injury
occurs, the inflammation phase begins after
activating the clotting and complement cas-
cade. Chemotactic factors such as prostaglan-
dins, complement factors, and interleukins (i.e.
IL-1) stimulate the migration of inflammatory
cells such as neutrophils and monocytes/macro-
phages. These cells help wound debridement.
Macrophages also release specific growth fac-
tors such as transforming growth factor Beta
(TGF-β) and platelet-derived growth factors
(PDGF), which initiate the formation of the
provisional wound matrix. The proliferation
phase involves the migration of fibroblasts,
increased endothelial cells and keratinocytes to
the site of injury. Fibroblasts are especially
important in forming the extracellular matrix,
which is made of collagens I and III, fibronec-
tin, elastin, and proteoglycans. The keratino-
Fig. 4.1  A pink, smooth, shiny, well-circumscribed linear
cytes start the re-epithelialization process with hypertrophic scar at the lower abdomen after trans-abdominal
reconstruction of the disrupted basement mem- hysterectomy
4  Laser for Scars 65

Fig. 4.2  Multiple keloids at the right

arm, shoulder and chest wall of an
African American woman

hyalinized bundles. Further, while angiogene- formation are ear piercings, tattoos, infections,
sis diminishes during normal remodeling, but vaccination, burns, and inflammatory acne.
persists during the development of keloids and The treatment of hypertrophic scars and
hypertrophic scars. keloids is challenging due to high recurrence
These can occur in all races, although they are rates and adverse side effects. Previous methods
more frequently found in ethnic skin, ranging for treatment have included surgery, cryotherapy,
from a 3 to 18 times higher incidence when com- electrocautery and desiccation, dermabrasion,
pared with Caucasians. The incidence has been intralesional corticosteroids, 5-fluorouracil, and
reported to be between 4.5% and 16% within radiation. In terms of lasers, Ablative CO2 and
African-Americans, Chinese, and Hispanics. Erbium: YAG lasers were used for hypertrophic
Patients in their second to third decade of life are scars but then discontinued. The pulsed dye laser
more commonly affected, with the same preva- (PDL) is currently the laser of choice for hyper-
lence in both sexes [1–3]. trophic scars, which have yielded more success-
Hypertrophic scars are red, raised, and firm, ful results compared to keloids. It works via the
and usually appear within 1  month at the injury principle of selective photothermolysis, in which
site, especially sites under pressure or frequent the laser targets blood vessels, with the 585 nm
movement. Keloids, which can often be disfigur- wavelength specifically absorbed by hemoglobin.
ing, are purple/red nodules that are often found It is suggested that the microvascular destruction
beyond the original injury site. Unlike hypertro- causes subsequent ischemia and reduction of
phic scars, these appear within weeks or even years scarring.
from the initial injury. Keloids frequently are found To appropriately treat hypertrophic scars and
on the earlobes, anterior chest, shoulders and upper keloids, a thorough understanding of the pro-
back. Common processes that may lead to keloid cesses by which they form is essential.
66 V. Vejjabhinanta et al.

Indications and Contraindications a

• Indications for treatment include side

effects, functional impairment, and
aesthetics.
• It is important to take into account
the patient’s skin type and lesion type
prior to therapy.

Patients typically seek medical help due to cos- b

metic issues or associated symptoms. Thus,
indications for treatment of hypertrophic scars
include functional impairment, cosmetic
appearance, and pruritis and dysesthesias. The
typical outcome of laser treatment is reduction
of the redness and height of the scar, improve-
ment of pliability, and symptomatic relief of
pruritis.
Factors that need to be taken into consider-
ation before treatment include patient skin type
and lesion type. Fair skinned individuals
(Fitzpatrick skin types I to III) tend to have a bet- Fig. 4.3 (a) A linear surgical scar on the anterior mid
ter response and fewer side effects to treatment. upper chest. The right section received 585 nm PDL with
Patients with Fitzpatrick skin types IV to VI have pulse duration of 450 μs, the middle remained as a con-
trol, and the left section received 585 nm PDL with pulse
an increased risk of laser light absorption by epi-
duration of 1.5  ms. (b) One month after the third PDL
dermal melanin, therefore less effective targeting treatment. There was a significant clinical difference
of the skin and increased risk of postoperative between treated and untreated sites
hypo- or hyperpigmentation. It is suggested that
in these patients, a test spot is done to predict any
potential side effects. Lesion type also plays a Techniques
role in the success of laser treatment. Lesions that
have formed in less than a year and those that are
red and raised have proved to be ideal for laser • Pre-operative management includes
therapy. obtaining a detailed history and exam
Lasers have been found to be useful as a pre- of the patient’s scars, and if any prior
ventative measure as well. The 585 nm PDL was therapy has been done. The area of
found to be effective in preventing the formation treatment should be cleaned thoroughly
of hypertrophic scars in burn wounds. Further, and topical anesthetic may be used for
treating surgical scars starting on the day of comfort. It is important to take a pic-
suture removal has yielded optimal results ture of the scar before therapy to track
(Figs. 4.3a, b).
4  Laser for Scars 67

comparative purposes. It should be taken with the

its progress and note any side effects same camera, lighting, and distance. The patient
that may occur. and physician should be wearing eye protection at
• Laser therapy involves appropriately all times during the procedure.
calibrating and setting the laser
parameters. It may be used alone or
in conjunction with intralesional Description of the Technique
medical therapy. Multiple treatments
are needed to obtain better results. The physician must first calibrate the laser and
• Post-operatively, the patient should set parameters to be used. The ideal setting is
avoid the sun and keep the treatment 585  nm PDL at 450  μs pulse duration, using a
area clean and protected. spot size of 7–10 mm, with the fluence ranging
from 3.5 to 7.5 J/cm2. When using a smaller spot
size, the fluence should be increased; however
initial treatments should all begin with a lower
Pre-operative Management fluence. In ethnic skin, we prefer using a lower
fluence (3–3.5 J/cm2 with a 10 mm spot size) in
It is important to get a good patient history before order to reduce any complications from this
laser treatment. The history of the scar or keloid procedure.
in terms of age, evolution, and previous treat- Once set, the physician should place the hand-
ments is helpful in determining treatment prog- piece over one end of the scar and start applying
nosis. It is ideal to treat hypertrophic scars early, the laser pulses over the entire scar surface in a
possibly within the first few months of appear- continuous pattern until reaching the opposite
ance. This is because of the numerous blood ves- end. A 10% overlap is generally accepted.
sels present at this time. Previous treatments, Laser treatment may be used alone or in com-
such as cryotherapy, may cause increased fibro- bination therapy with intralesional corticoste-
sis, and thus adjustments of laser parameters and roids or 5-FU. Alster compared PDL treatment
treatment sessions may need to be made. Location alone with laser therapy combined with intrale-
of the scar is also important to note. Dierickx sional corticosteroid treatment and found that
et al. have found that facial scars respond better both were similarly effective with no significant
to treatment [4]. Nouri et al. agree and have found difference [7]. It is important to remember, how-
that facial, shoulder, and arm scars respond better ever, that if using intralesional corticosteroids,
than those on the anterior chest wall [5]. However, the injections should be done following the laser
Alster and Nanni found no relation between scar procedure. If done before, blanching of the lesion
location and response to treatment [6]. occurs and there is substantial risk of losing the
The PDL treatment for hypertrophic scars and laser target. An average of 10–40 mg/mL imme-
keloids is an outpatient procedure. It typically diately after laser treatment can be used.
does not require anesthesia unless requested by
the patient. If so, a topical anesthetic cream may
be applied 30–60  min before the procedure. Post-operative Management
Make-up any other creams must be removed from
the treatment area with soap and water. In assess- Post-operative management includes strict sun
ing the lesion, the physician should note its size, avoidance to avoid pigmentation alterations. The
color, height, pliability, and associated symptoms. treated area should be cleansed as normal with
Vancouver Scar Scale or Miami Scar Scale, for soap and water. Trauma to the site should be
example, may be used to ensure consistency. A avoided. Subsequent treatments may be done
picture should be taken prior to treatment for within 4–6 weeks.
68 V. Vejjabhinanta et al.

 ide Effects/Complications and Their

S Atrophic scarring (such as those from acne,
Management and Prevention chicken pox, or even striae) is depression of the
skin due to the destruction of normal dermal or
A typical complaint from laser treatment is pain subcutaneous tissue architecture by inflamma-
similar to that of a rubber band snapping against tion, infection, or trauma.
one’s skin. A burning or itching sensation in the There are many treatment modalities for this
treated area is common as well, but subsides condition including topical vitamin A acid appli-
within a couple days if not sooner. Purpura is the cation, focal or regional chemical peeling, sub-
most commonly expected side effect, appearing cission, punch grafting, injection of fillers,
immediately after the procedure and lasting dermabrasion, and laser resurfacing.
7–10  days. Pigmentation alteration may also Nowadays, laser resurfacing for acne scar can
occur. If hyperpigmentation occurs, a bleaching be classified into three main categories:
cream may be used. Also, subsequent treatments
may need to be deferred to ensure effective laser 1. Ablative resurfacing
targeting of the scar. 2. Non-ablative resurfacing
Rare complications include crusting, oozing, 3. Fractional resurfacing
and vesiculation of the lesion. In these cases, the
area should be kept moist with ointment and may
be covered with nonocclusive dressing to avoid Ablative Laser Resurfacing
contact. Subsequent treatments must be post-
poned until complete healing of the site. Also, the The most common devices used for this tech-
physician must reconsider the settings used to nique are the carbon dioxide laser and Erbium
prevent further complications. YAG laser. Both of them are considered the gold
standard treatment for acne scars and offer prom-
ising results after treatment. However, this
Laser for Atrophic Scar method can be quite complicated and can have
multiple drawbacks including:

• Atrophic scars resulting from acne, • The need for antibiotic prophylaxis for
chicken pox, trauma, or even striae bacterial-­viral-fungal superimposed infections.
can be treated with laser therapy. The • The need for adequate anesthesia and sedation
three main categories of therapy (some are systemic administration in combi-
include ablative resurfacing, nonab- nation with local anesthesia injection).
lative resurfacing, and fractional • The need for complicated post-operative care
resurfacing. such as analgesia and dressing, along with
• Ablative resurfacing offers effective post-operative antibiotic coverage.
therapy, but side effects and adverse • The risk for post-operative bleeding when
events post-operatively limit its use. using Erbium YAG laser because it has a high
• Nonablative resurfacing is considered water absorption and thus cannot penetrate
safe, but may not be as effective as deeply (compared with the CO2 laser), pre-
ablative resurfacing. venting enough heat production to ligate blood
• Fractional resurfacing offers the vessels.
effectiveness of ablative resurfacing • A high tendency for post-operative erythema
and the safety of nonablative resurfac- or pigmentary alteration, which may prolong
ing. Studies have achieved improved downtime, especially for individuals with
results with this method, though a skin of color who experience post-inflamma-
small percentage of patients experi- tory hyperpigmentation and/or permanent
enced side effects. hypopigmentation.
4  Laser for Scars 69

In an effort to reduce these drawbacks, some of treatment, that they may require multiple ses-
modalities that have been introduced are pre-­ sions, and to hold realistic expectations of their
operative bleaching agents, combination topi- outcome.
cal anesthesia with regional nerve block, and
oral analgesic and sedation. Further, the follow-
ing devices were introduced to decrease Fractional Devices
complications:
Both physicians and patients have tolerated the
• The high energy-short pulsed CO2 laser, which high complication rate of ablative laser resurfac-
offers low tissue damage when compared with ing and low efficacy of non-ablative laser resur-
the conventional continuous mode CO2 laser. facing, but fractional resurfacing is a recently
• The variable pulsed or dual-mode Erbium introduced alternative that may be the best of
YAG laser, because the long pulse duration both devices. It particularly excels in offering
allows it to penetrate deeper than the short promising results for facial rejuvenation,
pulse duration alone, resulting in an optimal melasma, and acne scars. This system uses the
reaction for stimulating skin regeneration concept of fractional photothermolysis by creat-
and ligation of blood vessels to diminish ing numerous microscopic thermal injury zones
bleeding [8, 9]. of controlled width, depth and density that are
• The combined-mode Erbium YAG/CO2 laser surrounded by normal skin which serves as a res-
system, which offers the dual benefit of hav- ervoir for rapid tissue healing [20].
ing the ablative effect of the Erbium YAG The benefits of this system are less downtime
laser and the coagulation effect of the CO2 and side effects than the conventional ablative
laser [10]. laser has, and an increased efficacy of tissue
regeneration than the nonablative method offers.
There are many devices launched in the market
Nonablative Laser Resurfacing now, the most popular being the Erbium-doped,
Erbium YAG, CO2, radiofrequency, Xenon lights.
This is another modality that was quite popular at There are many studies that have demon-
the turn of the century due to low complication strated the efficacy of the 1550 laser system for
rates and very low to almost no downtime when acne scar treatment. Alster et al. used the 1550 nm
compared with ablative resurfacing, chemical erbium-doped fiber, with fluences of 8–16 J/cm2
peeling or dermabrasion. Some laser devices that at a density of 125–250 MTZ/cm2 in 8–10 passes
demonstrated improvement of acne scars include: on 53 patients (Fitzpatrick skin types I–IV) with
atrophic acne scars. They found that nearly 90%
• The 1064 nm Q-switched Nd: YAG Laser [11] of patients achieved clinical improvement aver-
• The 1064 nm Long pulse Nd: YAG Laser [12, aging 51–75%; however, multiple treatments
13] were necessary [21]. Lee et al. treated 27 Asian
• The 1320 Nd: YAG Laser [14, 15] patients (Fitzpatrick skin types IV-V) with mod-
• The 1450 nm diode Laser [16] erate to severe facial acne scars. Each patient
• The 1540-nm erbium-doped phosphate glass received three to five sessions of 3–4 weeks apart.
Laser [17] At 3  months after the final treatment, eight
• The 585  nm flashlamp-pumped pulsed dye patients (30%) assessed themselves as having
laser and Intense pulse light system also show excellent improvement, 16 patients (59%)
benefit for post acne erythema [18, 19] assessed themselves as having significant
improvement, and the final three patients (11%)
These lasers are alternatives for people who assessed themselves as having moderate improve-
may desire a less aggressive form of treatment; ment. Adverse events were limited to transient
however, patients must be informed of the cost pain, erythema and edema [22]. Emmy at el
70 V. Vejjabhinanta et al.

reviewed 961 patients who were treated with until resolution. 5-FU (45–50  mg/mL) may be
1550 nm erbium doped laser. They found that 73 injected a few times per week to once per month
(7.6%) patients developed complications. The depending on the quality of the lesion.
most frequent complications were acneiform Corticosteroids work by inhibiting migration of
eruptions (1.87%) and herpes simplex virus out- inflammatory cells, vasoconstriction, and inhibi-
breaks (1.77%). Other rare complications include tion of fibroblast and keratinocyte proliferation.
erosions, postinflammatory hyperpigmentation, The mechanism of 5-FU is primarily inhibition
prolonged erythema, prolonged edema, dermati- of fibroblast proliferation. Both of these methods,
tis, impetigo, and purpura [23]. though effective, can cause pain at the injection
Other fractional laser systems such as the frac- site and side effects such as pruritis and purpura.
tional CO2 laser and fractional Erbium YAG laser Studies combining these with PDL treatment are
are, by theory, more ablative than the 1550 promising.
erbium-doped laser. However, the optimal treat- Further studies, possibly combining various
ment parameters for achieving a successful acne lasers such as short-pulse and long-pulse, may
scar treatment with minimal side effects need to offer interesting results and a potential frontier
be studied. Interestingly, Vejjabhinanta et al. per- for scar treatment.
formed a study of acne scar treatment by using a
fractional radiofrequency microneedle system. Conclusion
They found that this system was safe and effec- The mechanisms of hypertrophic scar and
tive with minimal side effects in Asians [24]. keloid formation are interesting and important
in identifying optimal treatments. Various
treatment options are available, and lasers pro-
Future Directions vide a novel and efficacious approach to ther-
apy. While the 585–595 nm PDL seems to be
the optimal laser, recent results of the frac-
• Future directions in scar management tional laser resurfacings promising.
include attempting to prevent scar for- Abnormalities in wound healing remain a
mation at the start by using PDL or challenging topic. Patients suffer physical and
intralesional medical therapy. emotional consequences. Addressing and
• These methods, however, do not come managing these factors with minimal side
without their own side effects. effects in all patients should be the goal of
Combination lasers may provide opti- future studies.
mal results for laser scar therapy in the
future.
References

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color. Cutis. 2003;71(4):271–5.
tant. An effective way to do this is to use PDL 2. Alhady SM, Sivanantharajah K.  Keloids in various
routinely after suture removal. For new, red, races. A review of 175 cases. Plast Reconstr Surg.
hypertrophic scars, combination therapy with 1969;44(6):564–6.
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5. Nouri K, Jimenez GP, Harrison-Balestra C, et  al.
most commonly used steroids for intralesional 585 nm pulsed dye laser in the treatment of surgical
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be administered (10–40 mg/mL) every 4–6 weeks Surg. 2003;29:65–73.
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6. Alster TS, Nanni CA.  Pulsed dye laser treatment the treatment of acne scarring. Dermatol Surg.
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1998;102(6):2190–5. 16. Chua SH, Ang P, Khoo LS, Goh CL.  Nonablative
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nm pulsed dye laser with and without intralesional phic acne scars in type IV to V Asian skin. Dermatol
corticosteroids. Dermatol Surg. 2003;29(1):25–9. Surg. 2004;30(10):1287–91.
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resurfacing of the face with a combined CO2/Er:YAG 19. Cartier H. Use of intense pulsed light in the treatment
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 Laser Treatment of Leg Veins
5
Julie K. Karen and Shields Callahan

Abstract greatest burden of disease, with 54% of women

Damaged venous valves result in varicose or over the age of 65 affected by visible leg veins [2].
spider vein formation. Commonly, venous In addition to advanced age and female gender,
obstruction is caused by increased pressure of family history, standing occupation, history of
reverse blood flow within the superficial deep vein thrombosis (DVT), pregnancy and hor-
venous valve or from direct traumatic injury to monal therapy are additional risk factors for
the vein. venous disease [3]. Surgical stripping of the veins
remained the standard of treatment for varicosi-
Keywords ties for over 100 years but these procedures were
Leg veins · Spider veins · Sclerotherapy associated with high rates of serious complica-
Venous insufficiency · Endovenous ablation tions, long post-operative recovery periods and an
Laser unacceptably high risk of varicose recurrence [4].
Newer therapies and minimally invasive proce-
dures, including lasers and sclerotherapy, circum-
vent many of the pitfalls associated with the
Introduction/Background
previous vein treatments and have replaced tradi-
tional surgical techniques as the gold standard in
Visible leg veins are a common concern among
the treatment of leg veins. There are numerous
dermatology patients. It is estimated that half of
laser and light therapies that are currently avail-
the adult population is affected with venous dis-
able to treat leg veins and they play a crucial role
ease and approximately 20% of women have vis-
in specific patient populations.
ible varicosities [1]. The prevalence of varicose
veins is higher in women than men and it increases
with age in both sexes. Elderly women carry the
Basic Anatomy

The lower extremity venous system is comprised

J. K. Karen (*)
Department of Dermatology, CompleteSkinMD, of interconnected veins that function in a coordi-
NYU Langone Medical Center, New York, NY, USA nated effort to return blood flow to the heart. Leg
e-mail: [email protected] veins are classified as superficial, deep or perforat-
S. Callahan ing. The superficial venous system is a largely
Department of Dermatology, Virginia Commonwealth redundant network of thin walled vessels located in
University School of Medicine, Richmond, VA, USA the dermis and subcutaneous tissue. The superficial
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 73

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_5
74 J. K. Karen and S. Callahan

veins feed into the deep veins at various points by pump” that facilitate the return of blood flow to
way of the perforating veins. The deep veins are the heart.
located within the muscular fascia where they Effective return of lower extremity blood to the
travel alongside major arteries before ultimately heart relies on a properly functioning venous sys-
merging with the femoral vein. tem characterized by functioning valves and an
Chief among the superficial leg veins are the unobstructed path. The absence of one or both of
great saphenous vein (GSV), the small saphenous these components impedes the blood flow upward
vein (SSV) and the lateral venous system. The and out of the legs and results in a congested,
GSV, formerly known as the greater saphenous high-pressure system and dilated, leg veins.
vein, drains the majority of blood from the lower In response to prolonged periods of high pres-
leg. It originates at the medial aspect of the foot, sure, the veins become dilated, thicker and tortu-
courses anteriorly to the medial malleolus and ous. The appearance of these abnormal vessels is
travels up the medial aspect of the calf and thigh distressing to many patients prompting them to
before merging with the femoral vein at the seek cosmetic treatment. Later stages of chronic
saphenofemoral junction, which is located in the venous disease include progressively larger
inguinal region. veins, dyspigmentation, edema, lipodermatoscle-
The SSV is responsible for returning blood rosis and ulceration which correspond to more
collected from the posterior aspect of the lower severe venous disease [5].
leg. The SSV originates in the lateral aspect of Dilated vessels are further classified based on
the foot. It traverses the posterior calf between their size. Telangiectasias are collections of
the heads of the gastrocnemius muscle and typi- dilated venules that appear as red to purple,
cally merges with the popliteal vein at the level of thread-like vessels that measure <1 mm in diam-
the knee. In some individuals, an intersaphenous eter. Reticular veins are slightly larger, bluish
connection known as the Giacomini vein allows vessels which measure between 1 and 3  mm.
for direct communication between the SSV to the Telangiectasias and reticular veins are collec-
GSV. Instead of draining into the popliteal vein, tively referred to as “spider veins.” Varicose veins
the SSV merges with the Giacomini vein and are larger (>3 mm), bluish tortuous vessels that
travels medially before draining into the GSV. commonly represent tributaries of the saphenous
The lateral venous system or Albanese system veins (GSV and SSV).
is an embryologic venous remnant commonly
found in a subset of the population. Reflux may
occur in these aberrant veins even in patients with Evaluation
no other clinically significant evidence of venous
disease. All patients who present for leg vein treatment
require a thorough history and exam, including a
comprehensive, circumferential evaluation of the
Venous Structure and Function legs with photographic documentation. Imaging
is recommended for patients with venous bulging
The venous system differs from the arterial sys- at the zones of influence of the saphenous sys-
tem in several ways. Firstly, veins are under rela- tem, a history of prior venous surgery or inter-
tively lower pressure and therefore require vention, a strong family history of venous disease,
neighboring muscle contractions to “pump” the poor prior response to venous treatments, or
blood uphill against gravity. To that end, veins symptoms of chronic venous disease, which
also feature one-way valves to prevent backflow. include: heaviness, swelling, pain, pruritus, burn-
Lastly, vein walls are less elastic and less muscu- ing, cramping, or restless leg syndrome (RLS).
lar than their arterial counterparts, which accounts Duplex imaging is the modality of choice for
for their increased recoil and distension. In com- assessing the pattern and extent of venous disease
bination, these features comprise a “muscle-vein and informing interventional approaches [6].
5  Laser Treatment of Leg Veins 75

Contraindications Laser therapy represents an appropriate ther-

apy or adjunctive therapy for the treatment of leg
The majority of varicosities arise in the setting veins in the following clinical settings:
of valvular insufficiency and chronic reflux.
However, treatment of leg veins in patients with 1) Needle-phobic patients
venous outflow obstruction (including a DVT) is 2) Poor prior response to sclerotherapy or scle-
contraindicated, as the varicosities represent cru- rosant allergy
cial bypass routes that allow blood to circumvent 3) Treatment of matted telangiectasia induced
the obstruction. by prior sclerotherapy
4) Tiny vessels that may not be amenable to

sclerotherapy
Current Therapy Strategies
There are several challenges associated with
The current treatment approaches available for treating leg veins with laser therapy. Leg veins
leg veins include: are less responsive than facial vessels to laser
therapy owing to their heterogeneous size and
1) Surgical open technique diameter, deeper depth in the dermis, elevated
2) Minimally invasive procedures (Sclerotherapy, hydrostatic pressure and higher content of deoxy-
Laser and Light Sources) genated blood. However, over the past several
3) Endovascular Ablation (Endovenous Laser years, several advances in the field have allowed

Ablation and Radiofrequency Ablation) for safer treatment and more reliable outcomes.
Improved epidermal cooling modalities, deeper
Irrespective of the treatment approach penetrating wavelengths and variable, millisec-
selected, compression plays an important, ond pulse widths have contributed to more pre-
adjunctive role. Compression therapy in the form dictable and better-tolerated outcomes.
of graduated, medical-grade compression stock- Laser treatment is based on the principle of
ings has been shown to improve the efficacy of selective photothermolysis. Selective photother-
vein treatments and decrease post-procedural molysis is the process of destroying a targeted,
complications [7]. Although the ideal duration of microscopic biological structure (chromophore)
compression remains disputed, we recommend through the delivery of a specific wavelength of
strict compliance for at least 2–4  weeks post-­ light. The aim of selective photothermolysis is to
procedurally [7–9]. deliver adequate energy to destroy the selected
chromophore without causing damage to the sur-
rounding tissue [11]. Three fundamental con-
Laser Technology cepts form the foundation of selective
photothermolysis:
Although sclerotherapy remains the gold stan-
dard for the treatment of leg veins, lasers and 1) Wavelength should be preferentially absorbed
light sources are increasingly utilized in the man- by the target
agement of cosmetic and medically significant 2) Pulse duration must not exceed the thermal
venous disease. Patients may seek laser therapy relaxation time (TRT) of the target in order to
in an effort to avoid the discomfort associated minimize the transference of heat to surround-
with sclerotherapy injections, due to an inability ing structures
to comply with compression, or due to a poor 3) Fluence must be high enough to produce ade-
prior experience with sclerotherapy. In some quate thermal damage to the intended target
instances, patients mistakenly assume that laser
treatment will be less painful than sclerotherapy As the target chromophore in vascular lesions
injections [10]. is oxyhemoglobin, the three major absorption
76 J. K. Karen and S. Callahan

peaks in the visible spectrum are 418, 542 and leads to more complete vessel collapse [12].
577 nm. In addition, there is a broad, less selec- Furthermore, longer pulse durations (≥20  ms)
tive absorption peak in the near-infrared (750– are less likely to cause vessel rupture and associ-
1100) region. Accordingly, there is excellent ated purpura and post-inflammatory hyperpig-
absorption by the visible light lasers and intense mentation [13]. In practice, pulse durations of
pulsed light. However, these shorter wavelengths 10–100 ms are employed.
do not penetrate sufficiently and so may only heat Vessel heating results in the conversion of
the anterior vessel wall leading to incomplete hemoglobin to met-hemoglobin (met-Hb), which
thrombosis. Though less selective, longer wave- demonstrates altered absorption properties.
length devices penetrate deeper and achieve more Specifically, met-Hb has an absorbance 4.75
efficient vessel closure by heating the entire ves- times that of Hb-O2 and 20 times that of Hb.
sel circumference. However, due to lesser speci- Absorption therefore improves with subsequent
ficity, higher fluences are needed when employing pulses delivered sequentially due to this early
near-infrared lasers translating into a greater risk conversion to met-Hb, allowing for sub-threshold
of collateral damage. The following lasers may fluences to be used. Similarly, longer pulse dura-
be employed for the treatment of leg veins: tions may be effective at lower fluences due to
this early conversion.
1) Potassium Titanyl Phosphate (KTP): 532 nm Selection of spot size, like pulse duration, is
2) Pulsed Dye Lasers (PDL): 585–595 nm based on the size of the target vessel. Although
3)
Intense Pulsed Light Devices (IPL): scattering is not directly affected by spot size, the
500–1200 nm probability that a scattered photon will remain
4) Alexandrite: 755 nm within the collimated beam, thereby contributing
5) Diodes: 800–983 nm to the overall energy, is proportional to spot size
6)
Neodymium: yttrium aluminum garnet [14]. In short, there is a greater chance that a scat-
(Nd:YAG): 1064 nm tered photon will stay “in the fold” if the spot size
is larger. Therefore, a larger spot size loses less
Pulse duration, defined as the span of time that energy through scattered photons and can effec-
the laser interacts with the target, should be tively deliver more overall energy to the intended
selected based on the size of the target vessel. In target than a smaller spot size of the same wave-
general, longer pulse durations are required to length [14]. Caution must be exercised when using
effectively treat leg veins relative to those used larger spot sizes in order to avoid causing thermal
for the treatment of port wine stains or smaller damage to surrounding tissue. Smaller spot sizes
caliber facial telangiectases. Leg veins are non-­ are adequate and safe for more deeply penetrating,
uniform targets with both a strongly absorbing longer wavelength lasers. In practice, a spot size
portion (blood) and weakly absorbing portion that approximates (or is slightly larger than) the
(endothelial cells within vessel wall). Altshuler’s target vessel diameter is thought to achieve opti-
extended theory of selective photothermolysis mal results and minimal side effects [15].
dictates that a pulse duration that exceeds one-­ Fluence is selected to ensure that the tempera-
half of the calculated TRT is necessary to achieve ture inside the vessel target reach at least 70 °C;
effective vessel closure. Mathematical models the temperature at which point the blood coagu-
have demonstrated that intravascular tempera- lates and the vessel closes [16]. Thermal damage
tures are fairly similar within a wide range of to surrounding tissue may be lessened with the
pulse durations [12]. However, clinical observa- use of epidermal cooling modalities, which
tions have shown that 20–60  ms pulses outper- reduce epidermal temperature while allowing
form 3  ms pulses for the treatment of a broad peak temperatures to be achieved within target
range of vessels [12]. It is theorized that these vessels. The most commonly used devices
longer pulse durations cause more collagen include contact cooling, convection air-cooling,
shrinkage within the vein walls, which in turns cryogen spray cooling, and cold gels.
5  Laser Treatment of Leg Veins 77

 pecific Lasers for Leg Vein

S PDL must be used cautiously in patients with
Treatment darker skin types and those at risk for
hyperpigmentation. Like the KTP, the long
­
 otassium Titanyl Phosphate Laser
P pulsed PDL is an acceptable choice for the treat-
(KTP) ment of small caliber vessels (<1 mm) in lighter
skin patients who are at low risk for hyperpig-
The KTP laser, with its 532-nm wavelength, cor- mentation. There may be a role for combining
responds to the second absorption peak of hemo- sclerotherapy with PDL (or another laser) in a
globin (542  nm) and is an obvious choice for single treatment session to enhance treatment
vascular lesions. However, this hemoglobin efficiency, although optimal treatment parame-
absorption peak overlaps with melanin absorption ters have yet to be defined (Fig. 5.1).
and accounts for the high rates of associated dys-
pigmentation. One study of 56 patients with telan-
giectasia who underwent three treatments with a a
KTP demonstrated only modest results; 27% of
treated patients with telangiectasia ≤0.6 mm did
not have any benefit [17]. And none of the patients
with telangectias measuring between 0.7 and
1.0  mm improved at all [17], consistent with a
maximum penetration depth of 0.75 mm for this
wavelength Furthermore, 23% of all patients
developed hyperpigmentation [17]. For these rea-
sons, KTP should be reserved for the treatment of
isolated, small caliber vessels (<0.7  cm) in b
patients at low risk for dyspigmentation. Superior
results have been achieved with larger spot sizes
(3–5 mm), longer pulse durations (10–50 ms) and
higher fluences (14–20 J/cm2).

Long Pulsed Dye Laser (PDL)

The first generation PDL (585-nm) showed lim-

c
ited success in the treatment of telangiectasias
because it could not deliver adequate fluence
with its relatively short pulse duration. The sec-
ond generation PDL, with its longer 595-nm
wavelength, and modified pulse width, was
designed to allow for deeper penetration and
higher energy delivery. The 595-nm PDL has
been shown to effectively treat small, linear tel-
angiectasia at fluences of 10–20 J/cm2 and pulse
durations ranging from 1.5 to 40  ms [18].
However, commonly observed side effects
include purpura, edema and hyperpigmentation
Fig. 5.1 (a) Patient 1 immediate before leg vein treat-
[19]. Hyperpigmentation, which may persist for
ment (b) Patient 1 immediately after treatment with
weeks, has been observed at rates as high as 58% foamed sclerotherapy of the reticular veins and PDL of
of treated sites [18]. Therefore, the long pulsed the telangiectasia (c) Patient 1 1 week after treatment
78 J. K. Karen and S. Callahan

Intense Pulsed Light (IPL)  ong Pulsed 755 nm Alexandrite

L
Laser
IPL devices deliver high intensity, non-coherent
light over a range of wavelengths ranging from With its 755-nm wavelength, the long pulsed
500 to 1200  nm, thereby distinguishing them alexandrite (LPA) laser can reach larger diameter
from lasers. Filters may be applied to narrow the vessels situated deeper in the dermis than either
emitted spectrum and to allow for more specific the KTP or PDL lasers. However, the absorption
targeting of select chromophores. The theoretical coefficient of hemoglobin is much less at this
benefit of these devices is their ability to target longer wavelength. In 1999, a study of 28 patients
both oxygenated and deoxygenated Hb within with leg veins treated with the LPA outlined the
vessels at multiple depths. A 550- or 570-nm fil- optimal treatment parameters as a fluence of 20 J/
ter is typically used, delivering primarily yellow cm2 and pulse duration of 20  ms [22]. A 48%
and red light with a minimal component of near-­ clearance of vessels sized 0.4–1 mm cleared after
infrared light. Relatively longer filters may be three sessions, but smaller caliber vessels
used in patients with darker skin types to lessen responded poorly [22].
pigmentary adverse effects. More recently, higher fluences have been
In 1996, Goldman et al. demonstrated encour- shown to be safe when combined with skin cool-
aging results with an IPL device in the treatment ing modalities, as demonstrated by Kauvar and
of leg telangiectasias [20]. In a large, multicenter Lou in 2000 [23]. In their study of 20 female sub-
trial, 79% of the 159 subjects with leg telangiec- jects with leg veins ranging in size from 0.3 to
tasia ranging in size from 0.4 to 1 mm achieved 2  mm, they demonstrated marked clearance of
clearances of 75–100% after a series of treat- telangiectasia and reticular veins following a sin-
ments [20]. There were minimal adverse side gle treatment utilizing fluences of 60–80  J/cm2.
effects reported; the most common of which was Side effects included high rates of purpura and
dyspigmentation, which was seen in only 7% of pigmentation [23].
treatments [20]. Despite relatively low absorption by hemoglo-
However, another study in 1998 comprising bin, the LPA may have some utility for the treat-
120 subjects with either facial or leg telangiecta- ment of vessels sized 0.4–3 mm. The introduction
sia, did not yield the same promising results [21]. of skin cooling devices has allowed for higher
Although there was >80% clearance achieved fluences to be safely employed. Side effects,
after one treatment with a filter wavelength of including high rates of purpura, telangiectatic
either 570 or 590  nm, there were several study matting and pigmentation limit the utility of this
limitations [21]. All of the 40 patients with leg tel- device [24].
angiectasia underwent either selective surgery or
sclerotherapy prior to the IPL treatment, thereby
confounding the results [21]. In addition, there Diode
was a high rate of adverse side effects: approxi-
mately 50% of patients developed hyperpigmen- The diode laser is characterized by near-infrared
tation, and two patients development blistering wavelengths ranging from 800 to 983 nm, which
[21]. The high rate of side effects observed in this allow for deeper penetration into the dermis
study are likely due to the small therapeutic win- where they can target slightly larger veins. This
dow and the difficulty of handling the device. The wavelength corresponds to the tertiary hemoglo-
discrepancy between these two studies also speaks bin peak and explains its efficacy in targeting
to the high degree of inter-­operator variability. vessels. And because this wavelength is poorly
In general, like the visible light lasers, IPL absorbed by melanin, it is associated with less
should be reserved for use by experienced opera- risk of hyperpigmentation.
tors for the treatment of fair skinned individuals The 800-nm diode laser (DL) has been shown
with small (<1 mm), superficial vessels. to be effective in the treatment of leg vessels
5  Laser Treatment of Leg Veins 79

measuring 3–4 mm in diameter [20]. In a small The longer wavelength also allows for deeper
study of ten women with skin types II-IV, the DL penetration in the dermis and it can effectively
was used to treat leg veins at 2 month intervals treat larger leg veins, up to 3  mm in diameter.
for a maximum of three treatments [20]. After However, hemoglobin has a lower absorption
6  months, over half of the patients experienced coefficient at this wavelength, which necessitates
clearance [20]. Blue veins measuring 3–4  mm higher energies be used to achieve adequate ves-
located on the thigh responded best [20]. There sel heating. These higher energies account for the
was an overall high degree of patient satisfaction, increased pain associated with treatments. Skin
minimal discomfort, and no long-term complica- cooling modalities are of critical importance and
tions reported [20]. local anesthesia may be required. Furthermore,
A combination of the diode laser with a radio- vigilance to avoid overlap is essential and sequen-
frequency (RF) current may also have a place in tial pulses should be spaced more than 1  mm
the treatment of leg veins. A study of 40 patients, apart to avoid bulk heating.
skin types II-IV, who underwent a combination A 2006 study investigated the optimal pulse
of diode 900-nm with RF for a maximum of three durations of the Nd:YAG for treating leg telangi-
treatments, at 2 week intervals, showed encour- ectasias. The results of 18 women with leg telan-
aging results; 82% of patients had over 50% giectasias ranging in size from 0.1 to 1.6  mm
clearance at the 6  month assessment [21]. treated with the Nd:YAG demonstrated that lon-
Treatments were well tolerated and there were no ger pulse durations outperformed shorter dura-
significant side effects reported [21]. tions with respect to both vessel clearance and
More recently, intravenous injections of adverse side effects [14]. Short pulse durations
indocyanine-­ green (ICG) have been shown to (3–20  ms) were associated with higher rates of
enhance the efficacy of diode laser treatments for post-inflammatory hyperpigmentation and pur-
leg telangiectasia [25]. ICG, a green pigment, pura as compared to longer pulse durations (40–
strongly absorbs near infrared radiation and con- 60  ms) [14]. The authors recommend selecting
verts >90% of radiation into thermal heat energy the smallest fluence and smallest spot size to
[25]. This dye can be injected into vessels imme- achieve optimal vessel clearance with pulse dura-
diately prior to laser therapy (ICG + DL) where tion of 20–60 ms. Their study also uncovered dif-
the exogenous pigment acts as a transient, easily ferences in skin cooling modalities; patient pain
targeted chromophore thereby enhancing vessel was noticeably improved with the refrigerated air
coagulation. In a 2013 study, 29 subjects with device (Zimmerman Elektromedizin, Irvine, CA)
bilateral leg telangiectasia were treated with as compared to the cryogen spray (DCD Candela
Nd:YAG laser and ICG  +  DL in a side-by-side Corporation, Wayland MA) prompting a mid-­
comparison with one single treatment [25]. study transition to using refrigerated air for all
Clearance rates were significantly higher in the the subsequent study participants [14]. When
ICG  +  DL treated legs relative to the Nd:YAG cryogen cooling is employed, care should be
[25]. Further studies are needed to outline its taken to avoid excessive cooling, which can lead
clinical utility and define its safety parameters to cryogen burns.
but the initial results are promising. In general, when treating smaller vessels,
shorter pulse durations, smaller spot sizes and
higher fluences of 250–400  J/cm2 are required,
Nd:YAG whereas longer pulse durations, larger spot sizes
and more moderate fluences (100–200 J/cm2) are
The Nd:YAG laser emits a 1064 nm wavelength employed when treating larger vessels (which
of light. Compared to other lasers that target contain more target chromophore) [26]. As
hemoglobin, the Nd:YAG has the lowest absorp- always, laser safety precautions, including appro-
tion of melanin, which accounts for its improved priate protective eyewear for the patient and cli-
safety profile in patients with darker skin types. nician are essential to avoid devastating ocular
80 J. K. Karen and S. Callahan

a a

b b

Fig. 5.2 (a) Patient 2 before leg vein treatment (b) Fig. 5.3 (a) Patient 3 before leg vein treatment (b)
Patient 1 after leg vein treatment with 1064 nm Nd:YAG Patient 3 after leg vein treatment with 1064 nm Nd:YAG
laser laser

injury, which can occur with this deeply penetrat- complete contraction) or vessel darkening
ing wavelength. (which corresponds with coagulation) with or
Of important note, the Nd:YAG is the only laser without surrounding tissue erythema. Urtication
to date that has been shown to demonstrate results and blurring of the vessel margins typically
similar to sclerotherapy for the treatment of leg tel- occurs within 10  min of treatment. Blanching
angiectasias up to 3 mm in diameter. Several stud- may portend epidermal injury and should be
ies have demonstrated nearly equivocal outcomes avoided. Sequential passes should be spaced at
with the Nd:YAG 1064 nm as compared to sclero- least 1  mm apart when utilizing the 1064  nm
therapy, although laser is typically perceived as laser which carries a risk for bulk heating and
more painful [10, 27–29] (Figs. 5.2 and 5.3). collateral damage. A multiple (up to 3) pass
approach is acceptable and sometimes neces-
sary with the other devices. Purpura should be
Post-operative End Points avoided as it portends a higher risk of post-
inflammatory hyperpigmentation. Strict sun
The procedure end point of laser and light avoidance is essential both prior to and for
source treatments on leg veins includes either 4  weeks following treatment to further mini-
vessel disappearance (which corresponds to mize pigmentary alteration.
5  Laser Treatment of Leg Veins 81

Side Effects/Complications ings, may improve the efficacy of vein treatments

and minimize adverse side effects.
Side effects following laser treatment for visible
leg veins are typically mild and transient. The Conclusion
most commonly reported adverse effects include Although sclerotherapy remains the gold stan-
pain, purpura, and post-inflammatory hyperpig- dard for the treatment of leg veins, laser ther-
mentation (or less commonly hypopigmenta- apy represents an effective alternative or
tion) (Fig.  5.4). The incidence of pigmentation adjunctive treatment for the elimination of
increases with the size of the treated vessel and small vessels measuring <3  mm. Lasers
with darker skin types. In more severe cases, should be considered for those patients with
thermal injury, ulceration, blistering, persistent tremendous fear of needles, sclerosant allergy,
dyspigmentation and scarring may occur. telangiectatic matting from prior sclerother-
Furthermore, the risk that the patient may not apy and for vessels refractory to prior
achieve an appreciable improvement in the sclerotherapy.
appearance of their leg veins should also be Current lasers employed for leg veins
addressed. Lastly, patients should be counseled include: Nd:YAG, PDL, diode, LPA, IPL and
about the possible need for multiple treatment KTP.  Selection of the appropriate laser is
sessions. based on the size and location of the vessels in
The most feared consequences associated addition to the patient’s skin type. The single
with the treatment of visible leg veins is not most useful laser for leg telangiectasias is the
unique to lasers; elimination of enlarged leg Nd:YAG 1064, which can yield results similar
veins in the setting of venous outflow obstruc- to sclerotherapy and is safe for darker skin
tion removes the crucial bypasses of the venous types.
system. Obliterating these vessels with any Often times, a combination of different
modality (laser, sclerotherapy, surgery etc.) lasers may provide the most benefit owing to
could prove catastrophic, and the significance of the various size vessels that comprise most leg
a thorough pre-treatment evaluation cannot be disease. Common adverse effects include pur-
overstated. pura, post-­inflammatory dyspigmentation and
Diligent sunscreen and compression hose, in pain; the latter can be mitigated with skin
the form of medical-grade compression stock- cooling devices employed intra-procedurally.

a b

Fig. 5.4 (a) Widespread hyperpigmented patches hypopigmentation in an actinically damaged patient more
4  months following inappropriate use of PDL in dark than 10 years following KTP treatment for telangiectasia
skinned individual with unwanted leg veins. (b) Mottled of the medial ankle
82 J. K. Karen and S. Callahan

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ations. Lasers Surg Med. 2005;36:105–16. and sequential study of long pulsed Nd:YAG 1,064 nm
13. Altshuler GB, Anderson RR, Manstein D, Zenzie HH, laser and sclerotherapy in leg telangiectasias treat-
Smirnov MZ. Extended theory of selective photother- ment. Lasers Surg Med. 2004;34:273–6.
molysis. Lasers Surg Med. 2001;29:416–32. 29. Parlar B, Blazek C, Cazzaniga S, et al. Treatment of
14. Parlette EC, Groff WF, Kinshella MJ, Domankevitz lower extremity telangiectasias in women by foam
Y, O'Neill J, Ross EV. Optimal pulse durations for the sclerotherapy vs. Nd:YAG laser: a prospective, com-
treatment of leg telangiectasias with a neodymium parative, randomized, open-label trial. J Eur Acad
YAG laser. Lasers Surg Med. 2006;38:98–105. Dermatol Venereol. 2015;29:549–54.
 Lasers and Lights for Treating
Pigmented Lesions 6
Emmy M. Graber and Jeffrey S. Dover

Abstract shorter than the thermal relaxation time of

• Pigmented lesions were initially treated melanin.
with destructive non-selective lasers.
• Now pigment selective Q-switched lasers Keywords
used. Pigmented lesions · Tattoo removal · Q switched
• Pigmented skin lesions are exceedingly lasers · Solar lentigo · Selective photothermoly-
common. sis · Picosecond lasers Melanin · Nevus of Ota ·
• Selective destruction of pigmented lesions Melasma Hyperpigmentation
relies on the theory of selective
photothermolysis.
• Melanin has a broad absorption spectrum Outline
with absorption steadily decreasing with
increasing wavelength. Introduction
• Several Q-switched lasers fall within the History
melanin absorption spectrum. Their nano- • Pigmented lesions were initially treated
second pulse duration is effective since it is with destructive non-selective lasers.
• Now pigment selective Q-switched and
long pulsed green light lasers as well as
Initially Modified from: Kaminer, M.S., Dover, J.S., Intense Pulsed Light devices are used.
and Arndt, K.A.  Atlas of Cosmetic Surgery. 2002.
W.B. Saunders Company. Epidemiology
• Pigmented skin lesions are exceedingly
E. M. Graber (*) common.
Dermatology Institute of Boston, PC, Basic Science
Boston, MA, USA • Selective destruction of pigmented
e-mail: [email protected]
lesions relies on the theory of selective
J. S. Dover photothermolysis.
Dermatology, Yale University School of Medicine,
Chestnut Hill, MA, USA • Melanin has a broad absorption spec-
trum with absorption steadily decreas-
Surgery, Dartmouth Medical School,
Hanover, NH, USA ing with increasing wavelength.
• Several Q-switched and millisecond
Dermatology, Brown Medical School,
Providence, RI, USA domain lasers fall within the melanin
e-mail: [email protected] absorption spectrum. The nanosecond

© Springer International Publishing AG, part of Springer Nature 2018 83

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_6
84 E. M. Graber and J. S. Dover

or picosecond pulse durations are effec- Adverse Events

tive since they are shorter than the ther- Side Effects/Complications
mal relaxation time of melanosomes. • Post-inflammatory hyperpigmentation,
Millisecond domain pulses which are an inadequate response and recurrence
shorter than the thermal relaxation time of the lesion are the most common side
of melanocytes and pigmented epider- effects.
mal cells. Prevention and Treatment of Side Effects/
• Intense pulsed light and non-selective Complications
fractional non ablative lasers are also • Using the appropriate laser and fluence
effective can reduce side effects.
Indications and Contraindications • Educating patients so that there are
Epidermal Pigmented Lesions realistic expectations can also help to
• Lentigines, Café au lait macules, and reduce patient frustration and
ephelides are common epidermal pig- complications.
mented lesions that respond to laser Future Directions
treatment. • Pico second (10−12) domain lasers that are
• Shorter laser wavelengths may suffice as used for tattoo removal appear to be effec-
deep tissue penetration is not necessary. tive in other pigmented lesions.
• Multiple treatments are often needed for Conclusions
complete removal.
Dermal Pigmented Lesions
• Melanocytic nevi, nevus of Ota,
Introduction
melasma, post-inflammatory hyperpig-
mentation, and drug induced pigmenta-
• Pigmented lesions were initially treated with
tion are dermal pigmented lesions that
destructive non-selective lasers.
can be treated with lasers.
• Now pigment selective Q-switched nanosec-
• Longer wavelengths may be needed to
ond and picosecond domain and millisecond
reach the pigment.
domain lasers used.
• Multiple treatments are necessary.
• Intense pulsed light and non-selective frac-
• Anesthesia is not usually needed.
tional non ablative lasers are also effective
Techniques
• Pigmented skin lesions are exceedingly
Pre-operative Management
common.
• It is important to obtain a medical his-
• Selective destruction of pigmented lesions
tory prior to treatment and to educate
relies on the theory of selective
patients about the potential outcomes.
photothermolysis.
• Topical anesthesia may be needed for
• Melanin has a broad absorption spectrum with
some larger or dermal pigmented lesions.
absorption steadily decreasing with increasing
• Appropriate protective eyewear should
wavelength.
be on all persons in the room.
• Several Q-switched lasers fall within the mel-
Description of Technique
anin absorption spectrum. Their nanosecond
• Laser parameters depend on the particu-
or picosecond pulse durations are effective
lar laser, the patient’s skin phototype,
since they are shorter than the thermal relax-
and the type of lesion.
ation time of melanocytes.
• Adequate fluence should result in an
• Millisecond domain pulses which are shorter
immediate uniform ash white color.
than the thermal relaxation time of melano-
Post-operative Management
cytes and pigmented epidermal cells.
• An occlusive ointment should be applied
• Intense pulsed light and non-selective frac-
and patients should be educated on the
tional non ablative lasers are also effective.
healing process.
6  Lasers and Lights for Treating Pigmented Lesions 85

Abstract sources such as the argon [3] and carbon dioxide

lasers [4]. After using these more tissue destruc-
• Pigmented lesions were initially treated with tive devices, the selective Q-switched lasers at
destructive non-selective lasers. wavelengths other than 694  nm were found to
• Now pigment selective Q-switched lasers target melanin. In the late 1980s Anderson et al.
used. demonstrated that Q-switched Nd:YAG laser
• Pigmented skin lesions are exceedingly pulses at 1064, 532, and 355  nm selectively
common. diminished melanin. This group also showed that
• Selective destruction of pigmented lesions relies the longer wavelengths (which are less well-­
on the theory of selective photothermolysis. absorbed by melanin) required a higher energy
• Melanin has a broad absorption spectrum with fluence to be effective. Over the last 20  years,
absorption steadily decreasing with increasing after further investigation, pulsed lasers and
wavelength. intense pulsed light sources have become the
• Several Q-switched lasers fall within the mel- treatment of choice for epidermal, and pulsed
anin absorption spectrum. Their nanosecond lasers the choice for dermal pigmented lesions
pulse duration is effective since it is shorter and tattoos.
than the thermal relaxation time of melanin.

Epidemiology
Keywords
Pigmented skin lesions are exceedingly common
Pigmented lesions in all races. Some pigmented lesions are congeni-
Tattoo removal tal while many are acquired. With increasing sun
Q switched lasers exposure, pigmented lesions become more preva-
Solar lentigo lent. In a quest to reverse photoaging, there are
Selective photothermolysis countless patients that desire lightening or
Picosecond lasers removal of these lesions. For some patients, there
Melanin appears to also be a cultural influence to correct
Nevus of Ota dyspigmentation.
Melasma
Hyperpigmentation
Basic Science

History  aser-Tissue Interactions in Pigmented

L
Skin
The application of lasers for pigmented lesions The ability of laser and light sources to diminish
began in 1963 when Leon Goldman and col- pigmented lesions is based on the principle of
leagues found that 0.5  ms pulses of ruby laser selective photothermolysis. (3) Described in
radiation was selectively absorbed by pigmented 1983 by Anderson and Parrish, selective photo-
skin [1]. These investigators also discovered that thermolysis predicts that there can be selective
the threshold radiant exposure for epidermal thermal damage to an absorbing target using
damage was 10–100 times lower for a quality appropriate laser parameters and pulse character-
switched (Q-switched) ruby laser (QSRL) with a istics. This principle requires: 1) the use of a
pulse duration of 50  ns [2]. Despite these early wavelength that is well absorbed by the target, 2)
findings, the ability of the QSRL to selectively a pulse duration that is shorter than the thermal
target pigment was not initially appreciated. relaxation time (the time required for a heated
Instead, for many years, pigmented lesions were target to cool by 50%), 3) a sufficiently high
treated with nonselective continuous wave energy density to achieve the desired tissue
86 E. M. Graber and J. S. Dover

effect. Selective photothermolysis was originally relaxation time between 50 and 500  ns [5, 6].
applied to the treatment of vascular lesions with Based on the principle of selective photothermol-
oxyhemoglobin as the target chromophore. ysis, for this short thermal relaxation time, an
Thereafter selective photothermolysis was extremely short pulse duration should be used to
applied to pigmented lesions by targeting endog- effectively target melanosomes. The delivery of
enous melanin and exogenous carbon particles as an extremely high energy laser pulse within a
target chromophores. very short time span results in rapid heating of
As a target chromophore, melanin has a broad the target melanosome (estimated at 10 mil-
absorption spectrum within the ultraviolet, visi- lion °C per second), causing it to explode [7].
ble and near-infrared light range (Fig.  6.1). While electron microscopy has confirmed
However, light absorption in melanin decreases highly selective destruction of melanosomes
steadily with increasing wavelength [5]. within melanocytes and melanized keratino-
Melanocytes contain intracytoplasmic organ- cytes, it is not know precisely how the pigment-­
elles, melanosomes, which are the sites of mela- containing cells are destroyed. It is believed
nin biosynthesis (Fig. 6.2). After formation in the that destruction of melanocytes and melanized
melanocytes, melanosomes and their melanin are keratinocytes are destroyed due to mechanical
transferred to surrounding keratinocytes. These damage from acoustic waves that emanate from
melanin containing melanosomes are 1  μm in the absorbing melanosome [8, 9]. Damage to
diameter and are predicted to have a thermal these cells results in vacuolization and deposi-
tion of pigment and nuclear material at the cel-
lular periphery. In addition, subepidermal
Alexandrite

vesiculation may occur at the level of the lam-

Nd:YAG
Diode
Ruby

ina lucida. Following damage, repigmentation

PDL

results from migration of residual melanocytes

from either adnexal structures or adjacent unir-
radiated skin.
When treating pigmented lesions, Q-switched
lasers generate an immediate ash-white color at
the site of impact. The cause of this tissue response
is due to heat induced steam cavities in melano-
Absorption (log scale)

somes which cause a scattering of visible light,

producing a white color [10]. Well demarcated,
circular, highly reflective structures of 1–30  μm
within melanosomes have been identified by con-
focal microscopy, electron microscopy, and opti-
cal coherence tomography (Fig.  6.3). These
circular structures are presumed to be gas bubbles
and gradually disappear over 20 min, correlating
Melanin to the disappearance of the clinical ash-white
Oxyhemoglobin color over the same period of time [11]. The exact
Water
content of the gas bubbles is not known, but may
300 500 700 1000 2000
Wavelength (nm) be water vapor, nitrogen, or other gases. The ade-
quate laser exposure dose for melanosome dam-
Fig. 6.1  Absorption curves of melanin, oxyhemoglobin age correlates well with the clinical threshold for
and water (From Hirsch RJ, Anderson RR. Principles of immediate skin whitening. In other words, if the
Laser-Skin Interactions. In chapter 136, page 2148 in:
Dermatology (ed.) Bolognia JL, Jorizzo JL, and Rapini clinical ash-white color is not visible, the laser
RP. 1st edition, 2003) exposure dose is not sufficient. Darker skin has a
6  Lasers and Lights for Treating Pigmented Lesions 87

Fig. 6.2  Melanocyte residing

within the epidermis.
Melanosomes extend throughout
the dendritic processes and are
transferred to neighboring
keratinocytes (Modified from
Melanocyte

Epidermis
www.freethought-forum.com)
dendritic processes

Melanosomes

Melanocyte nucleus
Dermal-epidermal junction

Dermis
lower threshold for whitening due to a higher epi- Several lasers can be used today to treat pig-
dermal melanin content [11]. With increasing mented skin lesions (Table  6.1). These include
wavelengths, melanin absorption decreases, and lasers that are: 1) pigment nonselective, 2) highly
the required threshold laser exposure dose pigment selective, 3) and those that are somewhat
increases [12, 13]. Subthreshold fluences appear pigment selective.
to actually stimulate melanogenesis because of
activation of epidermal melanocytes after non-  igment Non selective Lasers
P
lethal injury [14] (Fig. 6.4). The carbon dioxide [4, 18] (10,600 nm), erbium-­
YAG (2940 nm) and Erbium glass (1540 nm) and
 -switched and Pulsed Lasers
Q yttrium scandium gallium garnet (YSGG)
and Light Sources (2790 nm) lasers are pigment nonselective lasers
Selective damage to melanosomes in human skin that remove epidermal pigment because of their
was first demonstrated with a 351  nm XeF ability to target water and ablate the entire epi-
excimer laser delivering 20  ns pulses [15]. dermis, including melanocytes and melanized
Although light at 351  nm is well absorbed by keratinocytes. Earlier devices removed a
melanin, this short wavelength only penetrates relatively uniform layer of the epidermis and
­
<100 μm into the skin due to light scattering [16]. with the epidermis went the associated pigment.
It was subsequently found that selective melano- Depending on the amount of energy delivered a
some damage could be produced by also the thinner or thicker layer of the epidermis and adja-
pulsed tunable dye laser [12, 17] (wavelength cent dermis is affected by the treatment. Over
435–750  nm, pulse width 300–750  ns), 24–48 h the epidermis is shed, including melano-
Q-switched ruby laser [6] (wavelength 694  nm, cytes and pigment laden keratinocytes, and is
pulse width 40  ns) and the Q-switched then regenerated, leaving behind a new epidermis
neodymium:YAG laser [13] (wavelength 355, with less unwanted sun induced pigment. Newer
532, and 1064 nm, pulse width 10–12 ns). While fractionated laser technologies damage columns
shorter wavelengths, such as 351 nm are better at of the epidermis and dermis while leaving inter-
absorbing melanin, longer wavelengths penetrate spersed areas unaffected. In this manner, there is
deeper into the skin, increasing their ability to faster healing as the surrounding normal tissue
reach deeper melanosomes (Fig. 6.5). heals each light column of damage (Fig.  6.6).
88 E. M. Graber and J. S. Dover

Fig. 6.3 Electron
micrograph obtained a b
immediately after
Q-switched ruby laser
irradiation. The targeted
melanosome shows
membrane disruption
with disorganization of
its internal contents (a)
prior to irradiation; (b)
immediately after
irradiation showing
early melanosome
disruption; (c) more
disruption; (d) almost
complete disruption of a
melanosome
immediately after
irradiation (From Arndt
KA, Dover JS, Olbricht
SM. Lasers in
Cutaneous and Aesthetic
Surgery. Philadelphia:
Lippincott-Raven; c d
1997.)

The fractionated CO2 and fractionated least some of the original pigmented epidermal
erbium:YAG lasers work in the same manner as lesion would remain even after a series of treat-
their non-­fractionated counterparts but deliver ments resulting in incomplete lesion removal.
the light in many small columns. Because only The fractionated technology is also employed
fractions of the pigmented epidermis are affected, with the 1927 nm thulium laser. Although a non-­
it stands to reason that a series of treatments is ablative laser, it targets waters and has a water
necessary to achieve the desired result and at absorption coefficient that is 10 times that of the
6  Lasers and Lights for Treating Pigmented Lesions 89

a b

Fig. 6.4  Histologic appearance of black guinea pig skin condensed nuclear and pigment material at their peripher-
immediately after irradiation with the Q-switched ruby ies. (b) Similar changes in a hair follicle (From Arndt KA,
laser. (a) Characteristic “ring cell” formation in the basal Dover JS, Olbricht SM. Lasers in Cutaneous and Aesthetic
lamina, representing melanocytes and keratinocytes with Surgery. Philadelphia: Lippincott-Raven; 1997.)

Excimer Nd:YAG CO2 Argon KTP PDL Ruby Alexandrite Diode Nd:YAG
193nm 2940nm 10,600nm 488-514nm 532nm 585-600nm 694nm 755nm 800nm 1064nm

Stratum comeum

Epidermis

Dermis

Dermal vessels

Subcutaneous fat

Fig. 6.5  Laser depth of penetration. Depth of penetration as the wavelength increases (From Bolognia, et  al.
for lasers of varying wavelengths. For lasers in the visible Dermatology. 2003)
and near infrared ranges, the depth of penetration increases

1550 and 1540  nm non-ablative infrared lasers.  ighly Pigment Selective Lasers
H
The 1927  nm thulium laser induces damage in Older technologies, such as continuous wave
the epidermis and the upper dermis thereby non (CW) and quasi-CW visible light lasers, including
selectively diminishing pigmented epidermal the argon laser (488, 514 nm), copper vapor laser
lesions [19]. (511 nm), and krypton laser (521, 530 nm), can be
90 E. M. Graber and J. S. Dover

Table 6.1  Lasers in the treatment of pigmented lesion

Spot Maximum
Wavelength Pulse size repetition
Device Manufacturer Laser type (nm) duration (mm) rate(Hz) Comments
Spectrum Palomar QS Ruby 694 28 ns 5, 6.5 0.8 Large spot size
RD-1200 promotes deeper
penetration
EpiTouch Lumenis QS Ruby 694 25 ns 5 0.8 Long pulse mode
available for hair
removal
Sinon Wavelight QS Ruby 694 15–40 ns 3–9 20 Long pulse mode
available for hair
removal
AlexLAZR Candela QS 755 50 ns 2, 3, 4 5 Fiberoptic delivery
alexandrite system
VersaPulse Lumenis FD Nd: 532 2–50 ms 2–10 6 Four lasers within
VPC YAG one box
QS FD Nd: 532 4 ns 2–6 10
YAG
QS Nd: 1064 5 ns 2–6 10
YAG
QS 755 45 ns 2–6 10
alexandrite
Medlite C6 HOYA QS FD Nd: 532 5–20 ns 2, 3, 4, 10 Handpiece
YAG 6 converts l–585 and
650 nm
ConBio QS Nd : 1064 5–20 ns 3, 4, 6, 10
YAG 8
Alex Candela QS FD Nd: 532 50 ns 2, 3, 5 5
YAG
TriVantage QS 755 2, 3, 4 5
alexandrite
QS Nd: 1064 2, 3, 5 5
YAG
SkinClear Sybaritic QS FD Nd: 532 10 ns 1, 2, 3
YAG
QS Nd: 1064 10 ns 1, 2, 3
YAG
Naturalase Focus QS FD Nd: 532 10–20 ns 7
YAG
Medical QS Nd: 1064 10–20 ns 7
YAG
QS Q-switched, FD frequency doubled

used to selectively remove epidermal pigmented KTP) laser (1064, 532  nm). These lasers selec-
lesions. However, spatial thermal injury confine- tively target melanin by delivering high-intensity,
ment is not possible and unaffected adjacent skin short-pulsed radiation at varying wavelengths.
may also be damaged. The risk/benefit ratio is “Q-switched” is an abbreviation for “quality-­
higher with these CW and quasi-CW devices. switched” and refers to lasers which release an
There are three short-pulsed, pigment selec- extremely high powered pulse (109  W) with an
tive lasers that are widely used today: 1) the ultra-short pulse duration. Through the use of an
Q-switched ruby laser (QSRL) (694  nm), 2) optical shutter, these lasers store large amounts of
the Q-switched alexandrite laser (755 nm), and 3) energy in the laser cavity and then release the
the Q-switched neodymium:YAG (Nd:YAG and stored energy when the laser fires.
6  Lasers and Lights for Treating Pigmented Lesions 91

impregnated handpieces can convert the 532 nm

wavelength to either 585 nm (yellow) or 650 nm
(red). An articulated arm delivers pulses with a
spot size to 1.5–8  mm, a pulse duration of
5–10 ns, and a repetition rate up to 10 Hz.
There are newer Q-switched lasers that emit
even shorter pulse durations, in the picosecond
range, as opposed to the nanosecond pulse dura-
tions of most Q-switched lasers. Picosecond
lasers were originally studied for tattoo removal
but more recently their effectiveness in the treat-
ment of epidermal and dermal pigmented lesions
has been demonstrated [20, 21].
Long-pulsed (millisecond rather than nano-
second domain) 532  nm (KTP) Nd:YAG lasers
and 595  nm pulsed-dye lasers, which are tradi-
tionally used to treat vascular lesions, can also be
used to treat superficial pigmented lesions.
However, the long pulse width of these lasers is
close to the thermal relaxation time of the entire
epidermis (about 10 ms) [22] and therefore does
not allow for selective damage to melanosomes.
Because of their longer pulse width, millisecond
domain lasers produce a purely thermal effect on
their target, unlike the photomechanical effect of
Q-switched lasers. The target in this case may in
Fig. 6.6  Fractionated erbium glass laser causing tissue fact be melanocytes rather than melanosomes.
coagulation in a narrow microthermal zone of injury
Regardless, these longer pulse duration devices,
(From Vikramaditya P, Bedi MS, et al. The effects of pulse
energy variations on the dimensions of microscopic ther- just like intense pulsed light devices are highly
mal treatment zones in nonablative fractional resurfacing. effective in removing unwanted epidermal pig-
Lasers Surg Med. 2007;39: 145–155, with permission of ment. These lasers are not suitable for treating
John Wiley and Sons.)
dermal pigmented lesions because of the limited
penetration depth [23] Although no longer manu-
The QSRL emits red light at a wavelength of factured, a pigmented lesion pulsed dye laser
694  nm and a pulse duration of 28–40  ns (non-Q-switched) used a xenon flashlamp to
(Table 6.1). Light is delivered through a mirrored pump a coumarin-containing dye that expelled
articulated arm at a spot size of 5 or 6.5 mm and pulses of green light at 510  nm. Although this
a repetition rate of 2 Hz. The Q-switched alexan- laser was useful for epidermal lesions, its shallow
drite laser has a near infrared wavelength of penetration made it much less effective on dermal
755 nm, pulse duration of 50–100 ns, spot size of lesions.
2–4  mm, and a repetition rate up to 10  Hz. The Q-switched ruby, alexandrite and Nd:YAG
Depending on the exact device, light is delivered lasers also have long-pulsed counterparts with the
either through an articulated arm or through a same wavelengths that operate in a normal (non-
semi-flexible fiber optic cable. The Q-switched Q-switched) mode. These normal mode lasers are
Nd:YAG laser emits infrared light at 1064  nm. often used for laser hair removal because their
The wavelength can be halved by placing a higher fluences and longer pulse durations target
frequency-­ doubling KTP (potassium-titanyl-­ large pigmented structures such as hair follicles or
phosphate) crystal in the laser beam’s path. Dye-­ nests of cells rather than individual melanosomes
92 E. M. Graber and J. S. Dover

or pigmented cells [24] Normal mode lasers have • Multiple treatments are often needed for com-
been shown to be effective in the removal of epi- plete removal.
dermal pigmented lesions but are not ideal • Anesthesia may be needed for larger or der-
because damage may be imparted on surrounding mal lesions.
tissue.
Non-coherent light sources (intense pulsed
light or IPL) can also be used for pigment Epidermal Pigmented Lesions
removal. Polychromatic light is emitted ranging
from 515 to 1200 nm (visible to infrared) and fil- Many clinical studies have proven the efficacy
ters are used to cut off the light above or below and safety of Q-switched lasers [25–27] and the
predetermined wavelengths. Since melanin 510 nm pulsed dye laser [28] in the treatment of
exhibits a broad absorption spectrum, monochro- various epidermal pigmented lesions, including:
matic laser devices are not necessary to target ephelides, lentigines, Café au lait macules, sebor-
superficial melanin. The shorter wavelengths rheic keratoses, nevi spilus, and Becker’s nevi.
emitted by IPL devices are highly absorbed by Since pigment in epidermal lesions is found
melanin. IPL devices release light as a series of superficially, shorter-wavelength devices can be
single, double, or triple pulses (millisecond used successfully despite their limited penetra-
domain). Like the millisecond domain lasers, the tion depth. For example, the 510 nm wavelength
millisecond pulse width of IPL devices approxi- of the pigmented lesion pulsed dye laser and
mates the thermal relaxation time of the epider- 532 nm pulsed lasers are highly absorbed by mel-
mis (10  ms) and produces a photothermal, not anin but penetrates only about 250  μm into the
photomechanical effect, on its target. To avoid skin [16] The Q-switched ruby and alexandrite
damage to normal surrounding epidermis, most lasers effectively treat both epidermal and dermal
IPL devices have skin cooling during treatment pigmented lesions since their wavelengths are
to protect the epidermis from excessive thermal still within the melanin absorption spectrum and
injury. The IPL devices should not be used for they penetrate deeply into the dermis. The
dermal pigmented lesions. Nd:YAG (1064 nm) laser penetrates deeply but is
poorly absorbed by melanin, making the 532 nm
wavelength preferable for epidermal lesions.
Indications and Contraindications When using the 510 nm and 532 nm wavelengths,
hemoglobin competes with melanin for absorp-
• Ephelides, lentigines, and café au lait mac- tion of light. Nanosecond pulses at these wave-
ules, are common epidermal pigmented lengths causes rupture of superficial blood
lesions that respond to laser and light vessels, manifesting clinically as purpura [12].
treatment.
• Melanocytic nevi, nevus of Ota and other Lentigines
dermal melanocytoses, melasma, post-­Lentigines are extremely common hyperpig-
inflammatory hyperpigmentation, and drug mented macules that are most often due to
induced pigmentation are dermal pigmented chronic sun exposure and are then referred to as
lesions that can be treated with lasers. Of solar lentigines. On pathology lentigines dis-
these, only nevus of Ota and other dermal play increased single melanocytes along the
melanocytoses respond predictably and basal layer with elongation of club-shaped rete
favorably. ridges. In addition to solar lentigines, there are
• Shorter laser wavelengths may suffice for epi- lentigines associated with a syndrome (e.g.
dermal lesions as deep tissue penetration is Peutz-Jeghers) and labial melanotic macules
not necessary. (labial lentigines). All three Q-switched lasers
• Long wavelengths are required for dermal are highly effective for treating all types of len-
pigmented lesions. tigines [29, 30] Both 35% trichloroacetic acid
6  Lasers and Lights for Treating Pigmented Lesions 93

peels and cryotherapy are inferior to Q-switched Its benefit is homogeneous improvement of the
lasers in the treatment of lentigines [31, 32]. entire treated area making it ideal for treating
With one treatment using a Q-switched laser, at dyspigmentation associated with photoaging of
least 50% clearing of lentigines is expected, and the face, neck, chest and extremities.
additional treatments may be utilized to remove
remaining pigment (Figs. 6.7 and 6.8). Although  afé au Lait Macules
C
less selective, non Q-switched (millisecond Café au lait macules (CALMs) are well circum-
domain) KTP, 595 nm pulsed-dye, ruby, alexan- scribed, homogenous light brown macules that
drite, and diode lasers may also be used to treat occur as isolated lesions in the general popula-
lentigines. A study of Asian patients with len- tion. Their prevalence varies amongst ethnicities
tigines found a long-pulsed KTP (532 nm) laser but ranges from 0.2% to 18% [37]. Café au lait
(without skin cooling) to be as effective as a macules may also be found as multiple lesions in
532 nm Q-switched Nd:YAG laser, and with less association with a syndrome (e.g. neurofibroma-
risk of post-inflammatory hyperpigmentation. tosis, Noonan syndrome). Histologically, there is
Additionally, a study using a 595 nm pulsed-dye an increase in melanocytes along the basal layer,
laser on lentigines in Asian patients showed a hypermelanosis of melanocytes and keratino-
mean of 82% improvement in lentigines by cytes, and giant melanin granules. Treatment of
reflectance spectrometry [23]. Several studies CALMs with lasers is minimally successful and
have also demonstrated the effectiveness of often unpredictable [38]. Temporary lightening
broad band light sources (Intense Pulsed Light) or clearing can be achieved after multiple treat-
in clearing lentigines. Adjunctive use of 5-ami- ments (Fig. 6.9). However, recurrences are seen
nolevulinic acid (5-ALA) with IPL provides in up to 50% of treated lesions, even when clear-
greater improvement of epidermal pigment than ing is initially achieved. Post-inflammatory
with IPL alone [33–35]. hyperpigmentation is frequent following laser
The fractional 1927 nm thulium laser is highly treatment of CALMs, especially in patients with
effective in treating lentigines and is safe for both darker skin types. Alster demonstrated complete
facial and non-facial sites. One study showed an elimination of most CALMs after an average of
average of over 50% improvement of lentigines 8.4 treatment sessions with the 510  nm pulsed
after three treatments with a 1927 nm laser [36]. dye laser, indicating that multiple treatments are

a b

Fig. 6.7 (a) A woman in her early 40 s with significant ruby laser. There is about 70% improvement of the lesion.
photoaging and numerous lentigines prior to treatment. No further treatments were requested by the patient
(b) Six weeks after one single treatment with a Q-switched
94 E. M. Graber and J. S. Dover

needed for complete resolution [39, 40]. Er:YAG winter. There is no increase in the number of
resurfacing has also been shown to eliminate melanocytes on pathology, but there is an
CALMs [40]. increase in melanin. Ephelides respond well to
Q-switched laser treatment. Another common
 ther Epidermal Lesions
O lesion, seborrheic keratoses, may respond to
Ephelides (freckles) are hyperpigmented small laser treatment. In general, thinner seborrheic
macules located on sun-exposed skin and keratoses respond better to laser treatment than
become darker in the summer and lighter in the thick lesions [28]. Cryotherapy or cryotherapy
in combination with laser treatment is preferred
to laser treatment alone for thick seborrheic ker-
atoses. A nevus spilus (speckled lentiginous
nevus) consists of a background CALM and
scattered nests of nevi cells. Successful clearing
of the darker nevocellular component has been
reported with the QSRL, but the CALM compo-
nent tends to recur [25]. A Becker’s nevus is a
hyperpigmented, hair-­bearing plaque that most
commonly occurs on the upper trunk or shoul-
der of males. These lesions may also be associ-
ated with a dermal smooth muscle hamartoma.
The hyperpigmented component of Becker’s
nevi respond similarly to laser treatment as
Fig. 6.8  A patient’s right hand with copious solar lentigi-
CALMs, having frequent recurrences (within
nes and the patient’s left hand with significantly fewer
solar lentigines after two Q-switched alexandrite 6–12 months) and post-­inflammatory hyperpig-
treatments mentation [41].

a b

Fig. 6.9 (a) A young Asian patient with a café au lait macule on her right cheek. (b) After a series of treatments with
the Q-switched laser, the café au lait macule has cleared markedly
6  Lasers and Lights for Treating Pigmented Lesions 95

Dermal Pigmented Lesions formation of a benign pigmented lesion simply

by reducing the population of existing potentially
Q-switched lasers have revolutionized the treat- premalignant cells. One study reported that no
ment of dermal pigmented lesions including: significant malignant markers (such as prolifera-
melanocytic nevi, nevus of Ota, and melasma. tion cell nuclear antigen, pyrimidine dimers,
Prior to the advent of Q-switched lasers, these 8-OhdG, and p53) were found following treat-
lesions were treated with nonspecific destructive ment of nevi with Q-switched lasers [53]. While
means such as excision [42, 43], dermabrasion these findings are notable, additional study is
[44], salabrasion [45], cryotherapy [46], solid needed to assess the outcome of Q-switched laser
carbon dioxide ice [47], or continuous wave laser treatment of nevi. Until more is known, it is pru-
ablation [48]. These older methods were ineffec- dent to perform a biopsy prior to laser treatment
tive and often caused scarring or dyspigmenta- to confirm the benign nature of the nevus. Laser
tion. By selectively targeting dermal melanin, treatment should not be performed on nevi in
Q-switched lasers provide effective treatment of patients with a personal or family history of
these lesions without risking textural or pigment malignant melanoma.
alteration. The Q-switched ruby, alexandrite and The Q-switched ruby, alexandrite, and
1064 nm Nd:YAG are the most commonly used 1064 nm Nd:YAG lasers all have some efficacy in
lasers. All of these lasers are still within the removing flat or slightly raised acquired nevi
absorption spectrum of melanin yet also have [54–56]. Lighter nevi respond best to shorter
wavelengths that are long enough to penetrate wavelengths that maximize melanin absorption,
into the dermis. Broad band light sources (such while darker nevi typically respond to any wave-
as IPL) lack wavelength specificity and have lon- length within the melanin absorption spectrum.
ger (millisecond range rather than nanosecond Multiple treatments are frequently necessary for
range) pulse durations, making them unsuitable optimal lightening. Clinical lightening is also
for treating dermal pigmented lesions. associated with the development of a subtle
microscopic scar up to 1 mm thick that obscures
Melanocytic Nevi residual nevus cells. It is often unfeasible to attain
Laser treatment of melanocytic nevi is controver- complete resolution of nevi [56], and recurrence
sial since it is unclear whether laser irradiation after laser treatment is common. There may be
has any potential to induce malignant change in persistence of nevus cells containing little pig-
nevus cells. In vitro studies of melanoma cells ment located in the deeper dermis that are
treated with Q-switched lasers have found shielded from laser radiation by the more pig-
changes in cell surface integrin expression, with mented superficial cells [54]. Q-switched laser
subsequent alteration of cell migration [49]. radiation does not penetrate sufficiently to effec-
Another in vitro study found a significant increase tively treat thicker papillated or dome-shaped
in p16INK4a in p16 positive cell lines following dermal nevi. The short pulsed erbium:YAG laser
irradiation with Q-switched laser light and sug- has been reported to be quite effective in remov-
gested that sub-lethal laser damage may increase ing flat or slightly palpable melanocytic nevi.
DNA damage leading to an increase in p16 Single pulses of 5.2–14 J/cm2 were found to clear
expression [50]. In clinical practice, benign 27 of 28 nevi on follow-up and histological
appearing nevi that tend to recur following laser examination [57]. The QSRL has been reported
treatment may show newfound clinical and histo- to successfully eliminate flat blue nevi [58].
logic atypia, referred to as pseudomelanoma Although Q-switched lasers may effectively
[51]. Despite this, there has never been a report of lighten congenital nevi, there is frequently repig-
true malignant transformation of a benign pig- mentation due to persistence of nevus cells within
mented lesion following laser treatment [52]. the deeper reticular dermis and within adnexae
Theoretically, laser treatment of melanocytic [52, 59]. In a split nevus study on 15 patients,
lesions may decrease the risk of malignant trans- Kono et al. showed greater clearing with combined
96 E. M. Graber and J. S. Dover

Q-switched and normal-mode ruby laser (NMRL) Japan [67]. Nevus of Ota is congenital in about
than in NMRL alone. They also showed a marked 50% of cases, with others appearing by the sec-
decrease in nevus nests at the dermal-­epidermal ond decade of life. Nevus of Ota may affect
junction, papillary and reticular dermis. In theory, mucosal surfaces such as cornea, sclera, nasal
millisecond-domain pulses are more appropriate and buccal mucosa, and tympanic membrane.
than Q-switched pulses for treating thick lesions Histologically, elongated dendritic melanocytes
such as congenital nevi because they produce less are scattered within the upper dermis. The occur-
selective thermal damage, destroying entire nests rence of melanoma within nevus of Ota has been
of cells rather than individual pigmented cells. reported [68] but is rare.
Japanese investigators have reported impressive Q-switched lasers are extremely helpful in
long-term clearing of congenital nevi treated with treating Nevus of Ota. The degree of lightening is
the millisecond-­domain normal-mode ruby laser usually directly proportional to the number of
[24, 60]. However, other investigators have treatments performed. Lightening of 70% or
reported poor results treating congenital nevi with more has been reported in the majority of patients
both Q-switched and normal mode ruby lasers treated four or five times with the QSRL [69]
[61]. Long-pulse ruby lasers also offer the poten- (Fig.  6.10). Post-treatment dyspigmentation
tial to reduce the amount of hair within congenital occurs occasionally, although textural change has
nevi. In Japanese studies, no histological or clini- not been reported. Post-treatment biopsies have
cal evidence of malignancy has been demon- revealed disintegration of melanocytes up to a
strated up to 8 years after normal-mode ruby laser depth of 1.5  mm from the skin surface [69].
treatment [24, 60]. However, since congenital While the QSRL has been most widely used [69–
nevi have the potential to transform into malig- 73], the Q-switched alexandrite [74] and Nd:YAG
nant melanoma, and residual nevus cells persist in [26] lasers seem as effective. Large-scale
the dermis after laser treatment, cautious long- ­comparative trials between these lasers have not
term follow-up of nevi treated with lasers is been performed.
required. Acquired nevus of Ota-like macules (also
Both continuous wave lasers [62, 63] and the known as Hori’s nevus) differ from the classic
QSRL [64] have been used to treat lentigo nevus of Ota in that they are bilateral, spare
maligna. Nonetheless, there are several reports of mucosa, and occur later in life. Various
lentigo maligna recurring following laser treat- Q-switched lasers have been reported effective in
ment, probably due to persistence of melanocytes treating nevus of Ota-like macules [75–77].
within deeper adnexal structures [65, 66]. Laser Mauskiatti et al. demonstrated greater clearing of
treatment of lentigo maligna should be reserved bilateral nevus of Ota like macules with a combi-
for extreme situations where surgical excision is nation carbon dioxide (CO2) and Q-switched
not feasible due to large lesion size, advanced ruby laser (QSRL) treatment than with QSRL
patient age, or underlying medical condition. alone [76]. Laser treatment of any pigmented
Close follow-up to detect any early recurrence is lesion is often complicated by post-inflammatory
critical. hyperpigmentation. A recent study of Q-switched
Nd:YAG treatment for acquired nevus of Ota-like
Nevus of Ota macules suggests that epidermal cooling may be
Nevus of Ota (also known as oculodermal mela- associated with an increased risk of post-­
noma or nevus fuscoceruleus ophthalmomaxil- inflammatory hyperpigmentation [78].
laris) is a mottled, blue-grey macule that is
usually located unilaterally within the distribu- Melasma and Post-inflammatory
tion of the first and second branches of the tri- Hyperpigmentation
geminal nerve. Lesions usually occur in a 5:1 Melasma is a common acquired hyperpigmenta-
female to male ratio. Asians are most commonly tion, most often affecting adult females with skin
affected, with an incidence of 1 in 500 reported in type III or higher. It occurs as brown to blue-grey
6  Lasers and Lights for Treating Pigmented Lesions 97

a b

Fig. 6.10 (a) A patient with a dark nevus of Ota extend- laser, there is impressive lightening of the lesion with no
ing over a significant portion of the face prior to treatment. textural change
(b) After a series of treatments with the Q-switched ruby

macules most frequently on the cheeks, forehead, and as a result these treatment modalities are not
upper lip, nose, and chin. It is associated with sun recommended. Some of the newer laser technolo-
exposure, pregnancy, and use of oral contracep- gies, such as the fractionated erbium fiber laser
tives, although it can also be seen in patients (Fraxel), can be useful in treating melasma [81,
without any predisposing factor. Melasma can 82]. A study of ten patients showed 75–100%
have increased melanin in either the epidermis, clearing of melasma in 60% of patients treated
dermis or both. Initial management consists of with the fractionated erbium fiber laser (Fraxel)
discontinuing any oral contraceptives or hor- [83]. These patients were treated at a low fluence
monal replacement, and strict sun avoidance. but a high density of microthermal zones.
Hydroquinone alone or in combination with topi- Fractionated laser treatment may work by expel-
cal corticosteroids or retinoids is the mainstay of ling columns of microscopic epidermal debris
treatment. Azeleic acid, kojic acid, and superfi- that contains melanin.
cial chemical peels also provide some benefit. The 1927 nm thulium laser can also be used
Melasma with dermal melanin is the most diffi- for melasma with studies demonstrating varied
cult to treat. Post inflammatory hyperpigmenta- success. In one study, over half of the subjects
tion has a similar clinical and histology with melasma had at least a 50% improvement.
morphology as melasma, but develops following However, a significant number of patients experi-
cutaneous injury or inflammatory process. enced rebound of their melasma in the months
Studies have shown that Q-switched lasers are after their treatment [84].
largely ineffective in the treatment of melasma Infraorbital hyperpigmentation (dark circles)
and post-inflammatory hyperpigmentation [26, may result from a variety of causes, including der-
79]. Q-switched laser treatment may actually mal melanin deposition, post-inflammatory hyper-
cause an increase in dermal melanophages and pigmentation from atopic or allergic contact
worsening of hyperpigmentation. Carbon dioxide dermatitis, prominent superficial blood vessels,
or erbium:YAG [80] laser resurfacing provides and shadowing from skin laxity and infraorbital
an alternative treatment modality for melasma, swelling [74]. The QSRL has been reported to
but post-inflammatory hyperpigmentation is effectively treat infraorbital hyperpigmentation
extremely frequent in the postoperative period when due to deposition of dermal melanin [85].
98 E. M. Graber and J. S. Dover

The other Q-switched lasers, especially the III.  Pigmentation will gradually fade after dis-
Q-switched alexandrite laser, are also effective continuation of minocycline, but may take years.
treatments. Improvement of this condition has also The Q-switched ruby laser is effective in treating
been reported following carbon dioxide laser resur- minocycline-induced pigmentation, with clearing
facing [86] and the combination of carbon dioxide occurring after one to four treatment sessions
laser followed by Q-switched Alexandrite laser. In [90–92]. Successful treatment has also been
one study, a striking 75–100% clearing of perior- reported with the Q-switched 532 nm, Q-switched
bital hyperpigmentation was noted using a com- alexandrite [93] (Fig.  6.11), and 1064  nm
bined CO2 resurfacing followed immediately by Nd:YAG laser [94, 95], although the latter wave-
Q-switched alexandrite laser treatment [87]. length has not proved effective in several reports
Blepharoplasty may be indicated when infraorbital [92, 94]. Amiodarone (an antiarrhythmic) and
darkening is due to excessive skin laxity. Soft tissue
imipramine (an antidepressant) can also induce
augmentation with fillers may be beneficial if there hyperpigmentation and have been treated effec-
is shadowing due to a hollow in the tear trough. tively with the Q-switched ruby laser [96, 97]. In
order to prevent recurrences, laser treatment of
Drug Induced Pigmentation these conditions should be deferred until the
Minocycline therapy may cause localized or dif- offending medication has been discontinued and
fuse mucocutaneous pigmentation. Minocycline-­ sufficient time has elapsed to allow most of the
induced pigmentation occurs in approximately pigmentation to resolve spontaneously.
5% of acne vulgaris patients treated with the drug Q-switched laser treatment may induce para-
after prolonged use [88]. Three patterns of pig- doxical hyperpigmentation in patients receiving
mentation have been reported. In type I, focal certain medications. In one report, localized chrysi-
blue-gray pigmentation occurs in inflamed or asis developed in a patient on parenteral gold ther-
scarred skin, often in acne scars. Histologic stud- apy who underwent treatment with a Q-switched
ies show pigment within dermal macrophages ruby laser for post inflammatory hyperpigmenta-
that stains positively for melanin and iron [89]. tion [98]. This phenomenon is due to a laser-
Types II and III consist of blue to brown discol- induced alteration in the physiochemical properties
oration that is more prominent on the anterior of dermal gold deposits. In the reported case, it was
shins and sun-exposed areas, respectively. found that the induction of this change in pigmen-
Histologically, epidermal and superficial dermal tation is irradiance-­dependent, i.e. related to the
pigment is present that stains for both melanin power delivered per unit area (W/cm2) rather than
and iron in type II only for melanin [89] in type fluence-dependent. It was concluded that any

a b

Fig. 6.11 (a) Minocycline pigmentation on the cheeks, upper lip, and chin. (b) Removal of pigmentation was achieved
after four Q-switched alexandrite laser treatments (From Alster et al. [101], with permission of Wolters Kluwer.)
6  Lasers and Lights for Treating Pigmented Lesions 99

millisecond laser emitting between 550 and Many patients are ill informed and harbour
850 nm should clear this pigment, and subsequent unrealistic expectations about the capabilities of
treatment with a normal mode (3  ms) ruby laser laser surgery. Patients should be fully informed
resulted in substantial clearing [99]. of what to expect from each treatment and the
potential side effects. It is vital that patients
understand that it will most likely take multiple
Techniques treatments and that the lesion may not clear
entirely. Pre-treatment photographs are essential
• It is important to obtain a medical history to document lesions prior to treatment.
prior to treatment and to educate patients
about the potential outcomes. Anesthesia
• Anesthesia may be needed for larger or der- The need for anesthesia when treating pigmented
mal pigmented lesions. lesions depends on the location, size and depth of
• Appropriate protective eyewear should be on the lesion as well as the pain threshold of the
all persons in the room. patient. The sensation of a laser pulse at the low
• Laser parameters depend on the particular fluences which are used for epidermal pigmented
laser, the patient’s skin phototype, and the lesions such as lentigines has been likened to a
type of lesion. rubber band snapping against the skin surface.
• Adequate fluence will result in an immediate The higher fluences used in the treatment of der-
uniform ash white color. mal pigmented lesions such as nevus of Ota pro-
• Appropriate wound care is essential to ensur- duce more discomfort and are more likely to
ing good outcomes. An occlusive ointment require some type of anesthesia. When limited
should be applied and patients should be edu- areas are treated, such as scattered lentigines,
cated on the healing process. many patients require no anesthesia at all. For the
treatment of larger pigmented lesions, one or
more of the following anesthetic techniques may
Pre-operative Management be required: topical anesthesia (e.g., LMX-5
cream), local infiltration of lidocaine with or
Patient Evaluation without epinephrine, regional nerve block, or oral
A general medical history should be obtained or intramuscular sedation. In many children and
prior to treatment, including medication history, rarely in adults, intravenous sedation or general
information on wound healing (specifically a his- anesthesia may be necessary.
tory of keloids), any bleeding diatheses, or his-
tory of infectious diseases, particularly hepatitis Safety
and HIV infection. Patients with a recent history Laser safety concerns can be divided into beam
of isotretinoin use or a history of hypertrophic or hazards, which are related to direct beam impact,
keloidal scarring should be treated with caution and non-beam hazards, such as plume hazards.
because they may have a higher risk of scarring Beam hazards can include fire, thermal burns, and
after laser treatment. ocular damage. The room should be designed in
Before treating any pigmented lesion, it is such a way that all reflective surfaces and win-
imperative to correctly diagnose the lesion in dows are covered, the door is locked from the
question. A pre-treatment biopsy should be per- inside, appropriate signs are posted, and no flam-
formed if there is any possibility of atypia in a mable materials or anesthetics are present.
pigmented lesion or if the diagnosis is at all in Flammability can occur when the laser is used in
question. Once the correct diagnosis has been the presence of oxygen (e.g. nasal cannula).
established, the appropriate laser can be selected Drapes, towels and sponges may also be flamma-
based on the probable depth and type of pigment ble and to avoid this wet or non-flammable mate-
in the skin and on the patient’s skin phototype. rial should be used. A nonflammable, water-­based
100 E. M. Graber and J. S. Dover

lubricant such as Surgilube or K-Y Jelly should be Q-switched laser pulses may produce a sig-
applied to the eyebrows to avoid singeing the hair. nificant amount of blood and tissue splatter, espe-
Ocular risks may be encountered when the eye cially the 1064  nm Nd:YAG laser. This is not
is exposed directly in the laser beam’s path or indi- really an issue when treating epidermal pig-
rectly by a reflected beam. Recalling basic geo- mented lesions but is of more significance treat-
metric optics, a parallel beam of light (i.e. a laser) ing dermal lesions. Use of universal precautions
that enters a convex element, such as the cornea, is mandatory, including use of gloves, goggles,
will be focused down to a smaller geometric point. and laser masks. The protective plastic cone pro-
This of course concentrates all the power in the vided with most Q-switched lasers should always
beam into a much smaller spot, and results in an be attached to the handpiece before use to mini-
infinite irradiance causing more damage. Laser mize tissue splatter and keep tissue debris off the
light in the visible to near infrared spectrum (i.e., handpiece lens. The plastic cone must be placed
400–1400 nm) can cause damage to the retina that in direct contact with the skin to efficiently trap
is painless at the time of injury. For this reason, tissue debris. To minimize tissue splatter, pulses
this spectrum of light is also known as the “retinal may be delivered through a clear hydrogel dress-
hazard region”. Without eye protection, observing ing (e.g., Tegaderm, Second Skin) placed on the
a laser beam in the visible spectrum of light is skin, although this reduces transmission of light
detected as a bright color flash of the emitted into the skin and raises the risk of ocular injury
wavelength and an after-­image of its complemen- from reflection of light off the dressing surface.
tary color (e.g., a green 532 nm laser light would Vacuum suction is useless at capturing tissue
produce a green flash followed by a red after- splatter because it leaves the surface of the skin
image). When the retina is affected, there may be far too rapidly—faster than the speed of sound.
difficulty in detecting blue or green colors second- Although there have been no cases of transmis-
ary to cone damage, and pigmentation of the retina sion, the presence of HIV proviral DNA has been
may be detected. Exposure to the Q-switched demonstrated in the laser plume generated by
Nd:YAG laser beam (1064 nm) is especially haz- carbon dioxide laser irradiation of HIV-infected
ardous and may initially go undetected because tissue culture [100].
the beam is invisible (in the near-infrared spec- All makeup and sunscreen should be removed
trum) and the retina lacks pain sensory nerves. from the area to be treated, as these products will
Photoacoustic retinal damage may be associated prevent transmission of light to the skin surface.
with an audible “pop” at the time of exposure. Furthermore, many of these products contain
Visual disorientation due to retinal damage may metal-based salts and oxides (such as titanium
not be apparent to the operator until considerable dioxide) that may ignite following exposure to
thermal damage has occurred. Laser light in the far Q-switched laser pulses.
infrared (1400–10,600  nm) spectrum can cause
damage to the cornea and/or to the lens because of
its preferential absorption of water. Exposure to Description of the Technique
the invisible carbon dioxide laser beam
(10,600 nm) can be detected by a burning pain at Q-switched lasers should always be calibrated
the site of exposure on the cornea or sclera. prior to treatment and should be placed in
All persons in the room should wear protec- standby mode until ready for use. The laser
tive goggles with the correct optical density for handpiece should be held perpendicular to the
the specific laser wavelength. When treating the skin with the attached plastic cone or guide rest-
face, the patient should wear snug metal goggles. ing on the skin to ensure that the laser beam is
If the immediate periocular area is to be treated, focused on the area to be treated. Exact param-
protective metal eye shields should be inserted eters vary depending on the particular laser, the
over the conjunctiva after application of a topical patient’s Fitzpatrick skin type, and the type of
ophthalmic anesthetic agent. lesion (Table  6.2). In general, lower fluence is
6  Lasers and Lights for Treating Pigmented Lesions 101

used for dark lesions that contain larger amounts treatment. While some pigmented lesions (e.g.,
of absorbing chromophore. lentigines) may require only one to two treatments,
One or two laser pulses should be fired at the other lesions (e.g., Café au lait macules) may need
lesion to ensure that a threshold response occurs, multiple treatments. Another approach to tattoo
which is defined as immediate whitening of the removal is to perform several treatments on the
lesion. The optimal tissue end point is uniform same day at intervals of 20 min. This is referred to
but faint immediate whitening without epidermal as the R20 method. With this method, the typical
disruption. The lowest fluence required to invoke immediate whitening reaction will occur with the
this response should be used. When the fluence is first laser pass, but there will be little or no whiten-
too low, the whitening will be barely noticeable. ing with subsequent passes. There is more epider-
If using subthreshold fluences, post-­inflammatory mal damage utilizing the R20 method than with
hyperpigmentation due to stimulation of melano- the traditional single pass method. This theoreti-
genesis can result. If the fluence is too high, whit- cally increases the risk of scarring with the R20
ening is a confluent bright white, and epidermal method but scarring has not been observed in clin-
damage with bleeding may occur. This may result ical trials. One study demonstrated that 3 months
in tissue sloughing, prolonged healing, and also a after treatment with the R20 method, the R20
greater likelihood of post-inflammatory hyper- method was more efficacious than the conven-
pigmentation or hypopigmentation or textural tional single-pass laser treatment [101].
changes. After the optimal fluence is determined, Unlike dermal pigmented lesions, epidermal
pulses can be delivered rapidly (up to 10  Hz, pigmented lesions can be treated with millisecond
depending on the laser), with overlapping of domain lasers and intense pulsed light devices.
about 10% to ensure confluent whitening. The clinical endpoint of treatment with these
In most cases, additional treatment sessions devices is significantly different from that seen
may be safely performed 6 weeks after the original after Q-switched laser treatment. Immediately

Table 6.2  Standard treatment parameters for pigmented lesions

Lesion Laser Spot size (mm) Fluence (J/cm2) Retreatment interval (weeks)
Lentigines QS ruby 6.5 2.0–4.0 4–8 weeks
QS Nd:YAG (532 nm) 3 0.7–1.0
QS alexandrite 4 3.5–5.5
Pulsed dye (510 nm) 3 2.5
Café au lait macules QS ruby 6.5 3.0–4.5 4–8 weeks
QS Nd:YAG (532 nm) 3 1.0–1.5
QS alexandrite 4 2.5–4.5
Pulsed dye (510 nm) 5 2.0–3.5
Becker’s nevus QS ruby 6.5 3.0–4.5 4–8 weeks
QS Nd:YAG (532 nm) 3 1.5–1.8
QS Nd:YAG 3 4.0–5.0
(1,064 nm)
QS alexandrite 4 3.5–5.0
Nevus spilus QS ruby 6.5 3.0–4.5 4–8 weeks
QS Nd:YAG (532 nm) 3 1.5–2.0
QS Nd:YAG 3 4.0–4.4
(1,064 nm)
QS alexandrite 3 5.0–6.0
Nevus of Ota QS ruby 6.5 5.0–6.0 6–12 weeks
QS Nd:YAG 3 4.0–7.0
(1,064 nm)
QS alexandrite 3 5.5–6.5
QS Q-switched
102 E. M. Graber and J. S. Dover

after treatment there is a slight darkening of len- Post-operative Management

tigines, although lighter lentigines may remain
unchanged. A faint erythema may also be The white tissue reaction that occurs immedi-
observed at the periphery of darker lentigines. ately after Q-switched laser treatment fades
After treatment, pigmented lesions develop a within 20  min. An urticarial reaction, causing
slight dark scale, which flakes away in a few days. erythema, edema, itching, and stinging, may
Active skin cooling is used during treatment with develop in and around the treated area. This may
most IPL devices to protect the epidermis from last for several hours and can be treated, but not
excessive thermal injury. Multiple treatment ses- prevented, by taking an antihistamine preopera-
sions with IPL are required for optimal clearing of tively. In all patients, the treated lesions appear
epidermal pigmented lesions. Lighter lentigines, darker for several days then develop a thin crust
which contain less of the melanin chromophore, that flakes off in 7–10 days. The amount of crust-
may be more resistant to IPL treatment and may ing that occurs depends on the aggressiveness of
respond better to Q-switched laser treatment. treatment. Overly aggressive treatment may
In general, dermal lesions require higher flu- result in vesiculation or frank blistering. The risk
ences than epidermal lesions. Larger spot sizes of blistering is highest when shorter wavelength
have a greater depth of penetration, and are pre- devices (e.g., QSRL) are used to treat patients
ferred to smaller ones. To achieve the same effect with dark skin phototypes. Following treatment
in the dermis, a larger spot size will require lower with the Q-switched 532  nm Nd:YAG, purpura
energy and therefore be gentler on the epidermis usually develops after skin whitening has faded.
and dermal-epidermal junction. This occurs because these wavelengths are well
Lower fluences should be used in the treat- absorbed by both melanin and hemoglobin, caus-
ment of patients with darker skin types, since the ing rupture of blood vessels. Purpura lasts for
threshold response will likely occur at a lower 5–10 days, and is a notable disadvantage of treat-
fluence. When treating both epidermal and der- ment with the above devices. Purpura can be
mal pigmented lesions, patients with darker skin minimized by treating through a microscope
are at greater risk for postoperative hyperpigmen- slide held firmly against the skin to compress
tation or hypopigmentation. It may be preferable blood vessels and remove hemoglobin as a
to use a longer wavelength device, such as the target.
1064 nm Nd:YAG laser, since longer wavelengths Postoperative discomfort may be treated with
penetrate more deeply than shorter wavelengths application of cold water-soaked gauze, ice
and produce relatively less epidermal damage for packs, or a hydroocclusive dressing such as
the same dermal effect. Patients with “suntans” Second Skin or Vigilon. Analgesics are usually
should not be treated because they are at risk of not needed. Antihistamines may be given if the
spotty hypopigmentation, which can last for patient has an urticarial reaction. Patients should
weeks to months after treatment. be instructed to gently wash the treated area with
Topical anesthesia is required for fractional mild soap and apply an occlusive ointment (e.g.,
non-ablative treatments. The 1927 Thulium laser petrolatum or Aquaphor Healing Ointment) twice
is best suited for w epidermal pigmented lesions. a day. Any crusting should be allowed to slough
Topical anesthesia usually left on for an hour spontaneously. To minimize the risk of hyperpig-
prior to treatment. Air cooling during treatment mentation and recurrence, patients should avoid
makes the procedure far better tolerated. After excessive sun exposure and use a broad-spectrum
treatment ice is applied for an hour to reduce dis- sunscreen of SPF 30 or higher for several months
comfort which lasts about an hour and then dis- after treatment.
sipated completely. Redness and swelling last an Because dermal lesions typically require the
average of 3 days. Bronzing starts on day 2 and use of higher fluences, postoperative changes are
lasts 3–5 days, longer after the first treatment. more apparent. In addition to the whitening
6  Lasers and Lights for Treating Pigmented Lesions 103

response, erythema and swelling are usually seen respectively. For many reasons, it is important to
in the immediate postoperative period, especially take quality pre-treatment photographs from
in the periorbital region. multiple angles. Photographs can be used to
judge improvement, document baseline findings,
and may have medico legal importance. It is
Adverse Events important for patients to have a realistic
understanding of potential outcomes prior to
­
• Post-inflammatory hyperpigmentation, beginning laser treatment. Potential laser candi-
hypopigmentation, an inadequate response dates should be educated regarding the need for
and recurrence of the lesion are the most com- multiple treatments and should be made aware of
mon side effects. possible side effects. This patient education
• Using the appropriate laser and fluence can should be documented in the patient chart. Side
reduce side effects. effects and expectations should be reinforced in
• Educating patients regarding realistic expecta- writing on the consent form.
tions can help to reduce patient frustration and
complications.
Future Directions

Side Effects/Complications • Femtosecond (10−15) domain lasers are being

developed.
Post-inflammatory hyperpigmentation is not a • Pico second (10−12) domain lasers currently
rare side effect when treating pigmented lesions, used for tattoo removal are being investigated
and is especially common in treating darker skin for pigmented lesion removal.
types. Subthreshold fluences can stimulate mela- • Enhanced effectiveness with less side effects
nogenesis in dark skinned patients. While post-­ in treating pigmented disorders in patients of
inflammatory hyperpigmentation is benign, it can color
last several months and can be cosmetically both-
ersome. Topical hydroquinone containing creams Manufacturers and scientists continue to
are usually effective in lightening the refine and optimize the current laser systems to
hyperpigmentation. enhance outcomes with fewer side effects. By
Although less common than post-­inflammatory adding cooling to many treatments systems the
hyperpigmentation, hypopigmentation can also risk of problems of pigmentation after treatment
occur, particularly when treating tanned patients. have decreased. Encouraging work is presently
For this reason, tanned patients should not be being done on lasers with even shorter pulse
treated. durations than typical Q-switched lasers. Pulse
A sub-optimal response to laser treatment is durations in the pico (10−12) and femtosecond
another unwelcome outcome. Most pigmented (10−15) domains may be more effective in disrupt-
lesions require multiple treatments and some are ing pigment in resistant tattoos than the typically
prone to recurrence. used shorter pulse durations.

Conclusions
 revention and Treatment of Side
P Pigmented lesions are an exceedingly com-
Effects/Complications mon occurrence, and often are cosmetically
disturbing to the patient. Topical treatment
Hyperpigmentation and hypopigmentation can options are ineffective for almost all of these
be avoided by treating with appropriately high conditions and surgical treatment options
fluences and by not treating tanned patients, often produce unacceptable results. Laser and
104 E. M. Graber and J. S. Dover

light therapy is often the preferred manner to pulsed radiation generates acoustic waves and kills
diminish a variety of pigmented lesions and cells. Lasers Surg Med. 1990;10:52–9.
10. Dover JS, Margolis RJ, Polla LL, et  al. Pigmented
disorders of pigmentation. In order to obtain guinea pig skin irradiated with Q-switched ruby
the optimal outcome, the physician needs to laser pulses. Arch Dermatol. 1989;125:43–9.
select the proper light source, the correct 11. Kossida T, Farinelli W, Flotte T, et al. Mechanism of
patient and skin characteristics and provide immediate whitening during tattoo Removal. Lasers
Surg Med. 2006;18:70.
appropriate wound care to achieve optimal 12. Margolis RJ, Dover JS, Polla LL, et al. Visible action
results. Thought should be given to the depth spectrum for melanin-specific selective photother-
of the lesion, the patient’s skin phototype, and molysis. Lasers Surg Med. 1989;9:389–97.
the laser or light device parameters. Despite 13. Anderson RR, Margolis RJ, Watenabe S, et  al.
Selective photothermolysis of cutaneous pigmenta-
the efficacy of laser and light treatments, they tion by Q-switched Nd:YAG laser pulses at 1064,
are not without potential side effects and 532, and 355 nm. J Invest Dermatol. 1989;93:28–32.
complications. Prior to beginning treatment, 14. Hruza GJ, Dover JS, Flotte TJ, et  al. Q-switched
both the physician and the patient should be ruby laser irradiation of normal human skin. Arch
Dermatol. 1991;127:1799–805.
well aware of the limitations and disadvan- 15. Murphy GF, Shepard RS, Paul BS, et al. Organelle-­
tages of laser therapy. Nevertheless, with a specific injury to melanin-containing cells in
thoughtful treatment plan and adequate human skin by pulsed laser irradiation. Lab Invest.
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18. Nakamura Y, Hossain M, Hirayama K, Matsumoto
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 Laser Treatment of Tattoos
7
Voraphol Vejjabhinanta, Caroline V. Caperton,
Christopher Wong, Rawat Charoensawad,
and Keyvan Nouri

Abstract 28% of people who get tattoos regret the deci-

Tattoos are a long-standing part of human sion within the first month.
culture.
Techniques used in tattooing have evolved Keywords
over the centuries. Tattoo removal · Q-switched Nd laser · YAG
Although 24% of Americans between the laser · Q-switched Ruby laser · Q-switched
ages of 18–50 years have at least one tattoo, Alexandrite laser

V. Vejjabhinanta (*)
Dermatologic Surgery and Lasers Unit, Department
of Medical Services, Ministry of Public Health,
Institute of Dermatology, Bangkok, Thailand
C. V. Caperton
R. Charoensawad
WK Allergy, Asthma, and Immunology Center,
Rawat Clinic, Bangkok, Thailand
Willis-Knighton Health System,
Shreveport, LA, USA Biophile Training Center, Bangkok, Thailand
e-mail: [email protected]
K. Nouri
C. Wong Department of Dermatology and Cutaneous Surgery,
Orthopaedic Associates of South Broward, University of Miami Miller School of Medicine,
Hollywood, FL, USA Miami, FL, USA
e-mail: [email protected] e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 109

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_7
110 V. Vejjabhinanta et al.

initial decision to get a tattoo. Approximately

Box 1 Overview 28% of people who get tattoos regret the decision
• Tattoos are a long-standing part of within the first month. While the minimum age to
human culture. obtain a tattoo is 18  years old, 71% of people
• Techniques used in tattooing have requesting tattoo removal have had the ink
evolved over the centuries. applied when they were under the minimum age.
• Although 24% of Americans between The most common reason to seek tattoo removal
the ages of 18–50 years have at least one was to further enhance self-esteem by freeing
tattoo, 28% of people who get tattoos oneself from the stigmatizing lesion that was the
regret the decision within the first source of many years of regret. In addition, tattoo
month. owners felt their marks were socially discredit-
• The three lasers most commonly used ing, perceived pressure by family members to
are the Q-switched Nd: YAG, Q-switched remove them, and believed improvement in
Ruby, and Q-switched Alexandrite. employment opportunities would result after
• Potential side effects of using lasers in removal [3]. On average, actual tattoo removal
the removal of tattoos include discolor- occurred 14 years later. Much of the delay can be
ation, redness, scarring, and rarely, attributed to perceived high financial costs, phys-
stimulating allergic reactions. ical pain, and risk of permanent disfigurement
associated with removal. Also, many potential
patients admit that they were unaware of the
Introduction availability of treatment options to remove their
tattoo [4].
A tattoo is a mark created by pigments that per-
manently reside in the dermal layer of the skin.
The word tattoo has roots from the Polynesian Historical Perspectives
word “ta” which means “to strike” and the
Tahitian word “tatau” which means “to mark.” As evidenced by “Ötzi the Ice Man”, a
The techniques of tattooing have changed over 5000-year-­ old man bearing 57 tattoos whose
the years, but the basic principle remains the body was discovered in 1991, tattoos have been
same. Dyes are manually applied through breaks a part of human culture for a very long time.
in the skin. By embedding the various pigments Some anthropologists even speculate that the art
below the epidermis, the pigments resist slough- of tattooing began as early as 12,000 B.C. The
ing due to the natural growth cycle of the skin, purpose of tattoos has varied from perceived
thus offering permanence. In the older methods, therapeutic benefits and religious or tribal iden-
dye-tipped needles were gently struck by stones tification symbols to self-expressions of unique-
and hammers to introduce the dye into the skin. ness and impulse. Regardless of their age or
Today, electrical tattoo machines utilize high-­ purpose, tattoos are a large part of human cul-
speed needle injections that minimize time and ture today and are becoming more and more
pain. popular.
In the United States, an estimated 7–20  mil- The first tattoos from thousands of years ago
lion people have at least one tattoo [1]. In a recent were created roughly. During bereavement cer-
study, the prevalence of tattoos among Americans emonies as signs of grief, primitive humans of
aged 18–50 years old was found to be 24% [2]. the Stone Age (12,000 B.C.) slashed their skin
Reasons for tattoo application include: fashion, and rubbed ash into the wounds [5]. It is highly
peer pressure, rebelliousness, and romance. For unlikely that the detail of the designs resembled
some individuals, regret appears as quickly as the anything near the tattoos that we see
7  Laser Treatment of Tattoos 111

today—although a few amateurs come close. Techniques of Tattooing

The discovery of crude needles and pigment
bowls in caves in France, Spain, and Portugal
provide circumstantial evidence that decorative Box 2 Summary
tattooing can be traced back to the Bronze Age • In order for a tattoo to be permanent, the
(8000 B.C.). More well known older techniques dye must be placed at a certain location
were practiced elsewhere in the Ancient world. within the dermis – too superficial and it
The Japanese utilized a hand-based tattooing will be sloughed off in the epidermis;
technique that involved elaborate needle-tipped too deep and it will be taken up by
bamboo handles. Samoans, among many other lymphatics.
Pacific cultures, used wooden hand tools such • Risks of unsterile tattooing techniques
as a bone-­tipped rake and a striking stick. The include transmission of bacteria, hepati-
ancient Thai employed a tool that closely tis B, hepatitis C, syphilis, and HIV.
resembles the electric tattoo devices of today.
They used a long brass tube with a sliding
pointed rod that ran down the center. The tattoo is actually the appearance through the
Thomas Alva Edison, the famous inventor epidermis of the ink located in the dermis. During
of the light bulb, played an unexpected role in the tattoo process, needles are dipped in various
the development of the tattoo. In 1891, Samuel inks. The electric tattoo device injects ink particles
O’Reilly modified Edison’s autographic from the epidermis to a constant depth (usually
printer to become the electric tattoo machine 1  mm) below the dermal-epidermal junction
of today. It was a steel instrument that utilized (Fig.  7.1). As part of the skin’s natural growth
needles that traveled in a vertical direction to cycle, the epidermis is continually sloughed off. In
pierce the skin at a rate up to 3000 times per the layers of the dermis, macrophages recognize
minute. the dye particles as foreign and attempt to remove

Epidermis

Tattoo

Dermis

Nerves

Blood vessels
Hair follicle

Fat
Fig. 7.1  Placement of
tattoo ink within the Sweat gland
dermis
112 V. Vejjabhinanta et al.

the molecules. However, most of the dye is cap- (PPD)-based chemicals, the notoriety of PPD
tured or ignored and remains in the dermis. had been previously established. In the 1930s,
Therefore, it is essential that the dye reaches the the practice of tinting the eyelashes and eye-
dermis in order to become a permanent mark. brows with PPD dye was common. Many
In addition, it is important that the dye not be adverse reactions to PPD became apparent, with
injected too deeply into the dermis. More some women suffering serious blistering reac-
­commonly reached by amateur-level tattoo art- tions, blindness, and even death, most notably to
ists, these greater depths will increase the likeli- the product “Lash Lure.” Since there were no
hood of the dye being carried away by body fluids laws in place to regulate these products, cos-
or for the tattoo to be accompanied by scarring. metic companies were not liable. By 1938, the
This can lead to blurring of the tattoo and reduc- Food, Drug, and Cosmetic Act was initiated
tion of its visualization. with the first mandate: to remove “Lash Lure”
Obtaining a tattoo carries with it inherent from the American market and ban the use of
risks. There have been reports that non-sterile tat- PPD on the skin [7].
tooing practices have led to the transmission of Other allergic reactions associated with tat-
infectious organisms such as bacteria, syphilis toos can be linked to the specific color of pig-
and hepatitis B; furthermore, there is also the ment that was injected into the skin. There
potential for transmission of other blood-borne have been numerous reports of patients with
pathogens such as HIV and hepatitis C [6]. known allergies to mercury or cobalt experi-
encing type IV hypersensitivity allergic reac-
tions in areas tattooed with red or blue pigment,
Allergenicity respectively [8]. There are many common
allergenic substances included in common tat-
too dyes (Table 7.1).
Box 4 Summary
It is important to note that tattoo pigments
• The most common medical techniques
have not FDA approved for intradermal injection.
currently used for tattoo removal are
Nevertheless, there have been dramatic advances
laser surgery, surgical excision, and
in the industry of body art, including the develop-
dermabrasion.
ment of a biodegradable and bioabsorbable
• Complications of these procedures,
organic dye encapsulated in synthetic polymer.
though rare, include discoloration,
The tattoo is permanent; yet, when targeted with
incomplete removal, scarring, or
a laser, the beads disintegrate, exposing the ink to
infection.
be resorbed into the body, thereby completely
• Topical products that lighten naturally
removing the tattoo [9].
pigmented skin are generally not meant
for tattoo removal, although current Table 7.1 Tattoo pigments and their common
research is ongoing. ingredients
Dye color Dye content
Black Carbon
Some patients have allergic reactions to either Red Mercury sulfide
Blue Cobalt aluminate
the pigments in the tattoo or to the additives that
Brown Hydrate of iron oxide
can be mixed in with the dye. Even though 2001 Green Chromium oxide
marked the first report of an adverse reaction Lilac Magnesium
following the application of a ‘black’ henna White Titanium oxide
tattoo darkened with paraphenylenediamine Yellow Cadmium sulfide
7  Laser Treatment of Tattoos 113

Methods of Removal Each tattoo is unique; so must each removal

technique match the demands of each individ-
ual situation. Tattoos that are professionally
Box 3 Summary applied tend to penetrate the deeper layers of
• Additives such as PPD can be mixed the skin at uniform levels. This uniformity
with tattoo dye, causing allergic reac- allows dermal surgeons to use techniques that
tions in patients. remove broader areas of inked skin at the same
• Allergic or pruritic reactions to tattoos depth.
can be linked to certain colors used in Figure 7.2 shows tattoo granules present in the
the design. dermis prior to treatment.
• No dye used in tattooing is FDA Currently, the most common tattoo removal
approved for deposition into the techniques employed by dermatological profes-
dermis. sionals are laser surgery, surgical excision, and
dermabrasion.

Prior to current medical technologies, there was

not much available to the patient requesting
removal of their tattoo. The patient was offered Laser Surgery
the choice of harsh exfoliation techniques, chem-
ical peels, thermal means, cryosurgery, or surgi- The tattoo is treated by targeting selective pig-
cal resection. In lieu of medical treatment, many ments with a high-intensity laser beam. The type
patients today still opt for covering up the tattoo of laser used generally depends upon the colors
with concealing makeup, or even voluntarily to be removed. This modality offers a highly
obtaining more tattoos in an attempt to modify or effective approach with minimal side effects,
camouflage the original tattoo into a new, often although frequently necessitates several treat-
larger design. ments for complete removal.

Fig. 7.2  Tattoo granules

present in the dermis
prior to treatment
114 V. Vejjabhinanta et al.

Surgical Excision 1  week, the tattoos were no longer detectible

either clinically or histopathologically [11].
The tattoo is cut out and either sutured or allowed Although no human models have demonstrated
to heal, depending on size. The efficacy of this these results, imiquimod remains an attractive
technique is highly dependent upon the ­individual non-invasive therapy for the treatment of tat-
surgeon, the size of the area to be resected, the toos. Ricotti and colleagues investigated
tension of the skin in the area, and the individu- whether imiquimod in conjunction with laser
al’s tendencies toward scarring or developing a therapy would be more efficacious in tattoo
keloid. removal than laser alone. The authors con-
cluded that, in addition to having more adverse
reactions than placebo, imiquimod was not
Dermabrasion an ineffective adjunct to laser treatment of
tattoos [12].
The tattoo is gradually removed via exfoliation
of the surface and middle layers of pigment by
machines, laser or salt. The upper layer of skin Lasers
is abraded or “sanded,” and the underlying lay-
ers of skin replace the damaged layers, allowing
the pigment to leach out of the skin. Side effects Box 5 Summary
and complications of this procedure are skin • Lasers are commonly used in various
discoloration (hyperpigmentation or hypopig- medical and cosmetic procedures,
mentation) at the treatment site, infection of the including treatment of vascular lesions,
tattoo site, incomplete pigment removal, or scars, dermal remodeling, hair removal,
scarring, even 3–6  months after the tattoo is and removal of pigmented lesions.
removed [10]. • Potential side effects of using lasers in
It is important to make the distinction between the removal of tattoos include discolor-
residual tattoo and post inflammatory hyperpig- ation, redness, scarring, and rarely,
mentation. Post inflammatory hyperpigmentation allergic reactions. These should be dis-
is different from tattooing in that it is mainly a cussed with the patient so that an
result of melanocyte stimulation and is exacer- informed decision may be made.
bated by exposure to ultra-violet radiation. • Specific lasers and wavelengths are bet-
Tattoos, on the other hand, are not associated ter suited for targeted removal of certain
with melanocytes, but are rather made up of dyes, colors of pigment than others.
which in contrast often fade with sun exposure as • The Q-switched lasers with pulse dura-
the pigment is oxidized and always confined tions in nanosecond range are the main-
within the previous tattoo position. stay devices for tattoo removal.
There are products available on the market • Q-switched Ruby (694 nm) is generally
that purport to lighten skin. Products containing used in the removal of black, blue and
hydroquinone are used to treat hyperpigmenta- green tattoos in individuals with fair
tion of the skin by reversibly depigmenting the skin.
skin. This is accomplished by inhibiting the oxi- • Q-switched Alexandrite (755  nm) is
dation of tyrosine to 3,4-dihydroxyphenyalanine best for removing the green ink
(DOPA) and other melanocyte metabolic • Q-switched Nd: YAG (1064 nm) is use-
processes. ful for treatment black and blue ink in
Recent data from Solis et al. demonstrated a individuals with darkly pigmented skin.
significant reduction of tattoo pigment in a • Q-switched Nd: YAG (532 nm) is useful
guinea pig model. Researchers treated the ani- for treatment red and orange ink.
mals’ recent tattoos with imiquimod. After
7  Laser Treatment of Tattoos 115

Laser is an acronym for Light Amplification by target is heated so quickly (within nanoseconds
Stimulated Emission of Radiation. The first or picoseconds [17]) that it shatters, allowing for
patient for the laser was obtained by Gordon selective photothermolysis.
Gould in 1977, although his work on light lasers Depending on the wavelength used, the laser is
dated back to 1958. The first medical application able to target the tattoo pigment while sparing other
of a laser was in 1987, when ophthalmologist chromophores in the skin, such as melanin. Due to
Steven Trokel performed refractive surgery on a its primary purpose of absorbing damaging ultravi-
patient’s eyes. Originally designed to precisely olet rays, melanin absorbs light, which can be detri-
cut glass and metal, lasers have revolutionalized mental when attempting to use light to remove a
the field of medicine with its numerous applica- tattoo. Nevertheless, this absorptive property of
tions and possibilities. melanin decreases with longer wavelengths, allow-
There are many dermatologic uses of lasers, ing targeted removal of pigment by lasers without
including treatment of vascular lesions, hypertro- interference or refraction. The biophysics underly-
phic or keloid scars, striae, acne, hair removal, ing the mechanism by which lasers are able to dis-
removal of pigmented lesions, and nonablative solve tattoos is not well understood, but the accepted
dermal remodeling, to name a few. Lasers have theory is that the pulse of light from the laser breaks
become widespread for use in the field for both up the tattoo pigment into smaller components to be
medical and cosmetic applications. digested by macrophages, taken up by scavenger
Due to the ability by some lasers to produce cells, or eliminated transepidermally [18].
pressure waves significant enough to penetrate the How efficacious the laser treatment is in the
stratum corneum, lasers have become attractive complete removal of the tattoo depends on mul-
new methods for transdermal drug delivery [13]. tiple factors, including size, length of time since
The first use of lasers for the treatment of tat- application, depth of pigment, colors used, and
toos was in the 1970s [14, 15]. Carbon dioxide patient’s skin type. Laser removal of pigment is
lasers, which emit a wavelength of 10,600 nm and highly color dependent, since the lasers used emit
target water in the skin, and argon lasers, which certain wavelengths that are better able to target
emit a continuous wavelength of either 488 or certain colors.
514 nm, were used non-selectively in an attempt to The three lasers most commonly used are the
remove tattoo pigment from the dermis. The CO2 Q-switched Ruby, Q-switched Alexandrite, and
laser ablates the top layer of skin and often results Q-switched Nd: YAG.
in scarring when used at a depth necessary for tat-
too removal. The argon lasers, due to their contin- • Q-switched Ruby (694 nm)
uous energy emitted, transmit heat to other tissue Light from this laser is red. Because light is
areas, also resulting in hyperpigmented skin, absorbed by its opposite color and reflected by
incomplete removal of the pigment, and scarring. its same color, this laser removes most ink
Modern lasers have become paramount in the ­colors well, except red. It is generally used in
treatment and removal of tattoos. By selective the removal of blue and black tattoos. It is
photothermolysis, lasers allow dermatologists to especially effective in the removal of amateur
selectively remove target pigments without and traumatic tattoos. This was the first laser
destroying the surrounding skin or tissue archi- to be used in the treatment of tattoos and pig-
tecture dramatically. The short-pulse (nanosec- mented lesions [19, 20].
ond or picosecond) lasers are optimal for tattoo • Q-switched Alexandrite (755 nm)
removal without significant scarring. The most This laser emits a purple/red light and is there-
commonly used lasers for this purpose include fore best for removing blue, black, and green
the Q-switched neodymium:yttrium-aluminum-­ ink. This laser offers an advantage over older
garnet (Nd:YAG), alexandrite, and ruby lasers models in that is reliable, with faster repetition
[16]. Q-switching refers to a switch that allows rates, and is the laser of choice in the removal
the release of energy in one pulse such that the of green pigment.
116 V. Vejjabhinanta et al.

• Q-switched Nd:YAG (1064 nm) removes red and orange ink. This wavelength
This laser emits light in the infrared range. It is absorbed by hemoglobin and thus, may
removes black and blue ink best. Because this result in temporary purpura after laser
wavelength is not well absorbed by melano- treatment.
cytes, it is useful for treatment in individuals
with darkly pigmented skin (Figs. 7.3 and 7.4). Amateur tattoos are generally easier to remove
• Q-switched Nd:YAG (532 nm) since they usually contain only black or blue ink
This is an alteration of the 1064 nm Nd: YAG and more superficial. Unfortunately, some ama-
laser made possible by using a potassium-­ teurs may tattoo too deeply, making the pigment
titanyl-­
phosphate crystal to double the fre- deposition irregular and difficult to target.
quency, thus halving the wavelength to Professional tattoo artists often mix colors for a
532  nm. This laser emits a green light and gradation effect, which is also more difficult to

a b

Fig. 7.3  Laser tattoo removal at the right wrist with Q-switches 1064 nm Nd: YAG; Amateur tattoo (a) Before treat-
ment (b) Two month after the first treatment (c) After three treatments
7  Laser Treatment of Tattoos 117

a b

Fig. 7.4  Laser tattoo removal at the upper leg; professional tattoo (a) Before treatment and (b) the result after seven
treatments with Q-Switched 1064 nm Nd: YAG laser

Table 7.2  Choice of laser for removal of tattoo by ink color

Laser Black Blue Green Brown Yellow Purple Red
Nd:YAG 532 nm X (Light) X X X
Ruby X X X X (Dark)
694 nm
Alexandrite 755 nm X X XX X (Dark)
Nd:YAG 1064 nm X X X (Dark)
Adapted from Mariwalla K, Dover JS.  The use of lasers for decorative tattoo removal. Skin Therapy Lett. 2006
Jun;11(5):8–11 [22], with permission of SkinCareGuide

remove, but will tattoo no deeper than the dermis The absorption spectrum of tattoos is
and at a consistent depth throughout the tattoo. unknown, with some colors responding better
A minimum interval of 4  weeks is generally than others. As a result, a combination of laser
required between laser sessions to allow the treat- systems may be used in stages for a single tattoo
ment area adequate time to heal and the immune (Table 7.2).
system a sufficient period for macrophages to Although Q-switched lasers are now the main-
phagocytize the broken pigment molecules [21]. stay of treatment for the removal of tattoos, it is
An average tattoo with a surface area of two important to note that there may be unwanted
square inches requires 6–7 months to be removed, complications associated with the practice. Most
on average, with sessions scheduled every commonly, patients experience hyper- or hypopig-
6–8 weeks [16]. mentation reactions or immediate erythema at the
118 V. Vejjabhinanta et al.

treatment site that generally subsides within min- laser treatment. Whether or not the tattoo is
utes of treatment [23]. Some patients may experi- being removed out of necessity (employment
ence scarring. Some patients, however, may requirements, social situations, familial pres-
experience hypersensitivity reactions, especially sures, etc.), it is important for the physician to
if they had previously experienced allergic reac- have an appreciation that the patient may
tions upon application of the tattoo pigment [24]. experience some degree of anxiety about
­
A rare and controversial topic of debate is whether becoming detached from a personal symbol
or not laser removal of certain pigments may be which was undoubtedly expected to be embed-
associated with the generation of carcinogenic or ded within him or her indefinitely. On the
hazardous compounds [25]. other hand, it is a paramount achievement for
There are significant costs associated with medicine that we are now able to safely
laser treatments of tattoos, which are not often remove tattoos and skin markings that hold
covered by health insurance companies. Most tat- negative connotations, that are regarded with
toos require multiple sessions for reasonably regret, or which have become irrelevant in the
anticipated pigment removal, which should be patient’s current life setting.
communicated with the patient beforehand to
ensure the patient possesses adequate expecta-
tions about the outcome of the treatment. More References
than half of all patients experience a 75–95%
reduction of tattoo pigment with a conventional 1. Anderson RR. Tattooing should be regulated. N Engl
series of three to four laser treatments [16]. These J Med. 1992;326(3):207.
issues should be discussed with the patient in 2. Laumann AE, Derick AJ. Tattoos and body piercings
in the United States: a national data set. J Am Acad
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his or her treatment and to ensure that realistic 3. Armstrong ML, Stuppy DJ, Gabriel DC, et  al.
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4. Varma S, Lanigan SW.  Reasons for requesting
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The information presented herein presents a 1999;140(3):483–5.
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methods of removal currently available, and a of tattoos. In: Goldman MP, Fitzpatrick RE, editors.
Cutaneous laser surgery. St. Louis, MO: Mosby, Inc.;
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varied based on the individual patient, the October 24. Schaumburg, IL: AAD; 1998.
7. Jacob SE, Caperton CV.  Allergen Focus: Focus on
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cussion 86-7
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 Laser for Hair Removal
8
Voraphol Vejjabhinanta, Keyvan Nouri,
Anita Singh, Ran Huo, Rawat Charoensawad,
Isabella Camacho, and Ali Rajabi-Estarabadi

Abstract • Lasers for hair removal are a fast-growing

Lasers for hair removal are a fast-growing area in cosmetic dermatology.
area in cosmetic dermatology. Selective pho- • Selective photothermolysis allows for target-
tothermolysis allows for targeting of specific ing of specific chromophores while minimiz-
chromophores while minimizing cutaneous ing cutaneous damage.
damage. Treatment of individuals should be • For best results, treatment should be individu-
individualized based on anatomical area, skin alized based on anatomical area, skin and hair
and hair color, by varying the wavelength, flu- color, by varying the wavelength, fluence,
ence, pulse duration, spot size, and cooling pulse duration, spot size, and cooling tech-
technique of the laser. nique of the laser.
• Adverse events to laser hair removal include
Keywords post-treatment erythema, edema, blistering,
Lasers · Hair removal · Cosmetic dermatology hypo/hyperpigmentation, scarring, and skin
Photothermolysis · Chromophores infections.
• Further standardized, well-controlled, and
long- term studies are needed to establish the
optimal treatment parameters for each laser
for each patient demographic.

V. Vejjabhinanta
Department of Dermatology, Siriraj Hospital,
Mahidol University, Bangkok, Thailand
R. Huo
K. Nouri · A. Rajabi-Estarabadi (*)
Broward Dermatology Clinic,
Department of Dermatology and Cutaneous Surgery,
Pembroke Pines, FL, USA
University of Miami Miller School of Medicine,
Miami, FL, USA R. Charoensawad
e-mail: [email protected]; Biophile Training Center, Bangkok, Thailand
[email protected]
I. Camacho
A. Singh Georgetown University, School of Medicine,
Montefiore Medical Center, Albert Einstein College Washington, DC, USA
of Medicine, Bronx, NY, USA e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 121

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_8
122 V. Vejjabhinanta et al.

Introduction with hypertrichosis or hirsutism, can be troubling

both socially and psychologically [4]. Past and
• Laser hair removal is the third most common present options for hair removal have included
nonsurgical procedure performed in the U.S. shaving, epilation, depilatories, electrolysis and
• Patients and physicians need to have realistic now most currently, lasers [5]. All methods for
expectations of results for laser hair removal. hair removal have side effects, but lasers are
The level of hair reduction may vary widely advantageous because they are fast, safe, and
amongst individuals. effective when used appropriately. With the
• Lasers are advantageous because they are fast, increased desire for and availability of laser hair
safe, and effective when used appropriately. reduction around the world, it is necessary to
• Hair removal with lasers or pulsed light are evaluate the current indications and potential side
more advantageous than previous hair removal effects of each laser.
methods such as shaving and waxing. The concept of hair removal was defined in
• The mechanism of selective photothermolysis 1998 by the US Food and Drug Administration
allows lasers to target specific cutaneous chro- (FDA), which allowed some manufacturers of
mophores while protecting the outer tissue. hair removal lasers and flash lamps used for hair
• Active cooling devices, such as cryogen removal to use the term “permanent hair reduc-
sprays and contact cooling devices help to tion.” The agency defined permanent hair reduc-
minimize injury by protecting the epidermal tion as, “The long-term, stable reduction in the
melanin, preventing adverse side effects. number of hairs regrowing after a treatment
regime. The number of hairs regrowing must be
The use of lasers for hair removal, or photo- stable over a time greater than the duration of the
epilation, is becoming an increasingly popular complete growth cycle of hair follicles, which
trend in the arena of cosmetic dermatology. varies from 4 to 12 months according to body
According to the American Society for Aesthetic location. Permanent hair reduction does not nec-
Plastic Surgery (ASAPS), 1,035,783 laser hair essarily imply the elimination of all hairs in the
removal procedures were performed in 2016 [1]. treatment area.” [6]. In addition, there needs to be
Laser hair removal is the top third most popular a distinction made between permanent and com-
nonsurgical procedure among Americans accord- plete hair loss. Complete hair loss is defined as a
ing to ASAPS’s list of the top five most popular lack of regrowing hairs, but may be either tempo-
nonsurgical procedures. There was a 37.2% rary or permanent. Permanent hair loss is defined
increase in hair removal, with laser or pulsed as a lack of regrowing hairs indefinitely. Hair
light, from 2014 to 2015 [2, 3]. Interestingly, removal with lasers usually produces complete
even though there was a 7.3% increase in total but temporary hair loss for 1–3 months. After this
nonsurgical procedures from 2015 to 2016, the time period, there is usually partial but perma-
number of laser or pulsed light hair removal pro- nent hair loss [7].
cedures decreased 8.9%. Women had more hair The theory of selective photothermolysis
removal procedures in 2016 compared to men, dictates the process of laser hair removal. By
however, hair removal still ranked top third non- varying specific parameters (wavelength, pulse
surgical procedure in both men and women. Men duration, and fluence), specific cutaneous chro-
accounted for about 12% of the total laser hair mophores may be targeted while protecting the
removal procedures that were performed. outer lying tissue [8, 9]. Applying this theory
Furthermore, individuals 35–50 years of age had to laser hair removal, the wavelength should be
the most number of laser or pulsed light hair the same as the target chromophore, the pulse
removal procedures in 2016, followed by patients duration should be less than the chromophore’s
between 19 and 34 years of age. thermal relaxation time (TRT), and the fluence
Hair removal has historically been of great must be great enough to sufficiently destroy
interest because excess hair, especially in patients the chromophore.
8  Laser for Hair Removal 123

In laser hair removal, the specific target is the density lasers and intense pulsed light treatments.
endogenous chromophore melanin. Melanin is PSF reduces post-treatment erythema and edema
found in the bulb, bulge, and hair shaft of anagen via the use of the vacuum assisted treatment that
hair. Lasers for hair removal must emit light within flattens the skin against the window. Treatment is
the absorption spectrum of melanin, 250–1200 nm, also faster, as it is not interrupted by acute pain
to be effective [10]. In addition, vascular reduction during the treatment [13]. A study demonstrated
has also been proposed as a mechanism for long- that when using high energy Nd:YAG lasers, this
term epilation [11]. One obstacle to laser hair new technology also reduced pain without side
removal is that melanin resides in the epidermis as effects on darker skinned individuals, mainly
well. This is a twofold problem because epidermal skin types IV–V [14]. In this study that used
melanin not only interferes with the laser’s treat- Nd:YAG lasers, it is explained that PSF relieves
ment capabilities by detracting some of the laser’s pain through the gate theory of pain transmis-
energy, but can also cause damage to the epider- sion; it activates the pressure skin receptors right
mis. Because pigmentation of the hair and skin before the laser is activated, blocking the pain
vary to such a great extent among patients, this is a from the laser from being transmitted to the brain.
difficult problem to resolve. All 28 patients experienced less pain, and also
Active cooling is an excellent method to mini- showed less erythema after treatment. Since hair
mize injury to the epidermis. Many lasers today removal efficacy was found to be the same with
are equipped with cooling devices such as cryo- and without PSF, this new technology could be
gen sprays or contact cooling devices. For exam- very beneficial to patients by reducing pain of
ple, the long-pulsed 694  nm ruby lasers have a laser treatments.
cooling hand piece that is applied during treat- Another way to limit thermal injury to the epi-
ment to lower the temperature of the skin and dermis, in keeping with the theory of selective
spare it from injury. This integrated cooling photothermolysis, is to use a pulse duration
device pre-cools the skin prior to laser pulse between the TRT of the epidermis (3–10 ms) and
delivery. The long-pulsed 755  nm alexandrite that of the hair follicle (10–100  ms) [5, 12].
lasers utilize a variety of cooling mechanisms. However, studies have sparked a reconsideration
These mechanisms include a cooling hand piece of the original theory suggesting a modification
that allows a continuous flow of chilled air to the whereby the target isn’t destroyed by direct heat-
treatment area, and a dynamic cooling device that ing, but by diffusion from the pigmented area
uses short (5–100  ms) cryogen spurts that is [12, 15]. This requires long pulses upwards of
delivered to the skin surface through an electroni- 100 ms known as superpulses. These superpulses
cally con- trolled valve. The 800 nm diode lasers would also damage other crucial targets, such as
use a sapphire-cooled handpiece that is placed in stem cells, which may be another factor for per-
direct contact with the skin to cool the area. The manent hair reduction [10].
1064 nm Nd:YAG lasers uses a variety of cooling The current market for laser hair reduction is
mechanisms and is based on the laser used; cur- growing so rapidly that the FDA has not main-
rently available options include a chill tip cooling tained an up-to-date listing of all approved laser
device, pulsed cryogen delivery to the skin, con- devices. Although new types of lasers are being
tact pre-cooling and air cooling. Finally, intense introduced into cosmetic dermatology, the com-
pulsed light uses a chilled handpiece that cools monly used lasers fall into one of four catego-
the skin and a transparent gel that provides opti- ries: the long-pulsed ruby laser (694  nm), the
cal coupling, as well as additional cooling [7]. In long-pulsed alexandrite laser (755 nm), the long-
addition to these methods, ice and refrigerated pulsed semiconductor diode laser (800–810 nm),
gels can also provide relief [12]. and the long-pulsed Nd:YAG laser (1064  nm).
A new technology called pneumatic skin flat- Additionally, the Intense Pulsed Light (IPL) sys-
tening (PSF) has been recently implemented to tem (500–1200  nm) is approved as a safe and
reduce pain in hair removal with high energy effective method for hair reduction (Table 8.1).
Table 8.1  Laser and intense pulsed light systems for hair removal
124

Method of hair Skin Hair Hair Type of hair Hair

Laser removal Example type color diameter removal reduction Side effects
Long-pulsed Photothermal E2000 I–III Dark to Fine Long term 38–49% Treatment pain, erythema,
light and hair
Ruby lasers destruction Epitouch Ruby Ruby Star Sinon brown coarse hair removal reduction edema, hypopigmentation,
(694 nm) hyperpigmentation, blistering, crusting,
erosions, purpura, folliculitis
Long-pulsed Photothermal Apogee I–IV Dark to Fine Long term 74–78% Treatment pain, erythema,
light and hair
alexandrite destruction Gentelase Epitouch ALEX brown coarse hair removal reduction edema, hypopigmentation,
lasers Ultrawave II/III Epicare hyperpigmentation, blistering, crusting,
(755 nm) Arion erosions, purpura, folliculitis
Pulsed diode Photothermal LightSheer I–IV Dark to Coarse Long term 70–84% Treatment pain, erythema,
light hair
laser (800 nm) destruction Apex-800 SLP1000 brown hair removal reduction edema, hypopigmentation,
MedioStar hyperpigmentation, blistering, crusting,
F1 Diode Laser erosions, purpura, folliculitis
Long pulsed Photothermal CoolGlide I–VI Dark Coarse Long term 29–53% Treatment pain, erythema,
hair
Nd:YAG lasers destruction Lyra hair removal reduction edema, hypopigmentation,
(1064 nm) Ultrawave I/II/III Athos hyperpigmentation, blistering, crusting,
Gentle Yag Varia Acclaim 7000 erosions, purpura, folliculitis
Smartepil II Dualis
Vasculight Elite Profile
Mydon
Intense pulsed Photothermal EpiLight I–VI Dark to Coarse Long term 49–90% Treatment pain, erythema,
light hair
light source destruction Quantum HR Ellipse PhotoLight brown hair removal reduction edema, hypopigmentation,
(500–1200 nm) Estelux ProLite Spatouch hyperpigmentation, blistering, crusting,
Quadra Q4 SpectraPulse erosions, purpura, folliculitis
Q-switched Photomechanical Softlight I–VI Dark to Fine Temporary 50–66% Treatment pain, erythema,
light and hair
Nd:YAG destruction MedLite C6 brown coarse hair removal reduction edema, hypopigmentation,
lasers hyperpigmentation, blistering, crusting,
erosions, purpura, folliculitis
V. Vejjabhinanta et al.
8  Laser for Hair Removal 125

Indications/Contraindications Techniques

• Unwanted hair is a very common problem • The lasers used in hair reduction include the
affecting individuals from all demographics. 694  nm ruby laser, the 755  nm alexandrite
• The ideal candidate for laser hair removal is a laser, the 800 nm diode laser, and the 1064 nm
person with fair skin and dark terminal hair. Nd:YAG laser. The intense pulsed light sys-
• Some contraindications include active cutane- tem is also used in hair removal.
ous infections, history of keloid or hypertrophic • Home-use laser hair removal devices, includ-
scar-ring, history of recurrent infections, and ing diode and IPL home-use devices, have
active vitiligo and psoriasis in targeted areas. become increasingly popular due to its
convenience.
• Some of the parameters that must be opti-
Indications mized for each patient include the wavelength,
pulse duration, cooling technique, and spot
Excess hair is an extremely common problem size of the laser.
affecting both men and women, of all ages, and • Dark skinned individuals generally have more
can have deep social and psychological impact side effects from laser hair removal.
on the patient. Some scenarios associated with • Patients must be notified at least 6 weeks prior
unwanted hair include patients with hirsutism or to treatment that they must not pluck, wax, or
hypertrichosis, procedures that involve grafted use electrolysis in the targeted areas.
donor sites, and transsexual transformations from
male to female. The patient must have a realistic
expectation of the results, as the level of reduc- Pre-operative Management
tion in hair varies from individual to individual.
The ideal candidate for laser hair reduction is a Laser Treatment Approach
person with fair skin and dark terminal hair. Obtaining an accurate patient history is very
important when interviewing a patient who is
considering laser hair removal. It is imperative
Contraindications to clarify the patient’s expectations, what med-
ications they are currently taking, their history
Patients with active cutaneous inflammation, of scarring, whether or not there is a local
infection, or active sunburn should not be treated infection in the targeted area, whether or not
until the area has resolved. A history of keloids they have tried other hair removal strategies in
and hypertrophic scarring is not an absolute the past, their endocrine status, and the amount
contraindication, but these patients should be of sun exposure they have had recently.
treated less aggressively. Patients with a history Physical examination is also crucial and should
of recurrent infections (e.g., herpes simplex and involve evaluation of the patient’s skin color,
staphylococcal) should be started on prophy- skin condition, hair color, hair diameter, and
laxis to prevent outbreaks. Patients who are on hair density.
hormonal therapy should be advised on the limi- Once a patient is determined to be a good can-
tations of hair removal treatment. Also, people didate for hair removal, certain pre-operative
with certain skin conditions such as vitiligo and counseling must be done. The patient must be
psoriasis should avoid laser hair removal in notified that at least 6  weeks prior to the laser
affected areas, as it may lead to koebnerization. treatment they must not pluck or use electrolysis
Finally, patients taking minoxidil, or who have in the areas that they would like to undergo treat-
spouses taking this medication, should be ment. They may, however, shave or use depila-
warned that hair removal may be disrupted by tory creams. It has been shown that greater hair
the stimulating effects of this drug [7]. loss occurs at shaven rather than epilated sites. In
126 V. Vejjabhinanta et al.

with moderate regrowth in patients who had

received a lower mean fluence of around 39 J/cm
[3]. While an increase in fluence may contribute
to overall efficacy, it also increases the frequency
of side effects, which may include post-treatment
erythema, crusting, blistering, hypopigmenta-
tion, hyperpigmentation, and scarring [16]. These
side effects, especially pigmentary alteration and
scarring, were much more commonly seen in
darker skin, specifically skin types IV–VI [18].
This is due to the fact that shorter wave-length
Fig. 8.1  Pretreatment of right axillary area 2 days after leads to greater absorbance of the laser by skin
shaving, only anagen hairs present melanin, which is more abundant in darker skin
types. Consequently, studies with this laser pri-
addition, the treatment area should not be exposed marily involve lighter skin patients [16]. It should
to the sun [7]. also be noted that using a ruby laser with a pulse
A few days prior to the laser treatment, the duration of 1  ms (as compared to 20  ms) has
patient should be instructed to shave or use a proven to cause greater epidermal damage in
depilatory cream on the treatment site (Fig. 8.1). patients with darker skin [19, 20].
They should also be advised to start the use of Overall, most studies performed with the
prophylactic antiviral agents, if there is a history 694  nm ruby laser have shown it to be a safe
of recurrent HSV.  On the day of treatment, the and effective method for non-permanent hair
area must be cleaned and free of make-up. A topi- reduction [16–18, 21, 22]. When comparing
cal anesthetic may be applied 1–2  h before the three treatments using the ruby laser with three
procedure [7]. treatments of waxing or electrolysis, it was
found that the laser provided a 38–49% hair
reduction while the alternatives provided no
Description of Techniques significant change [19, 21]. Increasing the num-
ber of treatments appeared to correlate with a
 ong-Pulsed 694 nm Ruby Laser
L decrease in overall hair count [19, 21–24]. Most
The ruby laser has the shortest wavelength of the of these studies have also noted better results in
lasers available for hair reduction. Emitting light patients with light skin and dark hair [16, 18,
at 694 nm, it has the best absorption by melanin 19]. These patients respond well to the laser
but the shortest penetration depth. Theoretically, and experience fewer side effects because they
this would imply that the ruby laser should be the have the ideal combination of profuse deposits
most effective at hair reduction under the right of melanin in the hair with lesser amounts in
conditions, but it also means that there is a greater the epidermis [17].
potential for epidermal injury [16]. A cooling
hand piece is concomitantly applied during treat-  ong-Pulsed 755 nm Alexandrite Laser
L
ment to lower the temperature of the skin and The long-pulsed alexandrite laser has a wave-
spare it from injury. length of 755  nm. This slightly longer wave-
Campos et al. reported very favorable results length allows a deeper penetration of the dermis
for long-term hair reduction using higher flu- with less absorption by epidermal melanin, theo-
ences of this laser system, with an average fol- retically making adverse side effects less of a
low-up time of about 8  months after the last concern for darker skin patients as compared to
treatment [17]. Study patients who had received the ruby laser. However, studies indicate that
treatment with a higher mean fluence of around blistering, hypopigmentation and hyperpigmen-
46 J/cm2 displayed sparse regrowth, as compared tation were still reported occurred in some
8  Laser for Hair Removal 127

patients with darker skin types [16, 18]. Results laser and the alexandrite laser produce light in the
have consistently shown good clearance rates for middle of the spectrum and are well absorbed by
hair reduction. follicular melanin. Eremia et al. compared results
Lloyd and Mirkov reported a 78% clearance after 1 year using the alexandrite and diode lasers
of hair 1 year following five treatments (parame- and concluded that both were excellent (85% and
ters were 10  mm spot size, 20  J, 20-ms pulse 84% respectively) for long-term hair reduction
duration, and 3 week intervals) for their patients with no statistical difference between the two
[25]. Similarly, Eremia et al. noted an average of laser systems [19, 33]. Furthermore, Bouzari
74% hair reduction in all patients following three et  al. compared the alexandrite, diode and
treatments with the laser [26]. Patients with Nd:YAG and found that the alexandrite and diode
lighter skin showed above average clearance lasers have similar efficacy [34].
whereas those with darker skin showed below The authors partially attribute the success of
average results, the latter of which may be due to their results to the use of relatively high fluences,
a lower fluence used for these patients. The which they were able to use by carefully select-
authors attribute their success partly to a larger ing patients who were untanned. Tanning
spot size which, at a given fluence, they believe increases the chance of epidermal damage and
would deliver more energy per pulse with less also lowers the laser’s effectiveness. Another
scatter and deeper penetration. Results of a study study found similar results between three treat-
by Nouri et al., supported their postulation, con- ments of either the alexandrite laser or diode
cluding that a larger spot size is more effective laser. However, in this study, the hair reduction
for laser hair reduction [27]. Three studies com- was about 37–46% for the two lasers. Patients
paring various pulse durations of 2–20 ms found from the study reported that the diode laser was
no significant differences in hair reduction [16, more painful and had greater side effects, partic-
19, 28, 29]. ularly hyperpigmentation and blistering, as com-
As with the ruby laser, there is a positive cor- pared with the alexandrite laser [19, 35].
relation between the number of treatments and A study comparing various spot sizes (8, 10,
the overall efficacy of treatment with the alexan- and 14 mm) found that after three treatments and
drite laser, in one study reaching a 55% hair at a 3 month follow-up, there was not a signifi-
reduction in patients with skin types III–V [19, cant difference in hair reduction [19, 36].
30]. Also, when comparing three treatments However, as with the ruby laser and the alexan-
using the laser with four treatments of electroly- drite laser, two treatments with the diode laser
sis, it was found that the alexandrite laser was not resulted in a greater hair reduction (35–53%)
only more effective (a 74% vs. 35% average hair than one treatment (28–33%) after an average
reduction), but also less painful [31]. 2-month follow-up. Also in this study, the diode
In a meta-analysis of hair removal laser trials, laser lead to a significant hair reduction as com-
the hair reduction for the diode, Nd:YAG, alexan- pared to shaving (13–36% vs −7%) [19, 37].
drite, and ruby lasers were 57.5%, 42.3%, 54.7%, Shifting away from the standard, a recent
and 52.8%, respectively, at least 6  months after study suggests that low-fluence (5–15  J/cm2)
the last treatment of at least three sessions. The 810 nm diode lasers has comparable hair reduc-
authors concluded that the diode laser is superior tion and less discomfort than high-fluence diode
for lighter skin, while the alexandrite laser is the lasers in phototype V skin type and tan patients
best choice for darker skin types [32]. [38]. The study results showed that using a low-
fluence diode laser and high repetition rate was
 00 nm Diode Laser
8 safe and effective. Another study agrees with
The 800  nm diode laser is comparable to the these results, stating that a 810  nm diode laser
755 nm alexandrite, and has become more popu- with 10 Hz at low-fluence has a high patient sat-
lar along with the Nd:YAG laser for treating isfaction and efficacy. Data was collected from
patients with darker skin types. Both the diode 368 body areas epilated in patients with skin
128 V. Vejjabhinanta et al.

types III–V after five treatments in a 6-month fol- longer wavelengths such as the diode and
low up [39]. When combining treatment plans, it Nd:YAG laser have fewer potential negative
was not found to be more beneficial to treat effects than lasers with shorter wavelengths [43].
patients with skin types I to IV with the diode While the Nd:YAG laser may be the safest
followed by the alexandrite laser, as it did not method to treat all skin types, it is not necessarily
produce greater hair reduction than the same the most effective. Bouzari et al. compared hair
number of treatments using only the alexandrite reduction by the long-pulsed Nd:YAG, alexan-
laser. Using the diode followed by the alexandrite drite, and diode lasers and found that after
laser actually showed an increase in folliculitis 3 months, the Nd:YAG was the least effective of
and blistering in patients [40]. the three [36]. An interesting aspect of their study
was that the best results were seen in five patients
 064 nm Nd:YAG Laser
1 who underwent combination laser therapy that
The 1064  nm Nd:YAG has the longest wave- included treatment with all three systems. They
length and deepest penetration amongst the hypothesize that using a variety of wavelengths,
aforementioned laser systems available. It is not they are able to damage hairs at different ranges
very well absorbed by melanin, but is sufficient in the skin; longer wavelengths would damage
in achieving selective photothermolysis and has the deeper hairs and the shorter wavelengths
superior penetration [41]. The Nd:YAG is able to would damage the more superficial hairs. This is
penetrate the skin 5–7 mm, a depth at which most analogous to laser tattoo removal, which incorpo-
of the target structures lay. Furthermore, the com- rates a combination of lasers to remove the mul-
bination of a low melanin absorption and deep titude of pigments found in a given tattoo.
penetration leads to less collateral damage to the A study determining the safety and efficacy of
melanin-containing epidermis (Fig.  8.2a, b). the long-pulsed Nd:YAG laser for all skin types
These characteristics make this system the safest found that the treatments were more successful
choice for tanned or darker skinned patients [10, (46–53% depending on location) in darker skin
41]. Long pulsed Nd:YAG has been shown to be patients (types V–VI). At 6 months, patients with
a safe and effective tool for hair reduction in skin skin types I–II obtained a 41–43% hair reduction,
types IV and V, with long term hair reduction depending on location, while patients with skin
after multiple sessions. Because skin types IV types III–IV obtained a 44–48% hair reduction
and V have higher probability of post inflamma- [44]. Another study comparing fluence levels
tory hyperpigmentation, adequate cooling is nec- found similar hair reductions for fluences of 50,
essary, hence the use of Nd:YAG laser with 80, and 100 J/cm2 (29%, 29%, and 27% respec-
sapphire tip cooling [42]. In general, lasers with tively) in patients with skin types II–IV [45].

a b

Fig. 8.2 (a) Pretreatment of right axillary area with coarse hair. (b) Only fine hair exist after 3 months and five treat-
ments with 1064 Nd:YAG laser
8  Laser for Hair Removal 129

I ntense Pulsed Light greater selective energy absorption [7]. Today,

The Intense Pulsed Light (IPL) system is not IPL is being used to cosmetically treat vascu-
technically a laser, but has recently entered the lar and pigmented lesions in addition to
hair removal arena as a competent contender. removing unwanted hair [46].
In fact, it has been used for virtually all of the Results using this system have been compara-
same indications as laser systems (Fig.  8.3a, ble to the more conventional lasers mentioned
b). Unlike lasers which emit monochromatic (Fig.  8.4a, b). Similarly to lasers, dark-haired
light, IPL systems have flash lamps which patients responded better to IPL treatment than
produce non-coherent light beams in the 500– did blonde or gray-haired patients, who also
1200  nm spectrum [43]. IPL systems work required more treatment sessions [47]. IPL is not
very similarly to lasers and rely on the princi- capable of achieving permanent hair removal, but
ple of selective photothermolysis. The IPL long-term hair reduction with few side effects is
systems generally use millisecond pulse dura- possible [48].
tion that is lower than the thermal relaxation A randomized controlled trial on hirsute
times of the targeted chromophores. IPL sys- women, with normalized testosterone levels,
tems uses polychromatic light, which irradi- reported that IPL and long-pulse diode laser both
ates multiple chromophores with both major obtained similar hair removal efficacies, with IPL
and minor absorption peaks, allowing for having a 77% to 40% hair reduction and the long

a b

Fig. 8.3 (a) Pretreatment of perioral area. (b) Immediately after treatment with IPL system, with perifollicular ery-
thema and edema, as well as burning of hair shaft

a b

Fig. 8.4 (a) Pretreatment of right axillary area. (b) Three months after three treatments with IPL system patient has fine
hair and delaying of hair growth
130 V. Vejjabhinanta et al.

pulse diode laser having 68% to 34% hair reduc- Home-Use Devices
tion. Although the efficacy declined in both treat- Home-use devices have recently become very
ments after 6  months, it was still reduced from popular due to their low cost and convenience.
baseline. Patient satisfaction scores were similar Home-use devices use a lower fluence than stan-
at the 6-month follow up [49]. dard 10–60  J/cm2 used in professional offices
In a prospective randomized intrapatient com- [54]. As a result, there have been questions on
parison between Nd:YAG laser and IPL system, whether they only produce temporary growth
it was concluded that in skin phototype II–III delay for several months rather than permanent
individuals, IPL is a better choice than long follicle destruction. Hession et  al. described a
pulsed 1064  nm Nd:YAG laser [50]. IPL had a few of the FDA-approved home-use hair removal
statistically lower pain score and number of side devices including diode lasers of 810 nm wave-
effects, leading to a higher patient satisfaction length with high, medium, and low fluence set-
score. In contrast, Nd:YAG-treated patients sta- tings (7, 12, 20  J/cm2) as well as a diode with
tistically showed higher side effects including 808 nm wavelength that could treat up to 60 and
erythema, edema, and burning. With each 20 hairs per pulse with a fluence below 5 J/cm2.
Nd:YAG-treatment, there was significant hair IPL home-use devices include treatment with
reduction compared to IPL, which only showed 475–1200 nm wavelength, delivering up to 5 J/
significant hair reduction after the third treat- cm2. Other available IPL devices emit similar
ment. Eight months after the last treatment, both wavelengths of 400–1200  nm or 530–1100  nm
Nd:YAG and IPL treatments showed significant with a fluence up to 10  J/cm2 or up to 7–10  J/
hair reduction. Because IPL is shown to treat cm2, respectively. Professional hair removal sys-
larger areas at the same time with a lower cost, tems can vary widely in wavelengths; however,
IPL is beneficial. However, another study con- the home-use hair removal systems are more
cluded that in darker skinned individuals, the limited. For instance, the diode lasers have 800–
long-pulse 1064  nm Nd:YAG laser had higher 810  nm wavelength, and the IPL home-use
levels of satisfaction and increased hair reduction devices have a wavelength range mostly from
than IPL treatment [51]. 475 to 1200 nm.
A non-randomized controlled trial which The home- use diode laser, (Tria Beauty, Inc.,
compared three treatments of IPL with three Dublin CA), was found to be safe and effective
treatments using a ruby laser found that in skin for hair reduction in individuals with Fitzpatrick
types II–IV, 94% of patients obtained an average skin type I–IV after 8 monthly treatments [55].
49% hair reduction using the IPL system at Although the study sample size was 13 individu-
6-month follow-up, as compared with only 55% als, 546 active sites and 182 controlled sites were
of patients obtaining an average of 21% hair analyzed. Low, medium, and high fluence (7, 12,
reduction with the ruby laser [19, 52]. In a split- 20  J/cm2) treatments demonstrated 47%, 55%,
face comparison of facial hair removal with the and 73% mean hair count reduction 1  month
IPL system and long pulsed alexandrite laser, 30 after the eighth treatment. At 12  months post
patients received six treatment sessions and data treatment, count hair reduction remained stable
was assessed at 1, 3, and 6 sessions. In compari- at 44%, 49%, and 65% for low, medium, and
son with the alexandrite laser, the IPL system high fluences respectively. The only observed
showed longer median hair-free intervals, larger side effects were mild transient erythema and
hair count reduction at the three sessions that data edema, more often seen in the higher fluence
was recorded, and a higher patient satisfaction sites. In another previous study, Wheeland con-
[53]. However, in a previous retrospective review firmed that the 810 nm portable diode laser was
of long- and short-pulsed alexandrite lasers and very effective at removing hair with a 33% mean
IPL, individuals needed a higher number of hair reduction 12  months after the third treat-
­treatments with the IPL device for the same ben- ment in 77 patients [56]. In addition, a random-
efit [48]. ized controlled trial with 32 women with skin
8  Laser for Hair Removal 131

phototypes I–IV treated with an 810 nm home- nea injury, many home-use devices will have
use laser at 5.0–6.4 J/cm2 had a stable hair count built in filters that do not enable them to emir
reduction and thickness during treatment [57]. wavelengths below 450 nm [61].
After three treatments, hair reduction increased Similar to standard professional laser devices,
to 38%, and with sustained usage reached a pla- darker skinned individuals need to be very care-
teau up to 59% hair reduction. However, hair ful with home-use devices, because their greater
growth gradually returned to baseline 3 months epidermal melanin content may increase their
after the final treatment, regrowing beyond base- risk for thermal burns. Some new models of
line levels by 29% after treatment cessation. home-use IPL devices actually have a skin color
An FDA-approved home-use IPL device for sensor, preventing the treatment of skin types V–
hair removal, commercially known as IPL (Silk’n VI [43]. Since many studies of home- use devices
device, home Skinovations, Kfar Saba, Israel), include skin types I–IV, more studies need to be
uses a wavelength ranging from 475 to 1200 nm done with individuals of skin types V–VI in order
and low fluences up to 5 J/cm2. A recent clinical to better assess the risks of home-use laser hair
trial including 15 patients that received six removal devices.
biweekly treatments with the home-pulsed light Overall, home-use devices within the scope of
device, concluded that this device is effective for hair removal continues to evolve and the increas-
facial hair removal in skin types I–IV, indicating ing popularity of home-use laser hair removal
a 78.1% mean percent hair count reduction at the devices due to their low cost, speed, and conve-
3 month follow up with no adverse effects [58]. nience is important to consider in cosmetic der-
Another study concluded that a novel low-energy matology. In the future, optimizing their safety
pulsed light device can effectively remove and efficacy will probably have longer-lasting
unwanted non-facial dark terminal hair in indi- treatment results while minimizing untoward
viduals with skin type I–IV [59]. In 20 women, side effects.
after three treatments at 2-week intervals using
the handheld IPL device, hair counts reduced
37.8% to 53.6% 6  months after the three treat- Radiofrequency Combinations
ments. Only 25% of the patients experienced
mild erythema, with no other side effects. Radiofrequency devices have been combined
with both IPL and diode lasers to provide optimal
Side Effects hair removal treatments to a wider range of skin
It is vital to provide education to patients on these types. The combinations are considered safe for
home-use devices in order to prevent injury. patients with darker skin types because the radio-
Since home-use devices have brought safety con- frequency energy is not absorbed by melanin in
cerns, devices need to be easy to use and have the epidermis. This technology, termed electro-
safety mechanisms built in. Because a potential optical synergy, or ELOS, has a dual mechanism
complication may be ocular damage due to the of heating the hair follicle with electrical energy
laser or IPL emission, several home-use laser and (namely radiofrequency) and heating the hair
IPL packaging will provide protective eyewear shaft with optical energy.
although it is not guaranteed that consumers will A new evolution in photoepilation involves
use them [60]. Other safety mechanisms to removing nonpigmented hairs such as “peach
reduce the risk of ocular exposure include skin fuzz” which the previous lasers fail to remove. A
contact sensors that do not allow the activation of combination of radiofrequency (RF) and lasers
the laser unless in contact with the skin. It is nec- have been used for white or blonde hair, but with
essary to take precautionary measures to avoid low efficacy. Studies have shown that the com-
injury to retina and iris that may cause blind spots bined use of RF and optical energy has been found
or glaucoma. Since wavelengths above 750  nm to be successful, though various mechanisms have
and below 400 nm can cause lens cataract or cor- been proposed to explain the success [62–65].
132 V. Vejjabhinanta et al.

Some claims of widespread safety have been needed. Mild topical steroid creams may be given
made because RF energy is not readily absorbed to the patient to decrease post-treatment ery-
by the melanin abundantly found in the epidermis thema and edema. If any epidermal injury occurs
of darker skin types, theoretically sparing it from during the procedure, a topical anti-biotic can be
damage. However, a low efficacy of this new tech- given to the patient. The patient should be noti-
nology has been reported so far. Results have indi- fied that they must use sun block and avoid direct
cated that the majority of subjects achieved less sun exposure [7].
than 50% hair reduction after 3  months [63]. In
two other studies, average clearances of 48% [64] Adverse Events
and 75% [65] were seen at 18-months follow-up. • Some of the reported adverse events have
Because this is a relatively new technology, more included post-treatment erythema, edema,
studies are clearly necessary to provide more reli- crusting, blistering, paradoxical hair growth,
able results for those with nonpigmented hair or hypo/hyperpigmentation, scarring, and skin
with darker skin types. infections.
• Methods to decrease the risk of adverse events
include effective epidermal cooling, long
 ther Removal Methods
O pulse duration, longer wavelength lasers, ice
for Nonpigmented Hair packs, analgesics, steroid creams, topical anti-
biotics, and avoidance of sun exposure
Meladine, a topical melanin chromophore, has
been studied in Europe with interesting results. Side Effects/Complications
The liposome solution dye, which is sprayed on, Patients should be warned before the laser pro-
is selectively absorbed by the hair follicle and not cedure that they might experience some discom-
the skin. This gives the follicles a temporary fort during and after the procedure. Reported
boost of melanin to optimize laser hair removal adverse events have included post-treatment
treatments. Clinical studies in Europe have shown erythema, edema, crusting, blistering, hypopig-
vast permanent hair reduction in patients who mentation, hyperpigmentation, and scarring
used Meladine prior to treatment. However, other (Fig. 8.5a, b). Other complications include her-
studies have found Meladine to only offer a delay pes simplex outbreaks in patients with a previ-
of hair growth as opposed to permanent hair ous history of outbreaks, folliculitis in patients
reduction [7]. Sand et  al. used a similar topical who sweat excessively or swim, transient and
liposomal melanin compound in a randomized, permanent pigmentary changes, temporary or
controlled, double-blind study with blond and permanent leucotrichia, loss of freckles or light-
white hair patients, and found that the substance ening of tattoos, livedo reticularis, intense pruri-
made almost no difference in treatment outcomes tus, and urticaria [7].
for the patients [66]. In some cases, laser treatment has actually
Photodynamic therapy may be an effective been reported to induce hair growth, particu-
option for those with nonpigmented or light-col- larly on the face and neck. For example, in one
ored hair. Because of the lack or diminished amount study, this was noted in young females of
of a natural chromophore in the hair follicle, a topi- Mediterranean and Middle Eastern descent and
cal photosensitizer 5-aminolevulinic acid (5-ALA) with darker skin types (III or IV) [67]. The
is used. Light exposure activates 5-ALA, which induction of hair growth occurred regardless of
subsequently creates reactive oxygen and allows the fluency or type of laser used for both
for destruction of the hair follicle [7]. intense pulsed light and long-pulsed alexan-
drite laser. Because neo-genesis of hair folli-
Post-operative Management cles after birth does not occur, it is likely that
Post-operatively, ice packs can be used to reduce the mechanism behind laser-induced hair
pain and minimize edema. Analgesics are rarely growth is that local vellus hair follicles trans-
8  Laser for Hair Removal 133

a b

Fig. 8.5 (a) Blister formation, a complication of IPL treatment 3 days after treatment. (b) Residual hyperpigmentation
is still noticed 9 months after blister formation

form into terminal pigmented hair follicles Future Directions

[67]. Another theory is that the laser induces
synchronization of hair growth cycles by direct • The FDA has approved lasers for permanent
light stimulation [68]. hair reduction.
• Strong data from standardized, well-con-
 revention and Treatment of Side
P trolled, long-term studies are needed to estab-
Effects/Complications lish the optimal treatment parameters for each
Dark-skinned patients are more prone to the laser.
adverse effects aforementioned. Several factors
may assist in minimizing these side effects. Currently, the FDA has not approved lasers to
Effective epidermal cooling can reduce epider- be marketed as a permanent hair removal option,
mal damage from the laser treatment. A long although manufacturers have been allowed to
pulse duration allows the hair follicle to be claim permanent hair reduction based on safety
heated effectively while the effect of epidermal and efficacy. Permanent hair reduction involves
cooling is at its peak. In addition, longer wave- the stable reduction in the total amount of hair in a
length lasers are associated with a lower degree given area over the long-term. To achieve the title
of epidermal damage. Ice packs, analgesics, and of permanent hair removal, future studies should
mild topical steroid creams can be used post- be concerned with the long-term efficacy of these
operatively to reduce pain and minimize ery- lasers. In general, the ruby laser can be used for
thema and edema. In cases of epidermal injury, a skin types I and II, although the alexandrite laser
topical antibiotic can be given to the patient. The and the diode laser are generally safer with less
patient should be advised to avoid sun exposure side effects for skin types III–IV.  The Nd:YAG
after the procedure. laser is ideal for tanned skin and skin types IV, V
In a prospective, randomized, placebo-con- and VI, but has a lower efficacy in lighter skin
trolled study, Akinturk et al. showed that piroxi- types. Current studies are beginning to investigate
cam gel provided adequate pain relief and lowered the safety and efficacy of specific and newer lasers
inflammation after Nd:YAG laser hair removal in for various skin types. This is important because as
patients as compared to placebo control [69]. the popularity of photoepilation continues to grow,
so will the population of patients interested in this
134 V. Vejjabhinanta et al.

procedure. The challenge ahead lies in gathering 8. Anderson RR, Parrish JA. Selective photothermolysis:
strong data from standardized, long- term studies precise microsurgery by selective absorption of pulsed
radiation. Science. 1983;220:524–7.
so that optimal parameters can be established. It 9. Dierickx C, Alora MB, Dover JS.  A clinical over-
must be noted that current trends in laser treatment view of hair removal using lasers and light sources.
choice and research have moved away from ruby Dermatol Clin. 1999;17:357–66.
lasers and to the longer wavelength systems such 10. Battle EF, Hobbs LM. Laser-assisted hair removal for
darker skin types. Dermatol Ther. 2004;17:177–83.
as the Alexandrite, diode and Nd:YAG lasers, 11. Adrian RM.  Vascular mechanisms in laser hair

which allow for deeper penetration to the level of removal. J Cutan Laser Ther. 2000;2(1):49–50.
hair bulbs [70]. 12. Tanzi EL, Lupton JR, Alster TS. Lasers in dermatol-
ogy: four decades of progress. J Am Acad Dermatol.
2003;49:1–31.
Conclusion 13. Lask G, Friedman D, Elman M, Fournier N, Shavit R,
Excess hair is an extremely common condi- Slatkine M. Pneumatic skin flattening (PSF): a novel
tion affecting both men and women of all technology for marked pain reduction in hair removal
ages. Many of the previous options for people with high energy density lasers and IPLs. J Cosmet
Laser Ther. 2006;8(2):76–81.
seeking to remove or lessen the presence of 14. Fournier N.  Hair removal on dark-skinned patients
hair have been painful or have only resulted in with pneumatic skin flattening (PSF) and a high-
short-term effects. With the advent of laser energy Nd:YAG laser. J Cosmet Laser Ther.
technology, the new generation nonablative 2008;10(4):210–2.
15. Rogachefsky AS, Silapunt S, Goldberg DJ. Evaluation
lasers and light systems have become some of of a new super-long-pulsed 810  nm diode laser for
the most popular procedures in all of cosmetic the removal of unwanted hair: the concept of thermal
dermatology. Although lasers are not yet a damage time. Dermatol Surg. 2002;28:410–4.
permanent solution for hair removal, they are 16. Nanni CA, Alster TS.  Laser-assisted hair removal:
side effects of Q-switched Nd:YAG, long-pulsed
able to provide a safe, fast, and effective ruby, and alexandrite lasers. J Am Acad Dermatol.
method for hair reduction. 1999;41:165–71.
17. Campos VB, Dierickx CC, Farinelli WA, Lin TY,
Manuskiatti W, Anderson RR.  Ruby laser hair
removal: evaluation of long-term efficacy and side
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 Lasers for Resurfacing
9
Rungsima Wanitphakdeedecha and Tina S. Alster

Abstract ciated with several weeks of postoperative

Many signs of cutaneous photodamage are recovery
amenable to treatment with a variety of abla- • Severe side effects and complications after abla-
tive and non-ablative lasers, light sources, and tive laser skin resurfacing can be minimized by
fractional photothermolysis. Ablative laser careful patient selection, proper surgical tech-
skin resurfacing offers the most substantial nique, and meticulous postoperative care
clinical improvement, but is associated with • Non-ablative laser skin remodeling is a good
several weeks of postoperative recovery. alternative for patients who desire modest
improvement of photodamaged skin without
Keywords significant post-treatment recovery
Lasers · Resurfacing · Ablative lasers · Non- • The noninvasive nature of fractional photo-
ablative lasers · Fractional lasers thermolysis treatment, coupled with an excel-
lent side effect profile, makes it an attractive
alternative to ablative laser techniques.
• Good candidates for non-ablative laser and light-
Outline source treatments are patients with cutaneous
• Many signs of cutaneous photodamage are photodamage and realistic clinical expectations
amenable to treatment with a variety of abla- • With ongoing advancements in laser technol-
tive and non-ablative lasers, light sources, and ogy and techniques, improved clinical
fractional photothermolysis. ­outcomes with minimal postoperative recovery
• Ablative laser skin resurfacing offers the most will be realized
substantial clinical improvement, but is asso-

Introduction
R. Wanitphakdeedecha (*)
Department of Dermatology, Faculty of Medicine
Siriraj Hospital, Mahidol University, Summary Box
Bangkok, Thailand • A wide variety of lasers and light-based
e-mail: [email protected]
sources is available to treat cutaneous
T. S. Alster photodamage including ablative and
Georgetown University Medical Center, Washington
Institute of Dermatologic Laser Surgery, non-ablative lasers, light sources, and
Washington, DC, USA fractional photothermolysis
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 137

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_9
138 R. Wanitphakdeedecha and T. S. Alster

Years of damaging ultraviolet (UV) light expo- tissue chromophore. Furthermore, the pulse
sure manifests clinically as a sallow complexion duration of laser emission must be shorter than
with roughened surface texture and variable the thermal relaxation time of the target–ther-
degrees of dyspigmentation, telangiectasias, mal relaxation time (TR) being defined as the
wrinkling, and skin laxity [1, 2]. Histologically, amount of time necessary for the targeted
these extrinsic aging effects are usually limited structure to cool to one-half of its peak tem-
to the epidermis and upper papillary dermis and perature immediately after laser irradiation.
are therefore amenable to treatment with a vari- The delivered fluence (energy density) must
ety of ablative and non-ablative lasers and light- also be sufficiently high to cause the desired
sources [3]. degree of thermal injury to the skin. Thus, the
laser wavelength, pulse duration, and fluence
each must be carefully chosen to achieve maxi-
History of Procedures mal target ablation while minimizing surround-
ing tissue damage.
The first system specifically developed for
Summary Box
cutaneous laser resurfacing was the pulsed car-
• Selective photothermolysis theory of bon dioxide (CO2) laser, which was approved by
laser-tissue interaction is used to create the Food and Drug Administration (FDA) in
thermal destruction of target tissue with- 1996. Earlier CO2 systems were continuous-wave
out unwanted conduction of heat to sur- (CW) lasers which were effective for gross
rounding structures by selecting the lesional destruction [5, 6], but were unable to
appropriate laser wavelength and pulse reliably ablate fine layers of tissue because of
duration. excessive tissue heating which produced unac-
• The first system specifically developed ceptably high rates of scarring and pigmentary
for cutaneous laser resurfacing was the alteration [7–9]. The unpredictable nature of the
pulsed carbon dioxide (CO2) laser. CW lasers prevented their widespread use in
• The short-pulsed erbium:yttrium–alu- facial resurfacing procedures. With the subse-
minum–garnet (Er:YAG) laser was sub- quent development of high-energy, pulsed lasers
sequently used as an alternative to the it became possible to safely apply higher energy
CO2 laser to minimize the recovery densities with exposure times that were shorter
period and limit side effects while main- than the thermal relaxation time of water-­
taining clinical benefit. containing tissue, thus lowering the risk of ther-
mal injury to surrounding non-targeted structures
[3, 10].
Although dermatologic laser surgery is nearly The short-pulsed erbium:yttrium–aluminum–
five decades old, the field was revolutionized in garnet (Er:YAG) laser was subsequently FDA-­
1983 when Anderson and Parrish elucidated approved for cutaneous resurfacing as an
the principles of selective photothermolysis alternative to the CO2 laser in an attempt to mini-
[4]. This basic theory of laser-tissue interaction mize the recovery period and limit side effects
explains how selective tissue destruction is while maintaining clinical benefit.
possible. In order to effect precise thermal In response to growing public interest in
destruction of target tissue without unwanted minimally-­ invasive treatment modalities, non-­
conduction of heat to surrounding structures, ablative laser and light source technology was
the proper laser wavelength must be selected later developed. Rapid advances in non-ablative
for preferential absorption by the intended technology have produced several lasers and
9  Lasers for Resurfacing 139

Table 9.1  Lasers and light sources for skin resurfacing

Laser type Wavelength (nm) –– Active bacterial, viral, fungal infec-
Ablative CO2 (pulsed) 10,600 tion or inflammatory skin conditions
Er:YAG (pulsed) 2940 involving the skin areas to be treated
Non-­ Pulsed dye 585–595 –– Patients with prior lower blepharo-
ablative Nd:YAG, Q-switched 1064
plasties using an external approach
Nd:YAG, long-pulsed 1320
Diode, long-pulsed 1450 are at greater risk of ectropion forma-
Er:glass, long-pulsed 1540 tion after infraorbital ablative laser
Intense pulsed light 515–1200 treatment
source
–– Patients with darker skin tones
Fractional Er-doped fiber 1550
(skin phototype IV–VI) have a
Er erbium, Nd neodymium, Q-switched quality-switched,
YAG yttrium-aluminum-garnet
high incidence of postoperative
hyperpigmentation
–– Concomitant isotretinoin use could
light-based sources capable of improving fine potentially lead to an increased risk
facial rhytides, dyspigmentation, and telangiec- of hypertrophic scarring
tasia associated with cutaneous photodamage. –– Patients with a propensity to scar will
The armamentarium of lasers and light-based be at greater risk for postoperative
sources currently available to treat cutaneous scarring
photodamage is larger than ever before
(Table  9.1). The most appropriate technique
depends upon the severity of photodamage and The ideal patient for ablative laser skin resur-
rhytides, the expertise of the laser surgeon, and facing has a fair complexion (skin phototype I
the expectations and lifestyle of the individual or II), exhibits cutaneous lesions that are ame-
patient. nable to treatment, and has realistic expecta-
tions of the resurfacing procedure. Adequate
preoperative patient evaluation and education
are absolute essentials to avoid pitfalls and
Ablative Laser Skin Resurfacing optimize the clinical outcome (Table  9.2).
Proper patient selection is paramount as abla-
Indications and Contraindications
tive laser resurfacing can be complicated by a
prolonged postoperative r­ecovery, pigmentary
Summary Box alteration, or unexpected scarring. The patient’s
• Indications emotional ability to tolerate an extended con-
–– Mild-to-moderate rhytides, preferably valescence is an important factor in determin-
in non-movement-associated areas ing the most appropriate choice of laser.
–– Other signs of photodamage (e.g., Although CO2 and modulated Er:YAG lasers
dyspigmentation and keratoses) often produce the most dramatic clinical
–– Shallow atrophic scars results, some patients may be unable to tolerate
–– Superficial skin lesions the intensive recovery period. For patients
• Contraindications unable or unwilling to withstand extended
–– Patients with unrealistic postoperative healing, a short-pulsed Er:YAG
expectations laser or application of a non-ablative or frac-
–– Patients with perpetual sun exposure tional laser procedure may be a more suitable
choice.
140 R. Wanitphakdeedecha and T. S. Alster

Table 9.2  Ablative laser resurfacing: patient selection, risks, and precautions
Preoperative patient evaluation
• Are the lesions amenable to ablative laser skin resurfacing? All suspicious lesions require biopsy before
treatment.
• Has the patient ever had the areas treated before? Ablative laser resurfacing can unmask hypopigmentation or
fibrosis produced by prior dermabrasion, cryosurgery, or phenol peels. Patients with prior lower blepharoplasties
using an external approach are at greater risk of ectropion formation after infraorbital ablative laser treatment.
• What is the patient’s skin phototype? Patients with paler skin tones (skin phototype I or II) have a lower
incidence of postoperative hyperpigmentation than do patients with darker skin tones.
• Does the patient have a history of herpes labialis? All patients should be treated with prophylactic antiviral
medication before perioral treatment, because reactivation and/or dissemination of prior herpes simplex
infection can occur. The de-epithelialized skin is also particularly susceptible to primary inoculation by herpes
simplex virus.
• Does the patient have an autoimmune disease or other immunologic deficiency? Intact immunologic function
and collagen repair mechanisms are necessary to optimize the tissue-­healing response due to the prolonged
recovery associated with ablative resurfacing.
• Is the patient taking any medications that are contraindicated? Concomitant isotretinoin use could potentially
lead to an increased risk of postoperative hypertrophic scar formation due to its detrimental effect on wound
healing and collagenesis. A safe interval between the use of oral retinoids and ablative laser skin resurfacing is
difficult to determine; however, most advocate a delay in treatment for at least 6 months after discontinuation of
the drug.
• Does the patient have a tendency to form hypertrophic scars or keloids? Patients with a propensity to scar will
be at greater risk of scar formation after treatment, independent of the laser’s selectivity and the operator’s
expertise.
• Does the patient have realistic expectations of the procedure and adhere to postoperative instructions? Patients
who can not physically or emotionally handle the prolonged postoperative course should be dissuaded from
pursuing ablative laser skin treatment.

Techniques ablative laser-induced wounds are intrinsically

different from those created by physically
Preoperative Management destructive methods, laser skin penetration is not
typically affected by the topical application of
any of these medications. In addition, being that
Summary Box postinflammatory hyperpigmentation is rela-
• Adequate preoperative patient evalua- tively common after ablative cutaneous laser
tion and education resurfacing, many laser surgeons originally
• Oral antibiotic prophylaxis as indicated believed that the prophylactic use of topical
bleaching agents would reduce the incidence of
this side effect, but investigators subsequently
There is no consensus among laser experts demonstrated that the preoperative use of topical
regarding the most appropriate preoperative regi- tretinoin, hydroquinone, or glycolic acid had no
men for ablative laser skin resurfacing. The use effect on the incidence of postablative laser
of topical retinoic acid compounds, hydroqui- hyperpigmentation [13].
none bleaching agents, or α-hydroxy acids for Due to the moist, de-epithelialized state of
several weeks before laser treatment has been ablative laser-resurfaced skin and the possibility
touted as a means of speeding recovery and of bacterial contamination and overgrowth, many
decreasing the incidence of postinflammatory laser surgeons advocate oral antibiotic prophy-
hyperpigmentation [11]. Topical tretinoin laxis; however, this practice remains controver-
enhances penetration of chemicals through the sial due to the results of a controlled study that
skin and has been shown to accelerate postopera- demonstrated no significant change in post-laser
tive re-epithelialization after dermabrasion or resurfacing infection rate in patients treated with
deep chemical peels [12]. However, because prophylactic antibiotics [14]. The most common
9  Lasers for Resurfacing 141

infectious complication is a reactivation of labial complete tissue vaporization [7, 17–19]. Studies
herpes simplex virus (HSV), most likely caused with these and other pulsed or scanned CO2 laser
by the thermal tissue injury and epidermal dis- systems showed that after a typical skin resurfac-
ruption produced by the laser [15, 16]. Any ing procedure, water-containing tissue was vapor-
patient undergoing full-face or perioral ablative ized to a depth of approximately 20–60  μm,
resurfacing should receive antiviral prophylaxis producing a zone of thermal damage ranging
even when a history of HSV is denied. It is 20–150 μm [7, 18, 20–22].
impossible to predict who will develop HSV The depth of ablation correlates directly with
reactivation, because a negative cold sore history the number of passes performed and usually is
is an unreliable method to determine risk and confined to the epidermis and upper papillary
many patients do not remember having had an dermis; however, stacking of laser pulses by
outbreak or are asymptomatic HSV carriers. Oral treating an area with multiple passes in rapid suc-
antiviral agents, such as acyclovir, famciclovir, cession or by using a high overlap setting on a
and valacyclovir are effective agents against HSV scanning device can lead to excessive thermal
infection, although severe (disseminated) cases injury with subsequent increased risk of scarring
may require intravenous therapy. Patients should [15, 23, 24]. An ablative plateau is reached with
begin prophylaxis by the day of surgery and con- less effective tissue ablation and accumulation of
tinue for 7–10 days postoperatively. thermal injury. This effect is most likely caused
by reduced tissue water content after initial desic-
cation, resulting in less selective absorption of
Description of the Technique energy [24]. The avoidance of pulse stacking and
incomplete removal of partially desiccated tissue
Carbon Dioxide (CO2) Laser is paramount to prevention of excessive thermal
accumulation with any laser system.
The objective of ablative laser skin resurfac-
Summary Box
ing is to vaporize tissue to the papillary dermis.
• Areas with thinner skin (e.g., perior-
Limiting the depth of penetration decreases the
bital) require fewer laser passes
risk for scarring and permanent pigmentary
• Non-facial (e.g., neck, chest) areas
alteration. When choosing treatment parame-
should be avoided due to paucity of
ters, the surgeon must consider factors such as
pilosebaceous units with diminished
the anatomic location to be resurfaced, the skin
capacity for re-epithelialization.
phototype of the patient, and previous treat-
• Avoidance of pulse stacking in order to
ments delivered to the area [17, 25]. In general,
decrease risk of scarring
areas with thinner skin (e.g., periorbital) require
fewer laser passes and non-facial (e.g., neck,
chest) laser resurfacing should be avoided due
The Ultrapulse (Lumenis Corp, Yokeam, Israel), to the relative paucity of pilosebaceous units in
one of the first high-energy, pulsed CO2 laser sys- these areas [25]. To reduce the risk of excessive
tems developed, emits individual high energy thermal injury, partially desiccated tissue
pulses (peak energy densities of 500 mJ in 600 μs should be removed manually with wet gauze
to 1  ms). Its earliest competitor, the SilkTouch after each laser pass to expose the underlying
(Lumenis Corp, Yokeam, Israel), was a continuous-­ dermis [24].
wave CO2 system with a microprocessor scanner The clinical and histologic benefits of cutane-
that continuously moved the laser beam so that ous laser resurfacing are numerous. With the CO2
light did not dwell on any one area for more than laser, most studies have shown at least a 50%
1  ms. The peak fluences delivered per pulse or improvement over baseline in overall skin tone
scan ranged from 4 to 5  J/cm2, which were the and wrinkle severity (Fig.  9.1a, b) [10, 26–30].
energy densities determined to be necessary for The biggest advantages associated with CO2 laser
142 R. Wanitphakdeedecha and T. S. Alster

a b

Fig. 9.1 CO2 laser resurfacing (a) before and (b) after

skin resurfacing are the excellent tissue contrac- that migrate into laser wounds after resurfacing
tion, hemostasis, prolonged neocollagenesis and may up-regulate the expression of immune
collagen remodeling that it provides. Histologic modulating factors that serve to enhance con-
examination of laser-treated skin demonstrates tinued collagen shrinkage [37].
replacement of epidermal cellular atypia and The CO2 resurfacing laser is a most effective
dyplasia with normal, healthy epidermal cells tool for improving photo-induced facial rhytides;
from adjacent follicular adnexal structures [7, however, dynamic rhytides are not as amenable
21]. The most profound effects occur in the papil- to laser treatment. Many patients experience
lary dermis, where coagulation of disorganized recurrence of movement-associated rhytides
masses of actinically-induced elastotic material (particularly in the glabellar region) within
are replaced with normal compact collagen bun- 6–12  months postoperatively. Thus, cosmetic
dles arranged in parallel to the skin’s surface [31, denervation with intramuscular injections of bot-
32]. Immediately after CO2 laser treatment, a ulinum toxin type A is often used concomitantly
normal inflammatory response is initiated, with with laser resurfacing to provide prolonged clini-
granulation tissue formation, neovascularization, cal improvement [38].
and increased production of macrophages and Absolute contraindications to CO2 laser skin
fibroblasts [21]. resurfacing include active bacterial, viral, or fun-
Persistent collagen shrinkage and dermal gal infection or an inflammatory skin condition
remodeling are responsible for much of the involving the skin areas to be treated. Isotretinoin
continued clinical benefits observed after CO2 use within the preceding 6-month period or his-
resurfacing and are influenced by several fac- tory of keloids also are considered contraindica-
tors [33, 34]. Thermal effects of laser irradia- tions to CO2 laser treatment because of the
tion of skin produce collagen fiber contraction unpredictable tissue healing response and greater
at temperatures ranging from 55  °C to 62  °C risk for scarring [39, 40].
through disruption of interpeptide bonds result- In an attempt to address many of the difficul-
ing in a conformational change to the colla- ties associated with the use of multiple-pass CO2
gen’s basic triple helical structure [35, 36]. The laser skin resurfacing, refinements in surgical
collagen molecule is thereby shortened to technique were subsequently developed. Single-­
approximately one third of its normal length. pass CO2 laser treatment was shown to effect
The laser-induced shrinkage of collagen fibers faster re-epithelialization and an improved side
may act as the contracted scaffold for neocol- effect profile [41]. Rather than remove partially
lagenesis, leading to subsequent production of desiccated tissue (as was typical with multiple-­
the newly shortened form. In turn, fibroblasts pass procedures), the lased skin was left intact to
9  Lasers for Resurfacing 143

serve as a biologic wound dressing. Additional averaging only 20–50 μm, are therefore produced
laser passes could then be applied focally in areas [45, 47–49]. Laser-induced ejection of desiccated
with more severe photodamage in order to limit tissue from the target site typically produces a
unnecessary thermal and mechanical trauma to distinctive popping sound. Thermal energy is
uninvolved skin. Subsequent reports have sub- confined to the selected tissue, with minimal col-
stantiated the improved side effect profile of this lateral thermal damage. Because little tissue
less aggressive procedure [42–44]. necrosis is produced with each pass of the laser,
manual removal of desiccated tissue is often
Erbium: Yttrium–Aluminum–Garnet unnecessary.
(Er:YAG) Laser The short-pulsed erbium laser fluences used
most often range from 5 to 15 J/cm2, depending
on the degree of photodamage and anatomic
Summary Box
location. When lower fluences are used, it is often
• Typical fluences range from 5 to 15  J/
necessary to perform multiple passes to ablate
cm2, depending on the degree of photo-
the entire epidermis. The ablation depth with the
damage and anatomic location
short-pulsed Er:YAG does not diminish with suc-
• When lower fluences are applied, it is
cessive passes, because the amount of thermal
often necessary to perform multiple
necrosis is minimal with each pass. It takes three
passes to ablate the entire epidermis
to four times as many passes with the short-­
• Shorter pulse durations are used for tis-
pulsed Er:YAG laser to achieve similar depths of
sue ablation and longer pulses are used
penetration as with one pass of the CO2 laser at
to effect coagulation and expand zones
typical treatment parameters [3, 11]. To ablate
of thermal injury
the entire epidermis with the short-pulsed
Er:YAG laser at 5  J/cm2, at least two or three
passes must be used which increases the possibil-
The Er:YAG laser is a more ablative tool that ity of uneven tissue penetration. Deeper dermal
emits light at 2940 nm, corresponding well to the lesions or areas of the face with extreme photo-
3000 nm absorption peak of water. The absorp- damage and extensive dermal elastosis may
tion coefficient of the Er:YAG is 12,800  cm−1 require up to nine or ten passes of the short-­
(compared with 800  cm−1 for the CO2 laser), pulsed Er:YAG laser, whereas the CO2 laser
making it 12–18 times more efficiently absorbed would effect similar levels of tissue ablation in
by water-containing tissue than is the CO2 laser two or three passes [7, 18, 45].
[45]. The pulse duration (averaging 250  μs) is Pinpoint bleeding caused by inadequate
also much shorter than that of the CO2 laser, hemostasis and tissue color change with multiple
resulting in decreased thermal diffusion, less Er:YAG passes can impede adequate clinical
effective hemostasis, and increased intraopera- assessment of wound depth. Irradiated areas
tive bleeding which can hamper deeper dermal whiten immediately after treatment and then
treatment. Because of limited thermal skin injury, quickly fade. These factors render it far more dif-
the amount of collagen contraction is also ficult for the surgeon to determine treatment end-
reduced with Er:YAG treatment (1–4%) com- points and thus requires extensive knowledge of
pared to that observed with CO2 laser irradiation laser–tissue interaction.
[11, 46]. Conditions amenable to short-pulsed Er:YAG
The erbium’s efficient rate of absorption, short laser resurfacing include superficial epidermal or
exposure duration, and direct relationship dermal lesions, mild photodamage and subtle
between fluence delivered and amount of tissue dyspigmentation. The major advantage of short-­
ablated leads to 2–4 μm of tissue vaporization per pulsed Er:YAG laser treatment is its shorter
J/cm2, producing a shallow level of tissue abla- recovery period. Re-epithelialization is com-
tion. Much narrower zones of thermal necrosis, pleted within an average of 5.5 days, compared
144 R. Wanitphakdeedecha and T. S. Alster

with 8.5 days for multiple-pass CO2 procedures coagulative CO2 laser pulses. The Er:YAG com-
[18, 47]. Postoperative pain and duration of ery- ponent generates fluences up to 28 J/cm2 with a
thema are reduced after short-pulsed Er:YAG 350 μs pulse duration, while excellent hemostasis
laser resurfacing, with postoperative erythema is provided by the CO2 component which can be
resolving within 3–4 weeks. Because there is less programmed to deliver 1–100  ms pulses at
thermal injury and trauma to the skin, the risk of 1–10 W power. Zones of thermal necrosis mea-
pigmentary disturbance is also decreased, mak- suring as much as 50  μm have been observed
ing the short-pulsed Er:YAG laser a good alterna- depending on the treatment parameters used and
tive in patients with darker skin phototypes [3, significant increase in collagen thickness has
50]. The major disadvantages of the short-pulsed been noted 3 months after four passes with this
Er:YAG laser are its limited ability to effect sig- hybrid technology [52]. Another modulated
nificant collagen shrinkage and its failure to Er:YAG device is a dual-mode Er:YAG laser that
induce new and continued collagen formation emits a combination of short (200–300 μs) pulses
postoperatively [3, 47, 51]. The final clinical and long coagulative pulses to achieve tissue
result is typically less impressive than that pro- ablation depths of up to 200  μm per pass. The
duced by CO2 laser skin resurfacing for deeper output from the two Er:YAG laser heads are com-
rhytides. However, for mild photodamage, bined into a single stream in a process called
improvement of approximately 50% is typical optical multiplexing [53]. The desired depth of
(Fig.  9.2a, b). Although clinical and histologic ablation and coagulation can be programmed by
effects are less impressive than those produced the laser surgeon into the touch-screen control
with the CO2 laser, short-pulsed Er:YAG laser panel. Several investigators have studied the his-
skin resurfacing still affords modest improve- tologic effects of dual-mode Er:YAG laser resur-
ment of photodamaged skin with a shorter recov- facing and found a close correlation between the
ery time [17, 47]. programmed and actual measured depths of abla-
To address the limitations of the short-pulsed tion [54, 55]. The actual zones of thermal injury
Er:YAG laser, modulated Er:YAG lasers systems correlate well to the first pass with decreasing
were developed to improve hemostasis and coagulative efficiency on subsequent passes. The
increase the amount of collagen shrinkage and variable-pulsed Er:YAG laser system delivers
remodeling effected. The Er:YAG-CO2 hybrid pulse durations ranging 500 μs to 10 ms. Shorter
laser system delivers both ablative Er:YAG and pulse durations are used for tissue ablation and

a b

Fig. 9.2  Erbium:YAG laser resurfacing (a) before and (b) after
9  Lasers for Resurfacing 145

longer pulses are used to effect coagulation and regarding the optimal dressing for the laser-­ablated
zones of thermal injury similar to the CO2 laser wound. The ‘open’ technique involves frequent
[53, 56]. application of a thick healing ointment to the de-
Since the modulated Er:YAG lasers were epithelialized skin surface; whereas occlusive or
developed to produce a greater thermal effect and semi-occlusive dressings are placed directly on the
tissue contraction than their short-pulsed prede- lased skin in the ‘closed’ technique. While the open
cessors, investigators compared collagen tighten- technique facilitates easy wound visualization, the
ing induced by the CO2 laser with that of the closed technique requires less patient involvement
CO2–Er:YAG hybrid laser system [57]. and may also decrease postoperative pain. Proposed
Intraoperative contraction of approximately 43% advantages of a closed wound care regimen include
was produced after three passes of the CO2 laser, increased patient comfort, decreased erythema and
compared with 12% contraction following edema, increased rate of re-epithelialization, and
Er:YAG irradiation. At 4  weeks; however, the decreased patient involvement in wound manage-
CO2 and Er:YAG laser treated sites were con- ment [58, 59]. On the other hand, additional expense
tracted to the same degree, highlighting the dif- and a higher risk of infection have been associated
ferent mechanisms of tissue tightening observed with the use of these dressings [3, 60, 61].
after laser treatment. Immediate thermal-induced In addition to postoperative wound care, ice
collagen tightening was the predominant response pack application and anti-inflammatory medica-
seen after CO2 irradiation, whereas modulated tions should be prescribed during this time.
Er:YAG laser resurfacing did not produce imme- Furthermore, pain medication is particularly
diate intraoperative contraction but instead important for ablative laser-resurfaced patients dur-
induced slow collagen tightening [53, 57]. ing the first few postoperative days.

Postoperative Management
Adverse Events
Summary Box
• During the re-epithelialization process,
Summary Box
an open- or closed-wound technique can
be used • Side Effects/Complications
• Ice pack application, anti-­inflammatories –– Mild: Prolonged erythema, milia,
and pain medications should be acne, contact dermatitis
prescribed –– Moderate: Infection (bacterial, viral,
• Early recognition and treatment of side fungal), hyperpigmentation
effects (e.g., topical bleaching creams –– Severe: Hypopigmentation, hyper-
for hyperpigmentation) trophic scarring, ectropion
• Prevention and Treatment
–– Adequate preoperative patient evalu-
ation and education are absolute
Wound care during the immediate postoperative essentials to avoid pitfalls and opti-
period is vital to the successful recovery of ablative mize clinical outcomes
laser-resurfaced skin. During the re-­epithelialization –– Preoperative examination to deter-
process, an open- or closed-wound technique can mine eyelid skin laxity/elasticity to
be prescribed. Partial-thickness cutaneous wounds prevent ectropion
heal more efficiently and with a reduced risk of –– Avoidance of pulse stacking, scan
scarring when maintained in a moist environment overlapping, and incomplete removal
because the presence of a dry crust or scab impedes of partially desiccated tissue to pre-
keratinocyte migration [58]. Although there is con- vent hypertrophic scarring
sensus on this principle, disagreement exists
146 R. Wanitphakdeedecha and T. S. Alster

the degree of inflammation [62, 63]. Its use should

–– Topical agents such as retinoic acid be reserved for at least 4 weeks after the proce-
derivatives, glycolic acid, salicylic dure in order to avoid irritation. Similarly, other
acid, fragrance-containing or topical agents such as retinoic acid derivatives,
chemical-­ containing cosmetics and glycolic acid, fragrance-containing or chemical-
sunscreens should be strictly avoided containing cosmetics and sunscreens should be
in the early postoperative period until strictly avoided in the early postoperative period
substantial healing has occurred until substantial healing has occurred [16].
–– Oral antibiotics may be prescribed Adequate preoperative patient evaluation and
for acne flares that do not respond to education are absolute essentials to avoid pitfalls
topical preparations and to optimize clinical outcomes.
–– Any patient undergoing full-face or Mild side effects of laser resurfacing include
perioral ablative resurfacing should milia formation and acne exacerbation which
receive antiviral prophylaxis, even if may be caused by the use of occlusive dressings
a history of HSV is denied and ointments during the postoperative period,
–– Postinflammatory hyperpigmenta- particularly in patients who are prone to acne [15,
tion can be hastened with the postop- 16, 25, 60]. Milia and acne usually resolve spon-
erative use of a variety of topical taneously as healing progresses and the applica-
agents, including hydroquinone, reti- tion of thick emollient creams and occlusive
noic, azeleic, and glycolic acid. dressings ceases. Oral antibiotics may be pre-
–– Regular sunscreen use is important scribed for acne flares that do not respond to topi-
during the healing process to prevent cal preparations [16, 30, 60]. Contact allergies,
further skin darkening. irritant or allergic, can also develop from various
topical medications, soaps, and moisturizers used
postoperatively. Most of these reactions are irri-
Side effects associated with ablative laser skin tant in nature due to decreased barrier function of
resurfacing vary and are related to the expertise of the newly resurfaced skin [16, 64].
the laser surgeon, the body area treated, and the Wound infections associated with ablative
skin phototype of the patient (Table 9.3). Certain laser resurfacing include Staphylococcus,
tissue reactions, such as erythema and edema, are Pseudomonas, or cutaneous candidiasis and
expected in the immediate postoperative period should be treated aggressively with an appropriate
and are not considered adverse events. Erythema systemic antibiotic or antifungal agent [61]. The
can be intense and may persist for several months use of prophylactic antibiotics remains controver-
after the procedure. The degree of erythema corre- sial [14]. After CO2 resurfacing, approximately
lates directly with the depth of ablation and the 7% of patients develop a localized or dissemi-
number of laser passes performed [3, 16]. It may nated form of HSV [16]. These infections develop
also be aggravated by underlying rosacea or der- within the first postoperative week and can pres-
matitis. Postoperative erythema resolves spontane- ent as erosions without intact vesicles because of
ously but can be reduced with the application of the denuded condition of newly lased skin. Even
topical ascorbic acid which may serve to decrease with appropriate prophylaxis, a herpetic outbreak

Table 9.3  Side effects and complications of ablative laser skin resurfacing
Complications
Expected side effects Mild Moderate Severe
Erythema Prolonged erythema Infection (bacterial, viral, fungal) Permanent hypopigmentation
Edema Milia Transient hyperpigmentation Hypertrophic scarring
Pruritus Acne Ectropion
Dermatitis
9  Lasers for Resurfacing 147

still can occur in up to 10% of patients and must

be treated aggressively [17]. In order to prevent
this complication, patients should begin prophy-
laxis by the day of surgery and continue for
7–10 days postoperatively.
The most severe complications associated
with ablative cutaneous laser resurfacing include
hypertrophic scar and ectropion formation [15,
16]. Although the risk of scarring has been sig-
nificantly reduced with pulsed laser technology
(compared to the continuous wave systems),
Fig. 9.3  Postinflammatory hyperpigmention following
inadvertent pulse stacking or scan overlapping, ablative laser resurfacing
as well as incomplete removal of desiccated tis-
sue between laser passes can cause excessive these products preoperatively, however, has not
thermal injury that could increase the develop- been shown to decrease the incidence of post-­
ment of fibrosis. Focal areas of bright erythema, treatment hyperpigmentation [13]. Postoperative
with pruritus, particularly along the mandible, hypopigmentation, on the other hand, is often not
may signal impending scar formation [25, 65]. observed for several months and is particularly
Ultrapotent (class I) topical corticosteroid prepa- difficult because of its tendency to be intractable
rations should be applied to decrease the inflam- to treatment. The use of an excimer laser or topi-
matory response. A pulsed dye laser also can be cal photochemotherapy to stimulate repigmen-
used to improve the appearance and symptoms of tation has proven successful in some patients
laser-induced burn scars [65]. [66, 67].
Ectropion of the lower eyelid after periorbital Side effects and complications following
laser skin resurfacing is rarely seen, but if Er:YAG laser irradiation are similar to those
encountered, usually requires surgical correction observed after CO2 laser treatment, but they dif-
[25]. It is more likely to occur in patients who fer in respect to duration, incidence, and severity
have had previous lower blepharoplasty or other [50, 68, 69]. Although greater postoperative ery-
surgical manipulation of the periorbital region. thema is seen after modulated Er:YAG laser
Preoperative examination is essential to deter- treatment than is usually produced with a short-­
mine eyelid laxity and skin elasticity. If the infra- pulsed Er:YAG system, the side effect profile and
orbital skin does not return briskly to its normal recovery period after modulated Er:YAG laser
resting position after a manual downward pull irradiation remain more favorable than after
(snap test), then ablative laser treatment near the multiple-­pass CO2 laser treatment. In an extended
lower eyelid margin should be avoided. In gen- evaluation of 50 patients, investigators reported
eral, lower fluences and fewer laser passes should complete re-epithelialization in an average of
be applied in the periorbital area to decrease the 5 days after dual-mode Er:YAG laser skin resur-
risk of lid eversion. facing with only three patients having prolonged
Hyperpigmentation is one of the more com- erythema beyond 4  weeks [68]. In a split-face
mon side effects of cutaneous laser resurfacing comparison of 16 patients after pulsed CO2 and
and occurs to some degree in all patients with variable-pulsed Er:YAG laser skin resurfacing,
darker skin tones (Fig. 9.3) [16, 25]. The reaction other investigators reported decreased erythema,
is transient, but its resolution can be hastened less edema, and faster healing on the Er:YAG
with the postoperative use of a variety of topical laser-treated facial half [70].
agents, including hydroquinone, retinoic, azeleic, Postinflammatory hyperpigmentation is not
and glycolic acid. Regular sunscreen use is also uncommon after any cutaneous laser resurfac-
important during the healing process to prevent ing procedure. While hyperpigmentation fol-
further skin darkening. The prophylactic use of lowing modulated Er:YAG laser skin resurfacing
148 R. Wanitphakdeedecha and T. S. Alster

(mean, 10.4  weeks) can last longer than after

treatment with a short-pulsed Er:YAG laser, it is • Contraindications
not as persistent as that observed after multiple- –– Patients with unrealistic
pass CO2 laser resurfacing (mean, 16  weeks) expectations
[69]. However, when comparing the most cur- –– Patients with darker skin tones
rent trends in ablative cutaneous laser resurfac- (skin phototype IV–VI) have a high
ing—single-pass CO2 versus multiple-pass, incidence of postoperative
long-­ulsed Er:YAG laser skin resurfacing— hyperpigmentation
postoperative healing times and complication –– Patients with perpetual sun exposure
profiles are comparable, even in patients with –– Patients with history of herpes labia-
darker skin phototypes. In a retrospective review lis may require prophylactic oral
and analysis of 100 consecutive patients, Tanzi antiviral medications.
and Alster [44] showed average time to re-epi-
thelialization was 5.5 days with single-pass CO2
and 5.1  days with long-pulsed Er:YAG laser Proper patient selection is critical to the success
resurfacing. Postoperative erythema was of non-ablative laser skin remodeling. Patients
observed in all patients, lasting an average of with mild-to-moderate facial photodamage or
4.5 weeks after single-pass CO2 laser treatment atrophic scars with realistic expectations of treat-
and 3.6  weeks after long-pulsed Er:YAG laser ment are the best candidates for non-ablative pro-
treatment. Hyperpigmentation was seen in 46% cedures. Patients seeking immediate improvement
of patients treated with single-pass CO2 and in photodamaged skin or those who desire a dra-
42% of patients treated with the long-pulsed matic result may be less than satisfied with the
Er:YAG laser (­ average duration 12.7 weeks and overall clinical outcome.
11.4  weeks, respectively). Delayed-onset per-
manent hypopigmentation—a serious complica-
tion that has been observed several months after Techniques
multiple-­pass CO2 laser skin resurfacing—has
not yet been reported following single-pass Preoperative Management
treatment. To date, only three cases of hypopig-
mentation after modulated Er:YAG laser skin
resurfacing have been reported [71, 72]. Since it Summary Box
is possible for hypopigmentation to present sev- • Adequate preoperative patient evalua-
eral years postoperatively, clinical studies are tion and education
ongoing to determine its true incidence follow- • Oral antiviral prophylaxis in patients
ing either single-­pass CO2 or modulated Er:YAG with history of herpes labialis
laser skin resurfacing.

Adequate preoperative patient evaluation and

 on-ablative Laser Skin
N education are absolute essentials (Table 9.4). For
Resurfacing patients with a strong history of herpes labialis,
prophylactic oral antiviral medications should be
Indications and Contraindications considered when treating the perioral skin.
Reactivation of prior herpes simplex infection
can occur after non-ablative laser treatment due
Summary Box to the intense heat produced by the laser or light
• Indications source.
–– Mild facial rhytides, atrophic scars, Prior to non-ablative laser procedures, sun
and photodamage exposure should be avoided, particularly when
using shorter-wavelength systems such as the
9  Lasers for Resurfacing 149

Table 9.4  Non-ablative laser resurfacing: patient selec- Most of the non-ablative laser systems emit light
tion, risks, and precautions within the infrared portion of the electromagnetic
Preoperative patient evaluation spectrum (1000–1500 nm). At these wavelengths,
• Is the amount of photodamage amenable to absorption by superficial water-containing tissue
non-ablative laser skin remodeling? Patients with
is relatively weak, thereby effecting deeper tissue
mild-to-moderate facial photodamage are the best
candidates for non-ablative procedures. Patients penetration [73]. Since non-ablative remodeling
with severe rhytides and skin laxity may be involves creation of a dermal wound without epi-
disappointed with the overall clinical outcome. dermal injury, all of these laser systems employ
• Does the patient have a history of herpes labialis? unique methods to ensure epidermal preservation
Reactivation of prior herpes simplex infection can
occur with perioral non-ablative laser skin
during treatment. These methods typically
modeling due to the intense heat produced by the include contact cooling handpieces or dynamic
laser. Patients with a strong history of herpes cryogen devices capable of delivering variable
simplex labialis may require prophylactic oral duration spray cooling spurts either before, dur-
antiviral medication to avoid a postoperative
outbreak.
ing, and/or after laser irradiation. Since laser
• What is the patient’s skin phototype? Although the beam penetration and dermal wounding must be
majority of current non-ablative systems used are targeted to the relatively superficial portion of the
within the mid-infrared range of the dermis, contact cooling devices that theoretically
electromagnetic spectrum and not avidly absorbed lead to excessive dermal cooling may affect the
by epidermal melanin, patients with darker skin
phototypes may develop postinflammatory level or degree of energy deposition in the skin.
hyperpigmentation after non-ablative treatment. As such, there remains no general consensus con-
This temporary reaction may develop due to cerning which method of cooling is most effica-
inflammation created by concomitant cryogen
cious during treatment.
spray epidermal cooling.
• Does the patient have realistic expectations?
In general, treatment of facial photodamage
Patients seeking immediate gratification after a with non-ablative technology does not produce
single non-ablative treatment are not good results comparable to those of ablative CO2 and
candidates as clinical improvement typically occurs Er:YAG lasers; however, many patients are will-
after multiple sequential treatments (usually three
to five) and is often delayed 3–6 months after the
ing to accept modest clinical improvement in
final session. Moreover, patients seeking dramatic exchange for fewer associated risks and shorter
results following non-ablative laser skin techniques recovery times.
should be dissuaded from treatment as clinical
improvement may be subtle.
Pulsed Dye Laser (PDL)

pulsed dye laser or intense pulsed-light source. Summary Box

Unwanted absorption of irradiation by activated • 585  nm and 595  nm pulsed dye laser
epidermal melanocytes can increase the risk of (PDL) can reduce mild facial rhytides
side effects, including crusting, blistering, and with few side effects
dyspigmentation. • Side effects include mild edema, pur-
pura, and transient postinflammatory
hyperpigmentation
Description of the Technique

Clinical studies have demonstrated the ability of

Summary Box 585  nm and 595  nm pulsed dye laser (PDL) to
• Infrared light (1000–1500 nm) creates a reduce mild facial rhytides with few side effects
dermal wound without epidermal injury [74]. The most common side effects of PDL treat-
• Epidermis is preserved during treatment ment include mild edema, purpura, and transient
by tissue cooling postinflammatory hyperpigmentation. Although
increased extracellular matrix proteins and types I
150 R. Wanitphakdeedecha and T. S. Alster

and III collagen and procollagen have been release of inflammatory mediators stimulated by
detected after PDL treatment, the exact mecha- vessel heating [80].
nism whereby wrinkle improvement is effected
remains unknown [75]. One theory states that vas-  064 nm Q-Switched (QS) Neodymium:
1
cular endothelial cells damaged by the yellow YAG (Nd: YAG) Laser
laser light release mediators that stimulate fibro-
blasts to produce new collagen fibers [76].
Summary Box
• Although absorption of energy by tissue
Intense Pulsed Light (IPL) Source
water is relatively weak at the 1064 nm
wavelength, it was possible to achieve
Summary Box dermal penetrative depths that could
• The IPL source emits a broad, continu- potentially induce neocollagenesis.
ous spectrum of light in the range of • The nanosecond range pulse duration of
515–1200 nm the QS Nd:YAG laser was also deter-
• Cut-off filters are used to eliminate mined to limit significant thermal diffu-
shorter wavelengths depending on the sion to surrounding structures, thereby
clinical application, with shorter filters making it suitable for non-ablative
favoring heating of melanin and rejuvenation.
hemoglobin. • Treatment is delivered by using the flu-
• Treatment is delivered by using the flu- ences of 2–6  J/cm2 with 3–7  mm spot
ences of 30–50 40 J/cm2. size and pulse duration, ranging 6–20 ns.

Several investigators have shown successful reju- The 1064 nm quality-switched (QS)
venation of photodamaged skin after intense neodymium:YAG (Nd:YAG) laser was the first
pulsed light (IPL) treatment [77, 78]. The IPL mid-infrared laser system used for non-ablative
source emits a broad, continuous spectrum of light cutaneous remodeling. Although absorption of
in the range of 515–1200  nm. Cut-off filters are energy by tissue water is relatively weak at the
used to eliminate shorter wavelengths depending 1064 nm wavelength, it was possible to achieve
on the clinical application, with shorter filters dermal penetrative depths that could potentially
favoring heating of melanin and hemoglobin. induce neocollagenesis. The nanosecond range
Bitter [78] showed improvement in wrinkling, pulse duration of the QS Nd:YAG laser was also
skin coarseness, irregular pigmentation, pore size, determined to limit significant thermal diffusion
and telangiectasia in the majority of 49 patients to surrounding structures, thereby making it suit-
treated with a series of IPL treatments (fluences able for non-ablative rejuvenation.
30–50  J/cm2). In a retrospective review of 80 In 1997, Goldberg and Whitworth [81] pub-
patients with skin phototypes I–IV, Weiss and col- lished their experience using a 1064  nm
leagues [79] reported signs of photoaging, includ- Nd:YAG laser for facial rhytide reduction.
ing telangiectasias and mottled pigmentation of Eleven patients (skin phototypes I, II) with mild
the face, neck, and chest, improved by a series of to moderate periorbital or perioral rhytides
IPL treatments. While substantial clinical improve- underwent treatment on one side of the face
ment of dyspigmentation and telangiectasia asso- with a QS Nd:YAG laser at a fluence of 5.5 J/
ciated with cutaneous photodamage is often seen, cm2 (3 mm spot size) and CO2 laser ablation on
neocollagenesis and dermal collagen remodeling the contralateral side for comparison purposes.
with subsequent improvement in rhytides follow- Pinpoint bleeding was used as the clinical end-
ing IPL treatment has been minimal. The effect on point of QS Nd:YAG treatment. Not unexpect-
dermal collagen is thought to be induced by heat edly, all of the CO2-laser irradiated sites
diffusion from the vasculature with subsequent demonstrated significant rhytide improvement,
9  Lasers for Resurfacing 151

whereas only three QS Nd:YAG laser-treated

patients demonstrated improvement. These maximizing dermal temperatures that
patients also developed prolonged post-­ effectively lead to collagen reformation.
treatment erythema (lasting up to one month), • In order to prevent unwanted sequelae
suggesting that the amount of dermal wounding (e.g., blistering) from excessive heat
(with subsequent collagen remodeling) was production, it is imperative that epider-
directly related to the degree of cutaneous mal temperatures be kept lower than
injury. Another study using the QS Nd:YAG 50 °C.
laser for rhytide reduction in 61 patients (242
sites) was conducted using a topical carbon
solution for improved optical penetration of the A long-pulsed 1320  nm Nd:YAG laser was the
1064 nm light [82]. Patients underwent a series first commercially available system marketed
of three monthly QS Nd:YAG laser treatment solely for the purpose of non-ablative laser skin
sessions at a fluence of 2.5  J/cm2, 7  mm spot remodeling. The 1320 nm wavelength is associ-
size, and pulse durations, ranging 6–20  ns. At ated with a high scattering coefficient that allows
least slight improvement was seen in 97% of for dispersion of laser irradiation throughout the
class I rhytides and 86% of the class II rhytides. dermis. Later models are capable of delivering
Side effects of treatment were mild and limited, energy densities up to 24 J/cm2 with a pulse dura-
including transient erythema, purpura, and tion of 350 μs through a 10-mm handpiece. The
postinflammatory hyperpigmentation. 1320 nm Nd:YAG laser handpiece contains three
Long-pulsed Nd:YAG laser treatment has more portals: the laser beam itself, a thermal feedback
recently been advocated for skin photorejuvena- sensor that registers skin surface temperature,
tion. Lee [83] evaluated a combination technique and a dynamic cryogen spray apparatus used for
using a long-pulsed 1064 Nd:YAG laser and long- epidermal cooling. When skin surface tempera-
pulsed 532 nm potassium-titanyl-­phosphate (KTP) tures are maintained at 40–45  °C, dermal tem-
laser, both separately and combined, for non-inva- peratures reach 60–65 °C during laser irradiation,
sive photorejuvenation in 150 patients with skin thereby effecting collagen contraction and neo-
phototypes I through V.  Patients treated with the collagenesis. In order to prevent unwanted
combined laser approach showed at least 70% sequelae (e.g., blistering) from excessive heat
improvement in erythema and pigmentation and production, it is imperative that epidermal tem-
30–40% improvement in fine rhytides. In the peratures be kept lower than 50 °C. A series of
patient groups treated with monotherapy, patient three or more treatment sessions are scheduled at
satisfaction was greater with KTP laser treatment regular intervals (typically once a month) for
than with the Nd:YAG laser primarily due to a optimal mitigation of fine rhytides [73]. Side
reduction in dyspigmentation and telangiectasias. effects of treatment are generally mild and
include transient erythema and edema.
Menaker et al. [84] reported effective rhytide
1320 nm Nd: YAG Laser reduction in an early study using a prototype
1320 nm Nd:YAG laser. Ten patients with peri-
Summary Box ocular rhytides received three consecutive laser
• The 1320  nm wavelength is associated treatments at bi-weekly intervals. Triple 300  μs
with a high scattering coefficient that pulses were delivered at 100  Hz and fluence of
allows for dispersion of laser irradiation 32 J/cm2 with a 5 mm handpiece. Epidermal pro-
throughout the dermis. tection was achieved with application of a 20 ms
• A thermal feedback sensor should be used cooling spray after a 10 ms preset delay. Patients
intraoperatively to select appropriate treat- were evaluated at 1 and 3 months post-treatment.
ment fluences delivered to the individual Although four of the ten patients showed clinical
patient’s cutaneous temperature, thereby improvement in rhytide severity by end-study,
these findings were not statistically significant.
152 R. Wanitphakdeedecha and T. S. Alster

Similarly, the slight homogenization of collagen improvement, and two showed substantial improve-
noted on histology at 1 and 3 months following ment in facial rhytides and overall skin tone.
treatment was not statistically significant and Others also studied the 1320 nm Nd:YAG laser
inconsistent with the clinical findings. for treatment of facial rhytides in ten women [88].
In another study, Kelly et  al. [85] treated 35 Full-face treatment was administered to three
patients with mild, moderate, and severe rhytides patients, whereas two patients had periorbital
using a 1320 nm Nd:YAG laser. Three treatments treatment, and five patients received perioral
were delivered at 2-week intervals using fluences treatment. Laser fluences of 30–35  J/cm2 were
ranging 28–36  J/cm2 with a 5  mm spot size. delivered in triple 300 μs pulses at a repetition rate
Cryogen spray cooling was applied in 20–40 ms of 100 Hz. Dynamic cryogen spray cooling was
spurts with 10 ms delays. Patients were evaluated used with a 30 ms spurt and a 40 ms delay between
at 12 and 24 weeks following treatment with sta- cryogen delivery and laser irradiation. A thermal
tistically significant improvement noted in all sensor was also used to maintain peak surface
clinical grades after 12  weeks. Only the most temperatures in the range of 42–45 °C in order to
severe rhytides; however, showed persistent avoid excessive tissue heating. Treatments were
improvement 24 weeks following treatment. administered twice a week over a period of
Goldberg devised two similar studies to exam- 4  weeks for a total of eight treatment sessions.
ine the effectiveness of the 1320 nm Nd:YAG laser Only two out of ten patients expressed satisfaction
for the treatment of facial rhytides. In the first with their final result despite clinician evaluations
study, ten patients with skin types I–II and class I– showing significant improvement in five of ten
II rhytides in the periorbital, perioral, and cheek patients and fair improvements in another three.
areas were treated [86]. Four treatments were Moreover, there was no correlation between his-
administered over a 16-week period using fluences tologic changes and the degree of subjective clini-
of 28–38  J/cm2 with a 30% overlap and a 5  mm cal improvement as judged by the patients.
spot size. One or two laser passes were applied to A more recent study by Fatemi et  al. [89]
achieve the treatment endpoint of mild erythema. demonstrated that the 1320  nm Nd:YAG laser
Skin surface temperatures were limited to 40–48 °C produced mild subclinical epidermal injury that
using the aforementioned dynamic cooling spray in could potentially lead to enhanced skin texture
order to provide epidermal protection, whilst and new papillary collagen synthesis by stimula-
effecting dermal temperatures ranging tion of cytokines and other inflammatory media-
60–70 °C. Six months after treatment, two patients tors. Thus, the long-term histologic improvement
showed no clinical improvement, six showed seen in photodamaged skin may not be based
‘some’ improvement, and two showed ‘substantial’ solely on direct laser heating of collagen, but
improvement. This study emphasized several key through stimulation of cytokine release by heat-
points in non-­ ablative laser resurfacing. It sug- ing the superficial vasculature. In addition, the
gested a thermal feedback sensor is best used intra- histologic findings suggested that multiple passes
operatively with this technology in order for with fluence and cooling adjusted to a Tmax of
appropriate treatment fluences to be selected based 45–48 °C can yield improved clinical results, as
upon the individual patient’s cutaneous tempera- compared to those specimens in which epidermal
ture, thereby maximizing dermal temperatures that temperatures above 45 °C were not achieved.
effectively lead to collagen reformation.
Furthermore, longer follow-up periods are usually 1450 nm Diode Laser
required to fully appreciate the effect of serial treat-
ment sessions on dermal collagen stimulation. In
the second study, ten patients underwent full-face Summary Box
treatments with the 1320  nm Nd:YAG laser at • The fluences ranging 10–20  J/cm2
3–4  week intervals [87]. As with the first study, should be applied in a single nonover-
treatment results were inconsistent—four patients lapping pass with 6-mm spot size.
showed no improvement, four showed some
9  Lasers for Resurfacing 153

The 1450  nm mid-infrared wavelength diode and that the non-specific injury induced by cryogen
laser targets dermal water and penetrates the skin spray cooling could not effect the changes seen.
to an approximate depth of 500  μm. This low-­ Hardaway and colleagues [91] demonstrated
power laser system achieves peak powers in the statistically significant mean wrinkle improve-
10–15 W range with relatively long pulse dura- ment of 2.3 (range 0–4, with four representing
tions of 150–250 ms. Because of these long expo- severe wrinkling) at baseline to 1.8 at 6 months
sure times, epidermal cooling must be delivered following a series of three 1450 nm diode laser
in sequence during the application of laser energy treatments. They concluded that although the
in order to avoid excessive thermal buildup 1450 nm diode laser is capable of targeting der-
within the superficial layers of the skin. mal collagen and stimulating fibrosis, clinical
Goldberg et  al. [90] reported on the effects of improvement of rhytides was mild and did not
1450 nm diode laser irradiation in 20 patients with correlate well with the degree of histologic
class I–II rhytides. Two to four treatment sessions change noted in previous studies.
were delivered with 6-month follow-up evaluation. In a controlled clinical and histologic study,
Patients were treated with laser and cryogen spray Tanzi and Alster [92] demonstrated improvement
cooling on one facial half and cryogen spray cool- in mild to moderate perioral or periorbital rhytides
ing alone on the contralateral side. On the laser- in 25 patients treated with four consecutive
treated facial halves, seven did not demonstrate any 1450  nm diode laser treatments using fluences
improvement, ten showed mild improvement, and ranging 15–20 J/cm2 with a 4 mm spot size. Peak
three had moderate improvement. None of the sites clinical improvement was seen 6 months after the
treated with cryogen alone showed any improve- series of laser treatments. The periorbital area was
ment after 6 months. Side effects of treatment were more responsive to laser treatment than the perioral
mild and included transient erythema, edematous area—a finding consistent with results obtained
papules, and one case of postinflammatory hyper- using other non-ablative laser systems (Fig.  9.4a,
pigmentation persisting for 6 months. The authors b). Side effects were limited to transient erythema,
concluded that the 1450 nm diode laser was effec- edema, and postinflammatory hyperpigmentation.
tive for treatment of mild to moderate facial rhytides In a separate controlled study performed by the
with minimal morbidity. Additionally, their study same group, 20 patients with transverse neck lines
demonstrated that non-ablative laser treatment received three consecutive monthly treatments
alone was responsible for the clinical improvements using a long-pulsed 1450  nm diode laser [93].

a b

Fig. 9.4 1450 nm
long-pulsed diode laser
(a) before and (b) after
154 R. Wanitphakdeedecha and T. S. Alster

Modest improvements in appearance and texture of been used for amelioration of fine facial rhytides
the transverse neck lines was reported, as measured and atrophic facial scars. Similar to other infrared
by blinded clinical assessments and through three- laser systems, the erbium:glass laser targets intra-
dimensional in  vivo microtopography (PRIMOS cellular water and penetrates tissue to a depth of
Imaging System; GFM, Germany). Mean fluences 0.4–2 mm [73]. The 1540 nm wavelength exerts
of 11.6 J/cm2 were used with a 6 mm spot size and less effect on epidermal melanin as do the
50 ms total cryogen. 1320 nm and 1450 nm lasers—a potential advan-
Due to the marked dermal remodeling effect tage of this system when treating tanned or
of the long-pulsed 1320-nm Nd:YAG and 1450-­ darker-skinned patients. Mordon et al. [95] stud-
nm diode lasers, Tanzi and Alster [94] reported ied the 1540 nm erbium:glass laser on hairless rat
the long-term clinical and histologic results of abdominal skin with pulse train irradiation (1.1 J,
these systems on atrophic facial acne scars in 20 3  Hz, 30 pulses) and varying cooling tempera-
patients. Facial halves were randomly assigned to tures (+5  °C, 0  °C, −5  °C). Biopsies obtained
received three consecutive monthly treatments after 1, 3, and 7 days following treatment dem-
with a 1320-nm Nd:YAG laser (CoolTouch; onstrated fibroblast proliferation and new colla-
CoolTouch Corp., Auburn, CA) on one side and a gen synthesis as early as the third day. The
1450-nm diode (SmoothBeam; Candela Corp., authors concluded that the erbium glass system
Wayland, MA) on the contralateral. The 1450-nm held promise for treating facial rhytides because
diode laser was used at fluences ranging 9–14 J/ of its high water absorption and reduced tissue
cm2 (average 11.8  J/cm2, 6-mm spot size) in a scattering effect that limits energy deposition to
single nonoverlapping pass; whereas, the 1320-­ the upper dermis where most solar elastosis is
nm Nd:YAG laser was used of fluences ranging evident.
12–17  J/cm2 (average 14.8  J/cm2, 10-mm spot Ross et  al. [96] studied the effect of the
size) in two passes. Mild to moderate clinical 1540 nm erbium:glass laser with a sapphire cool-
improvement was observed in the majority of ing handpiece on the preauricular skin of nine
patients. Patient satisfaction scores and in  vivo patients. A 5  mm collimated beam was used to
microtopography measurements paralleled the deliver fluences of 400–1200 mJ/cm2. Epidermal
photographic and histopathologic changes seen necrosis and scar formation were noted at the
without significant side effects or complications. highest pulse energies. Several key points were
The 1450-nm diode laser showed greater clinical illustrated by this study; namely, that denatured
scar response at the parameters studied. collagen located deep in the dermis (more than
600 μm) is associated with granuloma formation
1540 nm Erbium: Glass Laser and that the peaks of heating and cooling with
non-ablative laser remodeling are in proximity,
by necessity, since maximum wrinkle reduction
Summary Box
may be achieved by a zone of thermal injury
• The treatment should be performed on a
100–400 μm beneath the skin surface.
monthly basis for three to five sessions
Lupton et  al. [97] reported their use of a
using a 4  mm spot size, 10  J/cm2 flu-
1540  nm erbium:glass laser to treat 24 patients
ence, and 3.5 ms pulse duration.
with fine periorbital and perioral rhytides.
• Epidermal protection was achieved with
Patients underwent a series of three treatments on
concomitant application of a contact
a monthly basis using a 4 mm spot size, 10 J/cm2
sapphire lens cooled to 5 °C.
fluence, and 3.5  ms pulse duration. Epidermal
protection was achieved with concomitant appli-
cation of a contact sapphire lens cooled to
The 1540  nm erbium-doped phosphate glass 5  °C.  Histologic specimens demonstrated
laser is another mid-infrared range laser that has increased dermal fibroplasia at 6 months after the
9  Lasers for Resurfacing 155

series of laser treatments. Average clinical scores treatment tip and can be changed according to the
were improved at 1 and 6 months following the clinical application. Preliminary animal studies
third treatment session with slightly better results demonstrated selective dermal heating at the lev-
observed in the periorbital regions. Side effects els of the papillary dermis and as deep as the sub-
of treatment were mild and included transient cutaneous fat [80]. Ruiz-Esparza and Gomez [99]
erythema and edema. reported facial tissue tightening in 14 of 15
Fournier and colleagues [98] subsequently patients 3  months after a single radiofrequency
treated 42 patients (skin phototypes I–IV) with treatment with minimal side effects.
five consecutive 1540 nm diode laser treatments Alster and Tanzi [100] demonstrated signifi-
at 6-week intervals. Patients were evaluated using cant improvement in cheek and neck skin laxity
clinical data, patient satisfaction surveys, digital in 50 patients received one treatment with a
photography, ultrasound imaging, and profilom- radiofrequency device (ThermaCool; Thermage
etry data from silicone imprints. The majority of Corp., Hayward, CA) at fluences ranging
patients demonstrated modest improvement in 97–144 J/cm3 (level of 13.6–16; average of 130 J/
objective and subjective measurements which cm2) on the cheeks and 74–134  J/cm3 (average
remained stable throughout the 14-month evalua- 110 J/cm3) on the neck in a single, nonoverlap-
tion period. ping pass. Patient satisfaction scores paralleled
the clinical improvement observed with side
Radiofrequency (RF) Device effects limited to transient erythema, edema, and
rare dysesthesia. The tightening continued to be
evident 6 months after a single treatment.
Summary Box Another RF device, Polaris WR™ (Syneron
• The treatment should be delivered at the Medical Ltd., Israel), which combines bipolar RF
fluences ranging 90–150 J/cm3 in a sin- and diode laser energies has been developed in an
gle, nonoverlapping pass. attempt to address both facial rhytides and skin
• When combining treatment with other laxity. Doshi and Alster [101] demonstrated mod-
lasers or light sources, the fluences of est clinical improvement of facial rhytides and
RF can be reduced. skin laxity in 20 patients by using optical ener-
gies of 32–40 J/cm2 (mean 36.4 J/cm2) and radio-
frequencies of 50–85 J/cm3 (mean 67.4 J/cm3) for
three treatments at 3-week intervals. Side effects
A monopolar radiofrequency device (ThermaCool
were mild and limited to transient erythema and
TC; Thermage Inc., Hayward, CA) has also been
edema. No scarring or pigmentary alteration was
studied for deep dermal heating with subsequent
seen.
tightening of photodamaged skin. Unlike a laser
in which light energy is converted into heat, the
Postoperative Management
radiofrequency device generates electric current
which produces heat through dermal resistance.
The energy is delivered to the skin through a spe- Summary Box
cialized treatment tip with a capacitive coupling • Minimal to no care except sun
membrane which allows for uniform delivery of avoidance
heat over the entire treatment area. Epidermal
protection is provided by simultaneous cryogen
cooling within the contact treatment tip. Using Since the epidermis remains intact following
this technique, a reverse thermal gradient is gen- non-ablative laser skin remodeling, postoperative
erated. The depth of heat penetration is depen- care is minimal. Some patients experience mild
dent upon the size and specifics of the detachable erythema and edema lasting less than 24 h.
156 R. Wanitphakdeedecha and T. S. Alster

Adverse Events
• Contraindications
–– Patients with unrealistic expectations
Summary Box –– Patients with darker skin tones (skin
• Side Effects/Complications phototype IV–VI) at greater risk of
–– Transient postinflammatory hyper- postoperative hyperpigmentation
pigmentation in patients with darker –– Patients with perpetual sun exposure
skin phototypes or tans –– Patients with active bacterial, viral,
• Prevention and Treatment fungal infection or inflammatory
–– Topical bleaching agents and light skin conditions involving treatment
glycolic acid peels can hasten the areas
resolution of postinflammatory –– Patients with history of herpes labia-
hyperpigmentation. lis may require prophylactic oral
antiviral medications.
–– Concomitant isotretinoin use could
Rarely, postoperative hyperpigmentation can potentially lead to an increased risk
develop several weeks after non-ablative skin of hypertrophic scarring.
remodeling and is more likely to be experienced
by patients with darker skin tones and/or tans. In
some cases, investigators demonstrated an asso- Over the past decade, a novel approach in skin
ciation of post-treatment hyperpigmentation with resurfacing termed fractional photothermolysis
excess intraoperative epidermal cryogen cooling has been developed to address the shortcomings
[92]. Although always transient, topical bleach- associated with skin rejuvenation using pulsed
ing agents and light glycolic acid peels can has- and scanned ablative and non-ablative lasers
ten the resolution of postinflammatory and light sources [102]. Although dramatic clin-
hyperpigmentation. ical improvement can be achieved with these
In the weeks following a series of non-ablative ablative lasers, patients are often hesitant to pur-
laser procedures, in-office visits can help identify sue this treatment option because of the extended
patient concerns and increase the overall satisfac- postoperative recovery period and inherent risks
tion with treatment. Clinical improvements after of the procedure. Non-ablative lasers and light
a series of non-ablative laser procedures may sources, on the other hand, have demonstrated
take weeks to realize, thus reassurance by the modest efficacy in the non-invasive treatment of
laser surgeon regarding the patient’s progress can mild facial rhytides and atrophic scarring with
be particularly important. minimal side effects, but require multiple treat-
ments with delayed and often inconsistent clini-
cal results. Due to a need for more noticeable
Fractional Laser Skin Resurfacing clinical improvement than these latter nonabla-
tive systems could provide, fractional photo-
Indications and Contraindications thermolysis was introduced into the skin
resurfacing market to treat patients with rhyt-
ides, dyspigmentation, and atrophic scars [103–
Summary Box 108] (see Chap. 10). Currently, a variety of
• Indications ablative and nonablative fractionated lasers
–– Mild to moderate facial rhytides and have been developed and are being used to treat
photodamage a wide range of conditions. Fractionated tech-
–– Atrophic scars nology has virtually replaced pulsed and
–– Superficial epidermal/dermal lesions scanned ablative and nonablative systems due in
–– Melasma large part to their excellent clinical effects and
low risk profiles [109].
9  Lasers for Resurfacing 157

 onalative Fractional Skin Resurfacing

N treatment. Therefore, the wound created by
Nonablative fractional skin resurfacing (NAFR), fractional resurfacing is unique—not simply
typically involves the use of mid-infrared wave- that of an ablative laser used to make “holes” in
lengths (1440 nm, 1550 nm, 1927 nm) emitted the skin. In addition, fractional resurfacing can
by a variety of laser sources (e.g., erbium, thu- provide an advantage over purely non-ablative
lium) to create microscopic non-contiguous col- laser treatments due to the gradual exfoliation of
umns of thermal injury in the dermis (referred to the epidermis with resultant improvement in
as microscopic thermal zones or MTZ) at depths superficial dyspigmentation (Fig.  9.5a, b).
of 200–500  μm surrounded by zones of viable Because only a fraction of the skin is treated
tissue at 200- to 300  μm intervals [102]. The during a single session, a series of fractional
spatially precise columns of thermal injury pro- resurfacing treatments is required to achieve
duce localized epidermal necrosis and collagen optimal clinical improvement.
denaturation at 125 or 250  MTZ/cm2 [110].
Because the tissue surrounding each MTZ is  blative Fractional Skin Resurfacing
A
intact, residual epidermal and dermal cells con- Although the NAFR system is patient-friendly
tribute to rapid healing. Maintenance of the stra- and is associated with minimal recovery, its
tum corneum ensures continued epidermal clinical outcomes in the treatment of rhytides
barrier function. Histologic evaluation of the and scars are often less impressive than that
MTZ demonstrates ­homogenization of the der- achieved after ablative fractional resurfacing
mal matrix and the presence of epidermal (AFR) [109, 111, 112]. AFR systems, including
necrotic debris (MEND), representing the extru- carbon dioxide (CO2) [113], erbium-doped
sion of damaged epidermal keratinocytes by yttrium aluminum garnet (Er:YAG) [114], and
viable keratinocytes at the lateral margin of the erbium-doped yttrium scandium gallium garnet
MTZ [102]. Microscopic epidermal necrotic lasers [115], were developed in an attempt to
debris exfoliates over the next several days, pro- achieve the clinical results provided with full-
ducing a bronzed appearance to the skin. The field ablative resurfacing lasers with greater
wound healing response differs from that after safety profiles. These devices cause micro-
ablative laser techniques because the epidermal scopic treatment zones (MTZs) of complete
tissue that is spared between thermal zones con- epidermal ablation with variable amounts of
tains viable transient amplifying cells capable dermal coagulation. As with the NAFR sys-
of rapid re-epithelialization. Furthermore, tems, fractional delivery of an ablative laser
because the stratum corneum has a low water source results in a microscopic pattern with
content, it remains intact immediately after spatial separation of columns of thermally

a b

Fig. 9.5  Fractional photothermolysis (a) before and (b) after

158 R. Wanitphakdeedecha and T. S. Alster

affected epidermal and dermal tissue. Although

the results are not as effective as with full-field Description of the techniques: AFR
(pulsed/scanned) ablative laser resurfacing, sig-
nificant improvement in rhytides, atrophic • Fractional CO2 laser with 950  μs pulse
scars, and laxity of the skin has been demon- duration and 12.5 mJ energy creates aver-
strated after one or two treatments with the age depths of vaporization and coagula-
fractional ablative lasers [116–118]. tion of 160 and 350 μm, respectively
• Fractional Er:YAG laser with 350  μs
pulsed duration and 14 mJ energy pro-
Techniques duces average depths of vaporization
and coagulation of 65 and 100  μm,
Preoperative Management respectively

Summary Box The treatment areas should be cleansed free of

• Adequate preoperative patient evalua- debris (including dirt, makeup, and powder)
tion and education using a mild cleanser and 70% alcohol. A topical
• Oral antiviral prophylaxis in patients anesthetic cream is often applied to the treatment
with history of herpes labialis sites for 60 min before treatment. While the first
• Topical anesthetic cream application generation NAFL device required that a water-­
(60 min) prior to NAFL soluble blue tinted tracking dye solution be
• Additional anesthesia (e.g., oral analge- applied to the skin during treatment, current
sics, IV or IM medications) for AFL NAFL systems do not. NAFL treatment is deliv-
ered with concomitant forced air cooling at
energy settings ranging 25–70 mJ. Total energies
of 2–6 kJ are typically applied for full face treat-
Adequate preoperative patient evaluation and
ment. Re-treatments with gradually higher flu-
education are essential. Sun exposure should be
ences should be performed at 4  week intervals
avoided prior to treatment in order to decrease
until patients are satisfied with clinical outcomes
risk of postoperative dyspigmentation. For
(typically three to five sessions are necessary to
patients with a history of herpes labialis, prophy-
produce substantial clinical improvement). For
lactic oral antiviral medications should be con-
AFR, the fractional CO2 laser is typically used
sidered when treating perioral skin. Reactivation
with a 950 μs pulse duration and 12.5 mJ energy,
of prior herpes simplex infection can occur
creating average vaporization and coagulation
despite absence of an external wound due to the
depths of 160 and 350 μm, respectively. The frac-
intense dermal heat produced by the laser.
tional Er:YAG laser is often applied at a 350 μs
pulsed duration and 14  mJ energy, producing
Description of the Techniques
average vaporization and coagulation depths of
65 and 100 μm, respectively. Retreatment using
identical treatment techniques and parameters
Summary Box
can be performed at 6–8 week intervals as needed.
Description of the techniques: NAFR
Postoperative Management
• Laser treatment is delivered with con-
comitant forced air cooling. Energy set-
tings of 25–70  mJ at densities of Summary Box
125–250 MTZ/cm2 are applied to treat- • Mild cleanser, thermal spring water spray
ment areas in 8–10 passes (total energy mist, and moisturizer several times daily
applied per session: 2–6 kJ) for the first few postoperative days
9  Lasers for Resurfacing 159

Patients are instructed to use a mild cleanser, fractionated CO2 laser was associated with more
thermal spring water spray mist, and moisturizer pain during treatment. Although non-significant
several times daily for the first few days after differences in post-inflammatory hyperpigmen-
each treatment session (or as long as bronzing/ tation (PIH) rates were seen between the two
xerosis is apparent). systems, there was a trend toward higher PIH
risk with the fractionated CO2 laser. Taking all
Adverse Events risks and benefits into account, the fractionated
Er:YAG laser is often reported as a better treat-
ment choice for Asian patients. The prevention
Summary Box of PIH includes the application of topical bleach-
• Side Effects/Complications ing agents before and after laser treatment, the
–– Erythema, periocular edema, xerosis, use of a cooling device during treatment to pro-
and slight darkening of the skin tect the epidermis from laser heat, and the dili-
(bronzing) gent application of sunscreen after treatment
–– Post-inflammatory hyperpigmenta- [119, 120]. Additional research is ongoing to
tion in patients with darker skin tones determine optimal treatment parameters and the
• Prevention and Treatment long-term benefits and sequelae of fractionated
–– Ice pack application for first 48 h laser resurfacing in a variety of conditions and
–– Keep skin well-hydrated/moisturized skin phototypes.
for 48–72  h (or until xeroxis/bronz-
ing disappears). Conclusion
–– Strict ultraviolet light avoidance and Ablative laser skin resurfacing has revolution-
daily use of sunscreen ized the approach to photodamaged facial
skin. Technology and techniques continue to
evolve, further enhancing the ability to achieve
Side effects of fractional resurfacing are typically substantial clinical improvement of rhytides,
mild and transient, including erythema, periocu- scars, and dyspigmentation with reduced post-
lar edema, xerosis, and slight darkening of the operative morbidity. Utilizing proper tech-
skin (bronzing) during desquamation of the nique and treatment parameters, excellent
microscopic epidermal necrotic debris [112, clinical results can be obtained with any one
113]. Erosions are uncommon and can be man- or combination of CO2 and Er:YAG laser sys-
aged by liberal application of a healing ointment tems available. Therefore, the best choice of
or plain petrolatum with cool wet compresses laser ultimately depends on the operator’s
every 2–3 h. While permanent pigmentary altera- expertise, clinical indication, and individual
tion and scarring have not been reported after patient characteristics. Regardless of the type
NAFR treatment, use of an aggressive treatment of ablative resurfacing laser used, the impor-
protocol with high density microscopic thermal tance of careful postoperative follow-up can-
zones increases the risk of visible epidermal not be overemphasized.
ablation and its associated side effects. For those patients who desire a less aggres-
In clinical practice, the factors in choosing a sive approach to photorejuvenation than abla-
particular treatment are based not only on the tive laser skin resurfacing, non-ablative
anticipated treatment efficacy, but also on the dermal remodeling or fractional laser photo-
risk of adverse effects, recovery time, and pain thermolysis represent viable alternatives for
acceptability. A clinical study of patients with patients willing to accept modest clinical
darker skin [118] demonstrated that fractionated improvement in exchange for ease of treat-
Er:YAG laser treatment produced one-third the ment and a favorable side-effect profile.
coagulation depth of fractionated CO2 laser Treatments are typically delivered at monthly
treatment, but provided equivalent clinical out- intervals with progressive clinical improve-
comes and healing processes. In addition, the ment observed after each session. Recent
160 R. Wanitphakdeedecha and T. S. Alster

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9  Lasers for Resurfacing 163

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 Fractional Photothermolysis
10
Dieter Manstein, Hans-Joachim Laubac,
Sofia Iglesia, Alaleh Dormishian,
Ali Rajabi-­Estarabadi, and Keyvan Nouri

Abstract ates MTZs by thermal coagulation while

Traditional Resurfacing techniques are well Ablative FP generates MTZs by vaporizing
established treatments for modifying appear- microscopic zones of tissue which results in
ances and characteristics of the skin, but their immediate tissue loss and a surrounding zone
drawbacks include prolonged procedural of coagulated tissue. FP techniques include a
downtime, scarring risk and long-lasting hyper- wide spectrum of dermatological diseases that
pigmentation. Fractional Photothermolysis could be treated through the facilitation of drug
(FP) overcomes these drawbacks through the and cell delivery into the skin. FP demonstrates
generation of patterns of microscopic treatment to be an effective home-use product for self-
zones (MTZs), while leaving the surrounding treating wrinkles, 87% of patients have reported
skin undamaged, allowing for quick healing improvement in the appearance of wrinkles in a
and limits the development of inflammation 1–3 months period. The future for FP may
and fibrosis. The ability of delivering multiple include specialties beyond dermatology.
FP treatments and with the manipulation of the
laser parameters allows the physician to choose Keywords
between the two types of FP and customize the Fractional Photothermolysis · Microscopic
treatment regime that is best fit for the patients’ Treatment Zones · Ablative Fractional
needs and expectations. Non- Ablative gener- Photothermolysis · Non-Ablative Fractional
Photothermolysis · Dermatological Laser
Therapy · Fractional resurfacing ·
Microdermal Treatment Zones · Optical
D. Manstein (*)
penetration depth · Thermal coagulation ·
Wellman Center for Photomedicine, Massachusetts
General Hospital, Harvard Medical School, Vaporizing microscopic zones
Boston, MA, USA
e-mail: [email protected]
H.-J. Laubac Abbreviations
Dermatologische Abteilung, Universitäre Krankenhäuser
von Gen, Genf, Schweiz
FP Fractional photothermolysis
S. Iglesia · A. Dormishian · A. Rajabi-Estarabadi FR Fractional resurfacing
K. Nouri
MEND Microscopic epidermal-necrotic-debris
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, MTZ Microthermal treatment zone
Miami, FL, USA OPD Optical penetration depth

© Springer International Publishing AG, part of Springer Nature 2018 165

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_10
166 D. Manstein et al.

Introduction and Background

• Traditional resurfacing techniques have their

drawbacks

Traditional ablative resurfacing techniques

and non-ablative laser and light procedures are
well-established treatment modalities for modi-
fying the appearance and characteristics of skin
[1–3]. However, patients have become hesitant to
accept the side effects and risks associated with
traditional ablative techniques [4]. The main con-
cerns of ablative resurfacing are prolonged pro-
cedural downtime, risk of scarring, and the
incidence of delayed, long-lasting hypopigmen-
tation, also known as ‘alabaster skin’ [5, 6].
Further, traditional non-ablative techniques for
collagen remodeling have shown inconsistent
and often unpredictable results, frequently lead-
ing to unsatisfied patients and treating physicians
[7]. For a detailed description of the advantages Fig. 10.1  Concept of fractional photothermolysis. An
array of microscopically small zones of thermal injury, so
and disadvantages of traditional resurfacing tech- called MTZs (microscopic treatment zones, gray arrows),
niques, see Chaps. 9, 12, and 13 of this volume. is generated by multiple, focused laser pulses. Each of the
MTZ is surrounded by undamaged skin (orange, circular
• Fractional photothermolysis’ (FP) is a rela- arrow), allowing for fast repair (Laubach and Manstein [9])
tively new concept introduced by Manstein
et al. in 2004.
• FP is based on generating patterns of micro- of aesthetic and dermatological indications.
scopically small lesions, also called ‘micro- There is a broad range of possible treatment set-
scopic treatment zones’ (MTZs). tings that may be used to generate the resulting
• FP has become an established treatment— wound healing response. FP can be delivered in
technique in dermatological laser therapy. multiple treatments, each providing incremental
improvement within the limits of individual
To overcome the drawbacks of these tradi- patient’s tolerance for downtime and side effects.
tional resurfacing approaches, fractional photo- Therefore, FP gives the physician additional
thermolysis (FP) was developed by Manstein options to provide a customized treatment regime
et  al. [8]. In contrast to traditional laser tech- that is suited to fit their patient’s needs and expec-
niques, which provide laser exposure to the entire tations. FP procedures have become increasingly
skin surface, FP creates a pattern of microscopi- popular over the past few years and have become
cally small, 3-dimensional treatment zones an established concept in dermatological laser
(microscopic treatment zones or MTZs) while therapy. The rapid proliferation of publications in
leaving the skin surrounding each of these MTZs the dermatological literature related to FP is an
substantially undamaged (Fig.  10.1). The term indication of the significant impact that FP had
“fractional photothermolysis” was selected to on the field (Fig. 10.2). The success of FP is also
express that only a fraction (lat: frangere, to break documented by the wide variety of commercially
into pieces) of the skin is exposed to light (photo) available FP devices; virtually all dermatological
to thermally damage or destroy (thermolysis) laser device companies currently have at least
small treatment zones. FP procedures have been one FP device in their product portfolio (Tables
demonstrated to successfully treat a wide variety 10.1 and 10.2).
10  Fractional Photothermolysis 167

Citations of Selective and Fractional photothermolysis

350

300
Annual Citations 250
200

150

100

50

0
1980 1985 1990 1995 2000 2005 2010 2015 2020
Year
Sum of SP Citations Per Year Sum of FP Citations Per Year

Fig. 10.2  Annual citations of the original article for frac- SP. Further analysis reveals that recently SP citations are
tional photothermolysis (FP) and selective photothermol- increasingly for non-dermatological indications, e.g., in
ysis (SP). Data obtained from ‘ISI Web of Knowledge™’, ophthalmology or otorhinolaryngology. In contrast, FP
Thompson Reuters. The rapid proliferation of FP related citations are so far generally limited to dermatological
publications indicates an increasing impact of this concept indications (SP: Anderson and Parrish [10]; FP: Manstein
in the field of dermatology. The annual citations of FP et al. [8])
have already reached a level comparable to that of

Table 10.1  Characteristics of selected, commercially available non-ablative fractional photothermolysis (nFP)
devices, including manufacturer, device name, laser type, emitted wavelength, nominal spot size and range of energy/
MTZ. This table is not comprehensive, the pulse duration listed device parameters were obtained by manufacturer sur-
vey and are also subject to change
Wavelength Spot size [μm/ Energy [mJ/ Pulse duration
Company Device Laser type [nm] Delivery MTZ] MTZ] [ms]
Cynosure Affirm Nd:YAG 1440 ± 1320 Stamping 100–150 up to 4.1 1, 1.5, 2
Lutronic Mosaic Erbium 1550 Scanned 240 mJ 4–40 0.5–4.5
Stamping
Palomar Lux1540 Erbium 1540 Stamping 70 mJ per up to 100 5, 10
microbeam
Palomar Lux 1440 Nd:YAG 1440 2–240 0.25–5
Quanta Matisse Er:Glass 1540 Stamping up to 20 4–14
Sellas Sellas Erbium 1550 Scanned 312–1000 1–30 0.5
1550 Stamping
Solta Fraxel Erbium 1410 Rolling 4–70 5–20
re:fine
Solta Fraxel Er:Glass 1550/1927 Rolling 135/up to 600 4–70, 5–20 0.015–3
re:store Erbium 1440
(Former
SR 1550)
Clear+ Diode
Brilliant
DUAL Erbium+
thulium

• Individual MTZs are typically so small that section and the presence of adjacent unharmed
they induce neither extended inflammation tissue.
nor fibrosis. • MTZs can extend down to the deep reticular
• MTZs heal quickly due to their small cross dermis for certain laser parameters.
Table 10.2  Characteristics of selected, commercially available ablative fractional photothermolysis (FP) devices, including manufacturer, device name, laser type, emitted
168

wavelength, average optical emission power, nominal spot size and range of energy/MTZ. This table is not comprehensive, the pulse duration listed device parameters were
obtained by manufacturer survey and are also subject to change
Spot size [μm/
Company Device Laser Wavelength [nm] Delivery Power (W) MTZ] Energy [mJ/MTZ] Pulse duration [ms]
Alma Pixel CO2 CO2 10,600 Scanned stamping 40, 70 250 2500 mJ/p 50–300
Harmony (2940) Er:YAG 2940
Pixel Omnifit CO2 10,600
AMT Touch Cell CO2 10,600 Scanned stamping 30 200
Candela QuadraLase CO2 10,600 Scanned stamping 20
Cutera Pearl Fractional YSGG 2790 Scanned stamping 300 60–320 600
Cynosure Smart Skin CO2 10,600 Scanned stamping 30 0.2–20
Affirm CO2
Deka SmartXide CO2 10,600 Scanned stamping 50 300 0.2–80
DOT HP
Ellipse Juvia Fractional 10,600 Scanned stamping 0.1–15 500 5–15 5–7
CO2
Focus Medical NaturalLase Er Er:YAG 2940Up to 24 J/ 350
cm2
Fotona SP Pulse Nd: YAG/ 1064/2940 35–80 Up to 600 J/cm2 0.1–300
Er:YAG
SP Dualis Nd: YAG/ 1064/2940 35–80 Up to 400 J/cm2 5–200
Er:YAG
XS Dualis Er: YAG 2940 Up to 3000 mJ 0.1–1.5
XS Fidelis Er: YAG 2940 Up to 1000 mJ 0.1–1.5
Lasering USA Mixto SX CO2 10,600 Scanned stamping 0.5–30 180, 300 2.5–16
Velure S5 MiXto Diode 10,600 0.1–5 10–1000
VX
Lumenis Active FX CO2 10,600 Scanned stamping 60 1300 5–225 0.04–2
DeepFX 60 120 5–50 0.04–0.2
TotalFX – – 1–225 mJ <1 ms
Lutronic eCO2 CO2 10,600 Scanned stamping 30 120, 180, 300 4–120
D. Manstein et al.
 Spot size [μm/
Company Device Laser Wavelength [nm] Delivery Power (W) MTZ] Energy [mJ/MTZ] Pulse duration [ms]
Palomar Lux2940 Er:YAG 2940 Stamping 80–125 up to 25
Lux1540 1540
LuxDeepIR 850–1350
Infrared up to 175 J
light
Quanta youlaser CO2 CO2 10,600 Scanned stamping 30 0.05–20
Quantel BuraneFX Er:YAG 2940 Scanned stamping 30 150 0.7–32 0.35–250
EXELO2 CO2 10,600 40 350 Up to 2 J 1–100
10  Fractional Photothermolysis

Sandstone Matrix LS-25 CO2 10,600 25 100

Medical UltraFine-FS CO2 lasers 10,600
Technologies Scanner
Sciton ProFractional Er:YAG 2940 250 4–70
Halo™
Solta Fraxel re:pair CO2 10,600 Scanned stamping 40 136, 600 5–70 0.15–3
169
170 D. Manstein et al.

One of the key concepts of FP is that the tive resurfacing techniques, as confluent dam-
individual damaged tissue regions (MTZs) are age to such depth levels would impair the
so small in at least one dimension that the dam- skin’s ability to regenerate, and would most
aged or destroyed tissue is rapidly repaired likely result in scarring similar to that seen in
without any significance, the close proximity third-degree burns [11–13].
of surrounding viable tissue facilitates the
wound healing. Although the individual MTZs • Two distinct types of FP exist: non-ablative
induce a guaranteed wound healing response, FP (nFP) and ablative FP (aFP).
the extent of inflammation is limited and con- • Non-ablative FP (nFP) generates MTZs char-
fined to their close proximity. The overall acterized by thermal coagulation.
wound healing response is primarily deter- • Ablative FP (aFP) generates MTZs exhibiting
mined by the shape of individual MTZs and some degree of immediate tissue removal
their distribution (density) within the treatment (vaporization) and a surrounding zone of
area. This “fractional” approach contrasts with coagulated tissue.
thermal wounds having larger dimensions and • A distinction between superficial, medium
longer healing times, which are typically and deep FP procedures may facilitate descrip-
generated using conventional resurfacing pro- tion of the procedure, but is somewhat
cedures or the like. Another advantage of gen- arbitrary.
erating lesions on a microscopic scale is that
the individual lesions are so small that typi- At present, two distinct types of FP exist—
cally they cannot be resolved with the naked non-ablative FP (nFP) and ablative FP (aFP)
eye under clinical conditions, thereby ensuring (Fig.  10.3). Non-ablative FP (nFP) generates
a homogenous appearance of the treated area. MTZs having a small-diameter zone of thermally
MTZs heal quickly due to their small cross damaged epidermis and dermis extending down
section and the presence of unharmed tissue. to a particular depth. The shape of such MTZs is
They can extend down to the deep reticular either an inverted cone or a tapered column
dermis and still be well-tolerated in terms of extending into the dermis. The degree of thermal
rapid healing. Such deep tissue destruction has damage within an MTZ is typically sufficient to
to be carefully avoided with traditional abla- cause cell necrosis and to coagulate collagen.

a traditional b superficial c non-ablative d ablative

ablative fractional fractional fractional
ablative non-ablative

Fig. 10.3  Schematics of different resurfacing modalities. tissue. Despite of the thermal damage, the physical integ-
Traditional ablative procedures generate a confluent layer rity of the skin remains intact (c). AFP vaporizes some
of tissue removal and with thermal coagulation to the tissue, creating multiple MTZs which consist of a cavity
adjacent remaining tissue (a). Mainly, two distinct types lined by a thin layer of eschar and surrounded by a cuff of
of FP procedures exist, ablative (aFP) and non-ablative coagulated tissue (d). Further differentiation of FP proce-
(nFP) photothermolysis. nFP creates multiple micro- dures according to the depth of individual MTZ is possi-
scopic treatment zones (MTZs) consisting of coagulated ble, e.g., superficial FP, but somehow arbitrary (b)
10  Fractional Photothermolysis 171

The physical integrity of the skin remains intact, the Er:YAG laser(λ = 2940 nm) and 10 μm for the
in spite of the marked localized thermal damage laser (λ  =  10,600  nm) [17]. High volumetric
[8]. Ablative FP (aFP), on the other hand, creates energy densities are reached virtually instanta-
MTZs by vaporizing microscopic zones of tissue neously within the focus of the laser beam, and
up to a particular depth. This depth is primarily therefore such lasers can quickly advance a cav-
dependent on pulse energy and may extent into ity deep into the tissue during the pulse. Due to
the deep reticular dermis. The resulting tapered this process, it is possible that the resulting depth
cavity is lined by a thin layer of eschar and sur- of an MTZ can greatly exceed the optical
rounded by a cuff of thermal denaturation, which ­penetration depth of any particular laser wave-
is sufficient to destroy cells and coagulate colla- length. Once the local energy density exceeds the
gen. Ablative FP results in immediate tissue loss vaporization threshold, the depth of the laser cre-
due to the physical removal of portions of the ated cavity is primarily related to the total energy
skin by vaporization, and the physical integrity delivered for a given spot size, and relatively
and barrier function of the skin is locally compro- independent of the applied wavelength. It should
mised [14]. As the depth of MTZ can vary greatly, be noted, that the Er:YAG typically produces less
it appears reasonable to further distinguish thermal damage in the residual tissue as com-
between FP procedures generating MTZs of dif- pared to the CO2 laser due to the stronger absorp-
ferent depths, e.g., superficial, medium and deep. tion by water. As nFP procedures do not
While such a classification may serve to better physically remove tissue, the maximum depth of
describe a FP process, classification by damage MTZs in nFP procedures is limited by the optical
depth is somewhat arbitrary [15]. penetration depth of any particular laser wave-
length. Variation of the applied laser energy
• The laser wavelength determines primarily if allows some adjustment of the thermal injury
an FP procedure is ablative or non-ablative. depth within this physically imposed limit.
• Ablative FP procedures are performed with However, several points should be considered
lasers emitting at wavelengths corresponding when applying this concept to real procedures.
to strong absorption bands of water. The optical penetration depths provided are
• The depth of an MTZ for nFP is limited by the approximations of the penetration depth in water
optical penetration of the particular wave- provided by Hall [17]. The water content of tis-
length into skin tissue. sue can vary substantially and is approximately
30% for the epidermis and 70% for the dermis
FP procedures generate a 3-dimensional pat- [18]. As the optical properties of water are also
tern of MTZs in the skin and the wound healing temperature dependent, it has been reported that
response is primarily determined by the charac- the rapid change of tissue temperature during a
teristics of individual MTZs and their spatial dis- laser pulse can dynamically alter the penetration
tribution. The laser tissue effects generated depth substantially [19]. Also, other factors such
within individual MTZs depend primarily on as scattering, phase transitions (e.g., collagen
applied wavelength, pulse energy, focused beam denaturation), and non-linear phenomena should
diameter and pulse duration. The laser wave- be taken into consideration for a more detailed
length plays an important role in the characteris- analysis of the wavelength dependent effects on
tics and results of an FP procedure. The main the shape of MTZs. The following are examples
chromophore absorbing the laser energy, either of lasers that can be used for nFP, together with
for nFP or aFP, is water. Wavelengths that are their respective wavelengths (λ) and approximate
very strongly absorbed can result in local volu- optical penetration depth (OPD) : Er:YAG
metric energy densities sufficient to vaporize tis- (λ  =  1440  nm, OPD  ≈  300  μm) Er:Glass
sue [16]. Therefore aFP procedures are performed (λ = 1540 and 1550 nm, OPD ≈ 1000 μm), and
with lasers emitting at wavelengths correspond- Thulium fiber laser (λ  =  1927  nm,
ing to strong absorption bands of water. The OPD  ≈  100  μm). These differences in optical
approximate optical penetration depth (OPD) in penetration lengths indicate why the Thulium
water for such lasers is minimal, e.g., 1 μm for laser, with a relatively shallow penetration depth,
172 D. Manstein et al.

is often used to treat superficial lesions within the There are two general techniques currently
epidermis and papillary dermis, and why the available for generating the desired density of
Er:Glass laser with a relatively larger optical MTZs (number per unit area) within the treat-
penetration depth can generate MTZs extending ment area: the ‘stamping’ technique and the ‘roll-
down into the mid to deep reticular dermis. ing’ technique. The ‘stamping’ technique is
Because these provided numbers are estimates performed by forming a preset pattern of multiple
that which can be affected by various factors, MTZs on a skin region within a well-defined
they should serve only as a general guideline, exposure area of the fixed handpiece, and then
and not as a specific reference. moving the handpiece to another skin region and
repeating until the entire treatment area is cov-
• The pulse duration and temporal pulse profile ered. The density of MTZs at the end of a treat-
can affect the amount of thermal damage in ment session depends on the preset density within
the surrounding tissue. the exposure area of the handpiece and the num-
ber of passes performed over each skin region. A
The pulse duration for FP systems is typically pass is defined as the coverage resulting from a
in the range of up to a few milliseconds, but var- single application of the hand-piece to a particu-
ies with the preset energy applied per MTZ. The lar area of the skin. The ‘rolling’ technique is per-
MTZ energy is controlled for most FP systems formed by continuously rolling the handpiece
by adjustment of the pulse duration used to create across the entire treatment area. It is also referred
individual MTZs. In a first approximation, such as ‘brushing’ technique, because the movements
short pulse durations are within the thermal of the operator are similar to using a paint brush.
relaxation time of individual MTZs and minor As the velocity of the handpiece relative to the
variation of pulse duration should have limited skin varies during treatment, the delivery rate is
effects on lesion shape. However, variation of adjusted automatically in order to maintain a
pulse duration over an extended range of pulse defined, preset MTZ density per pass. The total
profiles will affect the MTZ shape, e.g., ablation density of MTZs at the end of a treatment session
depth and/or extent of residual thermal damage. can be estimated as the density of MTZs per pass
Tissue effects related to pulse duration and/or multiplied by the number of passes performed.
temporal pulse profile have not yet been charac- However, this presents only an estimate as with
terized in detail, but these parameters are likely each pass the remaining undamaged skin surface
to be the focus of future studies for optimizing decreases and therefore the effective amount of
FP procedures. The available average power of tissue that is newly damaged with each subse-
an FP laser system is a critical factor that limits quent pass decreases. Some MTZs formed on
the maximum overall coverage rate. For exam- subsequent passes may overlap or coincide with
ple, a laser that delivers a higher average optical MTZs already formed during prior passes. A
power can be capable of faster treatment of larger more detailed description of the determination of
areas. coverage in terms to number of passes is pro-
vided by Manstein et al. [20]. There appears to be
• Coverage of a treatment area can be achieved no single best technique for delivering the desired
by the ‘stamping’ or ‘rolling’ technique. density of MTZs. The ‘rolling’ technique can
• Typically, multiple passes are necessary to facilitate treatment of larger areas, while the
provide sufficient treatment coverage. ‘stamping’ technique can facilitate the precise
• Variation of the number of passes and expo- treatment of smaller areas, in particular areas
sure settings in different areas can be used to having an irregular surface profile. It is the opin-
adjust the clinical outcome in specific loca- ion of the authors that a reasonably well-defined
tions, e.g., ‘feathering’ at the edges of the MTZ density can be achieved with both tech-
treatment area. niques, and the choice between stamping and
• Excessively high treatment densities should brushing ultimately comes down to a personal
be avoided as they can result in undesirable preference of the operator. FP systems generally
side effects. allow the operator to adjust both MTZ density
10  Fractional Photothermolysis 173

and MTZ characteristics independently within mal effects on the tissue immediately surrounding
the treatment area. The MTZ density can be an MTZ have been observed. For example, apop-
adjusted by varying the preset number of pulses totic cell death and induction of various heat
per area and/or number of passes, while the shock proteins can be seen close to individual
dimensions of individual MTZs can be modified MTZs. Although the effects of such events on the
by adjustment of the MTZ energy, energy beam clinical outcome have to be further investigated,
focal characteristics, etc. Such control allows, for it can be speculated, that up to a certain extent,
example, formation of a decreased MTZ density these local heating effects around the MTZs may
at the periphery of a treatment area to avoid enhance wound healing and clinical outcome.
demarcation lines between treated and untreated Second, as each of the MTZs acts as a local
areas (feathering), or an increased MTZ density heat source, forming many MTZs within a short
or applied energy density within particular areas time period can lead to an increase in the average
that can benefit from an enhanced treatment out- tissue temperature of the treated region due to
come. The overall extent of the wound healing heat conduction. Such tissue heating is described
response, and thus the extent of both clinical by the term ‘bulk tissue heating.’ Bulk tissue
improvement and side-effects appear to be related heating can become a significant problem when
to the total amount of thermal injury or total the local average tissue temperature rises above a
energy delivered per treatment area. Treatment critical temperature such that confluent areas of
densities that result in confluent thermal injury tissue are damaged or destroyed, rather than lim-
can result in blistering or even scarring. iting such damage to discrete small microscopic
zones. Such gross thermal injury mimics that of a
• Bulk heating is the temperature rise of the tis- third degree burn, which can lead to substantial
sue between individual MTZs by thermal con- side effects including scarring.
duction as each MTZ acts as a local heat The following precautions should be taken
source. into consideration in order to avoid excessive
• Limited bulk heating may be desirable in FP bulk heating during FP procedures:
procedures.
• Excessive bulk heating can result in confluent (a) For higher individual MTZ formation ener-
tissue damage and severe side effects includ- gies, the spatial density of MTZs formed in
ing scarring. the treatment region should be decreased.
• Excessive bulk heating can be avoided by lim- (b) When multiple passes are performed on a
iting MTZ densities, extending the time inter- treatment region, the time interval between
val between passes and application of passes should be long enough to allow the
cooling. tissue to cool down between consecutive
• Changes in tissue temperature effect the shape passes.
of individual MTZs. (c) External cooling, e.g., forced air cooling, can
be used to remove some heat from the tissue
While FP procedures are designed to deliver region being treated.
localized thermal injury within individual MTZs,
it should be taken in consideration that energy Changes in tissue temperature have been
deposited into the tissue may accumulate under shown to affect the geometry of individual
certain conditions. The temperature gradient lesions. Reduction of MTZ dimension due to
tends to be very high within a single MTZ, often decrease of tissue temperature have been shown
resulting in a very sharp demarcation between to be more marked for nFP [21] as compared to
coagulated and non-coagulated collagen. aFP [22]. Skin cooling before, during and/or after
However, each MTZ represents a small heat FP treatments is often desirable because it can
source within the surrounding tissue. This heat- alleviate pain during treatment and also reduce
ing effect has two principal consequences. First, the risk of bulk heating. Because skin cooling can
although there is typically a very sharp demarca- also decrease the MTZ lesion size resulting from
tion at the perimeter of an individual MTZ, ther- particular system settings during an nFP
174 D. Manstein et al.

procedure, it is important to perform such proce- treatment intervals. The current intervals of sev-
dures under standardized cooling conditions to eral weeks are generally preferred because they
control the thermal damage within individual allow sufficient time for side effects to subside
MTZs. It should be noted that during aFP proce- and also arguably because such intervals are con-
dures, a substantial part of the laser energy is venient for the appointment scheduling of most
removed from the tissue with the hot laser plume. offices and patients. There is some controversy
This is in contrast to nFP procedures, and there- regarding the effect of multiple treatments ses-
fore it is reasonable to conclude that for the same sions on enhancement of treatment outcomes.
applied energy per MTZ energy and MTZ den- While it is generally accepted that multiple treat-
sity, the overall (bulk) heating of tissue is greater ments sessions can improve the overall outcome,
for nFP as compared to aFP. Although, no studies it is not clear exactly how the number of treat-
have been carried out to either confirm or quan- ments sessions is related to the overall improve-
tify this effect, the operator should be aware of ment. Also, it is still not known whether multiple
such potential interrelated effects that are based treatments performed at well-tolerated settings
on principles of laser tissue interaction. can mimic the outcome of fewer or single treat-
ments sessions performed with more aggressive
• FP procedures are typically performed as mul- settings that are associated with a marked wound
tiple treatments. healing response and prolonged downtime. FP
• Treatment outcome is typically incrementally treatments provide the possibility of obtaining
enhanced after additional FP treatments. particular degree of thermal wounding within
• Typically, a series of approximately 3–5 nFP individual MTZs and varying just the density of
or 1–3 aFP treatments are performed. such MTZs and/or adjusting the number of ses-
• There is some controversies regarding whether sions. In contrast, conventional treatments that
the clinical improvement of an aggressive cover the entire treatment area continuously do
treatment can be achieved by repetition of less not allow for this freedom. These full surface
aggressive treatments. procedures only allow for adjustment of the treat-
• FP treatments allow distribution of the ther- ment level by varying the fluence applied over the
mal wounding resulting from individual entire area.
MTZs at different densities and over distinct
treatment sessions. • Several factors beyond the laser parameter set-
tings can affect the thermal damage.
FP treatment of a particular skin region can be • Mechanical manipulation of the skin such as
delivered in single or multiple treatment sessions. compression, stretching and contraction can
Typically, 3–5 nFP or 1–3 aFP treatment sessions affect the shape and density of MTZs.
are performed, but the number of treatments can
vary within a wider range depending on indica- A variety of factors beyond an FP system’s
tions, treatment settings and patient response. preset MTZ exposure/energy and density settings
Each treatment is customized to a patient’s can affect the thermal injury of the tissue. The
individual condition to best manage side effects operator should be aware of such factors, as they
and downtime. The treatment is repeated until can impact the wound healing response, clinical
either the desired outcome is achieved or no fur- outcome, and side effects experienced by the
ther relevant improvement can be achieved. It patient. For example, mechanical factors such as
should be remembered that some of the effects, tissue stretching, contraction, or compression can
e.g., collagen remodeling, can progress over a affect MTZ lesion dimension and MTZ density.
period of weeks or months after a treatment. Stretching of the skin during exposure can lead to
Multiple treatments are generally performed at an increased actual density of MTZs. The density
intervals of approximately 4–8 weeks. However, per pass is typically preset by the system for a
there are no studies currently known that com- fixed exposure area, but skin stretching during
pare the outcomes achieved based on variation in the exposure can actually result in relatively
10  Fractional Photothermolysis 175

higher MTZ density. This can occur because as energy per MTZ and focal spot size), the number
the skin is able to retract after the stretching is of passes and time interval between them,
relieved, any number of delivered pulses is mechanical tissue manipulation, use of skin cool-
located within a relatively smaller area. MTZs of ing procedures, and others. The treatment inter-
smaller cross section can also result from stretch- val between individual passes within a single
ing of the skin prior to treatment, as the MTZs treatment session and the number of sessions can
that are formed in the stretched skin may shrink also be varied. This virtually unlimited number of
in size when the skin is allowed to retract. Point possible treatment combinations provides the
compression can distort the skin dimensions possibility of tailoring patient treatment proto-
locally during exposure, and relatively deeper cols to specific needs. However, this flexibility
MTZs with smaller cross sections can result from also leads to some complexity and uncertainty
such mechanical tissue manipulation. Also, associated with the choice and control of all pos-
because skin may contract as a result of localized sible parameters and factors. The multivariate
thermal injury to the collagen, the dimensions of complexity of FP procedures explains in part the
the skin can change during the delivery of a series current lack of clinical studies comparing the
of passes to generate individual MTZ patterns. effect of many specific FP parameters on patient
Ablative FP procedures performed, particularly outcomes. In spite of this complexity, it turns out
when performed with higher MTZ energies, tend that most FP treatment regimes result in some
to exhibit such shrinkage of the tissue during kind of clinical improvement for appropriate
multiple FP passes over a particular treatment indications. Also, the fundamental principles of
area. FP that guide the selection of treatment parame-
ters are relatively simple and can be summarized
• In addition to the shape and density of indi- by three basic rules. First, the dimensions of indi-
vidual MTZs, the number of treatment ses- vidual MTZs should not exceed certain dimen-
sions and intervals can be chosen by the sions, such that the induced wound healing
operator. results in tissue repair rather than inducing fibro-
• The broad variety of possible combinations sis. Second, the overall density of MTZs should
allows tailoring patient treatment protocols to not be excessively high to maintain sufficient
specific needs. undamaged tissue between the MTZs and facili-
• The multivariate complexity of FP procedures tate tissue repair. In particular, thermal damage to
represents a challenge to obtain comparative confluent tissue via bulk heating should be
clinical data. avoided. Third, the cumulative density of MTZs
• Most FP treatments result in varying degrees should be sufficiently high to induce sufficient
of clinical improvement for appropriate clinical improvement after a completed course of
indications. FP treatments.
• The three basic rules of any FP treatment are: When the concept of FP was first intro-
–– Individual MTZs should induce wound duced, the laser was used as the energy source
healing but not fibrosis. to generate fractional damage to the skin. The
–– Confluent damage and bulk heating should laser is still the most common energy source
be avoided. used in FP procedures. Its ability to quickly
–– The cumulative MTZ density should be deliver energy in the form of focused optical
sufficiently high to result in clinical radiation with high precision into small con-
improvement after the completion of a fined zones makes the laser a modality well
treatment course. suited for FP.  Recently, other energy sources
have emerged for generating fractional dam-
As discussed herein, many factors can affect age patterns. For example, radiofrequency
thermal damage patterns generated in the skin (RF) and ultrasound devices are now commer-
and subsequent wound healing responses. Such cially available that generate a pattern of small
factors include laser exposure parameters (e.g., and confined thermal damage zones in skin
176 D. Manstein et al.

tissue. The shape and anatomical location of tain conditions that traditionally have been a
MTZs generated using such modalities typi- domain of selective photothermolysis, includ-
cally differ from those induced by focused ing treatment of pigmented and vascular
optical radiation because of a different energy lesions. FP targets aqueous tissue that contains
distribution within the tissue. As RF energy such target lesions and therefore can affect a
quickly diverges with increasing distance from variety of lesions. Both, aFP and nFP have been
the delivering electrode, it is possible to gener- applied successfully to a variety of clinical
ate a spatially confined RF generated thermal indications, including collagen remodeling and
injury only within the tissue directly adjacent treatment of vascular and pigmented lesions.
to the tip of a needle electrode. Depending on Further details of indications and the wound
the location of the tip of such RF electrode, healing process are described in the following
damage can be generated either at the skin sur- sections. The balance between improved clini-
face [23], or virtually at any depth by inserting cal efficacy of aFP for selected indications as
needle electrodes into the skin [24], The use of compared to nFP and the additional risks and
stamping techniques with arrays or linear side effects of aFP associated with a impaired
arrangements of multiple needle electrodes epidermal barrier function and removal of
allows for coverage of a treatment area within entire columns of tissue in aFP is still being
a reasonable time. Focused ultrasound non- explored.
invasive generation of confined lesions [25], in
skin layers such as, e.g., the deep reticular der-
mis or even the superficial musculoaponeurotic Non-ablative Fractional
system (SMAS) without causing any surface Photothermolysis (nFP)
damage [26]. The MTZ cross section of RF or
ultrasound generated MTZs is typically larger • A variety of nFP devices are available in the
than that of laser generated MTZs because marketplace.
laser radiation can be more focused. However, • Principal treatment parameters for nFP are
the ability to focus optical radiation decreases applied energy per MTZ and density of MTZs
with increasing skin depth due to scattering (number per square centimeter).
and absorption of optical radiation. Further • To keep the areal fraction of damaged skin
investigations are needed to investigate how surface constant the MTZs density should be
the size and location of thermal lesions gener- decreased when higher MTZ energies are
ated using RF and ultrasound sources affect the applied.
clinical outcome as compared to laser-gener-
ated MTZs. An overview of certain systems currently
available commercial systems for nFP proce-
• aFP and nFP can treat a wide variety of clini- dures is presented in Table 10.1. These systems
cal conditions including some that have been use various lasers emitting in the near IR range.
traditionally the domain of selective photo- Spot sizes in these systems are all in the sub-­
thermolysis (SP). millimeter range, and the depth of the generated
• The relative benefits and disadvantages of MTZs is mainly wavelength dependent, varies
ablative and non-ablative FP approach are widely, and can extend into the deep reticular
being investigated. dermis for some systems. The depth and diameter
of individual MTZs is positively correlated with
Both aFP and nFP target water-containing energy [27].
tissue and, unlike selective photothermolysis Variation of the focusing optics can also affect
procedures [10], there is no significant selectiv- MTZ shape [28]. An example of the effects of
ity of specific components because virtually all different energies on the thermal damage and
cells of the skin are composed primarily of shape of MTZs is exhibited in Fig. 10.4. Primary
water. Nevertheless, FP can be used to treat cer- treatment parameters for nFP include the energy
10  Fractional Photothermolysis 177

a b

Fig. 10.4  Skin histology resulting from a nFP device at skin. The depth and diameter of the MTZs vary with energy,
different energy levels. NitroBlueTetrazolium stain was 40 mJ (a) vs. 100 mJ (b). Note, the unstained part of the
used to monitor for thermal damage. Lack of blue staining lesion consist of thermally damaged tissue rather than a cav-
indicates thermal cell injury. Lesions were produced with ity. Also, the commercial version of this laser is limited to a
Fraxel re:store, Solta, λ = 1550 nm within excised human maximum energy of 70 mJ/MTZ (Thongsima et al. [28])

applied per MTZ and the areal density of MTZs • The remodeling of the damaged dermis can
(e.g., the number per square centimeter). It is take several weeks and occurs without forma-
therefore necessary to decrease the MTZ areal tion of fibrosis.
density if higher energies are applied per MTZ to
keep the areal fraction of damaged skin surface Histological analysis immediately after nFP
constant. treatment shows a column of thermally denatured
dermis and epidermis that constitutes a micro-
• Histologically, a column of necrotic, coagu- scopic treatment zone (MTZ) (Fig.  10.5a). In
lated tissue is generally observed within the addition, subepidermal clefting may be observed
skin after formation of a MTZ via nFP. in the area of the MTZ.  This destruction of the
• The skin barrier is preserved in nFP and the dermal-epidermal (DE) junction corresponds to a
dam- aged epidermis is quickly replaced. microscopic blister, the size of which generally
• Oval balls of microscopic epidermal necrotic increases with the energy per MTZ.  The tissue
debris (MEND) on the skin surface are often surrounding the MTZs appears microscopically
observed within 24 h of an nFP treatment. undamaged. Further, the stratum corneum over-
• The ‘MENDs shuttle’ allows for controlled lying the MTZ often appears unaltered, thus, pre-
removal of epidermal and dermal content, serving an intact skin barrier is preserved after
e.g., melanin and elastin. nFP treatment. This is consistent with
• nFP is well-suited for treatment of ‘low con- the early studies of Manstein et  al. [8] who
trast’ superficial pigmented lesions. reported an absence of any significant change in
178 D. Manstein et al.

a b

Fig. 10.5  Skin histology at different time points after arrows), which represent the elimination of thermally
nFP treatment. H&E stain, 200×. Lesions were produced damaged keratinocytes. MENDs are loaded with melanin.
with Solta prototype, λ  =  1500  nm, 5  mJ/MTZ. (a) 1  h Subepidermal clefting is evident from 1  h after FP and
after treatment a column of denaturated collagen (black lasts up to 5  days (stars). The dermal part of the MTZs
arrow) can be seen within the MTZ (black outline). The appears the same as immediately post treatment and shows
entire stratum corneum remains intact, even above the thermally altered collagen and a lack of nuclear staining.
MTZ. There is no inflammatory infiltrate around the MTZ Subtle perivascular inflammatory infiltrate begins to form
yet. (b) Day 1 after nFP.  MTZs (black outline) contain in the dermis (white arrow) (Laubach et al. [29])
microscopic epidermal necrotic debris (MENDs, black

trans-­epidermal water loss after nFP. Due to the through the epidermis and stratum corneum, the
typically small (sub-millimeter) cross section of number of dyskeratotic cells is reduced within
the MTZ, a rapid repair of the thermally damaged the epidermis. About 1 week after the nFP treat-
epidermis is generally observed. Within 24 h fol- ment, the epidermis usually appears normal
lowing an nFP procedure, necrotic cells in the again. The MEND shuttle primarily facilitates
epidermis are replaced by viable keratinocytes controlled elimination of epidermal pigment, but
migrating to the damaged areas from the it also allows for the removal of dermal content.
unharmed tissue surrounding the MTZ The removal of pigment and dermal content by
(Fig.  10.5b) pushing the cellular debris of the MEND shuttle can be well-controlled by
necrotic cells upwards towards the skin surface. selection of the overall MTZ density formed dur-
Due to the excretion of the necrotic debris via the ing an nFP procedure. In contrast to laser proce-
upper portion of the MTZs, oval balls of tissue dures that utilize selective photothermolysis, the
may appear within about 24  h after nFP treat- relative amount of pigment removed by the
ment. This tissue is referred to as microscopic MEND shuttle is independent of the pigmenta-
epidermal necrotic debris (MEND) [8]. Immuno-­ tion of the treated tissue, because the wavelengths
histochemical staining has revealed that MEND utilized to form the MTZs are primarily absorbed
is mainly composed of necrotic epidermal tis- by water.
sue (including, e.g., melanin) but may also This feature allows for a gradual removal of
include portions originating from of dermal tis- pigment of all skin colors by adjusting the den-
sue (e.g., elastin) [30]. In the days following an sity of MTZs. The pigment is also laterally redis-
FP procedure, MEND migrates through the stra- tributed during the MEND shuttle process, so
tum corneum and can produce a small flaked that a relative homogeneous removal of epider-
shedding. The term ‘MEND shuttle’ describes mal pigment can be achieved. As this process
the release of dermal and epidermal material does not rely on the chromophore properties of
through the MEND migration and shedding. melanin, all skin types can be effectively treated
During the migrational period of the MEND by the nFP process. Therefore, nFP is a proce-
10  Fractional Photothermolysis 179

dure of choice for removing pigment that pres- beneficial effect on small vascular lesions. This
ents as a ‘low contrast lesion’, i.e., where the vascular effect generally requires application of
difference in pigmentation levels between the higher nFP energies to reach the tissue depth
lesion and the surrounding skin are relatively where the vascular targets are present. The clear-
small. While the epidermal damage produced by ance of vascular targets in the treatment region by
nFP is quickly repaired, the dermal (deeper) por- using an nFP treatment with a high energy
tion of the MTZs is still well distinguishable for applied per MTZ was achieved (Fig.  10.7a, b),
several weeks as a column of thermally coagu- whereas a similar region of the same patient that
lated collagen surrounded by minor perivascular, was treated with the same total energy applied
inflammatory infiltrate. Histological analyses per unit area of the treatment region—but using a
performed 3  months after an nFP procedure lower energy per MTZ formed—did not show
­indicate that the dermal portions of the MTZs are any significant clearance of vascular lesions
no longer distinguishable by standard H&E stain- (Fig. 10.7c, d). The authors are not aware of any
ing. However, overall dermal remodeling and published clinical studies that have been per-
restoration of a more undulated DE junction have formed to date on the treatment of vascular
been reported after nFP procedures [8]. lesions with nFP, and further research is war-
ranted in this area.
• nFP can also affect fine vessels, particularly
for higher MTZ energies. • The risk of bulk heating can be reduced by
con- current use of cooling.
The effects of nFP are not limited to removal • Cooling may alter the MTZ shape.
of epidermal pigment (Fig.  10.6a) and collagen
remodeling (Fig. 10.6b). It has been shown both Forming relatively deep MTZs can be benefi-
histologically and clinically that nFP can also cial due to an increase in the local volume of ther-
affect small vessels (Fig.  10.6c) [29]. Although mally altered or destroyed tissue within the skin.
there is no significant selective absorption of However, increasing the diameter of the MTZs
energy by vascular targets in nFP procedures, it and/or the areal MTZ density ultimately results
has been shown that small vessels having cross-­ in unwanted side effects arising from increased
section areas comparable to those of the MTZ damage to the dermoepidermal junction (DEJ)
lesions can be coagulated in a statistical manner, and a stronger wound healing response. Although
e.g., based on random intersection of the MTZs the optimal diameter and depth of MTZs formed
and vascular lesions. While selective photother- during nFP to produce the greatest clinical effi-
molysis remains the technique of choice for cacy and fewest side effects are yet to be deter-
removal of vascular lesions, nFP can also have a mined, some limitations on these parameters

a b c

Fig. 10.6  Histological summary of the main effects of engulfing MTZs (arrow). (c) Coagulation of small blood
nFP procedures. (a) Pigment removal (arrow) by MENDs vessels by statistical co-location of the MTZ and vessel
shuttle process (Fontana Masson stain). (b) Dermal (arrow)
remodeling as evidenced by positive colla gen type III
180 D. Manstein et al.

a b

c d

Fig. 10.7  Energy dependent response of telangiectasias 13 J/cm2) and outcome assessed 1 month after last treat-
to nFP treatment. A study patient with rosacea and acne ment. The side treated with a lower MTZ energy (6 mJ/
scars had similar distribution of fine telangiectasias in MTZ, ≈2200 MTZ/cm2) did not show any reduction of
contra-lateral areas of the face. 3 nFP treatments were per- telangiectasias (a) and (b). The side treated with higher
formed at 1  month intervals with Fraxel re:store, MTZ energy (70 mJ/MTZ, ≈200 MTZ/cm2) showed sig-
λ = 1550 nm. A similar Fluence (average energy per area) nificant reduction of telangiectasias (c) and (d)
was delivered at each side per treatment (approximately

have already been established. For example, it is short a time period can inhibit thermal relaxation
well known that too much thermal damage per of the tissue in between passes and result in bulk
unit area of skin tissue (e.g., resulting from a heating of the entire treatment area. The thermal
large number of MTZs formed per unit area of energy in such nFP procedures is no longer con-
tissue) can result in a loss of dermoepidermal fined to the MTZs but instead diffuses into the
integrity and generation of severe unwanted side surrounding tissue, leading to a thermal alteration
effects, such as blistering. Furthermore, creating of the entire tissue rather than limiting such ther-
too many MTZs within a region of skin in too mal effects to the well-defined MTZ volumes.
10  Fractional Photothermolysis 181

This spreading of the thermal energy ultimately and clinical improvement is not generally known,
may lead to unwanted side effects, including and depend at least in part on the particular nFP
scarring of the treatment area. The combination parameters used and the condition being treated.
of areal density of MTZs, energy used to form The optimal time interval(s) between successive
each MTZ, and the time interval in which they nFP treatment sessions for achieving optimal
are created that can generate beneficial effects efficacy and a minimum of side effects also
without introducing significant bulk heating to remains to be determined. In one particular
the treatment area remains an area in which more example, it has been proposed that longer inter-
studies are needed. Several techniques for reduc- vals between nFP treatment sessions, e.g., up to
ing the risk or extent of unwanted bulk tissue 2 months, are preferable when treating Fitzpatrick
heating are described above. In particular, the use skin type IV–VI to reduce the risk of post inflam-
of skin cooling (e.g., forced-air cooling) and/or matory hyperpigmentation (PIH) [32].
allowing sufficient time between consecutive
nFP treatment passes can facilitate cooling of the • Discomfort during nFP treatment increases
treatment region. A decrease in skin temperature significantly with the energy applied per MTZ
also tends to decrease the epidermal MTZ diam- and the MTZ density per pass.
eter for a particular set of applied energy param- • Different approaches such as prior and/or
eters [21]. Therefore, tissue cooling effects simultaneous skin cooling, local application
should be considered when planning or compar- of a topical anesthetic, etc. can be used to
ing nFP treatments. reduce or eliminate perceived pain.

• About 3–5 nFP treatment sessions are generally One of the side effects of nFP treatment is
recommended; the exact number depends on patient discomfort during the treatment itself.
the particular indication and desired end result. This discomfort increases mainly with the energy
• Other side effects associated with nFP treat- applied per MTZ, but also with the MTZ density
ment include a moderate erythema and/or per pass [32]. Several different approaches are
edema developing immediately after the treat- currently used to decrease discomfort during
ment and lasting up to 5 days; the severity of treatment. Concomitant skin cooling during laser
these side effects exhibit a positive correlation treatments not only reduces undesirable side
with MTZ energies and densities. effects such as bulk heating, but also reduces dis-
comfort associated with nFP laser treatments
FP is based upon the concept of restricting [33]. Providers of various nFP systems often rec-
thermal damage or alteration to well-defined ommend either contact or air convection cooling.
microscopic zones within of the skin, whereby Some nFP laser system providers recommend the
the surrounding healthy tissue can facilitate a use of anesthetic cream prior to the nFP treat-
rapid wound healing of the small damaged tissue ment, while others do not recommend the use of
volumes. Typically, about 10–30% of the skin additional anesthetics. Because of a lack of com-
surface is thermally damaged or destroyed using parative trials, it is currently not well investigated
focused laser beams in an nFP procedure. About whether there is a significant difference in patient
3–5 nFP sessions are generally recommended for pain perception with different nFP systems.
treating a particular region of skin; the exact
number of sessions can depend on the indication • Bronzing due to the MENDs formation and
and desired end result. Although patient satisfac- migration through the epidermis and stratum
tion (an indicator of treatment efficacy) generally corneum can be observed 3–7  days after an
improves with the number of treatment sessions, nFP procedure.
the improvement in satisfaction between the third
and the fourth treatment appears to be only mar- Other side effects associated with nFP treat-
ginal [31]. The optimal number of nFP treatment ment include a moderate erythema and edema
sessions needed for greater patient satisfaction developing immediately after the treatment and
182 D. Manstein et al.

typically lasting for up to about 1  week. The with the Thulium laser is shown in Fig. 10.8. For
severity of these side effects show a positive cor- post-nFP aftercare, a hydrating, non-greasy
relation with MTZ energies; MTZ areal densities moisturizer is generally recommended because
are not only associated with an increase in ery- patients commonly report a sensation of rough
thema and edema, but also correlate with and dry skin, most likely due to the MEND shed-
observed post inflammatory hyperpigmentation ding that commonly occurs several days after the
(PIH) [32]. Although a reduction in efficacy has procedure. Furthermore, there is an increased
been observed for nFP skin rejuvenation proce- risk of the formation of acne-like lesions, espe-
dures with lower energy settings, lower applied cially with the use of higher treatment energies.
energies are also correlated with a reduction in Using a non-occlusive aftercare product may
the duration and severity of side effects like ery- reduce this risk. Patients with a positive history
thema and edema [32]. A patient’s downtime cor- of facial herpes simplex should take oral antiviral
responds to the duration and the severity of the medication prior to nFP treatment to prevent or
post-treatment erythema and edema, and is typi- inhibit viral reactivation. The effectiveness of
cally on the order of a few days. The authors’ systemic or topical corticosteroids in reducing
experience suggests that the consistent use of side effects such as edema and erythema without
cooling pads during the first 24 h after nFP treat- compromising treatment efficacy is yet to be
ment further reduces the severity of erythema and determined.
edema. During the third to seventh days after an
nFP procedure, the treated skin often shows a • The risk of post-inflammatory hyperpigmen-
slight bronzing due to the MEND formation and tation in patients having darker skin types can
migration through the epidermis and stratum cor- be decreased significantly by reducing the
neum as noted above. This bronzing effect tends density of MTZs, and by simultaneous skin
to be evenly distributed over the treated area, and cooling.
most patients describe this effect as cosmetically
not unpleasant and feeling slightly “suntanned.” Non-ablative FP procedures can be associated
Such bronzing effect can contribute to the epider- with minor petechial bleeding, especially if
mal elimination of melanin. As this bronzing is patients continue to traumatize the skin during the
related to trans- epidermal melanin elimination, it first few days after the treatment (e.g., by wearing
is generally more accentuated for darker skin tight wristbands, necklaces, etc.). Chan et al. [34]
types and within treatment areas of enhanced observed that a mild-to-moderate post-­
melanin density. inflammatory hyper- pigmentation (PIH) occurs
The 1927 nm Thulium laser has been recently in about 7.1–17.1% of Asians undergoing nFP
introduced in an nFP system and promoted treatment; the likelihood of this side effect
among other indications the removal of superfi- depends on the laser settings and evaluation
cial pigment, including for non-facial areas. method. The risk of PIH, especially for darker
Published details or studies of this system are not skin type patients, can be reduced significantly by
available as of the publication date of this vol- decreasing the extent (including the overall area)
ume. This system can produce a larger MTZ of dermo-epidermal junction destruction, e.g., by
diameter of up to approximately 600  μm. Its reducing total MTZ densities and using simulta-
wavelength is more superficially absorbed neous skin cooling [32, 34, 35]. Furthermore, pro-
(OPD  ≈  100  μm) as compared, for example, to tection from sunlight during the weeks after nFP
nFP systems based on the 1540 nm or 1550 nm treatment should be emphasized to the patient to
lasers (OPD ≈ 1000 μm) but less absorbed than further reduce the likelihood of unwanted PIH. It
aFP systems based on CO2 lasers (OPD ≈ 10 μm). remains to be determined whether lengthening the
Thus it is designed to generate thermal injury in time intervals between successive nFP treatments
relatively superficially tissue without significant can help to reduce the occurrence of PIH.
disruption of the epidermal barrier. A representa- Currently available data suggests that nFP treat-
tive example of the clinical course after treatment ments can be customized to the patients’ desires
10  Fractional Photothermolysis 183

a b

c d

Fig. 10.8  Clinical course of after single treatment with significant improvement of the dyschromia at 1 and 6 months,
Thulium laser. Treatment was performed with Fraxel Dual there is partial recurrence of dyschromia at the 10 months fol-
(Solta), λ = 1927 nm, 10 mJ/MTZ, ≈800 MTZ/cm2, treat- low up. This is likely due to continued sun exposure as the
ment level 7, 50% density. Clinical appearance at baseline patient participated in frequent outdoor sports without
(a), 2  days (b), 6  months (c) and 10  months (d). After proper UV protection (Courtesy of Steven Struck, M.D.)
184 D. Manstein et al.

to balance the aggressiveness of treatments to ment of photoaging including fine and moderate
achieve a higher efficacy with the likelihood of rhytides (Fig.  10.9), treatment of traumatic
causing undesirable side effects. (Fig.  10.10), surgical, burn (Fig.  10.11) and
acne scarring, striae distensae, and treatment of
• The main indications for nFP are treatment of dyschromia e.g., superficial pigmented lesions
photoaging, various kinds of scars and treat- like solar lentigines. The authors would like to
ment of dyschromia. ­highlight the ability of nFP to improve various
• Improvement of deep rhytides and skin tight- kinds of scars including textural skin alterations
ening is limited. after involution of hemangiomas (Fig.  10.12),
• Melasma has a high risk of recurrence. as for these indications remarkable improve-
ment was reported that was previously difficult
Non-ablative FP has been shown to be effec- to obtain. Although, nFP has the ability to
tive on a wide variety of conditions [36–40], improve the appearance of rhytides, by increase
including but not limited to a variety of indica- epidermal thickness, papillary dermal collagen
tions related to collagen remodeling, e.g., treat- and increase the number of fibroblasts, [41]

a b

Fig. 10.9  Clinical improvement of fine and moderate after last treatment. Note: Treatment was performed as
(dynamic) rhytides. A series of 3 nFP treatments was per- part of a clinical study, and the use of neurotoxins (not
formed with Fraxel re:store (Solta), λ = 1550 nm, 70 mJ/ applied to this patient) would likely have provided similar
MTZ, approx. 200 MTZ/cm2. (a) Baseline. (b) 6 months results

a b

Fig. 10.10  Clinical improvement of a traumatic scar. A The scar virtually disappeared after the completion of the
traumatic scar that was persistent for more than 10 years series of treatments. (a) Baseline. (b) 6 months after last
received a series of 3 nFP treatments with Fraxel re:store treatment
(Solta), λ = 1550 nm, MTZ energy 70 mJ, ≈200 MTZ/cm2.
10  Fractional Photothermolysis 185

a b

Fig. 10.11  Clinical improvement of a burn scar. A burn ment level 8. Significant improvement of texture and pig-
scar which occurred 30 years ago, obtained a series of 5 mentation is observed. (a) Baseline. (b) 5 months after the
nFP treatments with Fraxel re:store (Solta), λ = 1550 nm, last treatment (Courtesy of Steven Struck, M.D.)
MTZ energy 40 mJ, ≈450 MTZ/cm2, 23% density, treat-

a b

Fig. 10.12  Clinical improvement of scarring. Skin alter- series of 5 nFP treatments achieved a significant smooth-
ations mimicking dermal scarring had developed after the ening of skin surface (Solta, re:store, λ  =  1550  nm,
involution of an early childhood hemangioma and were ≈40  mJ/MTZ, treatment level 8). (a): Baseline. (b):
stable for approximately 13 years prior to FP treatment. A 1 month after last treatment

abltaive FP hold superior clinical outcomes due • Many novel indications for nFP are emerging.
to reaching deeper dermal ablation and coagu- • Determination of optimal nFP parameters for
lation [42]. par- ticular indications is an area of ongoing
Treatment of melasma with nFP is an option study
but it should be used with caution, because of the
relative high rate of repigmentation and some- Other indications that have shown some prom-
times even an increase in pigmentation after nFP ise for treatment using nFP in small case studies
treatments [43]. are minocycline-induced hyperpigmentation [44],
186 D. Manstein et al.

granuloma anulare [45], striae rubra [46], Nevus turation. A varying degree of thermal damage in
of Ota [47], alopecia areata [48], and Poikiloderma the residual tissue immediately adjacent to the
of Civatte [49]. While results of these case reports evaporated tissue of aFP procedures has been
suggest promising results, further clinical studies observed, similar to that resulting from conven-
are needed before nFP can be established as a tional ablative resurfacing techniques. The ther-
standard of care for such indications. Nevertheless, mal coagulation zone around the laser cavity
it is encouraging to see that nFP may be an option typically varies with the type of laser and pulse
for treating such clinical problems. Although a duration used. For example, the CO2 laser used in
wide variety of nFP systems, treatment parame- conventional resurfacing procedures produces
ters, and regimens have been shown to provide typically more residual thermal damage as com-
measurable clinical improvement for various der- pared to the Er:YAG laser [50], and thermal
matological indications, determination of optimal effects generated by a laser tend to increase with
parameters and conditions for particular indica- longer pulse duration [51].
tions remains an area of ongoing study.
• The pulse duration and temporal pulse shape
affect residual thermal damage.
Ablative Fractional • Mechanical factors applied during the post
Photothermolysis (aFP) treatment regime might affect clinical skin
tightening.
• A variety of different aFP laser systems are
available, and most of them are based on CO2 Analogous to traditional ablative procedures,
and Er:YAG lasers. the amount of residual thermal injury in aFP pro-
cedures may also be affected by the temporal pro-
Ablative FP systems utilize wavelengths that file of the laser pulse. Typical temporal profiles
are strongly absorbed within tissue as compared for energy delivery include continuous wave
to wavelengths used in nFP systems. The result- (CW), superpulsed [52], and ultrapulsed [53]
ing high energy densities lead to vaporization of mode. Although such dependency of thermal in
tissue. An overview of selected aFP systems cur- jury on pulse profile appears reasonable, there is
rently available commercially is provided in currently no investigational data available that
Table 10.2. specifically relates the extent of thermal damage
for aFP procedures to the temporal pulse profiles.
• Ablative Fractional Photothermolysis (aFP) is The amount of immediate skin shrinkage result-
a procedure characterized by formation of ing from an aFP treatment (with CO2 laser) is
microscopically small zones of removed typically greater than that observed in nFP proce-
(ablated) tissue surrounded by a small cuff of dures. However, histological analysis indicates
thermally damaged tissue embedded in viable that nFP procedures may even exhibit a greater
tissue. total volume of denatured collagen, as compared
to an aFP process performed with similar energy
Vaporization of tissue within an MTZ gener- per MTZ (comparison of data from Hantash et al.
ated in an aFP procedure forms a tapered cavity [14] and Thongsima et  al. [28]). This seems to
lined by a thin layer of eschar [14]. The thin layer contradict the general observation that the extent
of eschar is surrounded by an annular coagula- of skin shrinkage is related to the total amount of
tion zone containing denatured collagen and cell denaturated collagen. The authors hypothesize
necrosis. While the zones of denatured collagen that as collagen denaturation and skin shrinkage
and cell necrosis substantially overlap, the extent occur at virtually the same time while the laser
of the zone of cell necrosis is slightly larger due cavity is being formed, that part of the denatur-
to the lower thermal damage threshold for cell ated collagen is removed during the cavity form-
necrosis as compared to that for collagen dena- ing process. Histology reveals a static image of
10  Fractional Photothermolysis 187

the amount of denaturated collagen after the com- each MTZ.  Figure  10.13 illustrates the increase
pletion of the MTZ formation. Further research is of depth and diameter of an ablated MTZ with
indicated to investigate the dynamics of the vari- increasing energy. Furthermore, because the stra-
ous processes occurring within the short time of tum corneum is also evaporated in the core of
the formation of ablative MTZs. In general, MTZs formed during aFP, there is an actual dis-
immediate tissue contraction during aFP due to ruption of the physical epidermal barrier that is
collagen shrinkage is an indicator of anticipated proportional to the size and density of MTZs.
skin tightening. However, the role of wound heal- Accordingly, aFP leads to more significant
ing on the clinically relevant skin tightening impairment of the protective and barrier function
should also taken into consideration. Animal stud- of the epidermis as compared with non- ablative
ies have demonstrated that the skin tightening, techniques. This aspect presents opportunities for
including the direction of contraction can also be the concurrent delivery of drugs to the tissue but
significantly affected by factors that were applied also imposes additional risks, such as an increased
during the wound healing process after the com- risk of bacterial infection following aFP proce-
pletion of an aFP procedure. In particular, direc- dures. Therefore, the use of antibiotic ­prophylaxis
tion of mechanical forces (e.g., gravity or elastic is typically indicated for aFP procedures of larger
wound dressings) applied during the initial sev- areas. The physical disruption of the epidermal
eral days have been shown to affect significantly barrier is also evidenced by serous oozing and
the outcome [54]. These observations should punctuate bleeding following aFP procedures.
stimulate further research before specific clinical However, such side effects related to the disrup-
recommendations on a modified post treatment tion of the epidermal barrier resolve typically
regime can be made. within about 12–24 h after the disruption occurs
[55]. Although ablated MTZs can reach a depth
• Ablative FP impairs the epidermal barrier and in excess of 1  mm, they heal relatively fast. A
can facilitate enhanced drug delivery but also representative time line of the histological wound
bacterial infections. healing for an aFP procedure is illustrated in
• The use of antibiotic prophylaxis is typically Fig.  10.14. Analysis of in-vivo histology at dif-
indicated for aFP procedures of a larger areas. ferent times after an aFP treatment revealed that
• Impairment of epidermal barrier results in tem- re-epithelialization has taken place within 48 h of
porary serous oozing and punctuate bleeding. the treatment. The basement membrane was
restored within 7  days, and a coagulation zone
The depth and diameter of MTZs formed could be observed up to approximately 1 month
using a particular aFP system is primarily depen- after the procedure. A representative time line of
dent on the energy applied to the tissue to form the clinical course after an aFP procedure is pre-

a b c d e f g

Fig. 10.13  Skin histology resulting from aFP at different energy. (a) 10  mJ, (b) 20  mJ, (c) 30  mJ, (d) 40  mJ, (e)
energy levels. H&E staining. Lesions were produced 50 mJ, (f) 60 mJ, (g) 70 mJ (Courtesy of Solta Medical,
within excised skin with Fraxel re:pair (Solta), Biomedical Research Team)
λ = 10,600 nm. MTZ diameter and depth increases with
188 D. Manstein et al.

a b c d e

Fig. 10.14  Wound healing resulting from aFP at differ- membrane was restored within 7 days, and a dermal coag-
ent time points. H&E staining. Skin lesions were pro- ulation zone could be observed up to approximately
duced with Fraxel re:pair (Solta), λ = 10,600 nm at 20 mJ/ 1 month after the procedure. At 3 months the lesions were
MTZ. Analysis of in-vivo histology at different times after resolved without evidence of fibrosis. (a) 0  day, (b)
an aFP treatment revealed that re-epithelialization has 2 days, (c) 7 days, (d) 30 days, (e) 90 days (Hantash et al.
taken place within 48  h of the treatment. The basement [56])

sented in Fig. 10.15. The duration of wound heal- Figures 10.16 and 10.17 illustrate cases of clin-
ing from aFP is shorter as compared to traditional ical improvement of photoaging with concur-
ablative CO2 resurfacing procedures, but is rent respectively moderate and severe rhytides.
considered longer than that observed in nFP
­ Although decreased patient downtime is desir-
procedures. able, traditional ablative resurfacing proce-
dures—with generally long downtime periods—
• Currently aFP is primarily used for dermato- are still the gold standard of treatment for
logical indications that require collagen marked photodamage.
remodeling.
• The relative efficacy of aFP and nFP for vari- • Options for anesthesia are similar to conven-
ous indications remains to be determined. tional ablative resurfacing techniques.

Almost all dermatological indications that Anesthesia for aFP treatments can be pro-
have been treated by nFP procedures have also vided by topical agents, local infiltration, cool-
been treated by aFP procedures [56–58]. The ing, and/or nerve blocks. The level of patient
authors are not aware of any extensive clinical pain tolerance, the laser parameters used (e.g.,
studies performed to date that the authors are pulse energies and durations), and treatment
aware of comparing the outcomes of nFP and location are all factors to be considered for indi-
aFP procedures for the same conditions. It is vidual pain management. The use of systemic
important for the clinician to have more com- agents, including narcotics, sedation or intrave-
parative data available to better assess whether nous anesthesia, may be warranted for some
the typically enhanced profile of side effects patients, particularly when treatment of larger
associated with aFP procedures is justified by areas is performed on sensitive patients.
improved clinical outcomes. Generally, aFP Postoperative management is aimed to alleviate
procedures are observed to provide enhanced edema, exudates, and postoperative. Discomfort.
collagen r­emodeling, e.g., for indications such Elevation of the treatment area, cool compresses,
as skin tightening [59], treatment of skin laxity, and application of petrolatum ointment are typi-
and treatment of moderate to severe rhytides cally used in postoperative care. When marked
[60], and overall produces satisfactory results edema and/ or erythema occur following aFP
for these collagen-­ sensitive responses with treatment, a short term course of oral corticoste-
acceptable post-treatment patient downtime. roids may be prescribed.
10  Fractional Photothermolysis 189

a b c

d e f

Fig. 10.15  Clinical course after aFP treatment. A single age. Photographs represent baseline (a), immediately
aFP treatment was performed with device Fraxel re:pair after treatment (b), 3 days (c), 1 week (d), 1 month (e) and
(Solta), 135 μm handpiece, λ = 10,600 nm, 70 mJ/MTZ, 6 months (f) (Courtesy of Steven Struck, M.D.)
≈300  MTZ/cm2, treatment level 8, 30% nominal cover-

 dverse Events and Clinical Pitfalls

A skin cooling, lowering MTZ areal densities,
of FP and providing sufficient time between passes
to allow cooling of the treated tissue.
• Excessive bulk heating (confluent thermal
damage) must be avoided. Although fractional photothermolysis is gen-
• Treatment of small areas can be particularly erally considered to be safer than traditional abla-
prone to bulk heating. tive techniques that damage a confluent tissue
• In order to minimize the risk of bulk heating, layer, there are some clinical pitfalls that should
the following strategies should be considered: be avoided. Following are several important
190 D. Manstein et al.

Fig. 10.16 Clinical
improvement of
moderate rhytides. A
single aFP treatment was
performed with Active
FX (80 mJ/MTZ,
density 4) and Deep FX
(15 mJ, 15% density)
(Lumenis,
λ = 10,600 nm). The
images exhibit baseline
(left) and 3 months after
a single treatment (right)
(Courtesy of Kevin
Duplechain, M.D.)

Fig. 10.17 Clinical
improvement of severe
rhytides. A single aFP
treatment was performed
with Active FX (80 mJ/
MTZ, density 4) and
Deep FX (15 mJ, 15%
density) (Lumenis,
λ = 10,600 nm). The
images exhibit baseline
(left) and 3 months after
a single treatment (right)
(Courtesy of Kevin
Duplechain, M.D.)

considerations and cautions that should be recog- rhytides, etc.). An appropriate density of MTZ
nized and addressed when performing FP proce- formation should also be selected based on the
dures. One major concern for FP treatments is patient’s skin type to produce effective results
generation of bulk heating in the treated tissue. while minimizing the risk of side effects due to
Bulk heating can facilitate undesirable effects bulk heating. Furthermore, it is important to cool
such as post-inflammatory hyperpigmentation the tissue in the treatment region during FP proce-
(which is more commonly observed in Asian dures. For example, a dynamic air cooling device
patients) or even result in scarring (Fig. 10.18). To (such as the one produced by Zimmer, Inc.) has
reduce the risk or extent of such side effects, been used simultaneously with many FP treat-
proper evaluation of the condition being treated ments. It is also recommended to allow sometime
should be performed (e.g., acne scars, melasma, between successive treatment passes over a
10  Fractional Photothermolysis 191

• Particular caution should be exercised at areas

of thin skin and low density of skin appendages.

For patients seeking FP treatment of non-­

facial (e.g., poikiloderma of the neck, periorbital
rhytides), the physician should also be aware of
the lower density of appendageal units in such
areas. This lower density may slow tissue healing
and leave the treated area more susceptible to
infection and scarring. Adequate selection of
MTZ density becomes very important when
Fig. 10.18  Scar on the upper lip several months after treating such areas of the body to avoid unwanted
nFP treatment delivered without adequate skin cooling. side effects.
Bulk tissue heating has occurred due to delivery of multi-
ple passes within small areas in relatively short time. • The use of antiviral prophylaxis is not clearly
Note: The lesion resolved over 6 months after intralesional
steroid injections and the patient requested additional FP established for FP; a history of herpes simplex
treatments because of otherwise excellent cosmetic virus (HSV), ablative treatments (aFP), and/or
improvement treatment of large areas are factors favoring
anti-viral prophylaxis.

specific body area. However, treatment of small Complications of FP treatment can be caused
face or body areas may not allow sufficient time by local infections, particularly when performing
for skin cooling between passes, which can lead aFP procedures that disrupt the stratum corneum.
to bulk heating and scarring. Some observations A universal prophylactic regimen has not yet
of neck and periorbital area scarring, likely been established for such procedures. Patients
caused by local bulk heating, have been reported with a history of herpes simplex virus affecting
[61]. the lips or any facial area are generally advised to
undergo a 1- or 2-day course of oral antivirals
• For highly-focused laser beams, a precise concurrent with the FP procedure. A consensus
positioning of the handpiece is needed. for appropriate antibacterial antibiotic prophy-
• Minor positional deviations from the focal laxis in conjunction with FP procedures is not
plane could cause significant alteration of spot clearly established, either. Antibiotic prophylaxis
size and fill factor. is typically indicated when treating large areas
using ablative modalities.
Operator technique is particularly important
when using ablative FP (aFP) systems. The • Pre-operative sun avoidance and discontinua-
highly-focused laser beams generated by these tion of retinoids are important factors for min-
ablative systems are configured to deliver a imizing side effects.
small spot size. Therefore, precise positioning
of the handpiece is relative to the tissue being Pre-operative and post-operative consider-
treated is extremely important. Any minor devi- ations must be discussed and addressed with the
ation of the laser beam focal point from the patient prior to initiating a course of FP treat-
desired focal plane can cause significant altera- ments. During the pre-operative interview and
tion of the spot size and fill factor because of the physical examination, it is important to confirm
convergent geometry of the focused beam. This the absence of sun burns and sun tanning, which
can lead to bulk heating in specific areas, fol- should be strictly observed for at least 2–4 weeks
lowed by potential scarring and pigmentation prior to the procedure and, ideally, for the
changes. same length of time after the treatment. This
192 D. Manstein et al.

is important in order to reduce the risk of post-­ a strong wound healing reaction and induces HSP
inflammatory hyperpigmentation, and may be production, FP procedures may be developed to
most relevant to patients living in the tropics and affect tissue regeneration, immune regulation,
with a history of sun tanning. Similarly, patients nerve fiber density, etc. Further investigation of
with solar lentigos and melasma may be given a these effects and others are warranted. FP appears
choice to first attempt chemical bleaching, fol- to be an important tool that is capable of affecting
lowed by FP in order to remove remaining pig- many different biological pathways, and therefore
mentation and address textural and rhytides it can be expected that more indications treatable
concerns. On the other hand, late-onset hypopig- using FP techniques, including a wide spectrum of
mentation is virtually never observed as result- dermatological diseases, will continue to emerge.
ing from FP treatments, in contrast to traditional
resurfacing modalities. During the pre-operative • Ablative FP can serve to facilitate drug and
period for FP, it is also important to address any cell delivery into the skin.
prior use of retinoids, either alone or in combi-
nation with other topicals. The patient must be Another important area of further develop-
instructed to stop the use of topical retinoids for ment is the use of aFP for enhanced delivery of
at least 1 week prior to each FP procedure. Use drugs and (stem) cells into different layers of the
of oral retinoid therapy (isotretinoin) should skin. It has been demonstrated that transcutane-
preferably be discontinued for a period of a few ous delivery of a photosensitizer can be enhanced
months prior to performing an FP procedure. using a low-density aFP procedure [62, 63]. The
delivery of drugs or other substances that typi-
• Post-operatively, sun avoidance, compliance cally do not pass through the epidermis can thus
with medication and proper recognition and be facilitated in a controlled manner over large
management of complications are key. areas using aFP treatment. aFP may make it pos-
sible to achieve topical delivery of a plethora of
Post-operatively, patients must be instructed effective agents into the skin. For example, entire
on proper skin care and strict sun avoidance in cell populations could be delivered through gate-
order to prevent side effects and complications, ways formed by ablated MTZs and open up new
including pigment alteration. Appropriate antivi- strategies for controlled distribution of targeted
ral or antibiotic prophylaxis, if recommended, (stem) cells into different layers of the skin. FP
must be followed by the patient in order to avoid may potentially be used, not only for the delivery
skin infection and/ or potential scarring. of (stem) cells, but also to simultaneously induce
Complications should be recognized early and an appropriate and controlled wound healing
without any delay appropriately managed. response within the recipient tissue. Such wound
healing response may create a microenvironment
that facilitates growth and differentiation of
Future Directions delivered and/or resident stem cells.

• New indications treatable by FP will continue • The channels created by aFP could be used for
to be identified. delivery of focused optical radiation of virtu-
ally any wavelength to deeper skin layers.
Fractional photothermolysis (FP) has been
established as a treatment modality for various indi- The microscopic ablated MTZ channels cre-
cations. To date, these indications are mostly aes- ated by aFP could also be used as a gateway for
thetic in nature. The beneficial effects of FP are not delivery of focused optical radiation to deeper
limited to collagen remodeling, pigment removal layers of the skin. The delivered optical energy
and closure of small vessels. Because FP can induce could be virtually of any wavelength as the opti-
10  Fractional Photothermolysis 193

cal barriers of tissue absorption and scattering photothermolysis laser that can be used for self-­
may be avoided when the radiation is directed treatment of wrinkles. The parameters of the
through these small channels. Spatial and tempo- laser were altered to increase the safety profile
ral alignment of ablative and delivered radiation for daily or multiple uses per week; operating at
sources is critical for forming such microscopic a low wavelength to eliminate the potential of eye
gateways and directing further radiation through damage, reducing skin coverage percent and
the newly-formed gateways. implements a contact sensor that ensure laser
emittance only when full contact around the opti-
• FP is also performed with a home-use product. cal window is achieved. Side effects of mild ery-
thema and trace edema are observed, while no
Home-use dermatology devices represent an severe side effects were reported. This device
area of growing interest and recent developments. demonstrated effectiveness at self-treating wrin-
The ability for the patient/consumer to perform a kles at home with 87% of patients reporting an
treatment conveniently at home and the huge improvement in wrinkle appearance after 1 and
commercial market potential are just two of the 3 months of treatment [64].
many factors driving the market for such devices.
A primary concern when using a home-use • FP can potentially be applied to other organs
device is guaranteed safety. This presents a chal- besides skin.
lenge as the consumer, typically possesses only
very limited skill with respect to medical device Although the focus of FP procedures to date
procedures. In particular, the ability to set the has been on treating skin tissue (skin is the most
treatment parameters sufficiently high, to treat a accessible organ of the body), the concepts and
wide range of skin types without completely effects associated with FP treatment of skin tis-
jeopardizing efficacy, is a prime challenge for sue will likely be applicable to other biological
home-use laser applications. FP offers three key organs and structures. For example, as we learn
characteristics that could facilitate the develop- how to improve scars within the skin by FP, this
ment of FP-based home use products. First, the could become a successful modality to improve
tissue effects of FP are not skin type dependent, fibrosis or degeneration in other organs. Virtually
as not melanin but water is the main chromo- any organ system is plagued by diseases or con-
phore. Second, although each individual MTZ ditions caused by such processes. FP procedures
induces a guaranteed wound healing response on may become a novel treatment option to improve
a microscopic scale, the density needed to achieve or restore the functionality of an affected organ.
a clinical improvement can be distributed over Potential examples of future non-dermatologi-
many treatments, e.g., using a daily application cal indications treated with FP are scars (fibro-
of low densities over a period of weeks. Such a sis) of the vocal cord or the heart. Obviously, the
treatment regime, which could be easily per- delivery systems for such FP procedures would
formed in an at home environment, could result have to be modified to be compatible with the
in safe, minimal incremental effects but signifi- specific anatomy, and further research has to be
cant overall improvement after completion of a performed to investigate the effects of FP on dif-
treatment course. And third, as relatively low ferent organ systems. Overall, it appears likely
energy is required to generate individual MTZs, that in the future FP will also be utilized by spe-
the energy source (laser) could be produced rela- cialties other than dermatology.
tively inexpensively and be battery operated. The
first FDA-approved home-use FP laser device • FP treatments show great future promise, but
was commercially released, (the PaloVia device alternative concepts, such as conventional
from Palomar Medical, MA.) This device is a laser resurfacing and peeling techniques
rechargeable, handheld, non-ablative fractional should still be considered.
194 D. Manstein et al.

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20. Manstein D, Zurakowski D, Thongsima S, Laubach H, treatment with laser and intense pulsed light sources.
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mal thermal damage pattern in nonablative fractional 36. Bak H, Kim BJ, Lee WJ, et  al. Treatment of striae
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size in fractional photothermolysis. Lasers Surg Med. tional photothermolysis: treatment indications and
2007;39(1):14–8. efficacy. Dermatol Surg. 2009;35(10):1445–61.
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tive fractional resurfacing: in-vitro effects on thermal tothermolysis for skin rejuvenation. Plast Reconstr
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23. Brightman L, Goldman MP, Taub AF. Sublative reju- 39. Haedersdal M, Moreau KE, Beyer DM, Nymann P,
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24. Hantash BM, Ubeid AA, Chang H, Kafi R, Renton 40. Laubach HJ, Anderson RR, Luger T, Manstein

B.  Bipolar fractional radiofrequency treatment D. Fractional photo-thermolysis for involuted infantile
induces neoelastogenesis and neocollagenesis. Lasers hemangioma. Arch Dermatol. 2009;145(7):748–50.
Surg Med. 2009;41(1):1–9. 41. Friedmann DP, Tzu JE, Kauvar AN, Goldman

25. Laubach HJ, Makin IR, Barthe PG, Slayton MH,
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energy variations on the dimensions of microscopic sis: a new option for treating melasma? Hautarzt.
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 Sub-surfacing Lasers
11
Michael Howard Gold

Abstract 2. Developed to meet need of efficacy in

Sub-surfacing lasers consist of a variety of rejuvenation without associated downtime
medical devices. (a) Erbium and CO laser resurfacing
KTP lasers. standards
Pulsed dye lasers. (b) Adverse events, too much downtime
(c) New devices to effect collagen in dermis,
Keywords minimal downtime
Sub-surfacing lasers · Non-ablative lasers · (d) Epidermal cooling required for treatment
Photorejuvenation · Laser toning · Fine lines to be safe and effective
and wrinkles · Skin dyschromias
(e) All have clinical studies showing
effectiveness
(f) All have a rejuvenation effect
Outline and Introduction (g) All have potential for adverse events

including blistering, burns, pigmentary
1. Sub-surfacing lasers consist of a variety of concerns, scars
medical devices
(a) KTP lasers Indications and Contraindications—
(b) Pulsed dye lasers Clinical information regarding these devices with
(c) 1064 nm Q-Switched Nd: YAG lasers published evidence of safety and efficacy.
(d) 1064 nm Long Pulsed Nd: YAG lasers
(e) 1319/1320 nm Nd: YAG lasers
(f) 1450 nm Diode lasers • Ablative laser resurfacing has been the
(g) 1540 Erbium Glass lasers gold standard throughout the 1980s and
(h) Intense Pulsed Light Sources 1990s for improving skin texture by ren-
ovating photo damaged and aging skin.
• Although excellent results have been
obtained with the use of ablative laser
devices, the use of non-ablative laser sys-
tems have been increasingly popular as an
alternative to obtaining the same results.
M. H. Gold
Gold Skin Care Center and Tennessee Clinical
Research Center, Nashville, TN, USA
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 197

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_11
198 M. H. Gold

These devices were developed, from a

• The mechanism of ablative laser historical point of view, to rival the ablative laser
resurfacing involves the removal of the resurfacing systems which enjoyed much
epidermis and the dermis, causing a popularity in the 1980s and 1990s. The ablative
wound to develop which may take up to laser systems, predominantly identified by the
several months to heal. erbium laser systems at 2940 nm and the carbon
• The use of non-ablative laser systems dioxide resurfacing lasers with a wavelength of
have minimal side-effects by causing 10,600  nm, were and are the mainstays of the
direct thermal damage to the dermis, ablative laser resurfacing systems. The ablative
while sparing the epidermis, and laser resurfacing systems are the gold standard
re-during the risk of post-treatment for skin resurfacing and still to this day are the
adverse effects and downtime. standards to which all other laser or light sources
for rejuvenation of the skin are judged as to their
safety and efficacy. The ablative laser resurfacing
Introduction systems work by removing the entire epidermis
and portions of the dermis which results in a
The field of sub-surfacing lasers is also known wound that, upon healing, gives a desired rejuve-
commonly by the terms non-ablative laser resur- nation effect. These devices have been used for
facing, photorejuvenation, and laser toning. A many years and have proven effective in improv-
variety of lasers and light sources have been ing skin roughness, fine lines and wrinkles, and
developed and utilized for sub-surfacing and will skin dyschromias which are common manifesta-
be the subject of this review. tions associated with skin aging and photodam-
Included in the overall category of sub- age. These ablative laser resurfacing devices can
surfacing lasers are a diverse range of technologies produce very nice and long-lasting results, as evi-
which include the KTP lasers at 532  nm; the denced in Figs.  11.1 and 11.2. However, when
pulsed dye lasers at 585–595  nm; the Nd:YAG performing these types of laser procedures,
lasers which encompass the 1064 nm long pulsed patients must understand that there will be sig-
systems, the 1064 nm Q-switched laser systems, nificant downtime with these treatments, lasting
and the 1319/1320 nm laser systems; the 1450 nm upwards of 1 week or more before full reepitheli-
diode laser systems; the erbium glass laser sys- zation will occur, and then several more weeks
tems at 1540  nm; as well as the spectrum of where the skin is still pink until complete healing
intense pulsed light (IPL) systems at wavelength has occurred. As well, some patients have pro-
range of 500–1200  nm. All of these medical longed erythema, as seen in Fig.  11.3, which
devices have proven successful for non-ablative requires appropriate and thoughtful intervention
laser/light source resurfacing, photorejuvenation, from qualified clinicians to help minimize. And,
and the improvement of acne scars [1, 2]. as a long term sequelae to many of these

a b c

Fig. 11.1 (a–c) Clinical examples of ablative laser resurfacing with long-lasting results
11  Sub-surfacing Lasers 199

a b

Fig. 11.2 (a, b) Clinical examples of ablative laser resurfacing with long-lasting results

a b

Fig. 11.3 (a, b) Clinical example of prolonged erythema after ablative laser resurfacing
200 M. H. Gold

Fig. 11.4  Clinical example of long-term sequelae after ablative laser resurfacing

procedures, a significant number (reported any- strated to work over a period of time and through
where from 10 to 20%) may develop a post-treat- a series of treatments, usually in the realm of five
ment hypopigmentation, which may not be to six treatments given at 3–4 week intervals [3].
evident for several months to years following the Maintenance therapy, although not addressed
initial procedure, as depicted in Fig.  11.4. in many accounts of sub-surfacing lasers, is usu-
However, these ablative laser resurfacing devices ally required at certain time intervals, as well as
still remain the gold standard for skin resurfacing proper skin care to maintain the rejuvenation
but other devices were developed in an attempt to effect one is attempting to achieve. In contrast to
reproduce these kinds of results, with minimal the amount of literature which the ablative laser
downtime, predictable results, and less chances resurfacing devices have enjoyed in the medical
for adverse or long term results [3–5]. literature, these sub-surfacing lasers have not had
The purpose of the development of the non- an overwhelming scientific base in the literature
ablative laser resurfacing is to affect changes in but have had descriptive coverage of the various
the skin similar to what the ablative laser resur- devices and their effects.
facing devices achieve. These devices were Various classifications of these sub-surfacing
developed to improve the skin’s texture, to lasers have been used over the past several
improve facial lines and wrinkles and surface years—we will classify them as shown in
irregularities including facial scars. In addition, Table 11.1. Table 11.1 shows that these medical
some of these devices also address pigmentary devices can be classified into (1) vascular
dyschromias and vascular changes in the skin lasers, (2) mid-infrared lasers and (3) intense
associated with photodamage and actinically pulsed light sources. The remainder of this
damaged skin. The non-ablative lasers and light chapter will review the literature of the vascular
sources work via thermal injury to the dermis, lasers, the mid-infrared lasers, and the IPLs.
with epidermal sparing, thereby reducing the This chapter will not review the realm of frac-
potential for any associated with these proce- tional lasers, which include non-ablative lasers,
dures. These medical devices have been demon- ablative fractional lasers, radiofrequency based
11  Sub-surfacing Lasers 201

Table 11.1  Sub-surfacing lasers

Device type Device name Manufacturer
1.  Vascular lasers
KTP laser Excel V™ Cutera http://www.cutera.com
The RevLite SI Cynosure http://www.cynosure.com/
Pulsed dye lasers Veam perfecta Syneron http://www.syneron-candela.com/na
Cynergy Cynosure http://www.cynosure.com/
NLite ICN Pharmaceuticals http://www.yestheyrefake.net/
NLite.htm
2.  Mid-infrared lasers
Q-switched 1064 nm Medlite C6 Cynosure http://www.cynosure.com/
RevLite
Long-pulsed 1064 nm YAG 5 Cynosure http://www.cynosure.com/
Gentle YAG Syneron http://www.syneron-candela.com/na
Apogee Elite Cynosure http://www.cynosure.com/
1319/1320 nm Profile 1064 nm Sciton http://www.sciton.com/
CoolTouch® C3 Syneron http://www.syneron-candela.com/na
1450 nm Profile 1319 Sciton http://www.sciton.com/
1510 nm SmoothBeam Syneron http://www.syneron-candela.com/na
Aramis Quantel http://www.quantelmedical.com/
3.  Intense pulsed light sources Lumenis one™/M 22 Lumenis http://www.lumenis.com/
BBL Sciton http://www.sciton.com/
Harnony Alma lasers http://www.almalasers.com/
PPX/isolaz Solta http://www.solta.com/
Ellipse flex DDD http://www.ellipse.org/

fractional lasers, or the microneedling frac- Vascular Lasers

tional lasers. They will be reviewed elsewhere
in this textbook. KTP Lasers

The KTP lasers have traditionally been utilized to

treat small caliber facial telangiectasias on the
• Studies have shown that KTP lasers
face and there is little in the medical literature
have better collagen formation results
which can be attributed to the use of the KTP
when compared to 1064 nm lasers in the
lasers in rejuvenation of the skin. In a study by
treatment of skin photo-rejuvenation.
Lee [6], 150 patients were treated with the KTP
• Pulsed dye lasers (PDL) function best in
laser and the 1064  nm laser separately and
the treatment of vascular lesions (i.e.,
together for non-ablative facial rejuvenation.
port wine stains and hemangiomas) with
Patients in this series received three to six treat-
significant production of procollagen
ments of both the KTP laser alone, the 1064 nm
type I and type III.
laser alone, and the combination of both devices.
• Increased activity of dermal fibroblasts
Skin biopsies looking at histologic effects in the
and mucin, as well as the thickening of
skin were performed at 1, 2, 3, and 6 months fol-
the stratum spinosum in the dermis, has
lowing the last treatment. The results showed that
been noticed in the restoration of degen-
the KTP laser was superior to the 1064 nm laser
erated skin.
in improving the parameters of photorejuvena-
• The use of modern PDL systems for
tion of the skin but that the combination of
skin rejuvenation provides non-ablative
devices was superior to either one of the devices
results by minimizing side-effects and
used alone. Post-therapy skin biopsies confirmed
reducing purpura.
the presence of new collagen formation as well as
202 M. H. Gold

a result of these lasers systems. Others, including thermal induced damage to vascular endothelium
Goldberg [7] found similar results in ten may produce cytokines leading to dermal remod-
patients—again treated with a millisecond Nd: eling and thus the improvement of fine lines and
YAG laser and a millisecond KTP laser showed wrinkles [3].
greater effects on tissue rejuvenation. Tan et  al. Several clinical evaluations have been
[8] also demonstrated this synergistic effect of performed which support the use of the pulsed
these two laser systems—25% more improve- dye lasers for a non-ablative rejuvenation effect.
ment with the combined systems at 1 month for Rostan et al. [16] utilized a long pulsed 595 nm
more than one third of the patients which laser in evaluating wrinkles of the cheeks. Fifteen
increased to 40% at the end of 4 months. patients received a series of four treatments at
monthly intervals, either with the laser on or with
cryogen only in the control group. The group per-
Pulsed Dye Lasers formed skin biopsies prior to the pulsed dye laser
treatments and at 4–6  weeks following the last
Pulsed dye laser, also known commonly as laser treatment, as well as 3 months following the
flashlamp-pumped pulsed dye lasers, are the last laser treatment. They specifically looked at
­prototype medical devices that were developed routine histology, procollagen I production and
which adhere to the principle of selective the activity of dermal fibroblasts. They found that
­photothermolysis [9]. Selective photothermolysis the Grenz zone was moderately thicker in 50% of
is a principle which states that a specific wave- patients in both groups treated, but the degree of
length of light can specifically destroy a chromo- thickening was greater in the treatment groups
phore within the skin, which in the case of the than the controls. Similar findings were also seen
pulsed dye lasers is hemoglobin. The pulsed dye at 3 months following the laser treatments, when
laser systems have improved in many facets over an increase in dermal collagen was also observed
the years, especially in their methods of epider- in the treatment sites. A statistically significant
mal cooling and in that they have longer pulse improvement in the clinical grading scale for
durations than their predecessor devices, which photodamage was also noted in the study.
reduces the incidences for purpura as a result of Zelickson et  al. [12] evaluated ten patients
the therapy, considered one of the necessities of with mild to moderate facial lines and wrinkles
the early pulsed dye lasers but also one of the and ten patients with moderate to severe facial
drawbacks from the treatment. These devices lines and wrinkles that were treated with a single
have been routinely used to treat vascular lesions laser treatment with a 585  nm pulsed dye laser
(facial telangectasia, diffuse erythema, and other with a 450 μm pulse duration. Clinically nine out
superficial vascular lesions) and their successes of ten patients in the mild to moderate wrinkle
in the treatment of port wine stains and heman- group showed 50% or more improvement with
giomas have been well reviewed in the medical 3/10 showing 75% or more improvement. All of
literature [10–12]. Pulsed dye lasers have shown the patients maintained their improvements for
to be useful in reducing the erythema and improv- 6 months following their last laser treatment. In
ing stretch marks [13] and these devices have and contrast, only 3/10 patients in the moderate to
these devices have also been used successfully to severe wrinkle group improved during the study.
treat hypertrophic scars and keloidal lesions, Skin biopsies from those patients in the mild to
especially being able to reduce the associated moderate group were performed at 6 and
erythema sometimes associated with these 12  weeks following the laser treatment. The
lesions [14, 15]. In the process, many of these biopsy specimens showed a thickened stratum
scars have shown dermal remodeling and an spinosum and a thickened collagen layer in the
associated shrinkage of the scar itself. The exact superficial dermis as well as increased mucin in
mechanism of pulsed dye induced collagen for- the superficial dermis. They also performed ultra-
mation is not clear but it has been proposed that structural evaluations which demonstrated an
11  Sub-surfacing Lasers 203

increase in collagen fibers and an increase in the divided into two groups of five. All of the patients
number of fibroblasts in the treated skin. They received 595  nm pulsed dye laser treatments to
also noted that there was an increase in normal the periorbital areas. The first group was treated
appearing elastic fibers and a decrease in the once, while the second group was treated twice at
clumping of degenerated elastic fibers in the skin. a 1  month interval. Each side of the face was
Zelickson and Kist [17, 18] have also reported treated with distinctly different laser settings.
results from skin biopsies performed after two Seventy percent of the patients noted mild to
periorbital 585 nm pulsed dye treatments or IPL moderate improvement clinically after treatment
treatments (6 week apart) in which in-situ hybrid- at 6  months following the last treatment. There
ization mRNA probe studies were performed was no difference between receiving one or two
6 weeks after the second treatment. treatments in this study. Histologic and electron
These studies showed an 18% increase in type microscopy improvement was noted in all of the
I collagen production after the IPL treatments patients.
compared to a 23% increase in type I collagen The major side effect of pulsed dye lasers in
production after the pulsed dye therapy. the past was purpura, which has virtually been
Collagenase transcriptase activity was 32% for eliminated with today’s more sophisticated
the IPL and 40% for the pulsed dye laser. The machines, with longer pulse durations and
authors concluded that the observed increases in improved epidermal cooling. However, purpura
mRNA in fibroblasts indicated that through this is a side effect still sometimes seen, and blister
non-ablative light, extracellular matrix protein formation, pigmentary dyschromias, as well as
production by dermal fibroblasts is increased, scarring have been noted with the pulsed dye
thus resulting in the effects seen. lasers.
Others have also looked at the pulsed dye
lasers for its potential in rejuvenation of the skin.
Bjerring et al. [19] utilized a 585 nm pulsed dye • Q-switched 1064  nm laser systems
laser with a 350 um pulse duration and studied stimulate deep dermal collagen
suction blisters which had been treated with the stimulation have shown to cause
pulse dye laser. Using special markers for the re-epithelization faster than carbon
production of type III procollagen they were able dioxide systems. Further studies have
to demonstrate significant increases in type III shown that Q-switched
procollagen levels after a single treatment with • 1064  nm laser devices significantly
the pulsed dye laser, but also demonstrated a drop decrease solar elastosis and thicken
in type III procollagen levels after a retreatment. upper papillary dermal zones of
Goldberg et al. [20] also performed skin biopsies collagen.
with a similar pulsed dye laser looking at facial • 1064  nm Nd: YAG laser devices have
lines and wrinkles. In this study, patients received useful skin tightening mechanisms for
two pulsed dye laser treatments. Pre-treatment skin rejuvenation.
and 6  month post-treatment clinical evaluations • With the use of epidermal cooling
and skin biopsies were analyzed. Forty percent of devices, such as cryogen, 1319/1320 nm
the individuals noted mild improvement in their laser devices have provided optimal
wrinkle appearance. Ultrastructural analyses results in the formation of new collagen,
showed increases in type I and III collagen in reduction of lines and wrinkles. These
those treated with the pulsed dye lasers. A second non-ablative laser systems leave the epi-
study by these authors [21] evaluated clinical, dermis intact and provide great results
histologic, and ultrastructural changes after non- in all skin rejuvenating procedures.
ablative treatments utilizing varying settings in • 1450  nm mid infrared diode laser
the same subject. Ten patients were included in systems have functioned successfully in
this clinical trial. The patients were randomly
204 M. H. Gold

result of this adjuvant care, patients had improve-

the treatment of active inflammatory ments in skin texture and skin elasticity. Goldberg
acne vulgaris, acne scars on the face, and Silapunt [24] evaluated skin biopsies from
fine lines and wrinkles. This laser infraauricular skin treated with two passes of the
system targets dermal water, creates a Q-switched laser before and after 3 months fol-
wound in the dermis and triggers the lowing the last treatment in eight patients.
regeneration process of collagen. Clinically, six of the eight patients in the trial
• 1540  nm Erbium Glass laser devices showed improvement by an independent observer.
have clinically proven dermal remodel- Four of the six biopsy specimens evaluated
ing by treating fine lines and wrinkles, showed decreases in solar elastosis and a mildly
acne vulgaris and acne scars, and atro- thickened upper papillary dermal zone of collagen.
phic scars on the face. These lasers use a More organization of the collagen bundles was also
sapphire lens cooling device throughout seen in this clinical study. Cisneros et al. [25] eval-
the treatment process. uated 22 patients who were treated twice with the
Q-switched laser system—all with improvement.

Mid-Infrared Lasers 1064 nm Nd:YAG Lasers

Q-Switched, 1064 nm Nd: YAG Lasers Very little literature exists as far as the efficacy of
utilizing the 1064 nm long pulsed Nd: YAG laser
Several investigations have evaluated the effects in the treatment of fine lines and wrinkles. In a
of the Q-switched 1064 nm laser system for the recent study by Taylor [26], a comparison was
treatment of facial lines and wrinkles. These made to the skin tightening ability of the long
Q-switched laser systems were originally pulsed 1064 nm laser in comparison to the mono-
designed for the treatment of densely pigmented polar radiofrequency device. In this particular
blue-black tattoos but have also been found to be clinical trial the results showed that the 1064 nm
potentially useful in the rejuvenation of the skin, was as useful in skin tightening as the radiofre-
due to its deep penetration into the skin and quency device. Clinical examples are shown in
thereby stimulating dermal collagen. Goldberg Figs. 11.5 and 11.6.
and Whitworth [22] evaluated the Q-switched
1064 nm laser in a comparative study to carbon
dioxide laser systems. Eleven subjects were 1319/1320 nm Laser Systems
included in this evaluation. All of the patients
treated with the carbon dioxide laser systems These mid-infrared laser systems have had a lot
improved in this clinical study. Nine of the eleven of play in the non-ablative, sub-surfacing laser
patients improved with the Q-switched 1064 nm field of rejuvenation. The 1320 nm laser system,
laser. Complete reepithelization occurred faster known as CoolTouch®, from the CoolTouch®
(3–6 days earlier) in the patients treated with the Corporation (Roseville, CA), now owned by
Q-switched laser as compared to the carbon diox- Syneron Candela was the original sub-surfacing
ide systems. The authors concluded that the device developed specifically for the treatment of
Q-switched 1064 nm laser may play a role in the facial lines and wrinkles utilizing the non-ablative
treatment of rhytids. Goldberg and Metzler [23] technique.
utilized a 1064 nm Q-switched laser and a topical Subsequently, a 1319  nm laser system from
carbon solution in an attempt to potentiate the Sciton (Palo Alto, CA) has also been introduced
laser effects. Two hundred forty two solar dam- to this realm of sub-surfacing lasers.
aged sites were treated with three treatments on The goal of these laser systems has always
61 patients. The investigators found that as a been to create a dermal wound resulting in the
11  Sub-surfacing Lasers 205

Fig. 11.5  Clinical example of skin tightening using 1064 nm

Fig. 11.6  Clinical example of skin tightening using 1064 nm

formation of new collagen, a reduction in lines Utilizing unique delivery systems for cryogen
and wrinkles, and to leave the epidermis intact. spray delivery to the skin and with thermal sen-
This has been achieved very well through the sors, the CoolTouch device was and is the proto-
use of these devices and appropriate epidermal type of the 1319/1320  nm laser systems on the
cooling. Clinical examples are shown in market. It has had extensive clinical investiga-
Figs. 11.7 and 11.8. tions performed using it over the years. Clinical
206 M. H. Gold

Fig. 11.7  Clinical example of 1319/1320 nm treatment

Fig. 11.8  Clinical example of 1319/1320 nm treatment

assessment and skin biopsy clinical studies have reported a subjective improvement in the quality
been carried out by Goldberg [27], Trelles et al. of their skin; only six of the ten were felt to be
[28] and Levy et al. [29]. In all of these clinical clinically improved by the investigator. All of the
evaluations, skin biopsies performed at the end of subjects showed evidence of new collagen for-
the treatments showed evidence of new collagen mation at 6 months in skin biopsies.
formation. All of the patients had solar elastosis Fatemi et  al. [31] showed that with the
prior to treatment and demonstrated improve- 1320 nm laser system that three passes from the
ment clinically and histologically following the device are better than a single pass in causing the
treatments. Goldberg [30] also evaluated ten early laser-induced histologic changes seen
patients with facial lines and wrinkles who which noted included vascular damage, apopto-
received treatment five times with the CoolTouch sis, and edema—the beginning of the
device over 3–4 week intervals. At 6 months fol- ­inflammatory mediator cascade required for col-
lowing the last treatment, all of the patients lagen formation to occur.
11  Sub-surfacing Lasers 207

1450 nm Diode Lasers (fluences from 9 to 14  J/cm2). The same group
also have investigated the 1450 nm laser for the
The 1450  nm mid infrared diode laser system, treatment of rhytids—periorbital rhytids
known as the SmoothBeam from Syneron improved more so than transverse neck lines
Candela Corporation (Wayland, MA), has been [33].
used as a treatment for active inflammatory acne Acne vulgaris treatment with the 1450  nm
vulgaris and for the treatment of acne scars on the diode laser has received much attention.
face. It can also be used in a non-ablative fashion Paithankar et al. [34] treated patients with acne to
for the treatment of fine lines and wrinkles as their entire back area affected with acne and
well. This laser system works similarly to the found that when treating four times at 3  week
1320 nm laser systems in that its wavelength tar- intervals, a statistical and clinical decrease in
gets dermal water, creates a wound in the dermis, acne lesions was noted. Friedman et al. [35] also
and in the regeneration process forms new der- studied the effects of the 1450 nm diode laser on
mal collagen resulting in the desired effect. sebaceous glands on the back and noted damage
In a study by Tanzi and Alster [32], they to the glands following therapy.
compared the 1450 nm diode laser to the 1320 nm The SmoothBeam laser has shown quite a bit
Nd:YAG laser in the treatment of atrophic facial of efficacy over the years. Even with its sophisti-
scars. Twenty patients with mild to moderate cated cryogen cooling, significant pain has been
atrophic facial acne scars received three monthly noted to occur in many patients, which has lim-
treatments with the 1450 nm laser to one half of ited this machines ultimate further widespread
the face and the 1320 nm laser to the other half of use. A clinical example is shown in Fig. 11.9.
the face. Clinical evaluations and skin biopsy
specimens were performed at various time inter-
vals, including up to 1  year post the last treat- 1540 nm Erbium Glass Laser
ment. Mild to moderate clinical improvement
was observed clinically in the majority of patients The 1540 nm erbium glass laser has seen extensive
studied. The 1450 nm diode laser showed greater study in Europe for the treatment of fine lines and
clinical scar response at the parameters studied wrinkles, acne scars, and for the treatment of

Fig. 11.9  Clinical example of 1450 nm treatment

208 M. H. Gold

Fig. 11.10  Clinical example of 1540 nm treatment

atrophic scars on the face. It has also been used including pigmentary alterations and scarring
successfully to treat active inflammatory acne of the skin. A clinical example is shown in
vulgaris. Less clinical work appears to have been Fig. 11.10.
done on this device in the United States. This
device utilizes a sapphire lens cooling device
which delivers its contact cooling. Clinical evalu-
• Intense Pulsed Light (IPL) devices emit
ations with the device include Fournier et al. [36]
polychromatic light in broad ranges of
in which patients treated with this device had a
wavelengths, selectively filtered to tar-
40% reduction in wrinkles and a 17% increase in
get specific chromophores, between 500
epidermal thickness at 6  weeks following the
and 1200 nm.
fourth treatment. The study evaluated 42 patients
• IPLs treat vascular lesions, pigmentation,
over a 14 month period of time. Lupton and Alster,
and have shown to have an effect in the
looking at histologic effects from the erbium glass
production of collagen and elastic fibers
laser, demonstrated significant dermal remodeling
in the dermis. Studies have shown that
and clinical satisfaction in 24 individuals 6 months
IPL photo-rejuvenation treatments
after their final treatment (four treatments at
using cooling apparatuses considerably
1 month intervals). In another study, Lupton et al.
increase epidermal thickness, and
[37] evaluated the use of the 1540 nm Er: Glass
improve skin texture.
laser in 24 patients’ facial wrinkles. Mild to mod-
• The necessary cooling devices are
erate improvement in facial lines and wrinkles
required in all non-ablative devices to
were seen in all of the study subjects; dermal
avoid the adverse effects relating to skin
fibroplasia was noted in the skin biopsy
damaged. Blisters and pigmentary
specimens.
lesions can occur without the proper
All of the mid infrared devices have shown
handling of cooling devices.
safety and efficacy. As noted with the 1450 nm
diode laser, pain is its most common adverse
event. All of the mid infrared laser systems can
cause significant discomfort without proper Intense Pulsed Light (IPL) Sources
epidermal cooling. As well, most of these
devices will result in some erythema and edema IPLs have been around since the early 1990s and
which, in the majority of cases, will resolve have withstood the test of time and criticism to
within 24–48 h. As with all laser systems, other become the most widely used medical devices in
adverse events can be seen with these devices, the world for photo-rejuvenation. The first of
11  Sub-surfacing Lasers 209

these light sources was a high-intensity flashlamp gectasias. Skin biopsies taken from the forehead
medical devices were initially developed for the and 4 weeks after the last IPL treatment showed
treatment of vascular anomalies of the skin, spe- new collagen in both the papillary and reticular
cifically leg veins and telangectasias [38]. IPLs dermis as well as a resolution of any superficial
are pulsed light sources which emit polychro- dermal infiltrates.
matic light in a broad wavelength of the light Other studies utilizing an IPL demonstrating
spectrum, usually between 500 and 1200  nm. non-invasive resurfacing have also been per-
Many different variations on the IPL theme are formed. In his study, Hernandez-Perez et al. [42]
now available, some with smaller absorption evaluated five patients with five treatment ses-
ranges, others with radiofrequency included to sions with an IPL.  Moderate to very good
potentiate the effect of the broadband light, and improvement in the signs of photodamage were
still others with a vacuum apparatus included to observed. Skin biopsy specimens were obtained
bring the light in a colder relationship to the light at baseline and at 1 week following the final (5th)
itself. IPL devices of today are much more treatment. These biopsy specimens showed an
sophisticated than their predecessors but always increase in epidermal thickness, and an improve-
are cautioned that not all IPLs are the same. In a ment in dermal concerns—specifically dermal
recent well performed study by Town et al. [39] elastosis, edema of the dermis, telangectasias
various IPLs were evaluated to determine their present, as well as any dermal infiltrate. In
true pulse width (in an independent means) and another investigation, Negishi et  al. [43] evalu-
to evaluate their true output in joules per centime- ated 73 individuals with an IPL. The patients in
ter squared over the time of the pulse. Differences this clinical evaluation received at least five treat-
were observed between devices and even based ment sessions with the IPL. Clinical results noted
on some of the manufacturers’ claims. These a greater than 60% improvement in skin texture,
devices are very popular in today’s culture; one in reduction of telangectasias, and in reducing
must be aware of the company developing it and pigmentary concerns in more than 80% of the
what clinical work rests behind it. patients who participated in the trial. Skin biop-
Although not true lasers, these devices also sies obtained at baseline and at 3 weeks follow-
follows the principles of selective photothermol- ing the final therapy showed an increase in types
ysis [9] in that with varying filters, or cut-off fil- I and III collagen, as demonstrated by immunos-
ters, one can use the IPL to selectively target a taining. Goldberg, in several clinical trials,
specific chromophore in the skin to cause a select looked at rhytids following IPL therapy and
affect upon that structure. It has been clearly clearly demonstrated an improvement in skin
demonstrated that the IPLs can treat vascular wrinkles which were also demonstrated histo-
lesions, pigmentary concerns, and does have an logically [44, 45]. Prieto et al. [46] in their evalu-
effect on the collagen and elastic fibers in the der- ation of IPL induced rejuvenation effects found
mal tissues [40]. These photorejuvenation effects similar collagen changes as compared to other
of the IPL will now be reviewed. authors but also found, through routine histology
The first major study in the field of and electron microscope analyses, that after
photorejuvenation associated with a series of IPL 1 week following therapy, there was no perifol-
treatments was published by Biter in 2000 [41]. licular infiltrate evident. Furthermore, at 3 and
In this trial, 49 individuals received a series of 12 months, demodex and an associated lymphoid
treatments with an IPL device, with a minimum infiltrate were observed. The authors postulated
of four treatments given at 3  week intervals. In that because of the transient therapeutic effect of
his study, he found that all of the parameters of the coagulative necrosis of demodex organisms, a
photodamaged skin were improved in over 90% nonablative effect can occur. A long term evalua-
of those entered into this clinical trial. These tion by Weiss et al. [47] demonstrates that once
included skin wrinkling, skin coarseness, irregu- the rejuvenation has had its effect, it can last for
lar pigmentation, large pore size, and skin telan- up to 5 years—83% of patients followed contin-
210 M. H. Gold

ued improvement in skin texture; telangectasias than ever before, most with exceptional cooling
improvement of 82%; and pigmentation remained apparatus’ to increase the safety of the devices,
improved in 79%. more and more physicians and others are utiliz-
Examples of photorejuvenation as a result of ing them on a daily basis all over the world.
IPLs are shown in Figs. 11.11 and 11.12. Remember, these are medical devices that can
As noted, IPLs have much play in today’s damage the skin and cause horrific effects, as can
laser world. Because they are more sophisticated all of the devices described in this report.

a Before b After 4 Treatments

Fig. 11.11 (a, b) Clinical example of photorejuvenation with IPL

a b

Fig. 11.12 (a, b) Clinical example of photorejuvenation with IPL

11  Sub-surfacing Lasers 211

Techniques/Devices so. Many of the devices described have shown

a great deal of clinical efficacy, although at
Table 11.1 lists the names and manufacturers of times, it has been difficult to document due to
the most commonly used lasers/light sources in these changes being, at times, subtle. But our
each category along with the web address of patients have been the ones who have bene-
those companies where further information to fited from these devices as they have always
specifics may be obtained. known the changes to be real, all with minimal
to no downtime, one of the most important
concepts of modern day lasers. Many of these
Adverse Events procedures are now being replaced with the
fractionated laser systems, which is covered
All of the sub-surfacing devices have the potential elsewhere in this text. Sub-surfacing devices
to do harm. Because their mechanism of actions can provide you and your patients with much
requires dermal injury with sparing of the satisfaction.
epidermis, skin cooling becomes of paramount
importance. Without proper epidermal cooling,
which these machines do have, skin burning and
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Hopefully, more devices of these kinds will be pulsed dye laser. Lasers Surg Med. 1993;13:368–73.
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pulsed dye laser for port wine stains in infancy:
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 Non-invasive Rejuvenation/Skin
Tightening: Light-Based Devices 12
Marina Perper, John Tsatalis, Ariel E. Eber,
and Keyvan Nouri

Abstract Keywords
The popularity of non-invasive cosmetic Non-invasive · Epidermal treatment · Skin
improvement of the skin has continued to rejuvenation · Skin tightening · Photoaging ·
grow amongst patients and practitioners alike. Light-based devices
Cost and pain remain the principal limiting
factors for patients.
The safety of epidermal treatment in dark
skin types has remained a challenge. Introduction
Today, non-invasive treatment of photoag-
ing can be achieved with light devices. A com- • The popularity of non-invasive cosmetic
bination treatment which in my experience improvement of the skin has continued to
has proven to be safe and painless is described grow amongst patients and practitioners alike.
here. • Cost and pain remain the principal limiting
factors for patients.
• The safety of epidermal treatment in dark skin
types remains a challenge.
• Today, non-invasive treatment of photoaging
can be achieved with light devices. A combina-
tion treatment which in my experience has
proven to be safe and painless is described here.

A place in modern aesthetic procedures for

non-invasive modalities is now well earned.
M. Perper · J. Tsatalis · A. E. Eber · K. Nouri (*) The appeal of such procedures in the eyes of
Department of Dermatology and Cutaneous Surgery, prospective patients is understandable. As for
University of Miami Miller School of Medicine,
doctors, the possibility of improving someone’s
Miami, FL, USA
e-mail: [email protected]; [email protected]; appearance without having to resort to drastic,
[email protected]; [email protected] painful and potentially risky procedures rapidly

© Springer International Publishing AG, part of Springer Nature 2018 213

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_12
214 M. Perper et al.

became the choice of many. It is to be under- 2. Pain: The interest of patients in these proce-
stood that the changes induced are not as dra- dures is, in general, inversely proportional to
matic as those obtained by aggressive the pain inflicted by them and therefore it is in
modalities, but they are not as drastic or irre- the interest of the practitioner to be able to
versible either, thereby becoming a plus not a provide his patients with procedures that can
minus. Good candidates for these procedures be performed with as little pain as possible.
are the ones who can live with the idea of grad-
ual, subtle changes that, on the other hand, will The procedures described here can be carried out
not draw unnecessary stares, such as after an without pain and without anesthesia whatsoever.
invasive Plastic Surgery correction. In addition, They are safe for all skin types and promote easy
non-invasive procedures can now be directed at patient’s acceptance because of lack of discom-
specific elements of photoaging, to specifically fort during and after treatment as well as carefree
correct them. In such manner, the skin may be post operative time. As mentioned before, patients
divided in three basic strata: Deep, being the should understand that a series of treatments may be
reticular dermis; mid, being the papillary der- necessary to achieve the desired change. They are to
mis and superficial being the epidermis. Each understand as well, that the changes obtained after
of these strata exhibit distinct changes attribut- these procedures are subtle and may not be noticed
able to premature aging, namely: flaccidity, after each individual session, but through comple-
thinning or loss of substance, and brown (pig- tion of a series and or, upon photographic com-
mentary) and red (vascular) dyschromias on the parison of before and after pictures. Improvement
surface of the skin. however, can be noticed after only one treatment
However, two are the limiting factors that session (Figs. 12.1, 12.2, 12.3, 12.4 and 12.5) and
need to be considered: improves after multiple or combined multiple ses-
sions (Figs. 12.6, 12.7, 12.8 and 12.9). If the patient
1. Cost: Being that multiple repeated procedures desires dramatic changes he or she is probably not a
are needed to effect a change and good candidate for these procedures.

Pre 6 months

Fig. 12.1  Six months post one Titan treatment

12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices 215

Fig. 12.2  Six months post one Titan treatment

Fig. 12.3  Eight months post one Titan treatment

216 M. Perper et al.

Pre 2 months

Fig. 12.4  82 year old woman before and 1 month post a single Titan treatment

Before After

Fig. 12.5  One month post one Titan treatment

12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices 217

Fig. 12.6 (a) Three months post one Titan 3 Nd:YAG showing better skin quality and (b) in lateral view
218 M. Perper et al.

Fig. 12.7  Pre and 6 month post combination treatment Titan plus Nd:YAG

Fig. 12.8  Pre and post one Titan and 5 Nd:YAG

12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices 219

Fig. 12.9  Seven days after combination treatment of one Titan, 3 Nd:YAG and 5 IPL

On the other hand, we have gradually improved • If the tissue is heated in this manner, it can be
our understanding of how skin tightening takes done painlessly
place and how it can be induced painlessly and • Immediate skin tightening is observed in nearly
immediately using light. A long way has passed all patients regardless of age or skin type
since we were trying to elicit a change using flash
intense heating with radiofrequency. In a simi- For the purpose of this writing we will limit
lar manner, when we use the Nd:YAG laser as ourselves to the mid and lower thirds of the face
later described, a change in skin quality is first and neck. Unwanted skin flaccidity starts at vari-
noticeable after only a few days when treating the able degrees for individual patients during the
mid layer with laser, and there is even a change third decade of life. Jowls, loss of sharpness in
that is noticed immediately: pore size reduction. the mandibular lines, laxity of cheeks and deepen-
Dyschromias will also improve within a matter of ing of the nasallabial fold individually or collec-
days, again using light, intense pulsed light. So, tively may appear. The traditional approach years
all in all, these change account for an excellent ago, was that of a rhytidectomy or face lift. The
acceptance level for the vast majority of patients problem was that this procedure, alone, corrects
who undergo these treatments, provided we have by pulling the lax skin following one vector of
outlaid a plan of treatment and of expected level movement, causing in some cases, distortion of
of improvement in all detail prior to starting the landmarks of the face such as the corners of the
series and never a posteriori. mouth. Inducing skin contraction by delivering
deep, sustained heat to the deep dermis, aims to
cause a minute global shrinking, that will revert
 hotoaging in the Deep Stratum
P the skin to its original position to some degree.
of the Skin Causing Skin Laxity Achieving that with light, requires a source of heat
Can Be Treated with Light that can be on for extended periods of time and
that does not cause pain on contact with the skin.
• Skin tightening can best be induced using long, In other words, a long pulse of light, and cooling
gradual, sustained multi second pulses of heat of the treatment surface of the device, the one that
220 M. Perper et al.

gets in contact with the surface of the skin while infrared light emission. Then the handpiece is
the light is on. The light must have a wavelength glided in a vertical fashion until the yellow light
which allows for penetration to the level of the stops. When the blue light alone continues, at the
target, i.e.,: the deep reticular dermis. The closest end of each pulse, care should be taken to with-
to such a device is Titan by Cutera, Inc. draw the handpiece from skin contact. This
Titan is an infrared light device emitting light at avoids unpleasant cold sensation for the patient.
1100–1800  nm in multi second cycles. At these As mentioned above, I use the “S” handpiece at a
wavelengths, there is a moderate level of water setting of 65 J/cm, with pulses of 9.2 s duration. I
absorption and therefore it can thoroughly heat the find the “V” and “XL” handpieces less adequate
dermis over a period of seconds. It differs from other for the glide technique due to their sharp edges.
infrared devices in that they usually have much At the beginning heat is almost impercep-
smaller spot sizes and also have very short pulse tible for the patient. The strokes are then
durations (milliseconds) as well as a very high water repeated, over and over with some overlapping
absorption which results in shallow heating only. It to produce the desired goal: incremental, sus-
has a spot area of 1 cm × 1.5 cm. Although it is an tained heating that because it is not sudden
infrared lamp, it is not a flashlamp. “Flashlamps” and intense, it is painless. Many strokes are
produce light at lower wavelengths (more visible necessary to elicit visible contraction, in my
light) and are usually pulsed at short (millisecond) experience from 40 to 60 in each area, consid-
durations. This is a broadband infrared lamp that ering each cheek one area, and each side of the
emits longer wavelengths and is better suited for neck one area as well. Gliding is facilitated by
multi-­
­ second pulse durations. Heat penetration the use of a hydrophilic gel such as K-Y Jelly.
depth from this device is estimated to be about (Johnson and Johnson). Contraction can be
1–2 mm, but some heating does occur down to about seen with the patient lying down but it becomes
5 mm. These calculations were done using dermal more apparent when the patient sits up. The
scattering coefficients and water penetration depths contrast with the untreated side demonstrates
for near infrared wavelengths to estimate an “effec- the contraction to the patient (Figs.  12.10,
tive penetration depth” for a particular wavelength. 12.11, and 12.12) with the simple use of a
The total intensity was then calculated by adding up
the contribution from individual wavelengths. These
models were then confirmed by actual thermal mea-
surements of ex-­vivo tissue samples and an appro-
priate filter design was selected based on the desired
thermal profile obtained by the manufacturer.
Technique: Both, physician and patient should
wear appropriate protection goggles. This author
uses now a technique that differs from the tradi-
tional one for this device. It is a gliding tech-
nique, in which the treatment window is glided in
vertical lines on the cheeks and neck. The
machine is then set to emit the highest possible
pulse which also has the longest possible pulse,
lasting several seconds. The fluence is set at 65 J/
cm2. But since the device is engineered to emit a
pre-cooling pulse of cold, as well as a trans-­
cooling and post cooling pulse, care is taken to
avoid the pre and post-cooling because they are
unnecessary in this particular technique. So, the
device is made to begin contact with the skin sur-
face immediately after the blue light indicator of Fig. 12.10  Immediate skin contraction after Titan on left
cold emission is followed by the yellow light of cheek
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices 221

Fig. 12.11 (a) a
Immediate skin
contraction on treated
cheek and (b) in close up

Treated side Untreated side

mirror. As mentioned, this technique, properly sensation. No pain is necessary to elicit con-
performed is painless even in the beard area in traction, with gentle heat applied for enough
men, in which the traditional “stamping” tech- time, thus 40–60 gliding strokes of the hand-
nique usually hurts. The following principle piece are needed. Intense heat applied by the
must be understood: The skin will contract by conventional “stamping technique” hurts and
applying heat slowly, steadily, progressively may not be the best for the patient. An animal
and sustainably. Overlapping strokes is per- hide will contract if put in a dryer with enough
mitted and desirable always guided by pain heat for enough time (Figs. 12.12 and 12.13).
222 M. Perper et al.

A Most Impressive Case of Tissue

Contraction: Animal hide subjected to
sustained slow heat for enough time

Pre Immediate Post

A Most Impressive Case of Tissue
Contraction: Animal hide subjected to
sustained slow heat for enough time

Pre Immediate Post

Fig. 12.12 (a, b) Animal hide contraction with slow sustained heat

Appropriate heating was applied to Sudden intense heat in brief pulses (such as
elicit contraction that produced by a flame) will fail to contract
the hide. Similar intense pulses in patients,
whether originated by radiofrequency or light,
will not offer the best contraction possible in
clinical practice.
No post-operative care is required. Post-­
operative pain, swelling or bruising do not
occur.
These treatment sessions can be repeated to
improve results. Usually at monthly intervals
until the desired level of improvement is
achieved. I also recommend maintenance treat-
ments every year for patients under 50 and
A Flame (intense brief heat) would have every 6  months for patients over 50  years of
burned the hide, not contracted it
age. Genetics, skin type, degree of sun protec-
Fig. 12.13  Slow and low heating can bring about appro- tion and outdoor lifestyles will necessitate dif-
priate contraction ferent maintenance schedules.
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices 223

 1064 nm Nd:YAG Laser Is Used

A 4. The operator will move to the next area in
to Treat the Mid Stratum of the Skin circles. Each will be treated generally with
five consecutive passes.
• The Nd:YAG laser can be used to improve 5. Pain or immediate redness are NOT treatment
skin quality. goals or endpoints.
• We use a repetition rate of 10 Hz at 15 J/cm, in 6. The machine counts pulses automatically. The
300 ms pulses. number of pulses will vary. Typically, 5000
• An airbrush technique about 1–2 cm from the pulses for 5 monthly sessions. Lately, I have
skin surface is used. found that more pulses in a single session are
• We use five sessions of 5000 pulses each. more rewarding and safe. We now deliver
• Improvement can be observed within a month 15,000–25,000 in a single treatment session.
from each procedure.
• When adequately performed, the procedure is
painless for most patients. Improvement of the Superficial
Stratum of the Skin Using Light
With this modality, an improvement in the
quality of the skin is sought for. Improvement • Intense pulsed light (IPL) can be used to
will start to be perceived by the patient usu- improve some epidermal signs of photoaging.
ally after 1  week and will be at a peak after • Pigmented or vascular dyschromias are
1 month. An improvement in skin texture, soft- exceedingly common and are ideal targets for
ening of very fine static rhytids, a reduction of this procedure.
pore size, a diminution of actinic bronzing and • The procedure can be safely applied in dark
an improvement in skin clarity and glow may skin types in the following manner: The pro-
result. Again, this technique is safe in all skin cedure is done at daily intervals for 5 days.
types. • We use the “Limelight” device by Cutera, Inc.
Because of its wavelength, this laser can be • We start at 8  J/cm, “C” mode for skin types
used to reach the level of the papillary dermis. III–V and “B” for skin types I–II.
When engineered to deliver 15  J, in 300  ms • We use increments of 2 J/cm daily.
pulses with a spot size of 5 mm, it can be deliv- • Mild burning sensation during each pulse is
ered painlessly even at a repetition rate of 10 Hz. expected. No pain afterwards.
Technique: Again, both, physician and patient • The cooled tip is kept in situ after each pulse
should wear appropriate protection goggles. long enough for the burning sensation to
First, we must understand the following disappear.
principles:
Intense pulsed light (IPL) has been used for a
1. The degree and speed of heating will be pro- number of years and an abundant body of litera-
portional to the speed of the hand of the ture has been published on the subject. We will
­operator as well as the distance between the deal in this chapter with the means to make this
handpiece and the skin. procedure safe for all skin types and to minimize
2. Small areas heat up faster than larger ones. A discomfort and post-operative the undesirable
repeated air brush movement is needed. treatment effects that we usually see when a con-
3. The face must be divided in relatively small ventional technique is used.
areas rather than attempting to treat the entire The device that we use (“Limelight” by
face at the same time. In this manner, the fore- Cutera, Inc.) emits light between 520 and
head is considered one area, each cheek with 1100  nm. It has a cooled sapphire handpiece.
the corresponding side of the nose will be Three distinct factory-set programs are available
another, and the perioral area and chin another labeled A, B and C. A delivers the shortest wave-
area. length and pulse duration and is aimed to treat
224 M. Perper et al.

skin types I–II mainly with vascular dyschro- aging. The therapy exposes tissue to low-levels of
mias. B has a longer wavelength emission and red and near infrared (NIR light) and stimulates
correspondingly shorter cooling times. It is used or inhibits a variety of cellular processes using a
in pigmented and vascular dyschromias in skin lesser degree of energy or power than more tradi-
type I–III. The C program is the safest for darker tional treatments such as ablation, cutting, and
skin types and emits in the longest wavelength thermally coagulating tissue. Unlike traumatic
range available for the machine. It also has the ablative (e.g., laser resurfacing) and non-ablative
longest pulse duration. A so-called “Pigment (e.g., intense pulsed light [IPL]), treatments that
mode” is available. This has a shorter cooling produce secondary tissue repair through con-
time and appears to be more effective in pigmen- trolled damage to either the epidermis or the der-
tary targets. We use this mode carefully in darker mis, Significant variation in dosimetry parameters
types. between different LLLTs, including wavelength,
The initial fluence used for treatments will irradiance or power density, pulse structure,
vary from 8 J/cm2 for skin types II–IV to 12 J/ coherence, polarization, energy fluence, irradia-
cm2 for skin type I–II. We do daily treatments for tion time, contact vs. non-contact application,
1 week with increments in fluence of 2 J/cm2 per and repetition regimen, warrants additional
day if tolerated. Two passes are the routine, per assessment of the devices. For our purposes, we
session. We take the time to cool the skin leaving will describe the use of LED (light-emitting
the cool handpiece in situ for a few seconds or diode) therapy, a type of LLLT which facilitates
after the burning sensation from the light pulse non-thermal, non-ablative skin rejuvenation, in
disappears, after the emission of the light pulse. improving wrinkles and skin laxity. Because
This aids significantly to decrease the level of the LED light sources have dot-shaped (punctiform)
discomfort produced by these treatments, espe- emission characteristics and narrow spectral
cially in dark skin types. We do not apply pre-or bandwidths, it is recommended to apply a poly-
post-treatment cooling pads. Daily sessions will chromatic spectrum covering a broader spectral
turn the chromophore in the skin darker by the region for skin rejuvenation and skin repair.
day, augmenting the ultimate effect on pigmented Although varying parameters may be
lesions. On the other hand, gradual increments in employed during LED treatment, treatments
fluence permit to reach higher levels safely. This applied on the face most typically involve 633,
is crucial in dark skin tones or suntanned skin. and 830 nm at fluences of 126 and 66 J/cm2. We
Patients can expect darkening of the pig- focus on successful treatment procedures
mented target lesions after 48 h and spontaneous described by Bhat et  al. using the Omnilux
sloughing of the lesions within 1 week. By doing Revive LED lamp for facial skin rejuvenation.
daily treatments we curtail erythema post treat- While using the Omnilux Revive LED lamp
ment and are able to deliver ultimately higher flu- for rejuvenation, patients are first seated comfort-
ences, which, we feel aids in the final result. In ably in a chair and are pre-cleansed with a cleans-
this manner for example we are able to deliver up ing lotion. The patient then receives non-coherent
to 16 J/cm2 in skin type IV by the fifth day. red light at a wavelength of 630(±3) nm and an
intensity of 80  mW/cm2 at a dose of 96  J/cm2.
Patients are treated three times weekly for 3
 ow-Level Light Therapy (LLLT)
L weeks for a total of nine treatments. Each session
for Skin Rejuvenation lasts 20 min.
Results using this method have proved prom-
Low level laser therapy, phototherapy or photo- ising, with substantial patient satisfaction indi-
biomedulation, is an upcoming, non-invasive cated just 5 weeks after treatment. Reduction in
treatment modality for improve the appearance of fine lines and wrinkles, smoother and firmer skin,
wrinkles, dyspigmentation, telangiectasia, and and perception of softer skin have been noted as
loss of elasticity occurring hand in hand with beneficial effects of the treatment. Further, unlike
12  Non-invasive Rejuvenation/Skin Tightening: Light-Based Devices 225

more invasive methods including ablative and skin to increase absorption of the photosensitiz-
non-ablative laser treatments, no pain or adverse ing agent. Three to six hours are allowed for the
effects have been noted from the LED treatment. drug to be fully absorbed. The second stage lasts
Limitations of this treatment modality include from 5 to 45 min and consists of the light being
little improvement in skin elasticity and directed at the treatment area. The third stage
hydration. involves skin sensitivity following the treatment
for up to 2 weeks. In one study, PDT was per-
formed twice at 1-month intervals, and results
Photodynamic Therapy (PDT) were evaluated 1 month after the final treatment.
for Skin Rejuvenation Lesions were treated with noncoherent red light
of emission wavelength 580–740  nm, dose of
Photodynamic therapy (PDT) is a treatment that 100  J/cm2, and fluence rate of 100  mW/cm2.
can be performed using both laser and nonlaser Parameters vary per clinician and should be
light. Mechanistically, PDT uses oxygen and based on prior success, however. Recomm­
light in combination with a photosensitizing endations for PDT for different lesions have been
agent to selectively target cells. Photosensitizing published.
agents are drugs that only activate when struck
with a specific wavelength of light. PDT can be
used to treat a variety of skin issues such as acne Bibliography
and unwanted ageing, although it has been tradi-
tionally used for the treatment of superficial basal 1. Alexiades-Armenakas M.  Assessment of the mobile
delivery of infrared light (1100-1800 nm) for the treat-
cell carcinoma and actinic keratosis. Other uses ment of facial and neck skin laxity. J Drugs Dermatol.
for PDT are still being investigated. 2009;8(3):221–6.
The most common complication of this treat- 2. Avci P, et al. Low-level laser (light) therapy (LLLT)
ment is the “PDT effect”. The “PDT effect” is in skin: stimulating, healing, restoring. Semin Cutan
Med Surg. 2013;32(1):41–52.
expressed as redness, peeling, and crusting of the 3. Dang Y, Ren Q, Hoecker S, Liu H, Ma J, Zhang J. 
skin. Exposure to sunlight during a 48-h period Biophysical, histological and biochemical changes
after treatment can make the reaction worse. after non-ablative treatments with the 595 and
Oftentimes, though, those with the most dramatic 1320 nm lasers: a comparative study. Photodermatol
Photoimmunol Photomed. 2005;21(4):204–9.
reactions have superior results. 4. Dang YY, Ren QS, Liu HX, Ma JB, Zhang JS. 
While PDT is not commonly used for facial Comparison of histologic, biochemical, and mechani-
rejuvenation, it is a less-invasive alternative that cal properties of murine skin treated with the 1064-
has gained traction with clinicians. When used in nm and 1320-nm Nd:YAG lasers. Exp Dermatol.
2005;14(12):876–82. Institute for Laser Medicine
combination with intense pulsed light (standing and Biophotonics, Shanghai Jiaotong University of
in as the photosensitizing agent), PDT is an effec- Shanghai, China.
tive treatment. This combination is used to treat 5. Goldberg DJ.  Non-ablative subsurface remodel-
vascular erythema, fine rhytides, epidermal dys- ing: clinical and histologic evaluation of a 1320-nm
Nd:YAG laser. J Cutan Laser Ther. 1999;1(3):153–7.
chromia, and photodamage. In treatment of pho- 6. Goldberg DJ, Samady JA.  Intense pulsed light and
toaging, PDT-IPL therapy has the added benefit Nd:YAG laser nonablative treatment of facial rhytids.
of treating premalignant lesions. Additionally, Lasers Surg Med. 2001;28(2):141–4.
healing times are brief. Unfortunately, PDT-IPL 7. Goldberg DJ, Silapunt S. Q-switched Nd:YAG laser:
rhytid improvement by non-ablative dermal remodel-
therapy is unable to resurface the skin and cannot ing. J Cutan Laser Ther. 2000;2(3):157–60.
penetrate deep enough to treat other unwanted 8. Hassan KM, Benedetto AV. Facial skin rejuvenation:
skin lesions. Other techniques involve using a Ablative laser resurfacing, chemical peels, or pho-
pulse-dye laser in conjunction with PDT. todynamic therapy? Facts and controversies. Clin
Dermatol. 2013;31(6):737–40.
There are three stages in photodynamic ther- 9. Min-Wei CL.  Novel 3-in 1 wavelength light source
apy. The first, involves the practitioner thor- for photorejuvenation. J Drugs Dermatol. 2009;7(4):
oughly cleaning the skin and gently scraping the 335–9.
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10. Morton CA, McKenna KE, Rhodes LE. Guidelines for 16. Sze-Hon C, et  al. Nonablative infrared skin tighten-
topical photodynamic therapy: update. Br J Dermatol. ing in type IV to V Asian skin: a prospective clinical
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of non-ablative skin tightening with a broadband B.  Clinical evaluation of enhanced nonablative skin
infrared light device. Presented at the 26th annual rejuvenation using a combination of a 532 and a
meeting of the American Society of Laser Medicine 1,064 nm laser. Lasers Surg Med. 2004;34(5):439–45.
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 Laser and Light Therapies for Acne
13
Ali Rajabi-Estarabadi, Ariel E. Eber,
and Keyvan Nouri

Abstract among the most common lasers used to

• Acne vulgaris is a very common cutaneous treat acne and acne scarring.
disorder which can cause permanent scar- • 1540  nm Erbium (Er):Glass Laser, and the
ring and disfigurement. 1550 nm Er:Glass fractional laser are among
• Acne is a multifactorial disorder of pilose- the most common lasers used to treat acne and
baceous units and affects the areas of skin acne scarring.
with the greatest concentration of seba- • These lasers target the underlying causes of acne
ceous follicles such as the face, neck, chest, including the colonization of Priopionibacterium
and back. acnes, high levels of sebum production, altered
• Common therapies for acne treatment keratinization, inflammation, and bacterial col-
include retinoids, keratolytic agents, anti- onization of hair follicles on the face, neck, and
microbials, and anti-inflammatory agents. back.
• The need for an alternative treatment has
led to the investigation of lasers and light
sources as a new treatment. Keywords
• The 1450 nm diode laser, 585- and 595-nm Acne vulgaris · Acne scarring · 1450 nm
pulsed dye lasers (PDLs), near infrared diode laser · 585- and 595-nm pulsed dye
diode lasers, 1320  nm Nd:YAG laser, lasers (PDLs) · Near infrared diode lasers ·
532 nm potassium titanyl phosphate laser, 1320 nm Nd:YAG laser · 532 nm potassium
1064  nm long-pulsed Nd:YAG laser, titanyl phosphate laser · 1064 nm long-pulsed
1540 nm Erbium (Er):Glass Laser, and the Nd:YAG laser · 1540 nm Erbium (Er):Glass
1550  nm Er:Glass fractional laser are Laser · 1550 nm Er:Glass fractional laser

A. Rajabi-Estarabadi (*) · A. E. Eber · K. Nouri

Department of Dermatology and Cutaneous Surgery,
University of Miami, Miller School of Medicine,
Miami, FL, USA
e-mail: [email protected];
[email protected]; [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 227

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_13
228 A. Rajabi-Estarabadi et al.

Introduction Although most patients will improve with time,

some do not and have serious long term effects
Acne vulgaris is the most common skin disorder. It from acne. These include redness, hyperpigmen-
affects approximately 35–90% of adolescents and tation, and permanent scars (atrophic, hypertro-
continues to be a common problem in those over the phic and keloids) [12].
age of 20 [1–3]. In fact, in the U.S., it is estimated Common therapies used for the treatment of
that approximately 9.6 million individuals visited a acne vulgaris include keratolytic agents, antimi-
doctor for acne treatment in 2010, and over 60% of crobials, anti-inflammatories, retinoids, hor-
these patients were over the age of 18 [4]. monal treatments, microdermabrasion, and
This common cutaneous disorder can cause chemical peels [12, 13]. The need for an alterna-
permanent scarring and disfigurement, which may tive treatment has led to the investigation of lasers
lead to severe consequences in psychological and and light sources as a potential treatment. The
personality development. In fact, it is associated mechanism of action relies upon the fact that
with a high prevalence of depression and skin dis- lasers can emit wavelengths that cause direct
ease related suicide [5, 6]. For these reasons, destruction of P. acnes or photo-thermal damage
effective management of acne can improve self- to the sebaceous glands.
esteem, body image and other life quality issues
[7, 8].
Acne is a multifactorial disorder of the piloseba- Laser-Based Therapies
ceous unit and affects areas of the body with the
greatest concentration of sebaceous follicles includ- Lasers release coherent light that can provide
ing the face, chest, neck and back. There are key very high radiance by focusing on a small tar-
components that are thought to contribute to the geted area of tissue. The mechanisms of action
development of acne and include: Hypercornification are that lasers can emit wavelengths which are
combined with excess sebum production provoking selectively absorbed by oxyhemoglobin of the
clogging of the pores, Propionobacterium acnes (P. dilated vasculature within inflamed acne, activate
acnes) proliferation in this environment causing an bacterial porphyrins resulting in self destruction
increase in inflammatory cytokine production and of P. acnes, or decrease sebum production by
free fatty acids, and finally, further irritation from photothermal damage to the sebaceous glands.
inflammatory factors and free fatty acids. Studies Lasers offer alternative options for acne treat-
also suggest genetic, neuroendocrine, and dietary ment which may have the benefit of rapid action,
factors may contribute to the multifactorial process low systemic adverse effects, and do not require
of acne vulgaris pathogenesis [9–11]. everyday treatment. Laser treatments of acne
Currently, no acne grading or classifying sys- include the 1450-nm diode, 585-nm pulsed dye
tem can be recommended. However, clinicians laser, 1320 Neodymium: Yttrium and 1540
may find it useful to determine the severity of Erbium (ER): Glass Laser.
acne according to certain specifications. Such
systems can assist in more specific classification
of disease, determining appropriate treatment 585-nm Pulsed Dye Lasers
options, and monitoring improvement during
a treatment course. There are several accepted The 585-nm and 595-nm pulsed-dye lasers (PDL)
tools that take into account type of acne, sever- directly target P. acnes. The mode of action of the
ity of acne, number of acne lesions (comedomes, PDL is based on the principle of selective photo-
papules, pustules etc.), anatomical location/ thermolysis, a targeted damaging of specific
extent of acne, quality of life and other psy- structures in the skin without damaging the sur-
chosocial metrics, and scarring among others. rounding area [14].
13  Laser and Light Therapies for Acne 229

It is traditionally useful for the treatment of vas- shown to be effective for the treatment of acne
cular lesions as well as hemangiomas, port-wine [23]. It uses a broad spectrum green light which
stains, and facial telangiectasia [15]. However, the is thought to photoactivate bacterial porphyrins
pulsed dye laser can also activate bacterial porphy- and produce limited non-specific thermal injury
rins and thereby produce selective photothermoly- to sebaceous glands [24].
sis of the dilated vasculature within inflamed acne In a split face study of 26 patients after four
[16–18]. treatments with a KTP laser, a 34.9% and 20.7%
Seaton et  al. did a randomized double-blind reduction in acne severity was shown at 1 week
study in 41 patients with mild to moderate facial and 4 weeks, respectively [25]. In another study,
acne. They randomly assigned patients to PDL or 25 patients who were treated with the KTP laser
sham treatment. Twelve weeks after a single PDL at fluences ranging from 6 to 12  J/cm2achieved
treatment, with two different fluences given at 60–70% clearing after six treatments [26]. Bowes
each side of the midline, they reported reduced et al. conducted a split-face study whereby they
inflammatory acne lesions by 49% on both sides treated one-half of the face of 11 patients with
of the face [19]. mild to moderate acne with the KTP laser. They
Orringer et  al. conducted a randomized con- reported a 35.9% decrease in acne after 1 month,
trolled study in split-face of 26 patients. After while the control half had a 1.8% increase. They
12  weeks lesion count did not significantly noted that there was decreased sebum produc-
change in comparison with non-treated sites; tion, but there was a minimal effect on P. acnes
however, a trend of improvement in inflamma- [24].
tory acne was described [20]. Yilmaz et al. also evaluated efficacy and safety
Leheta compared treatment outcomes of PDL of 532-nm KTP laser and compared the effect of
treatment with two regular acne treatments. One once and twice weekly application in the treat-
group of 15 patients was treated with PDL, and ment of mild to moderate acne vulgaris in two
compared with two other groups which received groups of 38 patients, group 1 applying once
regular topical treatments (topical vitamin A weekly and group two, twice weekly. They
acid, benzoyl peroxide) or chemical peels (tri- reported statistically significant improvement at
chloroacetic acid 25%). Significant decrease in second control session (p = 0.005) in group I, and
all three groups was seen; although, in the fol- at first (p = 0.004), and second (p < 0.001) control
low-up period remission was significantly higher sessions in group II for treated sides [27].
in the PDL group [21].
Jasim et  al. did a split-face study in ten
patients, in which half of the face was treated 1450-nm Diode Laser
with PDL and the untreated site served as a con-
trol side. They showed visible improvement of The 1450-nm laser with a dynamic cooling
acne lesions on the treated site in 50% of the device has received Food and Drug Administration
patients. PDL seems to be an effective treatment approval for the treatment of acne. The 1450-nm
for acne vulgaris [22]. diode laser is a longer wavelength laser that pen-
etrates to the level of the sebaceous gland within
the mid-dermis. This wavelength is primarily
Potassium Titanyl Phosphate absorbed by water, so it does not greatly affect
(KTP) Laser the epidermis but does thermally ablate sebo-
cytes, along with P. acnes [28, 29].
The potassium titanyl phosphate (KTP) laser has In a multicenter, blinded study, 61 patients
generally been used for the treatment of telangi- were treated every month for 4 consecutive
ectasia and rosacea but has also recently been months using the 1450-nm diode. There was a
230 A. Rajabi-Estarabadi et al.

26% drop out rate, but the remaining 45 patients They observed a maximum of 18% reduction in
had 65% improvement 1 month following treat- sebum output after three treatments [34].
ment, and at 6 months five patients required no A study recruited patients with moderate to
additional acne therapy [30]. severe acne vulgaris. A split-face format was
Friedman et  al. used three irradiation ses- used: the side of the face to be treated was ran-
sions of the 1450-nm diode laser to treat 19 domized with the other side serving as a within-
patients with inflammatory facial acne at 4- to patient control. They performed three treatments
6-week intervals. After one treatment, the aver- monthly using 1450 diode laser with a double-
age lesion count decreased by 37% (P < 0.01). pass technique. On average, the lesion count and
Mean lesion counts improved by 58% (P < 0.01) acne grade reduced by the same amount on both
after the second irradiation and by 83% sides of the face. Twelve months after the last
(P  <  0.01) after the third session. They also treatment the change in lesion count and grade
experienced erythema and edema for up to 24 h between the treated and control sides remained
after laser treatment [29]. similar. They reported improvement of both side
In another study, Alam et al. performed a trial of the face and they suggested a possible sys-
in a split-face of 25 patients and compared the temic effect of laser [35].
1450-nm diode laser with the 595 nm PDL. They
reported that the 1450-nm diode laser produced
similar acne reduction with longer remissions (up  320 Neodymium: Yttrium Aluminum
1
to 3 months) when compared to the 595 nm PDL Garnet Laser (Nd:YAG)
after 4 monthly treatments [31].
Astner et  al. applied 1450-nm diode laser The 1320 neodymium: yttrium aluminum garnet
twice in in the management of refractory acne laser (Nd:YAG) is a deep-penetrating, long wave-
vulgaris in 13 patients. This study demonstrated length, mid-infrared laser that has been shown to
that mean total lesion and inflammatory lesion have thermolytic effect upon sebaceous glands.
counts decreased from 66  ±  14 and 23  ±  5 at In one study the 1320 Nd: YAG laser was used to
baseline to 34 ± 12.9 and 14 ± 7 at 3-month fol- treat 50 patients with moderate to severe acne (6
low-up (p < 0.05). Side effects were mild, includ- weekly treatments). The patients were followed
ing transient erythema [32]. for 1  year thereafter. Eighty percent of patients
In another study, 11 patients were treated with felt they had 75–100% improvement after the
a 1450-nm diode laser in a split-face bilateral fourth of these six treatments. However, 72% of
paired trial, every 3  weeks for a total of three the patients felt that the benefit seemed to fade
treatments. One-half of the faces received a sin- beyond 3  months. 82% of the patients that had
gle-pass consisting of stacked double pulses. The acne scarring had ‘noticeable’ improvement. The
other side received a double-pass treatment of one major complication reported was one patient
single pulses. The mean acne severity scores developing a pitted scar from the treatment [36].
decreased from 3.3 at baseline to 2.1 and 2.2 for Orringer et al. conducted a randomized, con-
the stacked-pulse and double-pass sides, respec- trolled, single-blind, split-face clinical trial in 46
tively. One subject’s acne severity increased dur- patients with facial acne. Patients received a
ing the study from Grade 3 to Grade 5 [33]. series of three nonablative laser treatments using
Perez-Maldonado et  al. conducted study on 1320-nm Nd:YAG laser to half of the face. The
eight patients with a history of acne and used authors reported no significant differences
1450-nm diode laser on the right side of the nose between treated and control sides of the face in
over a 6-week period, for a total of three treat- terms of changes in mean papule or pustule
ments and left the other side of the nose untreated. counts [37].
13  Laser and Light Therapies for Acne 231

1540 Erbium (ER): Glass Laser Liu et  al. evaluated the short-term and long-
term effects of the 1550-nm erbium:glass frac-
Similar to the 1320-nm Nd:YAG laser system, tionated laser in the treatment of 45 patients with
the 1540-nm erbium glass laser is a novel, mid- facial acne vulgaris. Nine male and 36 female
infrared range laser that targets intracellular acne patients were treated four times at 4-week
water to a depth of 0.4–2 mm. Minimal absorp- intervals. After four treatments, all patients had
tion by melanin makes the laser essentially safe an obvious reduction of lesion counts and IGA
for the treatment of dark-skinned or tanned indi- score, with the peak lesion counts decreasing to
viduals [38]. Also, this laser was shown to pro- 67.7%. Eight patients had follow-up for 2 years,
vide deep dermal penetration and subsequent 27 patients for 1  year, and all patients for
alteration of sebaceous activity through thermal 6  months. The mean percentage reduction was
coagulation. 72% at the half-year follow-up, 79% at the 1-year
A study found that there was a 78% lesion follow-up, and 75% at the 2-year follow-up.
reduction in 25 patients with facial and truncal Three patients observed a significant improve-
acne after 4 monthly treatments with the 1540- ment in preexisting hyper-pigmentation after
nm laser [39]. Also, another study used this laser treatments. All patients reported that their skin
in 20 patients with facial inflammatory acne in was less prone to oiliness [43].
combination with an active contact-cooling
device over the patient’s entire face. Patients
underwent four sessions at 2-week intervals. Light Based Therapies
Investigators reported a lesion count reduction of
70% after 3  months. No side effects were • The most commonly used light based devices
observed after any treatment with the Er:glass are the blue light, red light, and intense pulsed
laser [40]. light system.
Bogle et al. evaluated the use of the 1540-nm • Propionibacterium acnes produces endoge-
erbium:glass laser to treat patients with moderate nous porphyrins, which absorb light to form a
to severe acne four times at 2-week intervals. highly reactive singlet oxygen which can
Patients rated improvement as 68%, and the mean cause self-destruction of P. acnes.
investigator improvement assessment was 78%
after 6-month follow-up [41].
Blue Light
 550-nm Fractionated Erbium Glass
1
The wavelength of 1550 nm fractionated Er:glass P. acnes containing fluorescent porphyrins can be
is absorbed primarily by water, targeting the killed by a blue light-induced photodynamic
sebaceous glands and surrounding dermal matrix. effect. Activation of protoporphyrin IX, found in
In a randomized controlled split-face study, 24 P. acnes, in the presence of oxygen produces a
patients with active acne lesions were treated metastable intermediate that destroys the bacte-
using 1550-nm fractionated erbium:glass laser on rium. Protoporphyrin IX absorption peaks occurs
one side of the face for four sessions with a at wavelengths found in the visible light spec-
2-week interval. This study showed a significant trum [43–48].
reduction (p  <  0.0001) in the mean count of Thirty patients with mild to moderate acne
lesions and the size of sebaceous glands after lesions on the face and/or the back and/or the
treatment. Also, the authors reported complete chest participated in this study by Kawada et al.
clearance of all lesions after treatment and during The patients were irradiated with high-intensity,
the follow-up in 17 (70.8%) patients [42]. narrow-band, blue light twice a week up to
232 A. Rajabi-Estarabadi et al.

5  weeks. This study showed 64% reduction of patients were irradiated by using blue light for 8
acne lesions [49]. times twice a week, and 30 patients were treated
Elman et  al., treated 46 acne patients with with topical Benzoyl Peroxide 5% formulation,
420 nm UV-free blue light for eight treatments of auto-applied twice a day, every day. The authors
8–15 min. 80% of patients showed a significant reported the same improvement result by the blue
reduction of 59–67% of inflammatory acne light and benzoyl peroxide (p > 0.05) and the side
lesions after eight treatments. The reduction in effects were less frequent in the group treated
lesions was steady in the follow-up, at 8 weeks with blue light [55].
after the end of therapy [50].
In a split face study, 28 patients with symmet-
rical facial acne received blue light on one side of Blue/Red Light Combinations
the face twice weekly for 4 consecutive weeks.
The authors reported that the mean percentage Although by theory porphyrins should respond
improvement was 52% after eight sessions and well to blue light, it is a shorter wavelength, and
first significant improvement happened after four therefore does not penetrate well into the skin
sessions of irradiation (P  ≤  0.009). After eight [56].
sessions of blue light irradiation acne exacerba- Longer wavelengths with Q-bands, such as
tion was found in four patients [51]. red light, has been combined with blue light in
Tremblay et al. treated 45 patients with pure acne therapy. Red light (wavelength 600–650 nm)
blue light (415  nm) for two treatments of penetrates deeper into the skin than blue light. In
20 min per week for a period of 4–8 weeks. The fact, 635 nm light may penetrate through the skin
mean improvement score of the acne lesions was up to 6 mm compared with 1–2 mm for light at
3.14 at 4 weeks and 2.90 at 8 weeks, after which 400–500 nm. Red light has also been shown to be
lesions of nine patients were cleared completely. effective in acne treatment by activating porphy-
They reported that 50% of patients were highly rins in the Q band and decreases inflammation by
satisfied with the treatment and no adverse event controlling cytokine release from macrophages
occurred [52]. [57–61].
In a study, Omi et al. investigated the use of In a randomized, controlled, single-blind
high-intensity, narrow-band, blue light on 28 study, Papageorgiou et al. compared mixed blue
patients with facial acne. The study showed and red light (415 nm and 660 nm, respectively)
64.7% improvement in acne lesions after eight phototherapy with blue (415 nm) or 5% benzoyl
serial biweekly 15-min treatment sessions [53]. peroxide in 140 patients with mild-to-moderate
Morton et al. evaluated the effect of narrow- acne. With the use of the combined blue-red light
band blue light in the reduction of inflammatory radiation, a final improvement of 76% in inflam-
and non-inflammatory lesions in 30 patients with matory lesions was noted with follow-up of
mild to moderate acne. The patients received 12  weeks, which was significantly superior to
eight treatment sessions (each session 10 or those achieved by blue light or benzoyl peroxide.
20-minute) over 4 weeks. This study concluded Also, the final mean improvement in comedones
that the aforementioned modality was effective in by using blue–red light was 58%, which was bet-
reducing the number of inflamed lesions in sub- ter than the result of other active treatments; how-
jects with mild to moderate acne. They reported a ever, the differences was not statistically
statistically significant decrease in inflamed significant [57].
counts at 8  weeks assessments and no adverse Goldberg and Russel evaluated 22 patients
events [54]. with mild to severe symmetric facial acne vul-
In a study by De Arruda et al. the efficacy of garis with a combination of blue and red light.
blue light treatment was evaluated in comparison They were treated over eight sessions, two per
with topical benzoyl peroxide 5% formulation in week 3 days apart, alternating between blue light
60 patients with facial acne grades II and III. 30 (20 min/session) and red light (20 min/session).
13  Laser and Light Therapies for Acne 233

Patients received a mild microdermabrasion als, and 1 retrospective observational study) for a
before each session. Acne was assessed at base- total of 544 patients. They categorized the studies
line and at weeks 2, 4, 8 and 12. At the 4-week into two groups of IPL alone and IPL in combi-
follow-up, the mean lesion count reduction was nation with PDT. The authors reported that effi-
significant at 46% (p  =  0.001). At the 12-week cacy of IPL in treatment of acne ranged from
follow-up, the mean lesion count reduction was 34% to 88.3% (depending on the type of acne
also significant at 81% (p = 0.001). Severe acne lesion: inflammatory or noninflammatory), with
showed a marginally better response than mild most of the studies showing an improvement
acne. Comedones did not respond as well as between 40% and 60%. Also, this review stated
inflammatory lesions [61]. that although IPL monotherapy showed benefit in
In a study performed by Lee et al., 24 patients the treatment of acne vulgaris, but the evidence
with mild to moderately severe facial acne were supports greater efficacy for treatment with IPL
treated with quasimonochromatic LED devices, in combination with PDT [65].
alternating blue and red light twice a week for Ianosi et al. compared the effectiveness of IPL
4  weeks. 8  weeks after the final treatment the and vacuum versus IPL with placebo in 180
mean percentage improvements in non-inflam- patients with mild to moderate comedonal and
matory and inflammatory lesions were 34.28% inflammatory acne (group A—60 patients treated
and 77.93%, respectively. None of the patients with vacuum and IPL, group V—60 patients
reported any adverse reaction related to the treat- treated with IPL, and control group—60 patients
ment [60]. treated with Sebium H2O Micellaire Solution).
They reported a significant reduction in the num-
I ntense Pulsed Light (IPL) ber of papules, pustules, and comedones in
Intense pulsed light (IPL) uses a flash lamp to groups A and V compared with those in the con-
deliver wide spectrum, non-coherent visible light trol group (p < 0.001) with decrease of the pap-
(green, yellow, and red) to near-infrared wave- ules in group A being rapider than group V. Also,
lengths. Treatment of acne with IPL has shown patients belonging to group A were more satis-
some very promising results. In a study by fied compared with those in group V (p = 0.004)
Gregory and co-workers, 50 patients with mild to and significantly more satisfied compared with
severe acne were treated with IPL for 1 month. those of the control group (p < 0.001) [66].
These patients showed a 60% lesion reduction at In a study, the investigators compared the clin-
the 1-month follow-up, versus 32% increase in ical efficacy of IPL with benzoyl peroxide 5% in
controls [62]. In a study done by Elman and co- the treatment of inflammatory acne in 50 patients
workers of 19 patients with acne, they showed with mild-to-severe acne. The study showed
that the IPL produced an 85% clearance of treatment with both benzoyl peroxide and IPL
inflammatory lesions and 87% clearance of non- resulted in improvement of the acne after 5 weeks
inflammatory lesions in 2 months [63]. of treatment. Benzoyl peroxide showed better
They also conducted a study to test the role of results than IPL which was statistically signifi-
pulsed light and heat energy in acne clearance. A cant at the midpoint of the study (after the 3rd
system with light pulses and heat was used in bi- week of treatment). However, this difference was
weekly treatments for 4 weeks with wavelengths insignificant at the end of study [67].
between 430 and 1100  nm. This study showed Mohamad et  al. performed controlled, sin-
approximately a 75% clearance of the inflamma- gle-blind, split-face clinical trial to compare the
tory lesions 1 month after the last treatment [64]. clinical efficacy of IPL with 1064-nm long-
Wat et  al. evaluated efficacy of IPL in treat- pulsed Nd:YAG in treatment of 74 patients with
ment of acne vulgaris in a systematic review. facial acne vulgaris. All participants received
They identified twenty-one studies (2 random- three sessions of IPL on the right side of the face
ized controlled trials, 7 prospective right–left and 1064-nm Nd:YAG on the left side of the
comparison trials, 11 uncontrolled open-label tri- face at 4-week intervals. The inflammatory acne
234 A. Rajabi-Estarabadi et al.

lesions were reduced on the IPL and 1064-nm ditions in a defined American population. Mayo Clin
Proc. 2013;88(1):56–67.
Nd:YAG treated sides by 67.1% and 70.2%, 9. Muizzuddin N, Giacomoni P, Maes D. Acne—a mul-
respectively (p < 0.05), while non inflammatory tifaceted problem. Drug Discov Today Dis Mech.
acne lesions were reduced by 18.3% and 19.3%, 2008;5(2):e183–8.
respectively (p > 0.05). Also, the authors stated 10. Toyoda M, Morohashi M. Pathogenesis of acne. Med
Electron Microsc. 2001;34(1):29–40.
no significant difference in the efficacy of the 11. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guide­
two modalities in reducing both types of acne lines of care for the management of acne vulgaris. J
lesions (p > 0.05) [68]. Am Acad Dermatol. 2016;74(5):945–73. e933
A study by Barakat et al., accursed 24 patients 12. Leyden JJ. Therapy for acne vulgaris. N Engl J Med.
1997;336(16):1156–62.
with acne vulgaris to evaluate efficacy of IPL in 13. Keri J, Shiman M.  An update on the management
six treatment sessions. They showed a significant of acne vulgaris. Clin Cosmet Investig Dermatol.
reduction of all acne lesions especially inflamma- 2009;2:105–10.
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The efficacy of pulsed dye laser treatment for inflam-
treatment (p < 0.05) [69]. matory skin diseases: a systematic review. J Am Acad
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The treatment of acne is a difficult process due Dermatol. 2006 Jan-Feb;24(1):26–32.
16. Bjerring P, Clement M, Heickendorff L, Lybecker H,
to its multifarious pathogenesis. Using laser Kiernan M.  Dermal collagen production following
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apy have been shown to be an effective treat- Cosmet Laser Ther. 2002;4:39–43.
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of acne scarring with 585  nm flashlamp pulsed dye
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the optimal parameters to maximize the effec- tunable dye laser. N Engl J Med. 1989;320:416–21.
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 Lasers for Psoriasis
and Hypopigmentation 14
Laura Jordan, Summer Moon,
and James M. Spencer

Abstract Keywords
Psoriasis and pigmentary disorders have a pro- Excimer laser · Psoriasis · Vitiligo · Pigmentary
found impact on the quality of life of affected disorders · Hypopigmentation · Leucoderma ·
patients. Despite multiple medical therapies for Scleroderma · Pityriasis alba · Psoralen and
psoriasis, certain clinical scenarios present ther- ultraviolet A (PUVA) · Minimal erythema
apeutic dilemmas. The excimer laser has been dose (MED) · Light therapy · Tacrolimus
found to be efficacious not only for patients
suffering from psoriasis but also for several dis-
orders of hypopigmentation including vitiligo,
Introduction
linear scleroderma, pityriasis alba, and chemi-
cal, punctate, and post-resurfacing leucoderma.
• Psoriasis and vitiligo have been found to ben-
Additionally, due to the excimer laser’s reduced
efit from light therapy in the UVB range
cumulative dose and number of treatment ses-
(290–320 nm).
sions, it offers several potential advantages
• The 308  nm xenon-chloride excimer laser is
over whole-body phototherapy, including low-
now utilized for select patients with psoriasis
ered carcinogenicity, phototoxicity, and cost of
and vitiligo.
treatment. This paper considers the variety of
• The efficacy and safety of the excimer laser is
applications for the excimer laser on psoriasis
well documented.
and hypopigmentation and reviews its associ-
• Striae, linear scleroderma, pityriasis alba, and
ated indications, contraindications, techniques,
chemical, punctate, and post-resurfacing leu-
adverse events, and future directions.
coderma have been found to respond to the
308 nm excimer laser.
L. Jordan (*)
Kansas City University Consortium, One of the most recent advancements in pho-
Tri-County Dermatology Residency Program, totherapy is the development of localized deliv-
Cuyahoga Falls, OH, USA
ery systems. One such device is the excimer laser.
S. Moon The use of the excimer laser was first reported in
Dermatology Specialists of West Florida, FL, USA
dermatology by Bónis et al. in 1997 for psoria-
J. M. Spencer sis treatment [1]. Psoriasis has been reported to
Spencer Dermatology and Skin Surgery Center,
respond best to light at a wavelength of 313 nm
Spencer Dermatology, Carillon Outpatient Center,
St. Petersburg, FL, USA [2]. Since the excimer laser emits light at a
e-mail: [email protected] wavelength of 308 nm, it was a logical choice for

© Springer International Publishing AG, part of Springer Nature 2018 237

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_14
238 L. Jordan et al.

investigation. Further, these lasers, as with UV The benefits of using the 308  nm excimer
light in general, offer a selective immunosup- laser for psoriasis were fully elucidated in the late
pressant action which provides a safe treatment 1990s. Bónis et al. showed that psoriatic lesions
for chronic skin manifestations [3]. The excimer treated with the excimer laser cleared with fewer
laser has been found to be efficacious not only treatments than narrow band UVB therapy [1].
for patients suffering from psoriasis but also for Utilization of the laser also spared the unin-
several disorders of hypopigmentation including volved skin from UV exposure, reducing the risk
vitiligo. Additionally, due to the excimer laser’s of carcinogenicity and photoaging. Kemény et al.
reduced cumulative dose and number of treat- also found that remissions for up to 2 years were
ment sessions, it offers several potential advan- seen in some patients [6]. Laser therapy demon-
tages over whole-body phototherapy, including strated efficacy at lower cumulative doses when
lowered carcinogenicity, phototoxicity, and cost compared to conventional light therapy. It was
of treatment [4]. This chapter serves to discuss also noted that psoriatic plaques can tolerate sev-
the use of the excimer laser for psoriasis and dis- eral times the minimal erythema dose (MED) of
eases of hypopigmentation. normal skin without burning. Exposure of three
Excimer lasers are a group of lasers utilized to four times the MED has demonstrated early
in a variety of medical specialties, most notably clearance and long remissions. Doses greater
ophthalmology. There are several types of excimer than six times the MED, however, have shown to
lasers, all of which operate in the ultraviolet spec- be complicated by blistering, pain, and reduced
trum. Excimer refers to the formation of “excited compliance. In 2002, Feldman et  al. reported
dimers” via an inducible mixture of a halogen that 80 patients treated with lower multipli-
and noble gas. Electric current is delivered to the ers of the MED given twice weekly achieved
gas producing unstable, high-energy dimers that 75% or greater clearance in 72% of subjects in
quickly dissociate giving off laser light [5]. The an average of 6.2 treatments [7]. The pulse dye
laser light is delivered to its target via a fiber optic laser (PDL) has also been studied for the treat-
cable. The mechanism of physiologic response ment of psoriasis. The basis for using the PDL
is poorly understood but does not appear to be a is selective photothermolysis of the exagger-
thermal mechanism. Thus, the excimer lasers do ated vascular network within psoriatic plaques.
not operate under the theory of selective photo- Small studies have revealed its possible benefit
thermolysis. Excimer lasers are capable of “cold [8–10]. Additionally, Al-Mutairi et al. studied 42
ablation,” which is precise tissue ablation with patients, finding PDL to be more beneficial than
minimal surrounding thermal effects. This unique the excimer laser in treating nail psoriasis [11].
property enables the laser to be used in precision Nonetheless, stronger data exists to support the
surgeries such as corneal reshaping. It is theorized use of the 308 nm excimer laser for the treatment
that the energy of the photons from excimer lasers of psoriasis [7].
exceeds the energy of many chemical bonds which The use of excimer lasers is a source of research
keep organic material together. This principle in the field of psoriasis treatment. Kagen et  al.
forms the theory termed “ablative decomposition,” determined that a single 10 MED a­ dministration
under which excimer lasers are thought to operate. of lesion-limited high-dose (TURBO) ultraviolet
B light using the excimer laser was sufficient in
clearing a psoriatic plaque. The study hypoth-
Excimer Lasers esizes that this success is likely due to the laser’s
focus on the pathogenic T cell mechanisms which
Psoriasis are active in psoriasis [12]. Additionally, com-
bination therapy using excimer lasers has been
• Total cumulative dose is lower than traditional investigated. Tang et  al. studied the combination
light therapy. of the excimer laser with topical Calcipotriene
• Uninvolved skin is spared. and Dong et  al. with topical flumetasone on the
• Psoriatic plaques can tolerate several times the treatment of psoriasis vulgaris. Both studies found
minimal erythema dose (MED). that combination therapy potentially improved
14  Lasers for Psoriasis and Hypopigmentation 239

long-term treatment goals for psoriasis vulgaris Similarly to psoriasis treatment, combination
and reduced the number of laser doses and adverse therapy has been explored in vitiligo treatment
effects [13, 14]. Rogalski et al. compared the effi- using the excimer laser. Kawalek et  al. showed
cacy of combination therapy between calcipotriol that the addition of tacrolimus 0.1% ointment in
and dithanrol with the excimer laser, concluding combination with the excimer laser induced faster
that the most success arose from combination with and perhaps greater response to treatment, and
dithranol [15]. Nisticò et  al. also found this combination treat-
ment was effective, safe, and well-tolerated [18,
19]. Hui-Lan et  al. illustrated that the combina-
Vitiligo tion of picrolimus with the laser in the treatment
of childhood vitiligo was statistically better than
• The excimer laser is as effective as oral PUVA, excimer laser monotherapy [20]. Ebadi et  al.
but with less associated risk. studied the efficacy of combining melanocytes-
• Over 25% of treated patients achieve 100% keratinocytes transplantation (MKT), a graft-
repigmentation. ing treatment specified for stable vitiligo, with
excimer laser and found that the combination
The 308  nm excimer laser has also been therapy was more beneficial than monotherapy
shown to treat hypopigmentation of various eti- [21]. Excimer laser treatment of vitiligo can also
ologies. Vitiligo, which affects 1–2% of the improve social aspects in vitiligo patients as dem-
population, is well known to be recalcitrant to onstrated in the Al-Shobaili et  al. study of 134
most medical therapies. The disease has been vitiligo patients which applied the Dermatology
treated with multiple forms of light therapy; Life Quality Index to assess patients’ quality of
however, treatment requires many months of life [22].
therapy exposing large areas of unaffected skin
to ultraviolet radiation. Therapy is aimed at
stimulating adjacent melanocytes to migrate and Other Forms of Hypopigmentation
repopulate the affected skin. The use of the
excimer laser for vitiligo was based on the find- • Striae and post-resurfacing leucoderma can be
ing that narrowband UVB therapy was as effec- safely treated with the excimer laser. However,
tive as oral Psoralen and Ultraviolet A (PUVA) results are not sustained; striae associated
with less associated risk. Hadi et  al. demon- atrophy remains unchanged after therapy; and
strated 50.6% of 221 vitiligo patients had 75% the possible side effect of splaying the pig-
or greater repigmentation after an average of 23 ment may occur.
sessions. Also noteworthy is the fact that 25.5% • Linear scleroderma, pityriasis alba, chemi-
of the patients achieved 100% repigmentation of cal leucoderma, and punctate leucoderma
the treated lesions. Two year follow-up did not have been found to respond to the 308  nm
reveal any loss of new pigmentation. Some excimer.
patients even had continued repigmentation
after treatment was completed [16]. These stud- Leucoderma is a generic term defined as, “defi-
ies support the notion that the excimer laser ciency of pigmentation of the skin.” [23]. Some
works as well as Narrow Band Ultraviolet B authors have used this term more specifically to
(NB-UVB) or PUVA for vitiligo but in much describe post-resurfacing hypopigmenation. These
less time. Further, Cheng et  al. found that hypopigmented macules and patches are known
excimer lasers are effective in treating both seg- complications of carbon dioxide laser resurfacing.
mental and non-segmental vitiligo even in recal- In 2001, Friedman and Geronemus reported using
citrant cases. However, they discovered that the 308  nm excimer laser for post carbon dioxide
scalp lesions in particular may require a higher resurfacing leucoderma [24]. Two patients demon-
number of treatment sessions in order to pro- strated 50–75% improvement with eight to ten treat-
duce initial pigmentation, citing the need for ments. This therapy stimulates residual melanocytes
combination therapy research [17]. while limiting cumulative UV-B exposure. In 2004,
240 L. Jordan et al.

Alexiades-Armenakas et  al. studied the response like punctate leucoderma, combination therapy
of hypopigmented scars, including striae alba, to was pursued to achieve a better outcome [30].
the excimer laser. Thirty-one patients received up The excimer laser has also illustrated success in
to ten treatments starting at 1 MED minus 50 mJ/ treatment of linear scleroderma and pityriasis alba.
cm2. Visual analysis found 61% and 68% increase Hanson et  al. described a pediatric patient with
in pigmentation for leucoderma and striae, respec- refractory localized scleroderma on her left flank.
tively, compared to control after nine treatments. The patient was initially treated with topical calci-
However, the treated areas slowly depigmented potriene and steroid injections. Due to progression
back to baseline within 6 months of treatment ces- of the lesion, the calcipotriene was ceased, and
sation [25]. In addition, Goldberg demonstrated methotrexate was added. However, after 6 months
76% or greater darkening of striae after an aver- of methotrexate treatment without remission,
age of eight treatments [26]. Nevertheless, atrophy the excimer laser was added twice weekly for
remained unchanged, and the pigmentary improve- 7  months. The combination therapy of metho-
ments were not sustained. Ostovari et al. evaluated trexate and the excimer laser resulted in com-
the efficacy of the excimer laser in treating ten sub- plete remission of the disease [31]. Additionally,
jects with striae alba, finding that the laser displayed Al-Mutairi and Hadad studied the efficacy of the
a weakly positive effect in repigmenting the striae excimer laser in treating 12 patients with pityria-
alba. Additionally, the treatment produced the major sis alba, finding that near-complete resolution was
side effect of splaying the pigment [27]. For patients achieved after 3 months of treatment [32].
with mature hypopigmented striae and hypopig-
mented scars, the 308 nm excimer laser presents a
safe option for a common cosmetic concern with Indications and Contraindications
few other effective treatments, but patients should be
aware of the longevity of the treatment and possible Psoriasis
side effects.
Chemical leucoderma, a skin disease which Indications
presents with depigmentation due to contact
with specific chemicals, has also been success- • Patients with localized plaques that involve
fully treated with excimer laser. Ghazi et al. pre- less than 10% of the body surface area.
sented a case of chemical leucoderma caused by • Patients with lesions in non-exposed sites and
hair dye which was completely resolved using resistant sites.
an excimer laser [28]. Similarly, Vine et  al. • Mild to moderate psoriasis.
described the case of an HIV patient who expe-
rienced chemical leucoderma in the nasal and Contraindications
perioral areas after spilling liquid amyl nitrite,
a recreational drug, on his face. The patient was • Patients that report worsening of their lesions
treated with excimer laser and attained 90% upon light exposure.
repigmentation [29]. Kim et al. presented a case
of a patient exhibiting punctate leucoderma and The excimer laser is indicated for mild to mod-
melasma who was managed successfully using erate psoriasis, for localized plaques, and for resis-
combination therapy of a low-fluence 1064-nm tant sites. Patients who have lesions in non-exposed
Q-switched neodymium:yttrium-aluminium- sites such as in the groin and axilla also respond
garnet (QSNY) laser and a 308-nm excimer well to the excimer laser [33, 34]. These areas
laser. As it is common practice in Asian coun- are notoriously difficult to treat with traditional
tries to utilize the QSNY laser to treat melasma, NB-UVB. The excimer laser also works well for
and such treatment can result in complications recalcitrant psoriatic lesions in areas such as the
14  Lasers for Psoriasis and Hypopigmentation 241

scalp [35]. The most difficult areas to treat are the disease limited to the scalp or flexural areas. Most
palms and soles, and the excimer laser has dis- importantly, the patient must be committed to the
played success in these areas [4]. However, Sevrain course of treatment (Figs. 14.1, 14.2, and 14.3).
et al. investigated the efficacy of excimer lasers in
the treatment of palmoplantar pustular psoriasis
(PPPP) and discovered that outcome measures
varied according to the studies, concluding that
treatment for PPPP needed further evaluation [36].
The excimer laser may also be used in conjunction
with other systemic treatments for recalcitrant
lesions.
The excimer laser may be used in all skin
types; however, skin types II, III, and IV appear
to respond the best. Very fair skin may burn more
easily, and care must be taken when treating these
patients [37]. Further, patients being treated in
combination with acitretin should have their
laser exposure times managed closely as acitretin
Fig. 14.1  21 y/o female with scalp psoriasis
therapy may increase the patient’s susceptibility
to erythema. Patients who have darker skin types
with very thick lesions may benefit more from
PUVA photochemotherapy as UVA offers supe-
rior penetration over the UVB from the excimer
laser [34]. Additionally, excimer laser treatment
is more beneficial for mild to moderate psoria-
sis. Schaarschmidt et  al. studied the treatment
satisfaction of 200 psoriatic patients who had
moderate to severe psoriasis using the Treatment
Satisfaction Questionnaire for Medication. The
study found that patients who received biologi-
cals and traditional systemic medications had
significantly greater satisfaction than those who
received phototherapy or topical agents [38]. Fig. 14.2  After 12 treatments excimer laser
Additionally, as mentioned earlier, the excimer
laser is not as beneficial as PDL in the treatment
of nail psoriasis [11]. Nevertheless, appreciating
these proper indications, the only true contrain-
dication is the rare psoriatic patient that reports
worsening of lesions upon exposure to light.
A suitable patient is one who is able to commit
to multiple treatments per week for potentially
several weeks. Thus, compliance is usually the
limiting factor for improvement. Increasing insur-
ance copayments is also a substantial obstacle.
Insurance coverage varies, and documentation of
prior treatment failure is usually required for
approval. The ideal candidate lives or works near
the unit location, has skin type II–IV, and has Fig. 14.3  One year follow up, still clear
242 L. Jordan et al.

Vitiligo which experienced a peak MI at 7  days.

Ultimately, the study found that pigmentation
Indications caused by UVB varied based on skin color and
body site [41].
• Patients who have vitiligo with less than 20%
involvement.
• Patients with locally distributed lesions. Psoriasis

Contraindications • Preparation.
• Determine skin type and/or MED.
• Patients who are light sensitive. • Treat two to three times per week on non-con-
secutive days.
The excimer laser is indicated in both pediat- • Start at 3 MED and increase every other ses-
ric and adult populations and in all skin types for sion unless burning occurs.
the treatment of limited or localized lesions of
vitiligo. However, similarly to the excimer laser Initial evaluation of potential candidates
treatment of psoriasis, very fair skin may burn should include extent, distribution, and past treat-
more easily, so care must be taken when treating ments of psoriatic lesions. The patient should be
these patients [37, 39]. Anatomic location is a interviewed regarding any history of worsening
major predictor of response rate when evaluating psoriatic lesions upon light exposure. Risks and
a vitiligo patient for possible excimer laser ther- benefits should be discussed including the fre-
apy. The most to least responsive areas are: face, quent and potentially long term visits for therapy.
scalp/neck, genitals, trunk, extremities, hands The cost of therapy including copayments should
and feet, including bony prominences [40]. Skin be addressed, and informed consent should be
type is also important, with Fitzpatrick III or reviewed and obtained. Pretreatment photographs
higher skin types responding the best, while may also be useful, and the skin should be free of
smaller lesions respond more quickly. Age, gen- any topical agents. Eye protection should be
der, and duration of lesions do not appear to be a worn by all persons in the treatment room, and it
factor. It is not practical to treat large lesions due is also commonly recommended to apply a small
to the small spot size of the laser unit. amount of mineral oil to thick scaly plaques to
The ideal candidate has Type III skin or darker help reduce light scatter.
with disease limited to the head, neck, or trunk. The Initial dosing can be chosen by skin type or
only contraindication is a photosensitive patient, determination of the MED. The MED is the mini-
and patients taking medications that increase pho- mal fluence required to induce pink erythema of
tosensitivity should be treated with caution. The unexposed skin, which is commonly tested on the
inconvenience of multiple office visits and poten- lower back or gluteal area. A template is marked
tial cost of therapy are significant hurdles when for orientation on a sun-protected area. Usually,
treating patients with psoriasis or vitiligo. doses of 100 mJ/cm2 through 350 mJ/cm2 are used
in 50 mJ/cm2 increments. Therefore, six test doses
are usually given. The patient avoids additional
Techniques UV radiation to the area and returns for evaluation
24 h after test dosing. The lowest dose that induces
Shin et  al. studied the melanin index (MI) to detectable erythema is the MED [42].
UVB in different skin colors and body sites. The However, most manufacturers have treatment
study noted that following the first day of UVB protocols for psoriasis based on plaque thickness
exposure, MIs lowered, especially in fairer skin. and skin type. These guidelines avoid the incon-
However, the MIs increased in the light-skin venience of determining the MED.  Treatment
group from day 3–21 versus the dark-skin group guidelines usually consist of an initial dosing
14  Lasers for Psoriasis and Hypopigmentation 243

table followed by a protocol for subsequent treat- Vitiligo

ments based on response. These guidelines are
based on the following principles (see Tables • Preparation and evaluation.
14.1 and 14.2). Treatments should begin two to • Starting dose is 100–150 mJ/cm2 on the head
three times per week on non-consecutive days for and neck.
up to a month or longer if needed. Treatment ses- • Dose is increased by 50 mJ/cm2 per treatment
sions may take longer than typical light therapy until redness develops.
due to the small spot size; however, it should be • Treatment is two to three times per week for
emphasized that less treatments are required up to 36 weeks.
(approximately 10 treatments versus 25 for con- • Consider combination therapy with tacroli-
ventional light therapy). Treatment should start at mus 0.1%.
3 MED and increase every session, or every other
session unless burning occurs. Dosage should be Initial evaluation of potential candidates with vit-
maintained to induce slight erythema within 24 h iligo should include extent, distribution, and past
of treatment. The erythema should not last greater treatments of hypopigmented lesions. A Wood’s light
than 24 h and should not cause pain. If excessive may be used to enhance any pigmentary changes.
erythema or pain occurs, decrease the subsequent Risks and benefits should be discussed including the
dose by 25%. Most patients will continue topical frequent and potentially long term visits for therapy.
therapy throughout the treatment. Typically, ses- The cost of therapy including copayments should be
sions are performed two to three times a week addressed, and informed consent should be reviewed
while maintaining at least 48 h in between treat- and obtained. Pretreatment photographs may also be
ments for 3–6 weeks [4]. useful, and the skin should be free of any topical
Debbaneh et al. offer a new method of dosime- agents. Eye protection should be worn by all persons
try called Plaque-based Sub-blistering Dosimetry, in the treatment room, and the patient should be pro-
which is a more aggressive protocol in which tected from natural light between treatments.
8–16 multiples of MED is administered to psori- Determination of MED is not necessary for
atic plaques with the goal of achieving an earlier vitiligo patients as the calculated MED for the
and longer remission than traditional dosimetry. surrounding normal skin is not indicative for the
The authors present a patient who achieved a skin affected by vitiligo. Other factors such as
PASI score of 75 after only two treatments with an location, duration, and size are more important in
excimer laser [43]. determining response to laser therapy. The start-
ing dose is 100–150 mJ/cm2 on the head and neck.
This dose is increased by 50 mJ/cm2 per treatment
Table 14.1 First dose determination for psoriasis
Fitzpatrick skin type. Adapted from Vitiligo treatment until redness develops. If a severe burn occurs,
guidelines, 12-95362-01 Rev. A reduce the dose by half or skip the following treat-
Plaque Induration 1–3 (mJ/ 4–6 (mJ/ ment. Avoid treatments on consecutive days [44].
thickness score cm2) cm2) Similar to the excimer treatment protocol for pso-
None 0 riasis, vitiligo treatment typically consists of ses-
Mild 1 300 400 sions performed two to three times a week while
Moderate 2 500 600 keeping a minimum of 48 h in between treatments
Severe 3 700 900 for 4–36  weeks [37, 39]. Much like psoriasis, a

Table 14.2  Subsequent dose determination for psoriasis. Adapted from Vitiligo treatment guidelines, 12-95362-01
Rev. A
Clinical No effect Minimal effect Good effect Considerable Moderate/severe
observation improvement erythema
Typical dosing Increase dose Increase dose Maintain Maintain dose or reduce Reduce dose by
change by 25% by 15% dose dose by 15% 25%
244 L. Jordan et al.

table and protocol for subsequent treatments are –– Advances in surgical techniques, grafting
provided by the laser manufacturer (see Tables techniques, and combined photodynamic
14.3 and 14.4). Note the variability in initial dos- therapy.
ing for various anatomical sites.
There has been great progress in understand-
ing the nature of pigmentary and psoriatic dis-
Adverse Events ease. Advances in understanding the molecular
pathogenesis of psoriasis has led to the devel-
• Erythema. opment of the revolutionary class of medica-
• Rarely bullae and pain. tions known as the biologics. Currently, there
are 25 oral, topical, and injectable medications
Erythema is common and is the goal of treatment in phase II trials and 15 in phase III trials for
in vitiligo [45]. Patients may perceive slight warmth psoriasis or psoriatic arthritis [47]. Despite
upon laser application; however, most feel no sensa- the great advances in medical treatments for
tion. Very few patients report transient stinging, blis- psoriasis, light therapy will likely continue to
ters, or perilesional pigmentation [46]. Rare possible play a role for a large number of patients who
adverse events include sunburn reaction, corneal may not be candidates for systemic therapy
burn, freckling, irregular pigmentation, increased or may require systemic and localized light
risk of skin cancer, and accelerated aging. Eye pro- therapy for recalcitrant lesions. Several recent
tection and limiting treatment to the affected areas is combination therapy studies with the excimer
recommended to minimize these risks. laser have proven successful including com-
bination with topical Calcipotriene and with
topical flumetasone [13, 14]. Other forms of
Future Directions treatment that are currently being researched
include a purified gel form of adrenocortico-
• Psoriasis tripic hormone, calcitriol ointment in pediatric
–– Advances in medical therapy. patients, newer retinoids, and photodynamic
• Vitiligo therapies [48].
Vitiligo patients that fail multiple medical
therapies including topical and light therapy may
Table 14.3  First dose determination for vitiligo. Adapted
from Vitiligo treatment guidelines, 12-95362-01 Rev. A
be candidates for surgical techniques. Various
grafting techniques such as mini-punch or blister
Vitiligo location Initial dose (mJ/cm2)
grafts may be tried. Tattooing has also been used.
Periocular 100
Face, scalp, ear, neck, axilla, 150
Another new and important treatment includes
bikini the autologous melanocyte-keratinocyte trans-
Arm, leg, trunk 200 plant [21]. In this treatment, healthy skin is sam-
Wrist 250 pled, the melanocytes are grown in culture, and
Elbow 300 then they are transferred to the diseased skin. In
Knee 350 addition to surgical therapy, research in gene
Hands, feet 400 therapy will shed more light on new and promis-
Fingers, toes 600
ing treatments.

Table 14.4  Subsequent dose determination for vitiligo. Adapted from Vitiligo Treatment Guidelines, 12-95362-01
Rev. A
Clinical No effect Good effect Moderate erythema Severe erythema
observation
Typical dosing Increase dose by Maintain dose Decrease dose by Postpone treatment or reduce
change 50 mJ/cm2 50 mJ/cm2 dose by 100 mJ/cm2
14  Lasers for Psoriasis and Hypopigmentation 245

Other forms of treatment for vitiligo currently results of a multicenter study. J Am Acad Dermatol.
being researched include the effect of antioxi- 2002;46:900–6.
8. Erceg A, Bovenschen HJ, van de Kerkhof PC, Seyger
dants on vitiligo, biologics, and combination MM. Efficacy of the pulsed dye laser in the treatment
therapy of betamethasone oral mini-pulse ther- of localized recalcitrant plaque psoriasis: a compara-
apy and oral azathioprine. Several therapies com- tive study. Br J Dermatol. 2006;155:110–4.
bining NB-UVB are also being investigated, 9. Ilknur T, Akarsu S, Aktan S, Ozkan S.  Comparison
of the effects of pulsed dye laser, pulsed dye laser +
including NB-UVB and fluticasone propionate salicylic acid, and clobetasole propionate + salicylic
0.05%, lipoic acid tablets, and oral ginkgo biloba. acid on psoriatic plaques. Dermatol Surg. 2006;32:
Additionally, Photocil, a topical cream that selec- 49–55.
tively delivers NB-UVB therapy upon sunlight 10. Bovenschen HJ, Erceg A, Van Vlijmen-Willems I, Van
De Kerkhof PC, Seyger MM. Pulsed dye laser versus
exposure is also being researched [49]. treatment with calcipotriol/betamethasone dipropio-
nate for localized refractory plaque psoriasis: effects
Conclusion on T-cell infiltration, epidermal proliferation and
Psoriasis and pigmentary disorders have a pro- keratinization. J Dermatol Treat. 2007;18:32–9.
11. Al-Mutairi N, Noor T, Al-Haddad A. Single blinded
found impact on the quality of life of affected left-to-right comparison study of excimer laser versus
patients. Despite multiple medical therapies for pulsed dye laser for the treatment of nail psoriasis.
psoriasis, certain clinical scenarios present Dermatol Ther (Heidelb). 2014;4(2):197–205. Epub
therapeutic dilemmas. The 308 nm xenon chlo- 2014 Jul 3.
12. Kagen M, Cao LY, Oyetakin-White P, Tacastacas JD,
ride laser provides another option that is both Yan C, McCormick TS, et  al. Single administration
safe and effective for psoriatic and hypopig- of lesion-limited high-dose (TURBO) ultraviolet B
mented lesions such as vitiligo, linear sclero- using the excimer laser: clinical clearing in associa-
derma, pityriasis alba, and chemical, punctate, tion with apoptosis of epidermal and dermal T cell
subsets in psoriasis. Photodermatol Photoimmunol
and post-resurfacing leucoderma. Combination Photomed. 2012;28(6):293–8.
therapy, including tacrolimus 0.1% and the 13. Tang YJ, Xu WW, Liu XM, Zhang RZ, Xu CX, Xu B,
308 nm excimer laser, is likely the most effec- et  al. Self-control study of combination treatment
tive and safest option for patients suffering of 308  nm excimer laser and calcipotriene ointment
on stable psoriasis vulgaris. Int J Clin Exp Med.
from vitiligo [18, 19]. 2014;7(9):2844–50. eCollection 2014.
14. Dong J, He Y, Zhang X, Wang Y, Tian Y, Wang J. 
Clinical efficacy of flumetasone/salicylic acid ointment
combined with 308-nm excimer laser for treatment
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 Lasers for Adipose Tissue and
Cellulite 15
Molly Wanner and Mathew M. Avram

Abstract
Noninvasive and Invasive
The use of lasers and light devices for the Treatments for Adipose Tissue
removal of adipose tissue and cellulite repre-
sents a new and exciting frontier in the laser Removal of adipose tissue can be accomplished
field. To date, there are few non-invasive non-invasively and invasively. Non invasive fat
devices in the laser field all of which can only removal is accomplished using an external hand
claim limited efficacy. This chapter will piece or device in combination with ultrasound,
review the laser, light sources, as well as cooling, radiofrequency, laser or light. Invasive,
devices with radiofrequency and ultrasound also called “minimally invasive,” devices use
devices that currently purport to treat cellulite laser and light in combination with a fiber that is
or adipose tissue. inserted under the skin or ultrasound in combina-
tion with liposuction.
Keywords
Adipose tissue · Cellulite · Laser ·
Radiofrequency · Ultrasound · Coolsculpting Non Invasive Fat Removal

It’s important to emphasize that non invasive fat

removal is primarily meant to be a body sculpting
The use of lasers and light devices for the removal procedure. These are not treatments for weight loss.
of adipose tissue and cellulite represents a new The body does not excrete fat after these procedures.
frontier in the laser field. This chapter will review These devices remove fat non-invasively from a
the laser, light sources, radiofrequency and ultra- localized area, not the entire body. Adipose tissue
sound devices that treat cellulite or adipose stores triglycerides. Unlike cholesterol, which can
tissue. be excreted, triglycerides are not excreted by the
body. Rather, the triglycerides are metabolized for
energy, stored, or redistributed to the liver for further
M. Wanner (*) · M. M. Avram processing to be used for such molecules as plasma
Department of Dermatology, lipoproteins [1]. Studies of serum lipid levels and
Massachusetts General Hospital,
liver function tests suggest that non invasive fat
Harvard Medical School,
Boston, MA, USA removal devices do not negatively impact these
e-mail: [email protected] markers.

© Springer International Publishing AG, part of Springer Nature 2018 247

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_15
248 M. Wanner and M. M. Avram

Table 15.1  Mechanism of non invasive fat removal

Approach Mechanism
Cryolipolysis Cooling
High intensity high Thermal damage
frequency focused
ultrasound
Low frequency focused Mechanical damage
ultrasound
Low level laser Unclear—pore in
adipocyte may cause
Fig. 15.1  Bulge in lower abdomen
leakage
Field radiofrequency Thermal damage
treatments in the same area may have less effect
Monopolar radiofrequency Thermal damage
[6, 8]. Treatments can be scheduled 1–2 months
apart, although the results will not be see until
Non invasive options include focused ultra- 4 months after the final treatment.
sound, high frequency ultrasound, radiofre- Prior to treatment, the patient is weighed, and
quency, laser, and light (see Table  15.1). Non photographs should be taken. The treatment
invasive laser and light options are the focus of begins with surgical marking of the area. A gel
this chapter; however, a description of other pad is applied, and then the device is attached to
energy devices will be included. the skin. The device is a vacuum suction that
pulls the area to be treated between two cooling
Cryolipolysis plates. The physician can set the strength of the
Adipose tissue is sensitive to cool temperatures. vacuum during the treatment, but the degree of
Cryolipolysis harnesses this fact and utilizes an cooling, known as the “Cooling Intensity Factor”
external and non invasive device to cool and is fixed. The treatment is 60 min. The device is
selectively destroy the fat, while avoiding injury handsfree and does not require the physician to
of the overlying skin [2, 3]. Cryolipolysis is be present in the room. Post treatment, the device
thought to induce apoptosis, inflammation of the is removed, and the area is massaged. Post treat-
fat, and subsequent clearing of the fat by macro- ment massage was shown to improved efficacy
phages in a process that takes 3–4  months. On by 68% in one study [9].
average, this device removes approximately 20% Post treatment, the area is red and swollen (see
of fat in the treated area after 4 months [4–6]. It Fig. 15.2). The erythema resolves in 24 h; edema
has not been associated with statistically signifi- and tenderness can last several days. Bruising can
cant changes in liver function tests or lipid panel result. Approximately 40% of patients will experi-
(cholesterol, triglycerides, LDL or VLDL) [7]. ence numbness and tingling that can last 8 weeks,
Although cryolipolysis has been FDA cleared for but typically resolves in 3–4  weeks [10]. Less
the waist, it has been used on other areas such as common side effects include transient blanching
the inner thigh and back. of the skin and persistent erythema and edema.
The ideal patient for cryolipolysis has a bulge Rare side effects include severe pain, paradox-
in the area of concern (Fig. 15.1). Evaluation of ical hyperplasia, post inflammatory discoloration
the patient should include a history of cold of the skin, subcutaneous induration, treatment
induced disorders, coagulation disorders, sys- area demarcation. Severe shooting or stabbing
temic disease, hernia, impaired sensation or cir- pain can develop in the first week after treatment,
culation in the area. Patients with hernias should lasts 2 weeks on average and may require oral or
not be treated as the device is a vacuum device. topical pain medication [11]. The incidence of
Skin should be evaluated for laxity which would severe pain was reported to be approximately
not be expected to improve and for skin condi- 0.03% [12]. The abdomen is the most common
tions that koebnerize and may worsen with the area, and larger applicators are more likely than
treatment. Patients should expect at least two smaller applicators to be associated with this
treatments for best results, although subsequent adverse event. Severe Paradoxical hyperplasia
15  Lasers for Adipose Tissue and Cellulite 249

Fig. 15.2  Before, Immediately after, results S/P 1 treatment

has a reported incidence of 0.0051% [13]. It can culation or sensation in the area of treatment. The
develop anywhere from 2–3 months to 6 months patient should also be examined for laxity, as this
after treatment. There is no spontaneous remis- condition would not be expected to improve with
sion. Surgical intervention, such as liposuction, is this treatment.
curative. Prior to treatment, the area is marked, the
patient is weighed, photographs are taken, and
 igh Intensity High Frequency
H measurements of the area to be treated are taken.
Ultrasound Areas close to the bone should not be treated. The
There are two types of focused ultrasound: high HIFU treatment typically lasts an hour if the
intensity focused ultrasound (HIFU) and low fre- entire abdomen is treated. Although protocols
quency ultrasound. HIFU utilizes high frequen- vary, typically 3–5 pulses per site are completed
cies to create thermal damage and fat necrosis at at fluences of 30–60 J/cm2 to reach a goal of 140–
a specific focal point in the fat. Low frequency 180 J/cm2. Patients should expect, on average, a
ultrasound uses low frequencies to cause mechan- decrease of an inch after 2–3 months.
ical damage and fat lysis. The treatment can be painful, although most
HIFU (Liposonix, Solta, CA) is FDA cleared patients can complete the treatment using distrac-
for treatment of the waist, although other areas tion with forced cool air, ice packs, cold spray, or
such as the leg have been treated. The efficacy a vibrating massager. Other pain medications
of this treatment was established in a random- such as benzodiazepines, opioid, NSAIDs, or
ized sham controlled trial of 180 subjects [14]. acetominophen can be tried.
At 3  month follow up, subjects were found to Common side effects include erythema, swell-
have a 2.44 cm decrease in adipose tissue in the ing, and tenderness. Bruising can arise in two
group treated with three passes of 59 J/cm2 for a thirds of patients. Rare side effects include pro-
treatment total of 177  J/cm2 compared to a longed erythema, prolonged tenderness, and hard
1.43 cm decrease in the sham group. There was lumps under the skin. Superficial burns were
a slightly smaller decrease of 2.1  cm in the reported in association with the original proto-
group treated with three passes of 47 J/cm2 for a type [15, 17].
treatment total of 141  J/cm2. These findings
were statistically significant. A histologic study  ow Frequency Focused Ultrasound
L
found that most healing is complete at The Ultrashape™ System (Ultrashape Ltd, Israel)
8–14  weeks, and therefore, it will take is a focused ultrasound system that destroys adi-
2–3  months for patients to notice results [15]. pose tissue by mechanical means. It is used in
HIFU does not appear to cause changes in liver combination with radiofrequency pre and post
tests or lipid panel [16]. treatment. This system delivers focused ultra-
The device has a fixed focal depth of 1.3 cm, sound waves at a precise depths of 7, 10, and
and therefore, in order to use HIFU, patients 15 mm. Typically, three treatments are completed
much have at least an inch of pinchable fat in [18, 19]. Most of the fat reduction occurs in the
the area. Other patient considerations include first 14  days, and response to treatment can be
a history of coagulation disorders which would assessed rapidly ([19]-Teitlebaum). The proce-
increase the risk of bruising; pregnancy; meta- dure is 35–60  min per treatment, depending on
bolic disease; or hernia, surgery or impaired cir- the size of the area treated.
250 M. Wanner and M. M. Avram

In a large prospective trial of 164 subjects with A double blind randomized controlled trial
27 controls, subjects were treated once on the abdo- with a sham of 67 subjects found a decrease in cir-
men, thighs, or flanks [19]. At 3 month follow up, cumference after six treatments [29]. A double
a statistically significant mean reduction of 1.9 cm blind, randomized controlled trial with sham of 40
was reported after one treatment, in the setting of subjects found a decrease in total arm circumfer-
weight maintenance, compared to baseline, control ence [30]. The decrease in arm circumference was
group, and internal control for patients treated on measured at three different points and added
the thigh. Liver ultrasound at 14 and 28 days and together for a total decreased of 3.7  cm versus
serial laboratory evaluations showed no clinically 0.2  cm in the control group. Two retrospective
significant treatment associated changes, with studies of low level laser plus nutritional supple-
no elevations in serum lipids or lipoproteins. No mentation found a statistically significant reduc-
systemic adverse effects were noted, and cutane- tion in circumference [31, 32]. One small study of
ous adverse effects were rare and included a tin- five subjects found an increase in circumference in
gling sensation, erythema, purpura, and blisters. three subjects [33].
Ninety-two percent of patients reported minimal to The procedure utilizes a handsfree device
no discomfort after 90  min of topical anesthesia. (Zerona, Erchonia, Texas) that emits 635  nm
In a study of 30 patients, after three treatments, a laser at 17 mW. The device is positioned above
statistically significant decrease of 2.3 cm in local the patient. There is no contact between the
deposits was found. These patients maintained patient and the device. Typically six treatments
constant weight during the treatment period [18]. are completed, three times a week for 2 weeks.
Several additional studies have found a decrease The treatment takes 40 min.
in circumference [20, 21]; one study found an
increase in circumference [22]. Radiofrequency
Pain is minimal with the device. Redness, Radiofrequency has been used for tissue tighten-
blisters, and rarely bruising have been reported, ing, skin laxity, and cellulite; only more recently
but are uncommon [18–22]. has radiofrequency been applied to non invasive
fat removal. Radiofrequency devices utilize cur-
 ow Level Laser Therapy
L rent to create heat. Radiofrequency has been
Low level laser therapy has been used with and found to induce fat atrophy [34]. The radiofre-
without ultrasound for fat removal. It is FDA quency devices used for non invasive fat removal
cleared for the hips, waist, thighs, and upper include monopolar radiofrequnecy and focused
arms. Low level laser activates cytochrome C field radiofrequency. Bipolar radiofrequency,
oxidase in mitochondria, upregulates ATP, and which penetrates superficially is typically used
induces transcription factors [23]. The mecha- for cellulite treatment.
nism of fat removal is unclear. It is postulated Field radiofrequency (Vanquish, BTL Industries,
that low level laser creates a pore in the adipo- CR) is accomplished with a device that is posi-
cyte membrane, causing leakage of lipid into tioned over the patient. There is no contact between
the interstitial space [24]. An ex vivo study of the patient and the device. The device is designed
12 tissue samples and found that after 6 min of to have a focal point approximately 10 mm below
low level laser, fat was completely removed the surface and to heat the area to 43–45  °C.  A
from the cell [25]. A change in the consistency small porcine study demonstrated a reduction in
of fat with MRI evaluation has been reported as adipocytes after four 30 min treatments [35]. A non
well [26]. One histologic study did not find a randomized, uncontrolled study of field radiofre-
change in treated and untreated adipocytes [27]. quency evaluated 40 subjects after four treatments.
Histologic analysis of the effects of low-level Thirty-five subjects were included for analysis, and
laser of adipose tissue in rats found enlarge- of these subjects, 32 had an average decrease in
ment and fusion of the brown, but not yellow circumference of 4.93  cm. Three subjects did not
fatty tissue [28]. respond. BMI decreased on average across subjects
15  Lasers for Adipose Tissue and Cellulite 251

0.263  kg/m2 [36]. The treatment was reported to metic advantage to this procedure compared with
cause mild erythema that resolved. 90.5% of sub- traditional liposuction, although patients may
jects did not feel pain during the procedure. Patients have less post operative pain with laser-assisted
are monitored during the treatment. lipoplasty. The procedure may be helpful for the
A monopolar radiofrequency device with cool- surgeon, requiring less effort, particularly in dif-
ing has been studied (Exilis, BTL industries, CR). ficult to treat areas [11], but it can be more time
This device uses a handpiece that is continuously consuming [13].
circled on the patient to achieve a goal surface An illustrative example is a prospective, dou-
temperature of 42–43 °C. Each 5 × 7 cm2 area is ble blind, controlled trial of 25 patients and 110
treated for 6–8 min. An abdomen can be treated in areas of treatment with patients serving as their
30 min. Four treatments, spaced 1 week apart are own control with suction lipoplasty on one half
performed. The device penetrates 0.4–2.5  cm and laser-assisted lipoplasty on the other with a
beneath the skin, and the depth of penetration is 2  mm 1064  nm Nd:YAG laser fiber follow by
controlled by cooling. In a trial of 60 subjects, suction with a 3 mm cannula [9]. No clinical dif-
subjects received 4–5 treatments [37]. Fat was ference in cosmetic result was found, although
reduced by ultrasound measurements 0.04 cm on postoperative pain was higher in the suction-
the thighs to 0.06 cm on the abdomen/flank areas. assisted side versus the laser-assisted side at the
first follow up visit only.
1210 nm Laser Without liposuction, the Nd:YAG may have a
Selective photothermolysis of adipose tissue has role in the removal of local deposits of fat. The
been reported at 1210 and 1720 nm wavelengths use of a 1064 nm Nd:YAG laser with a 300 μm
and may offer another non invasive option for fiber encased in a 1  mm microcannula, without
treatment of adipose tissue, but a clinical device combining it with liposuction was studied in a
is not yet available [38]. randomized study of 30 female patients with
focal areas of fat less than 100 cm3 on the arm,
submental area, thigh, and abdomen [12]. An
Invasive Fat Removal average 17% reduction in fat volume (p < 0.01)
was seen on MRI. Bruising, swelling, and tender-
 064 nm Laser with and Without
1 ness were seen, and uncommonly, transient tin-
Liposuction gling, hyperpigmentation, and a subcutaneous
The Nd:YAG laser has been used alone or in com- nodule were reported. As with non invasive
bination with suction liposuction. SmartLipo™ approaches, use of this device without liposuc-
(Cynosure, USA), a 300  μm 1064  nm fiber tion may be best suited to small collections of fat.
encased in a micro-cannula, is an example of
this type of device. The cannula is inserted sub-  35 nm Laser and Liposuction
6
cutaneously to destroy lipid membranes and Low level laser has been used in combination with
release lipids. Adipocytes appear to swell at liposuction. Neira has combined low level 635 nm
lower energies and lyse at higher energies [39]. laser and liposuction in a technique labeled the
The laser also heat coagulates collagen fibers. “Neira 4L technique” [47]. Patients are irradi-
This process is termed “laser lipolysis” [40]. It ated with a low-level 635  nm laser after tumes-
is worth noting that the term “lipolysis” appears cent anesthesia. Following irradiation, removal of
to be misused in this context. Strictly speaking, fat is accomplished with a cannula or other tech-
“lipolysis” is defined not as destruction of the nique. Neira reported a case series of 700 patients
adipocyte membrane, but rather as shrinkage of of whom 95% were satisfied with results [15]. A
the fat cell due to the use of lipid for energy at well designed randomized, controlled, blinded
the cellular level. study found a statistically significant decrease in
The Nd:YAG laser has been extensively stud- pain and swelling post operatively after treatment
ied [6, 41–46]. There appears to be minimal cos- with low level laser [48]. Investigators reported a
252 M. Wanner and M. M. Avram

greater ease of fat extraction after low level laser smoothness was not quantitatively defined and no
therapy, also statistically significant. Based on statistical evaluation was done.
these studies, low level therapy may influence These studies contrast with a double blinded
healing, but the histologic effects and the effect on study of 19 patients who served as their own
cosmesis remain unclear. control to evaluate external ultrasound-
assisted liposuction [29]. The treatment side
 xternal Ultrasound and Liposuction
E received ultrasound at 2–3 W/cm2 for 10 min
External ultrasound and liposuction have been and the control side received 0.2–0.3  W/cm2.
combined to remove adipose tissue [49–51]. Fat was sampled in two patients. There was no
External ultrasound is theorized to relax the difference between resistance to removal and
bonds between cells, affecting the septa, enhanc- the rate of fat removal in 14 of 19 patients.
ing skin contraction after liposuction and allow- Patients assessed the treatment as well, and
ing for the use of thin cannulas [52]. Fat cells can only 4 of 19 reported a better operative and
be used for grafting [53]. The typical procedure post operative course with external ultrasound.
involves application of a 2–3  W/cm ultrasound Statistical significance was tested for physi-
device for 5–15 min. cian and patient assessments, and no benefit to
Several studies have found external ultrasound using external ultrasound with liposuction was
to be beneficial [25, 54–56], although one double found. Histologic evaluation showed no differ-
blind study casts doubt on the utility of this pro- ence between the experimental and control
cedure [57]. In most of the studies, there appears side. Although the study was limited by the
to be a slight advantage of the ultrasound assisted small number of patients, the double blind,
approach in terms of physician fatigue (50–70% controlled framework provides strong support
preferred the ultrasound treated side). Patients that the use of external ultrasound may not
had less bruising (40–70% of patients), swelling yield significant benefit.
(40–70% of patients), and discomfort (50–80%
of patients) on the ultrasound treated side [26– I nternal Ultrasound and Liposuction
28]. The cosmetic result appears to be similar Liposuction in combination with internal ultra-
[26–28]. One of the studies reported increased sound was pioneered by Zocchi [58]. Several
skin retraction of 30% on the side treated with studies reported large series of patients treated
ultrasound [27]. These studies were randomized with ultrasound assisted lipoplasty [59–63], and
and controlled, but statistical significance was the purported benefits of this technology include
not tested. The surgeon was blinded in one of the less blood loss, less surgeon fatigue, and
trials [26]. The number of patients in these stud- improved skin retraction [64, 65]. Ultrasound
ies ranged from 10 to 30. Adverse effects includ- assisted liposuction has been found to be more
ing erythema, mild warmth, burns, blisters, and selective for adipocyte removal; however, this
seroma were reported during the procedure [22, selectivity may not yield superior results [32]. In
24, 25, 28]. studies that compare standard versus ultrasound-
A larger study of 59 patients comparing exter- assisted lipoplasty, the ultrasound-assisted
nal ultrasound assisted to standard liposuction approach has not had better cosmetic outcome
also reported that patients had less bruising and [32, 34, 66]. It may be that ultrasound-assisted
discomfort [25]. A faster recovery time was lipoplasty is better for certain indications such as
reported, but patients receiving external ultra- fibrous areas [67].
sound were given different instructions about A well designed study of 63 patients who
reduction of physical activity, leading to a poten- received both traditional and ultrasound-assisted
tial bias in recovery time. Skin shrinkage as evi- lipoplasty provides an example [34]. Patients were
denced by a smoothness of the skin was apparent blinded to the procedure in this trial. In addition to
on the ultrasound side at 30 days and on the stan- the evaluations by patient and surgeon, an indepen-
dard liposuction side at 6 months; however, this dent panel evaluated ten randomly selective
15  Lasers for Adipose Tissue and Cellulite 253

patients. Ultrasound-assisted lipoplasty was not poorly studied, casting doubt on their efficacy.
found to be superior to traditional lipoplasty with In this section, these devices will be reviewed
no difference in sensory, pigment change, surface as well as those that incorporate radiofrequency.
irregularity, skin contraction, bruising, or swelling. Radiofrequency devices represent the best stud-
Similarly, a randomized, controlled study of ultra- ied devices in the cellulite market. There is only
sound-assisted liposuction compared with tradi- one energy based invasive or “minimally inva-
tional liposuction in 28 patients found no significant sive” device available. This device incorporates
difference in cosmetic result and adverse effects laser and will be reviewed.
[38]. Physicians reported less fatigue. Theoretically, those devices that best treat
Skin necrosis, burn, fat necrosis and fibrosis, cellulite should be the devices that affect some
sensory alteration, infection, lower limb edema, aspect of the pathogenesis of cellulite. There are
and seromas have been reported [31–33, 38, multiple theories to explain cellulite, but those
39, 68, 69]. Skin necrosis is a particularly con- with the most evidence suggest that cellulite is
cerning adverse effect. It is thought to be due caused by sex specific differences in skin struc-
to ­destruction of deep dermal vessels despite ture and hormonal milieu [74–80]. Cellulite is
higher perfusion with ultrasound-assisted lipo- present in the large majority of women and
suction compared with suction liposuction [70, rarely in men, except in cases of androgen defi-
71]. Postoperative sensory changes occur in ciency [46]. Unlike in men, the subcutaneous
both traditional and ultrasound-assisted liposuc- tissue in women is loosely reinforced, and her-
tion; immediately after surgery, these changes niations of the superficial fat are more likely to
may be more prominent in those patients treated develop. Therefore, therapies that remove the
with ultrasound [72, 73]. Surgeon experience and fat herniations and alter the septated connective
surgical technique may play a role in ultrasound tissue reinforcements would be expected to
assisted complications [31]. improve cellulite.
With respect to invasive options for fat removal,
internal or external ultrasound and laser assisted
lipoplasty appear to offer minimal advantages Lasers and Light Sources
over traditional lipoplasty. Nearly all blinded and
controlled studies have failed to show improved I ntense Pulsed Light
cosmetic outcome with these devices. Intense pulsed light (IPL) has been shown to
stimulate collagen production, and it is used in
the treatment of cellulite with the purpose of
Cellulite Treatments thickening the dermis to diminish the appear-
ance of cellulite [81, 82]. The theory is that a
There are several devices that have been used thicker dermis will hide the fat herniations bet-
for noninvasive treatment of cellulite including ter. A 12  week trial of 20 women of whom 8
devices that incorporate laser or light sources received IPL alone and 12 received IPL in com-
(see Table  15.2). Most of these devices have bination with retinyl based cream for a total of
temporary or limited efficacy or have been 9–12 treatments found that the majority of
patients with improvement used the cream in
combination with IPL [83]. Nine patients
Table 15.2  Laser and light based treatments for cellulite
reported improvement greater than or equal to
Non invasive Invasive 50%, and seven maintained this improvement at
Intense pulsed light 1440 nm side 8  months. This study was limited as only 15
660–950 nm LED firing laser
1064 nm laser patients completed the study, and no statistical
810 nm laser with suction massage analysis was done. The use of IPL alone as a
650 nm light source and 915 nm treatment for cellulite does not appear to be
laser with suction massage indicated.
254 M. Wanner and M. M. Avram

 ight Emitting Diode

L twice weekly for 6 weeks with the TriActive™ or
A light emitting diode at 660 and 950 nm has been VelaSmooth™, a radiofrequency device, found
used in combination with a cellulite gel comprised similar results [90]. In this study, photographs
of several active ingredients (bupleurum falcarum, were evaluated by blinded investigators and sig-
caffeine, coenzyme A, and phosphatidylcholine). nificance was tested. The average improvement in
A randomized, double blind controlled study eval- cellulite was 7% and 25% for the VelaSmooth™
uated nine patients who received an active gel on and the TriActive™, respectively. VelaSmooth™
one thigh and placebo controlled gel on the control and TriActive™ also yielded a 28–56% and a
thigh in combination with light [84]. Cellulite was 30–37% improvement in the thigh circumfer-
improved in eight of nine patients on the active ence, respectively. The difference between the
thigh and no patients on the control side, suggest- two devices was not significant. Adverse effects
ing that the light emitting diode had little effect. included bruising seen in 10 of 20 patients with
VelaSmooth™ and 4 of 20 with TriActive™.
1064 nm Laser SmoothShapes has been evaluated in several
Thickening the dermis to mask fat herniations is studies [91–93]. Two of these studies focused on
the rationale behind a 1064 nm laser for cellulite. fat reduction, finding a statistically significant
This device was studied in 12 subjects. Three decrease in fat thickness of 1.19 cm2 on MRI and
months after the third treatment, a statistically a statistically significant reduction in thigh cir-
significant reduction in dermal thickness and cumference. Another study assessed cellulite
increase echogenic density on ultrasound was more closely: 3D Imaging revealed a 2.3  mm
noted. Subjects were “a little to somewhat satis- change in surface elevation and a 4.9 mm change
fied”. Erythema was the main side effect [85]. in flattening 6 months after treatment.

Light Sources and Massage Radiofrequency

A few devices incorporate massage with light to Radiofrequency represents the best studied treat-
treat cellulite. Massage is included in the treat- ment for cellulite. Radiofrequency can be mono-
ments based on the idea that vascular and lym- polar in which the current is delivered from an
phatic alterations promote cellulite, although electrode to a grounding pad; bipolar in which
there is limited evidence to support this the- the current is delivered between two electrodes
ory [86–88]. Examples include TriActive™ and unipolar in which the energy is delivered
(Cynosure™, USA), a low fluence 810 nm diode without grounding. Multiple electrode radiofre-
laser with vacuum massage; Synergie Aesthetic quency in which the energy is delivered between
Massage System™ (Dynatronics, USA), a vac- three probes, one positive and two negative has
uum massage with or without a 660–880  nm also been reported [94, 95].
probe or 880 nm light pad; and SmoothShapes® The VelaSmooth™ is a bipolar radiofre-
(Elemé Medical, USA), a 915  nm laser and quency, infrared heat, and suction device that is
650 nm light source combined with vacuum and FDA cleared for the treatment of cellulite. The
mechanical massage. VelaSmooth™ has been evaluated more exten-
The TriActive™ appears to yield a transient sively than any of the other devices for cellulite;
21–25% improvement in cellulite after mul- however, many studies are flawed, without a con-
tiple treatments. In an uncontrolled study of 16 trol group or without statistical evaluation. Most
patients who received twice weekly treatments studies report a decreased circumference of the
of TriActive™ for 6  weeks, photographs evalu- treated area and an improvement in cellulite of
ated by blinded investigators showed a 21% aver- 25–50% in most subjects [96–100]. The duration
age improvement that was not present 1  month of benefit is unclear, and one investigator noted a
after the last treatment [89]. Significance was diminution of effect at 6 months [64]. Bruising is
not tested. A comparison of 20 patients treated a common side effect noted in up to 10–31%
15  Lasers for Adipose Tissue and Cellulite 255

[63–65]. Crusting and burn have rarely been dence for effect, albeit marginal. These devices
reported [62, 65]. generally yield a 25–50% improvement after
One of the better and illustrative studies of multiple treatments. This effect seems to dimin-
the VelaSmooth™ is a controlled trial of 20 ish over time.
patients [63]. Of the 20 enrolled patients, 16
were treated twice weekly for 6 weeks on one
leg, while the other leg served as control. A sta- 1440 nm Nd:YAG Laser
tistically significant decrease of thigh circum-
ference (0.44–0.53  cm) was seen at 4  weeks, A 1440 nm side firing laser fiber represents the
but not immediately or at 8  weeks. A greater only invasive energy based device treatment for
than 51% improvement was seen in 25–31% of cellulite (CelluLaze, Cynosure Inc, MA). The
patients at 8  weeks after the last treatment. concept behind this laser is that the treatment
There was no histologic evidence of structural melts the fat herniations associated with cellulite
change, however. Lipid, hormone, and liver as well as shearing septae that contribute to these
function tests were tested in five patients and herniations and the dimples associated with cel-
showed no change. Thirty-one percent of lulite. The 1440 nm wavelength is absorbed more
patients had bruising. by adipose tissue than by water.
The Alma Accent RF System (Alma Lasers™, The treatment uses a laser fiber associated
Buffalo Grove IL) utilizes unipolar and bipolar with a cannula that is inserted under the skin. The
radiofrequency. The Alma Accent RF System laser has a temperature sensor. The fiber is passed
was evaluated in an uncontrolled study of 26 under the skin in three positions: pointed up,
patients [101]. In this study, the patients received sideways, and down. After treatment, pressure is
two treatments on the thigh and buttock. Patients used to remove the fat from the cannula insertion
were evaluated by ultrasound for a change in dis- points. The treatment requires tumescent anes-
tance from the dermis to the first line of fibrous thesia. Compression garments are worn after
tissue (Camper’s fascia) and the dermis to mus- treatment. Side effects of the treatment include
cle. The majority of patients (64–72%) showed a bruising, swelling, pain, numbness and itching.
15.49–27.8% decrease in these measures. On Prolonged discomfort, bruising, swelling, and
average, there was a 6.8–11.55% decrease in the numbness was reported and found to be resolve
measurements among all patients, although some by 3 months.
of the patients showed an increase in the distance. A preliminary study of ten subjects found an
Findings were not uniformly significant, and this improvement of cellulite that persisted 1 year
study is limited by the lack of a control group. after a single treatment [104]. A multicenter
The authors evaluated ultrasound for qualitative study of 57 subjects and 87 sites compared cel-
changes in the skin structure and found improve- lulite 6 months after treatment to baseline [105].
ment in 50–57% of patients. Adverse effects were Ninety-one percent of treated areas improved 1
rare with small blisters developing in two patients point on a 5 point scale. On average, the 81 treat-
and bruising in three patients. ment sites evaluated at 6  months improved 2.7
Unipolar radiofrequency was evaluated in a points on a 5 point scale.
study of 30 subjects that was neither controlled
nor blinded nor randomized. In this study, graded Conclusion
improvement of cellulite was found to be 2.9 The currently available options for laser or
on a scale of 1–4 after six treatments [102]. In light based removal of adipose tissue or cel-
a randomized, controlled, blinded study of ten lulite are limited. The 635 nm laser is the only
subjects treated six times with unipolar radiofre- clinically available device that has been well
quency, dimples improved 8%. This finding was studied for non invasive removal. In fact, the
not statistically significant [103]. best studied devices for non invasive fat
Of the available devices on the market, those removal, do not rely on light or laser. Cooling
with radiofrequency seem to have the most evi- and ultrasound devices may offer superior
256 M. Wanner and M. M. Avram

results for non invasive fat removal. Although 11. Dover J, Saedi N, Kaminer M, Zachary C.  Side
SmartLipo™ may have a role for removal of effects and risks associated with cryolipolysis. Lasers
Surg Med. 2011;43:928.
small collections of adipose tissue, it has not 12. Post marketing information from company through
been shown to be cosmetically advantageous 12/31/2012.
as compared with traditional lipoplasty. 13. Jalian HR, Avram MM, Garibyan L, Mihm MC,
Anderson RR. Paradxoical hyperplasia after cyroli-
With respect to cellulite treatment, non inva- polysis. JAMA Dermatol. 2014;150:317–9.
sive laser and light devices have either not been 14. Jewell ML, et  al. Randomized sham-controlled
studied or have been proven to have modest, trial to evaluate the safety and effectiveness of a
temporary effect. The best studied non-invasive high-intensity focused ultrasound device for non-
invasive body sculpting. Plast Recontr Surg. 2011;
approach is radiofrequency; however, this too 128:253–62.
offers results that are generally mild and tempo- 15. Fatemi A.  High-intensity focused ultrasound effec-
rary. CelluLaze is a newer, minimally invasive tively reduces adipose tissue. Semin Cutan Med
treatment that may provide better and longer Surg. 2009;28(4):257–62.
16. Gadsen E, et al. Evaluation of a novel high intensity
term results, but is associated with a greater pain focused ultrasound device for ablating subcutane-
requiring tumescent anesthesia and greater risks ous adipose tissue for noninvasive body contouring
compared with non invasive devices. safety studies in human volunteers. Aesthet Surg J.
2011;31:401–10.
17. Fatemi A, Kane MAC. High intensity focused ultra-
sound effectively reduces waist circumference by
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 Photodynamic Therapy
16
Ariel E. Eber, Marina Perper, Sebastian H. Verne,
Robert Magno, Ibrahim Abdullah Omair ALOmair,
Mana ALHarbi, and Keyvan Nouri

Abstract Introduction
Photodynamic therapy with ALA or MAL
is an excellent treatment for multiple actinic It was a medical student, Oscar Raab, who first
keratoses. discovered photodynamic therapy (PDT) at the
Large field photodynamic therapy can beginning of the twentieth century [1]. PDT
eradicate multiple actinic keratoses with a ­combines the administration of a photosensi-
shorter downtime than 5-fluorouracil or tizer or photosensitizer precursor with its activa-
imiquimod. tion by light of appropriate wavelength. Reactive
Multiple large field photodynamic therapy oxygen species (ROS), which can be used to
sessions can delay the appearance of actinic destroy a target cell, are created in the presence
keratosis. of oxygen. The concept, however, that a mole-
cule activated by light could be used to destruct
Keywords pre-malignant and malignant cells, did not enter
Photodynamic therapy (PDT) · wide practice until the 1990s. Since then, uses
Aminolevulinic acid (ALA) · Methyl for PDT have been expanded to treat a variety of
aminolevulinate (MAL) · Actinic keratosis dermatologic ailments including sun-damaged
skin and acne [1].
Kennedy and Pottier were the first to dis-
cover the application of Aminolevulinic Acid
(ALA) [2] for treating skin disorders and the
first to successfully treat them [3]. ALA has
A. E. Eber · M. Perper · S. H. Verne · R. Magno ·
K. Nouri (*) been approved for dermatologic indications by
Department of Dermatology and Cutaneous Surgery, the Food and Drug administration (FDA) for
University of Miami Miller School of Medicine, many years. PDT utilizes the heme biosynthetic
Miami, FL, USA
pathway to produce endogenous porphyrins,
e-mail: [email protected]
particularly protoporphyrin IX, which is an effec-
I. A. O. ALOmair · M. ALHarbi
tive photosensitizer. Protoporphyrin IX has two
Department of Dermatology, College of Medicine,
Al Imam Muhammad Ibn Saud Islamic University important spectral peaks, 404–420  nm and
(IMSIU), Riyadh, Kingdom of Saudi Arabia 635 nm in the blue and red wavelengths, respec-

© Springer International Publishing AG, part of Springer Nature 2018 261

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_16
262 A. E. Eber et al.

tively. In order to achieve optimal therapeutic phic lesions might be micro-invasive squamous
effect, the light source used in PDT should cor- cell carcinomas (SCCs). The current approval is
respond to the excitation peaks of the photosen- based on phase III studies where ALA was
sitizer [1]. applied to visible lesions for 14–18 h followed
Biochemically, heme is normally synthe- by 10 J/cm2 of blue light from a Blu-U unit [4].
sized from glycine and succinyl CoA. The rate- However, in practice very few physicians use
limiting step in the pathway is the conversion of ALA-PDT with a 14–18 h incubation. Most will
glycine and succinyl CoA to ALA, which is use a shorter incubation of 45 minutes (min) to
under negative feedback control by heme. 2  h. This off label use is supported by a small
Excess exogenous ALA, however, can bypass pilot study which showed that incubation of
this feedback mechanism and produce an accu- 1–3  h in patients with extensive sun exposure
mulation of porphyrins that, when activated by leads to AK lesion cure rates that are similar to
visible light, generate the photosensitizing what has been shown with longer incubations in
effect of PDT [4]. Methyl aminolevulinate phase III studies [5].
(MAL) is another photosensitizer approved by Complete responses on basal cell carcino-
the FDA. MAL theoretically works in the same mas (BCCs) have been reported following
manner as ALA because it is converted to ALA ALA-PDT [6]; however, the efficacy of ALA-
in the cytosol of cells, however it have a slower PDT for the treatment of BCC has never been
onset of action. studied in multicenter phase III trials and the
Since the approval of ALA and MAL in the long term recurrence rates have not been well
United States for actinic keratosis, PDT is now a studied. MAL is currently FDA-approved for
well-established procedure. Furthermore, these the treatment of non-hypertrophic actinic kera-
drugs are approved in several other countries for toses of the face and scalp in immunocompetent
the treatment of non-melanoma skin cancers patients when used in conjunction with lesion
and they are used for other indications as well. preparation and when other therapies are con-
sidered medically less appropriate. Use of PDT
has evolved from its application as a monother-
Indications and Contraindications apy to an adjunct with other treatments. The
value of sequential treatment with MAL-PDT
Indications and imiquimod was investigated in a random-
ized trial (n = 105). Better response rates were
Aminolevulinic acid is approved in the US, seen for combination treatment than for either
Canada, and Brazil for the treatment of mini- monotherapy; however, the difference in
mally to moderately thick actinic keratosis of response was statistically significant only for
the face and scalp in combination with the the comparison between combination therapy
Blu-U unit (Fig.  16.1). It was originally and MAL-PDT monotherapy [5, 6]. AK cure
approved for nonhypertrophic actinic keratoses, rates following either a single MAL-­PDT ses-
but is now indicated for minimally to moder- sion repeated at 3  months if necessary or two
ately thick AK at the FDA’s request. In practice, MAL-PDT sessions performed 7  days apart
this wording is similar and refers to the fact that have been reported to be around 90% [7, 8].
PDT is not approved for thick and hypertrophic Studies presented at meetings suggest that mul-
AKs. There are two issues related to treatment tiple large surface ALA or MAL PDT sessions
of hypertrophic AKs with PDT. The first is inad- can delay the appearance of new actinic kerato-
equate penetration of ALA through the hyper- ses in organ transplant patients. This suggests
keratotic portion of the lesion and the second is that large surface PDT may be able to prevent
the possibility that some of the more hypertro- skin cancer. Combination therapy with sequen-
16  Photodynamic Therapy 263

Fig. 16.1  Blu-U device.

This non-coherent light
source is approved for
the treatment of actinic
keratosis with ALA

tial MAL-PDT and imiquimod has also shown was 22% [12, 13]. The main advantage of
effectiveness in the treatment of AKs. PDT for the treatment of sBCC and Bowen’s
Several countries have also granted approval disease are the excellent c­ osmetic outcome as
of MAL-PDT for the treatment of various non-­ compared to surgery, cryotherapy or electrodes-
melanoma skin cancers. The indications vary sication, and curettage [6, 9]. Some countries
from one country to another, but in general have also approved MAL-PDT for thin nodular
most countries approved MAL-PDT for the BCC, but because the cure rate is lower than
treatment of Bowen’s disease and superficial for sBCC, many countries have restricted their
BCC when other therapies such as surgery were approval to sBCC.  Recurrences with superfi-
considered inappropriate [9–11]. The complete cial BCCs, nodular BCCs and Bowen’s disease
response rate of superficial BCC (sBCC) fol- usually occur during the first 2–3 years after
lowing MAL-PDT has been shown to be 97% therapy with no increase in recurrence between
and the 48-month long-term recurrence rate the third and the fifth year. PDT demonstrated
264 A. E. Eber et al.

superior efficacy and less scarring in the treat-

ment of SCC in situ when compared with cryo-
therapy or 5-fluorouracil in a Cochrane review
(n  =  363). In particular, ALA-PDT appeared
to have greater efficacy than 5-­fluorouracil but
MAL-PDT was not demonstrated to be supe-
rior over 5-fluorouracil. Also, there was no dif-
ference in recurrence rates at 12  months with
either MAL-PDT or ALA-PDT when compared
with 5-fluorouracil [6, 7]. A consensus group in
Canada and Europe analyzed nine studies and
reported that use of MAL-PDT can be consid-
ered as a safe and effective treatment for BCC
in patients with Gorlin syndrome, with an effi-
cacy level being proportionate to the thickness
of the lesion. PDT has been observed to have
chemopreventive effects in patients with Gorlin
syndrome [8]. MAL is not yet commercially
available in the US because the FDA approved
MAL only in combination with the Curelight
device, an earlier LED light source that is
rather cumbersome. In most countries MAL is
Fig. 16.2 Aktilite device. This LED light source is
approved with the Aktilite (Fig. 16.2), a smaller approved in several countries for the treatment of AK and/
and more convenient device. Studies comparing or Bowen’s disease and/or superficial basal cell carcinoma
the efficacy of the Curelight and the Aktilite in with MAL
the treatment of AK are currently being com-
pleted in the US, and should ultimately lead to these report efficacy of MAL-PDT and ALA-­
FDA approval of MAL-PDT performed with PDT in the treatment of plaque-type (stage
the Aktilite device. Initial studies conducted I) mycosis fungoides, but decreased efficacy
with PDT for skin diseases often used lasers. against tumor-type (stage II) mycosis fun-
However, the current off-label trend with ALA- goides, and there has been a single report of
PDT is to use broad area application ALA or erosive mycosis fungoides on the face treated
MAL in order to treat non-visible lesions, successfully with ALA-PDT using red light
improve photoaging, and eventually prevent [9]. One prospective study (n = 29) reported an
the appearance of new lesions. This trend, objective response in 75% of plaque or patchy
combined with the cost and limited availability lesions after monthly treatments for 6 months.
of lasers in the 400–450  nm and 630–640  nm However, a recent study observed two of five
ranges, has limited the use of lasers for PDT in patients who appeared to have had a complete
dermatology. When physicians are using ALA response initially, but relapsed at follow-up
with a non-approved light source, they tend to (10.0 ± 10.5 months). MAL-PDT was success-
favor LEDs or intense pulsed light. However, ful in treatment-­refractory mycosis fungoides
the pulsed dye laser at 595  nm has also been (four patients with complete remission and one
used for the treatment of actinic keratoses and with partial remission). In conclusion, several
acne [14]. PDT has been widely used in the consecutive treatments of PDT can be consid-
treatment of mycosis fungoides, an indolent ered as an adjunct for treatment of mycosis fun-
subtype of cutaneous T cell lymphoma. Most of goides, particularly for patch and plaque-stage
16  Photodynamic Therapy 265

mycosis fungoides, with good cosmetic results still be a role for combined blue and red light
in sensitive skin areas [10]. activation of ALA in the treatment of acne [11].
ALA and MAL have been reported to success- Most controlled studies which have shown good
fully treat various non oncologic skin conditions efficacy report a strong post PDT phototoxic
in small pilot studies or in single case reports. reaction. Clinical photographs published in some
These include acne, rosacea, sebaceous hyperpla- of the articles which used MAL under occlusion
sia, hidradenitis suppurativa, photoaging, and for 3 h show moderate to severe erythema with
other cutaneous infections [14–19]. MAL and crusting 1 day post-PDT. These publications also
ALA are both in phase II for the treatment of report severe pain in many patients during light
acne [14, 15, 20, 21]. This is in part due to the exposure [15, 21]. Such a strong phototoxic reac-
intense accumulation of porphyrin in sebaceous tion is probably not needed to see improvement
glands following topical application of ALA and in acne. However, it is possible that prolonged
MAL (Fig.  16.3). Light exposure could induce remission requires a certain degree of phototoxic
partial necrosis of sebaceous glands and reduce reaction as necrosis of sebaceous gland tissue
sebum excretion thus reducing acne lesions. might be necessary. The current literature sug-
Preliminary findings with ALA suggest that this gests that PDT for acne is more efficacious for
is one of the mechanisms of ALA-PDT when patients with moderate to severe inflammatory
used for the treatment of acne [22]. Studies per- acne, although the best treatment parameters
formed with PDT in acne are complicated by the remain unknown. The use of ALA-PDT in rosa-
fact that blue or red light alone can improve acne cea is primarily anecdotal, with few randomized
by elimination of Propionibacterium acnes as controlled studies published thus far. MAL-PDT
these bacteria naturally accumulate porphyrins. with red light has been shown to improve the
Studies have also shown that blue light with and appearance of rosacea, in particular papulopustu-
without ALA is more effective than red light. In lar lesions, when compared with the erythemato-
vitro studies comparing ALA followed by blue telangiectatic types [12]. Evidence for the use of
light, 415 nm, or red light, 635 nm, and examin- PDT in treating rosacea is minimal, but MAL-­
ing the bactericidal effects on P. acnes, found that PDT with red light has resulted in rosacea
red light phototherapy was less effective for the improvement. Touma and colleagues have dem-
eradication of P. acnes than blue light photother- onstrated that the use of ALA-PDT with a 1–3 h
apy with or without ALA. Therefore, there may incubation followed by blue light exposure in

a b

Fig. 16.3 (a) Porphyrin fluorescence in sebaceous glands 3 h after application of MAL. (b) Same section stained with
hematoxylin
266 A. E. Eber et al.

patients with multiple actinic keratoses can Candida albicans intertrigo have been treated
improve photoaging [5]. Small wrinkles, pig- successfully using PDT [2, 18–20]. Treating
mentation, and sallowness parameters best warts caused by human papilloma virus, ALA-­
improved with ALA-PDT. ALA-PDT performed PDT has been used with clearance rates as high
with IPL has also been shown to improve photo- as 88%. ALA-PDT with white light was shown
aging [18, 24]. Small studies have also shown to be more effective than red or blue light PDT
complete response in AKs treated with ALA and or cryotherapy. One study used chemical avul-
IPL [24, 25]. There is currently a very wide vari- sion to treat onychomycosis with urea followed
ety of devices approved and used for the treat- by ALA-PDT with red light with a cure rate
ment of photoaging. Most physicians using ALA of  36.6% at 18  months. Other studies demon-
or MAL-PDT for photoaging either combine strated complete resolution using urea and
PDT with other devices and treatments or favor MAL-PDT or PDT alone. Both dermatophyte
ALA or MAL-PDT for patients with actinic kera- and nondermatophyte molds have been cleared
toses who would also like to have improvement with PDT; cutaneous leishmaniasis, erythrasma,
in photoaging. and Candida albicans intertrigo have also been
PDT has been used to treat different types of treated with PDT.
infections. ALA-PDT has been shown to suc-
cessfully treat cutaneous warts caused by human
papilloma viruses without significant side effects Contraindications
and excellent cosmetic results in several studies.
Reported clearance rates are as high as 88%. The It may be obvious but, ALA and MAL are contra-
clearance rate seems proportionate to the size of indicated in patients sensitive to visible light cor-
the warts, and mean treatment time. ALA-PDT responding to the spectral output of the light
with white light (halogen lamp; 250 W Osram; source used (400–450  nm for Blu-U and 630–
delivered via slide projector) was found to be 640 nm for Aktilite). Patients with porphyria and
more efficacious than red or blue light and stan- those with solar urticaria, systemic lupus erythe-
dard cryotherapy [13, 14]. Several studies have matosus, and other photosensitive dermatoses are
showed that PDT is an effective modality in also sensitive to the visible light of PDT [1]. PDT
treating onychomycosis. One clinical trial has not been thoroughly studied on patients using
(n = 30) used chemical avulsion (occlusion with concomitant photo-sensitizing drugs such as phe-
urea for ten consecutive nights prior to PDT) and nothiazines, tetracyclines, thiazides and sulphon-
20% ALA-PDT (3-h incubation) followed by red amides. Theoretically, this could increase the
light therapy, and demonstrated a 43.3% cure phototoxic reaction seen after PDT. Additionally,
rate at 12-month follow-up, which dropped to current use of topical or systemic retinoids such
36.6% at 18-month follow-up [15]. Two other as tretinoin, adapalene, acitretin or isotretinoin
case series reported complete resolution of fun- could also increase the phototoxic reaction.
gal infection with PDT. One case demonstrated Interestingly MAL contains peanut oil. It should
successful treatment of subungual onychomyco- not contain the protein allergen present in pea-
sis after occlusion with urea for 7 days followed nuts, but many physicians refrain from using
by MAL-­PDT with broadband red light (37  J/ MAL-PDT in patients allergic to peanuts. Further,
cm2). This was repeated every 2 weeks for a total histologic variants of BCCs at high risk of recur-
of three treatments. In this case, Trichophyton rence such as morpheaform BCC, are a contrain-
rubrum was the causative organism and it has dication to PDT with MAL. Pigmented basal cell
been previously demonstrated to be sensitive to carcinoma is usually considered a contraindica-
PDT in vitro. Nondermatophyte molds have also tion to PDT as well as pigment limits light pene-
been cleared with MAL-PDT and red light [16, tration. Despite this, several physicians have
17]. Cutaneous leishmaniasis, erythrasma, and reported complete responses of pigmented BCCs
16  Photodynamic Therapy 267

with PDT.  Also, recurrent lesions and large that can alter the stratum corneum such as topical
lesions may be better treated with other modali- retinoids can increase ALA and MAL penetration
ties [21]. and create a more severe phototoxic reaction fol-
lowing PDT. The use of systemic treatments that
increase visible light sensitivity such as St-John’s
Techniques wort should be avoided.
Patients should be well informed about the
Pre-operative management procedure including difficulty in predicting the
phototoxic reaction generated by PDT. If only a
• Informed consent with emphasis on difficulty few AKs or a single BCC are treated, the photo-
to predict phototoxic response toxic reaction is usually not a problem. However,
• Thorough examination of skin areas to be a full-face treatment can lead to erythema associ-
exposed to detect malignant lesions ated with tenderness and sometimes with focal
• Consider herpes simplex prophylaxis areas of crusting. It is suggested to obtain a writ-
ten informed consent that mentions this informa-
Description of the technique tion as well as potential complications like
hyperpigmentation, hypopigmentation, scarring
• Skin preparation to enhance penetration (mostly when treating basal cell carcinoma), sun
• Photosensitizer application and visible light sensitivity, and prolonged ery-
• Interval to allow porphyrin build-up thema. Patients should be advised to bring a hat
• Light exposure (when treating the face) or other pieces of cloth-
ing to cover the treated area.
Post-operative management The risks of triggering light sensitive recur-
rences of herpes labialis following PDT are cur-
• Sun avoidance rently unknown. For patients who experience
• Ferrous oxide containing sunscreen recurrences following sun exposure, antiviral
• Moisturizer prophylaxis should be discussed. Light exposure
during PDT sometimes leads to an urticarial
reaction immediately after PDT.  This is more
Pre-operative Management intense when red light is used and when large sur-
faces are exposed. This phenomenon has recently
A complete skin examination of the areas to be been attributed to histamine release by mast cells
treated is necessary. This is of the utmost impor- and could be prevented by pre-treatment with
tance when performing large surface PDT.  The antihistamines such as cetirizine.
examination should focus on the identification of
malignancies such as basal cell carcinoma, squa-
mous cell carcinoma and melanoma. Sub-optimal Description of the Technique
treatment of these malignant lesions could lead to
later, deeper recurrences. Any suspicious lesion  reatment of Actinic Keratoses
T
should be biopsied. If PDT is performed to treat a with ALA
malignant lesion such as BCC or Bowen’s dis-
ease, a pre-treatment biopsy is recommended. A A gentle curettage of keratotic AKs should be per-
complete medical history including the existence formed prior to ALA application. This is not
of visible light sensitivity diseases such as por- included in the current product monograph but the
phyria or solar urticaria should be recorded. author finds that this increases the clinical response
Patients should be asked about current use of any of individual lesions, probably by increasing drug
topical product on the areas to be treated. Products penetration. Skin preparation is suggested when
268 A. E. Eber et al.

performing short ALA incubations. The face can for the treatment of AKs. The intensity of the
be washed vigorously with acetone or treated with phototoxic reaction generated by ALA-PDT var-
microdermabrasion. These techniques are believed ies greatly from one patient to another and is
to increase ALA penetration through degreasing highly dependent on the type of pre-treatment
and/or partially removing the stratum corneum. used. For patients with extensive photodamage
Microdermabrasion can significantly reduce and numerous ill-defined AKs, a 45–60 min incu-
ALA incubation time [27]. Care should be taken bation period is usually sufficient, and this dura-
to use the same technique with the same pre-­ tion time can even lead to a severe phototoxic
treatment method by the same person when treat- reaction post-PDT.  Some physicians prefer to
ing a patient at different sessions as differences in perform the first treatment with a 30–45  min
skin preparation can have a dramatic impact on incubation time in these patients. The incubation
porphyrin build-up and therefore on the extent of time can be adjusted at subsequent treatments
the post-PDT phototoxic reaction. based on the phototoxic reaction and the clinical
ALA (Levulan) is available in the form of two response observed.
glass vials inserted in a plastic tube that is cov- After a proper incubation time, patients are
ered by cardboard (Fig.  16.4). The two vials placed inside the Blue-U device with appropriate
should be crushed with fingers and the stick eyeshields to protect their eyes. As the U-shaped
shaken for about 3 min to ensure proper mixing unit rotates, treatments can be performed with the
of ALA powder and hydroalcoholic vehicle. ALA patient sitting or lying down. The current product
should be applied on all AKs present in the treat- monograph recommends a light dose of 10 J/cm2
ment area. Most physicians will also apply ALA of blue light that corresponds to an incubation
on the entire face in order to treat non-visible time of 16  min and 40  s. This was the fluence
lesions and prevent new AKs. Broad area ALA used in phase III, but a lower fluence is probably
application also has the advantage of improving enough in most patients to completely photo-­
signs of photoaging [5]. Care should be taken to bleach porphyrins present in lesions. Many phy-
avoid applying ALA too close to the eyes as the sicians use a shorter incubation time, but the
solution will sting if it inadvertently gets into efficacy of shorter incubation times has not been
them. Facial zones with more sebaceous glands, thoroughly studied in clinical trials.
such as the nose and chin, often display a more Blue light exposure after ALA applica-
pronounced phototoxic reaction than the rest of tion generates a burning sensation that gradu-
the face when performing PDT. This is probably ally increases until it reaches a plateau around
due to more intense accumulation of porphyrins 3–8 min, which is then followed by a gradual
in the sebaceous glands. If ALA or MAL is decrease. This decrease in burning sensation
applied on these zones during a full-face treat- intensity corresponds to photo-inactivation of
ment, patients should be told to expect a strong porphyrins present in skin lesions. Blue light
phototoxic reaction the day following light expo- exposure is usually well tolerated by most
sure. A delay of 45  min to 2  h is suggested patients if they have been properly warned about
between ALA application and light exposure the sensation to expect during light exposure. An
when ALA-PDT is used on large skin surfaces assistant should be present in the room ­during

Fig. 16.4 ALA
(LEVULAN Kerastick).
The cardboard has been
removed to show the
two glass vials. Areas
where pressure needs to
be applied to crush the
two glass vials are
identified in red
16  Photodynamic Therapy 269

PDT, especially for the first PDT session, to should be exposed to 37 J/cm2 (Aktilite device)
reassure patients and to monitor the burning of red light, which corresponds to approximately
­sensation. The assistant can use cool air, spray 7 min and 30 s.
cool water or even temporarily interrupt light
exposure if the pain is too intense.
Post-operative Management

Treatment of BCC with MAL Excess ALA and MAL should be removed by

thoroughly washing the skin with tap water
A biopsy is suggested before treating a BCC to prevent further porphyrin synthesis. This is
with MAL-PDT.  The biopsy serves to confirm especially important when ALA or MAL has
the diagnosis and exclude histological subtypes, been applied to large areas such as the entire
such as morpheaform BCCs, for which PDT is face. Since patients are mostly sensitive to the
contraindicated. Gentle curettage of the lesion is visible part of the electromagnetic spectrum,
mandatory before MAL application as 5-year the use of high SPF sunscreens does not provide
cure rates have been established for MAL-PDT adequate sun protection in the days following
with pre-treatment curettage. Figure 16.5 shows PDT.  Patients can use a sunscreen containing
a patient with multiple BCCs before and imme- inorganic sunscreening agents, such as Avene
diately after lesion preparation. MAL is pro- 50 Compact which provides some, although not
vided in 2 g tubes. Once opened, the cream must complete, protection [28]. Patients should avoid
be used within 7 days. This allows for treatment sun exposure or exposure to intense visible light
of more than one patient with the same tube or such as surgical lighting or a high power dentist
treatment of the same patient 7 days later with lamp for 2 days after PDT. Patients should also
the same tube. MAL should be applied on the avoid driving or walking under the sun on the
entire lesion including a 1-cm margin and should day PDT is performed. They should be reminded
be occluded. Three hours after application, the that there is significant visible light exposure
occlusion is removed, the cream is wiped out of even on cloudy days and through window glass.
the treatment field, and the device (Aktilite) is There is no visible light sensitivity beyond
positioned at 5–8  cm from the skin. There is a 2 days after PDT with ALA or MAL. However,
risk of unsatisfactory treatment if the device is patients should use a high SPF sunscreen which
positioned beyond 8  cm. The irradiance varies provides adequate UVA protection to prevent
according to the distance between skin and light hyperpigmentation. The use of Avene thermal
source. The area where MAL has been applied water, a low mineral content water, after PDT

a b

Fig. 16.5  Patient with multiple BCCs (Gorlin’s syndrome) on the back before lesion preparation (a) and immediately
after lesion preparation but before MAL application (b)
270 A. E. Eber et al.

has been shown to be superior to a higher min- Side Effects/Complications

eral content water ­comparatively for decreasing
post-treatment pruritus [29]. Crusting and ero- Most patients will report a burning sensation,
sions over AKs and BCCs is expected and desir- pain, or pruritus during light exposure. This is
able when treating malignant or pre-malignant usually well tolerated. All patients should
lesions with PDT.  Simple occlusion combined expect a phototoxic reaction after PDT.  The
with the use of petrolatum jelly or an antibiotic absence of a phototoxic reaction on pre-malig-
ointment is usually all that is required to pro- nant or malignant lesions following PDT is
mote healing and decrease pain. The regular use usually a sign that the treatment will not be effi-
of a bland moisturizer is recommended. Patients cacious. The phototoxic reaction manifests
should avoid any topical products containing itself primarily by mild to severe erythema on
urea, retinoic acid or other alpha hydroxyl acids, exposed sites. This is usually associated with
alcohol or propylene glycol in the weeks follow- crusting on areas were AKs were present and
ing PDT. Patients should also be advised to call sometimes associated with vesicles, pustules,
their physician if the reaction increases beyond and/or erosions.
2  days, as this may be suggestive of bacterial Erythema and edema are often more severe
infection or reactivation of extensive herpes when the lesion to be treated is located on the
simplex. nose. This is probably related to the abundance of
sebaceous glands on the nose. Tenderness is usu-
ally present for a few days after PDT. Whole face
Adverse Events treatments are often associated with pain and ten-
derness that are exacerbated with pressure (con-
Expected tact with pillow when sleeping for example) and
followed by desquamation.
• Erythema Bacterial infections such as impetigo and/or
• Burning sensation during light exposure cellulitis or reactivation of herpes simplex are
• Crusting on AKs and BCCs possible possible but very rarely seen with ALA and
• Pain after light exposure MAL-PDT. PDT can induce hyperpigmentation
• Hyperpigmentation on treated areas. This is rarely seen in patients
• Hypopigmentation with phototype I or II.  Hypopigmentation is
• Scarring by loss of substance (e.g., nodular possible but rare. Scarring by loss of substance
basal cell carcinoma) can be seen after treatment of lesions that
• Urticarial reaction on exposed area invade the dermis such as nodular basal cell
• Prolonged erythema carcinoma. A few cases of prolonged erythema
• Cellulitis, impetigo have been reported following PDT on the face
• Reactivation of herpes simplex [22]. This phenomenon can sometimes last
many months. In the author’s experience, this is
Rare more frequent in patients with rosacea and usu-
ally fades over time.
• Allergic contact dermatitis Allergic contact dermatitis to MAL has been
• Keratoacanthoma reported and documented by patch testing. One
• Squamous cell carcinoma case of contact dermatitis was occupational as the
• Erosive pustular dermatosis of the scalp patient was working as a nurse in the dermatol-
• Koebner phenomenon ogy department [23, 24]. Clinicians should think
• Leg ulceration about this possibility in patients who have under-
• Peripheral facial palsy gone several MAL-PDT treatments and present
• Amnesia with a dermatitis type of reaction that was not
• Hypertension present at previous treatments.
16  Photodynamic Therapy 271

Recently, a small number of patients were continuous synthesis of porphyrin, which

reported to develop keratoacanthomas after treat- increases post-treatment sensitivity to visible
ment with PDT and some of these were self-­ light. Patients should thoroughly wash their face
limited [25–28]. Additionally, squamous cell with soap and water after light exposure. In a
carcinoma has also occurred post treatment with small pilot study where MAL was applied for
PDT [29, 30]. Other anecdotal situations have 3 h under occlusion, porphyrin fluorescence was
been reported including a Koebner phenomenon maximum at 1  h after cream removal but there
in one patient, resulting in re-activation of inac- was enough porphyrin present in the skin at 24 h
tive psoriasis [31]. Although uncommon, an after MAL application to induce a phototoxic
elderly patient with peripheral vascular disease reaction following light exposure in 6 out of 16
and Bowen’s disease on her leg was treated with subjects [42]. Patients must be warned to avoid
PDT and resulted in leg ulcer [32]. Other rare sun exposure for 2  days after PDT.  The use of
complications include erosive pustular dermato- a sunscreen containing a physical sunscreening
sis of the scalp, peripheral facial palsy (bell’s agent is recommended during the first 2  days.
palsy), amnesia, and elevation of blood pressure Sun protection with a high SPF sunscreen and
requiring immediate treatment [33–36]. good UVA protection is also important during
the weeks following PDT in order to prevent
hyperpigmentation.
 revention and Treatment of Side
P
Effects/Complications
Future Directions
Pain during the treatment session is a common side
effect that might cause discomfort for patients. • Treatment of Acne
When large surfaces are treated with MAL or • Hidradenitis Suppurativa
ALA, the use of water spray, ice packs, fan or cold • Daylight PDT
air (such as from a Zimmer device), can allevi- • Personalized Medicine
ate this sensation [37]. Temporary interruption of • Sonodynamic PDT
light exposure is another alternative as the burning
sensation subsides rapidly when the light device PDT has been available for over a century and
is turned off. If the pain is severe enough, other will most likely continue to be used as a stand-­
methods such as subcutaneous infiltration anesthe- alone treatment or in combination with other ther-
sia or even nerve block can be considered [38, 39]. apies for various medical and cosmetic purposes.
Topical anesthetic creams such as eutectic mix- It has been implicated with aminolevuninic acid
tures of local anesthetics (EMLA cream) do not (ALA) and methylaminolevulinate (MAL) for
seem to be effective [40]. Super-potent topical cor- treating acne, possibly through the decrease of
ticosteroids can decrease inflammation and ery- sebaceous gland activity from light activation of
thema associated with PDT if used immediately the photosensitizer [43]. While PDT is not the
before or after the treatment session without com- standard of care for treating hidradenitis suppura-
promising the therapeutic outcome [41]. Careful tiva, it may be a beneficial adjuvant to treatments
history taking for other diseases such as psoriasis such as rifampin and clindamycin [44]. Moreover,
or peripheral vascular diseases and hypertension although cancer was the main target for PDT
may decrease unwanted side effects. research from the 1970s to 2010, PDT is now also
As discussed in the “Post-operative Manage­ being explored for its antimicrobial properties, for
ment” section, application of petrolatum jelly, a there is currently a dangerously high rise of multi-
bland moisturizer or an antibiotic ointment will drug-resistance among pathogenic microbes [45].
make the phototoxic reaction more tolerable. Daylight PDT is also becoming increasingly pop-
Furthermore, removal of MAL and ALA after ular, especially in European nations, for treating
treatment is important in order to reduce the actinic keratoses. Instead of performing therapy
272 A. E. Eber et al.

with a conventional light source, daylight PDT tal mycoses of the feet with topical application of
5-aminolevulinic acid. Photodermatol Photoimmunol
harnesses daylight exposure to continuously acti- Photomed. 2004;20:144–7.
vate protoporphyrin IX (PpIX) 30 min after MAL 3. Kennedy JC, Pottier RH, Pross DC.  Photodynamic
application, when the protoporphyrin begins therapy with endogenous protoporphyrin IX: basic
forming in the skin. Daylight PDT facilitates principles and present clinical experience. J Photochem
Photobiol B Biol. 1990;6:143–8.
treatment to much larger areas of skin than con- 4. Peng Q, Berg K, Moan J, Kongshaug M, Nesland JM.
ventional PDT and also has the advantage of 5-Aminolevulinic acid-based photodynamic therapy:
inducing fewer adverse effects [46]. Additional principles and experimental research. Photochem
prospective uses for PDT and future directions Photobiol. 1997;65:235–51.
5. Serra-Guillen C, Nagore E, Hueso L, et al. A random-
include photochemical internalization, theranos- ized pilot comparative study of topical methyl ami-
tics, genetically coded protein photosensitizers, nolevulinate photodynamic therapy versus imiquimod
sonodynamic therapy using ultrasound, and two-­ 5% versus sequential application of both therapies
photon absorption PDT [45]. Lastly, combination in immunocompetent patients with actinic kerato-
sis: clinical and histologic outcomes. J Am Acad
therapy with PDT is on the horizon. In fact, a Dermatol. 2012;66:e131–7.
study recently demonstrated that sequential appli- 6. Bath-Hextall FJ, Matin RN, Wilkinson D, Leonardi-­
cation of PDT and imiquimod provides a signifi- Bee J.  Interventions for cutaneous Bowen’s disease.
cantly better clinical and histologic response in Cochrane Database Syst Rev. 2013:Cd007281.
7. Salim A, Leman JA, McColl JH, Chapman R, Morton
the treatment of AK’s than PDT or imiquimod CA. Randomized comparison of photodynamic ther-
alone [5]. apy with topical 5-fluorouracil in Bowen’s disease. Br
J Dermatol. 2003;148:539–43.
Conclusion 8. Basset-Seguin N, Bissonnette R, Girard C, et  al.
Consensus recommendations for the treatment of
To conclude, photodynamic therapy is a basal cell carcinomas in Gorlin syndrome with topical
unique modality currently widely used as field methylaminolaevulinate-photodynamic therapy. J Eur
therapy for the treatment of actinic keratosis, Acad Dermatol Venereol. 2014;28:626–32.
in situ squamous cell carcinomas (Bowen’s 9. Coors EA, von den Driesch P. Topical photodynamic
therapy for patients with therapy-resistant lesions of
disease), and superficial basal cell carcino- cutaneous T-cell lymphoma. J Am Acad Dermatol.
mas. For multiple AK’s, PDT treatment is 2004;50:363–7.
associated with less downtime than other full- 10. Quereux G, Brocard A, Saint-Jean M, et  al.

face or large surface treatments like 5-fluoro- Photodynamic therapy with methyl-aminolevulinic
acid for paucilesional mycosis fungoides: a prospec-
uracil or imiquimod alone. Further, PDT in tive open study and review of the literature. J Am
dermatology is being used to treat acne vul- Acad Dermatol. 2013;69:890–7.
garis, combat microbial disease, and other 11. Choi MS, Yun SJ, Beom HJ, Park HR, Lee JB. 
skin conditions. Daylight PDT is gaining pop- Comparative study of the bactericidal effects of
5-aminolevulinic acid with blue and red light on
ularity and so is the use of other vehicles, Propionibacterium acnes. J Dermatol. 2011;38:661–6.
delivery methods, and combination therapy. 12. Bryld LE, Jemec GB.  Photodynamic therapy in

Currently, PDT is still more widely used in a series of rosacea patients. J Eur Acad Dermatol
Europe most likely due poor reimbursement Venereol. 2007;21:1199–202.
13. Stender IM, Lock-Andersen J, Wulf HC. Recalcitrant
rates for PDT in the US.  Strong studies are hand and foot warts successfully treated with photo-
needed to show the efficacy of PDT in order to dynamic therapy with topical 5-aminolaevulinic acid:
justify its use, and hopefully insurance com- a pilot study. Clin Exp Dermatol. 1999;24:154–9.
panies will follow suit. 14. Schroeter CA, Pleunis J, van Nispen tot Pannerden
C, Reineke T, Neumann HA. Photodynamic therapy:
new treatment for therapy-resistant plantar warts.
Dermatol Surg. 2005;31:71–5.
15. Sotiriou E, Koussidou-Eremonti T, Chaidemenos G,
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 Intense Pulsed Light (IPL)
17
Sanjana Iyengar, Keyvan Nouri, Peter Bjerring,
Kåre Christiansen, Robert A. Weiss,
Girish S. Munavalli, Sonal Choudhary,
and Angel Leiva

Abstract trolled transfer of thermal energy from an

Intense Pulsed Light (IPL) is a light-emitting object at high temperature to an object at
system that is capable of emitting filtered lower temperature.
polychromatic broad bandwidth wavelengths
between 515 and 1200 nm. Keywords
The emission of wavelengths is con- Intense pulsed light · Leg vein treatment ·
trolled by both an internal filter that blocks Telangiectasias · Hemangiomas ·
undesired wavelengths from being emitted Poikiloderma of Civatte · Pigmentation ·
and a “heat-­sink” effect that allows the con- Photorejuvenation · Scarring · Hair removal ·
Acne · Seborrheic keratosis · Sarcoidosis ·
Hidradenitis suppurativa · Nail psoriasis
S. Iyengar
Department of Dermatology, Feinberg School
of Medicine, Northwestern University,
Chicago, IL, USA
K. Nouri P. Bjerring
Dermatology, University of Miami, Miami, FL, USA Department of Dermatology, Swansea University,
Ophthalmology, University of Miami, Swansea, Wales, UK
Miami, FL, USA K. Christiansen
Otolaryngology, University of Miami, Molholm Research, Molholm Hospital,
Miami, FL, USA Vejle, Denmark

Dermatologic Surgery, University of Miami, R. A. Weiss (*)

Miami, FL, USA Department of Dermatology, Maryland Dermatology
Laser Skin and Vein Institute, University of Maryland
Department of Dermatology and Cutaneous Surgery, School of Medicine, Hunt Valley, MD, USA
University of Miami Medical Group, e-mail: [email protected]
University of Miami, Miami, FL, USA
G. S. Munavalli
Dermatology Services at Sylvester Comprehensive Dermatology, Laser, and Vein Specialists of the
Cancer Center, University of Miami Hospital Carolinas, Charlotte, NC, USA
and Clinics, Miami, FL, USA
S. Choudhary · A. Leiva
MOHS, Dermatologic and Laser Surgery, Department of Dermatology and Cutaneous Surgery,
University of Miami, Miami, FL, USA Miller School of Medicine, University of Miami,
Surgical Training, University of Miami, Miami, FL, USA
Miami, FL, USA

© Springer International Publishing AG, part of Springer Nature 2018 275

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_17
276 S. Iyengar et al.

Introduction is no clinical difference between selective pho-

tothermolysis treatments with coherent (lasers)
Intense pulsed light (IPL) treatments are based and incoherent light (IPLs).
on selective photothermolysis where a specific Medical lasers intended for vascular treat-
target is selectively heated up by a light pulse and ments deliver sub-millisecond light pulses with
heat damaged, without destroying the surround- high energy for the treatment of very thin vessels
ing tissue components [1]. in portwine stains and hemangiomas [2]. IPL sys-
The IPL technology was clinically intro- tems have until now not been able to produce suf-
duced in 1994 and Photoderm™ (ESC/Sharplan, ficiently high energy levels at pulse durations
Norwood, MA, now Lumenis, Santa Clara, CA) shorter than approximately 2.5 ms. However, in
received as the first FDA clearance for the treat- 2015 the first real sub-millisecond IPL system
ment of lower extremity telangiectasias in 1995 was introduced (Nordlys, Ellipse A/S, Hoersholm,
[2]. The IPL technology has evolved a great deal Denmark), making IPL a genuine competitor to
since its introduction 20  years ago [3]. Today pulse dye laser [4].
there are more than a dozen companies produc-
ing IPL systems FDA-cleared for several differ-
ent dermatologic treatment procedures, including The IPL Device
vascular and pigment lesions, hair removal,
photo-rejuvenation, acne, and PDT treatments. In the IPL, the xenon flash lamp is located inside
Recently, small and still relatively effective IPL a handheld applicator where a sapphire or quartz
devices for at-home-use have entered the market, crystal guides the light from the flashlamp to the
allowing patients to treat themselves in the pri- skin surface [3]. A water-filled gel is normally
vacy of their homes [2]. used as an optical matching layer between the
On the high-end clinical IPL devices, the crystal light guide and the skin surface. The light
emitted band of wavelengths, the pulse duration guide may be actively cooled to lower the skin
(or train of pulses), and energy per pulse can be temperature for patient comfort and to protect
set individually [3]. All IPL systems on the mar- the skin surface. As the xenon lamp produces
ket today are based on pulsed xenon-flash lamps light with wavelengths ranging from the UV to
emitting non-coherent, polychromatic light with the infrared region, one or more filters are placed
wavelengths ranging from 400 to 1200  nm. in the light path to restrict the band of wave-
Different optical filters restrict the emitted band lengths reaching the skin. Commonly used low-­
of wavelengths reaching the skin surface to fit wavelength cut-off filters are 515, 550, 560, 570,
with the absorption spectrum of a specific skin 590, 615, 645, 690, 755 nm. The longer infrared
chromophore and hence the treatment proce- wavelengths are blocked from reaching the skin
dure. This flexibility gives IPL system the surface by the use of an infrared glass filter or by
advantage of being able to perform several clini- passing the light through a water chamber which
cal procedures using a single system compared acts an infrared light filter.
to lasers where a separate laser is often needed
for each treatment indication. Laser light is by
nature coherent, but due to the high scattering Wavelengths
coefficient in human skin, the laser light will be
in-coherent after few tens of μm penetration of The band of wavelengths has to be selected
the skin. Therefore for practical purposes, there according to the absorption of light in the tar-
17  Intense Pulsed Light (IPL) 277

get chromophores. For blood containing tar- phore (e.g. melanosomes) as well as the entire
gets, these chromophores may be reduced target (e.g. a hair). In clinical practice, the TDT is
hemoglobin, oxyhemoglobin, and methemo- often the TRT multiplied with a factor 2–5.
globin; for pigment and hair treatment, the
chromophore is eumelanin and pheomelanin
located inside the hair or in the epidermis [5]. Energy
If the optical target is located deeper in the der-
mis, longer wavelengths will be chosen as The correct energy level is obtained when enough
these penetrate deeper with less absorption in heat is delivered to lethally damage the target by
the upper skin layers. reaching a tissue temperature of 70° for at least
1 ms.

Pulse Duration
Spot Size
The IPL pulse duration can be adjusted according
to the target type and size. The duration of the The IPL light spot size, similar to the wave-
light pulse is selected so that only minimal length band, is important for light penetration
amounts of heat is conducted to the surrounding depth. The smaller the spot size, the relatively
tissue. The optimal pulse duration can be calcu- more lateral light scattering occurs and less
lated according to the theory of selective photo- energy will reach the deeper skin layer. The lat-
thermolysis and will approximately be equal to eral scattering is relatively less in larger spot
the thermal relaxation time (TRT) for the target. sizes resulting in deeper penetration. Clinical
TRT is the time taken for the target to dissipate practice as well as computer simulations of
about 63% of the incident thermal energy. A large light penetration have shown that a spot size
volume target will have a longer TRT and hence greater than 10 mm does not add further to the
requires longer IPL pulse durations to reach a penetration depth [5].
destructive target temperature than a target with a
smaller volume.
The TRT for a target with a diameter d can be Clinical Treatment Indications
calculated by [1]:
• Leg Vein Treatment
TRT = d 2 / 16 × k where k = 1.3 × 10 -7 m 2 .
• Telangiectasias
However, according to the extended theory of • Hemangiomas
photothermolyisis, the IPL light pulse duration • Poikiloderma of Civatte
for treatment of non-uniformly pigmented struc- • Pigmentation
tures in biological tissues (thicker vessels and • Photorejuvenation
hairs) can be calculated according to the “Thermal • Scarring
Damage Time” (TDT), which is significantly • Hair Removal
longer than the TRT. TDT is defined as the time • Acne
required for the entire target, including the pri- • Seborrheic Keratosis
mary chromophore and the surrounding target • Sarcoidosis
(hair follicle, vessel wall etc.), to cool by about • Hidradenitis Suppurativa
63%. It includes cooling of the primary chromo- • Nail Psoriasis
278 S. Iyengar et al.

 eticular Leg Veins with Associated

R achieved using IPL in another study by Schroeter
Telangiectasias et al. in 45 patients with telangiectasias and spi-
der nevi [9–15].
Leg telangiectasias are visible dermal arterioles, Erythematotelangiectatic (ET) rosacea mani-
capillaries, or veins with a diameter of 0.1–2 mm. fests as facial telangiectasias, persistent ery-
The primary chromophores for vascular lesions thema, and flushing involving the central face.
are hemoglobin and its derivatives: oxyhemoglo- PDL with wavelengths of 585 and 595 nm have
bin, deoxyhemoglobin, and methemoglobin. previously been widely used and are considered
Oxyhemoglobin absorbs up to 630  nm, while effective [16, 17]. In a study published by
deoxyhemoglobin absorbs up to 750 nm. Multiple Schroeter et al., the effect of IPL on 60 patients
closely spaced light pulses (train of single pulses) resulted in 77.8% clearance of facial telangiecta-
convert oxygenated hemoglobin to deoxygenated sias with the forehead showing the best clearance
hemoglobin in the early part of the light pulse of 87% [18]. Out of all the areas, the nose required
making the procedure more effective. Hence, the highest number of treatment sessions for
blue telangiectasias, which are more deoxygen- lesions to disappear.
ated, are treated with light pulses between 530 Compared to lasers, IPLs offer several advan-
and 750 nm. Shorter wavelength bands are more tages. IPL emits non-coherent broad spectrum
effective in treating superficial, oxygenized red light which allows deeper penetration into the
vessels but not deeper blue veins. Longer wave- skin via wide wavelength bands that incorporate
lengths may also be used to treat larger diameter longer wavelengths. The IPL also treats a larger
blue venulectasia and smaller veins due to better surface area in a single shot (>5 cm2) compared
penetration of these wavelengths [6–8]. to the small spot size of a PDL (80 mm2). In addi-
The IPL device can be adjusted to provide tion, through the use of multiple pulses, IPL
optimal fluence, pulse, wavelength band, and allows the skin to cool between the individual
pulse duration based on the vessel characteristics. pulses in the pulse train and thus minimize the
Spot size can be altered to provide more or less risk of epidermal damage.
light penetration [5]. Longer pulse durations,
higher low wavelength cut-off filters, and cooling
mechanisms allow IPLs to minimize epidermal Hemangiomas
injury while effectively treating the lower extrem-
ity telangiectasias. Hemangiomas are proliferative tumors which
slowly regress overtime. Lesions persist in
35–50% of children with 15% of children having
Facial Telangiectasias residual discoloration [19]. Ulceration is a com-
plication of infantile hemangiomas. While sys-
Facial telangiectasias can be classified as linear, temic beta-blocker therapy is now the mainstay
arborizing, spider, and punctiform. Sun exposure, of hemangioma treatment, the IPL is often used
steroids, and hormone replacement may play a to treat residual hemangioma after the primary
role in the development. IPL can be used to involution.
improve these telangiectasias. Until recently, the
pulsed dye laser (PDL) with 0.5 ms pulse dura-
tion was the preferred treatment, but often lead to Poikiloderma of Civatte
intracutaneous hematomas and purpura. IPL sys-
tems have less side effects and are the patients’ Poikiloderma of Civatte (POC) is a condition
choice for telangiectasia treatment. A study by resulting from photodamage and hence, is found
Angermeier showed clearance rates of 75–100% on sun exposed areas such as the neck, forehead,
in treating over 100 patients with essential telan- and upper chest. Skin appears erythematous, pig-
giectasias. Clearance rates of 90–95% was mented and wrinkled in appearance. IPL can be
17  Intense Pulsed Light (IPL) 279

used to treat POC as the 515  nm filter allows improve the skin’s appearance [3]. Brief thermal
absorption by both the melanin and hemoglobin. damage to capillaries in the skin may induce or
Higher low wavelength cut-off filters up to release growth factors leading to neocollagenesis.
590 nm filters may be necessary initially in more Wavelength bands utilized range from 515 to
severe cases to reduce excessive light absorption 1000 nm with longer wavelengths stimulating col-
and hence side effects. Studies have shown that lagen synthesis and shorter wavelengths targeting
IPL has a clearance of more than 75% of telangi- pigmentation and telangiectasias. In two studies
ectasias and hyperpigmentation with only 5% by Zelickson, IPL treatments appeared to be suc-
developing pigmentation side effects [20]. cessful in increasing skin collagen [24, 25]. One
study showed IPL had an 81% increase in collagen
type 1 transcripts compared to the 23% increase
Pigmented Lesions seen with PDL treatment. Collagen I, III, elastin,
and collagenase increased in 85–100% of patients
Pigmented lesions, such as solar lentigines, con- and procollagen increased in 50–70% of patients.
genital nevi, postinflammatory hyperpigmenta- A study conducted by Negishi et al. examined IPL
tion, and café-au-lait macules, can be treated for pigmentation and telangiectasias [26]. A
with an IPL device. A study by Bjerring et  al. 550 nm filter for pigment and 570 nm cut-off filter
examined the use of IPL device on 96 patients for telangiectasia were used on 97 Japanese
with solar lentigines and melanocytic nevi [21]. patients. Subjects were treated three to six times at
The IPL device had a dual filter configuration 2–3  week intervals with IPL 28–32  J/cm2, 2.5–
with a low wavelength cut-off filter, water filter, 4.0/4.0–5.0 ms, and 20–40 ms delay without topi-
and water chamber, which absorbed all infrared cal anesthesia. Results showed 49% of patients
light and produced the desired spectrum of light had greater than 75% improvement in pigmenta-
when combined. Results from one session tion with 33% having greater than 75% improve-
revealed a 96% reduction in pigment, 74.2% ment in telangiectasia and 13% having greater
clearance for solar lentigines, and 66.3% decrease than 75% improvement in skin texture. Another
in melanocytic nevi. Similarly, IPL has been study by this group examined the effect of
examined in treating melasma. A study by Li Quantum IPL every 3–4  weeks on 73 Japanese
et al. reported a 51–100% improvement in 77.5% patients. Quantum IPL has a cooling system which
of patients after four IPL treatments at 3  week cools the epidermis to 40C compared to 65C with-
intervals [22]. According to the authors, epider- out cooling. In 80% of patients, a greater than 60%
mal melasma seemed to respond better to the improvement in pigmentation and erythema was
treatment compared to the mixed type. noted. Similarly, the use of IPL as a therapeutic
device for freckling has been examined. A study
by Huang et al. using 550–590 nm filters (25–35 J/
Photorejuvenation cm2, 4 ms single or double pulse, 20–40 ms delay
time) for one to three treatments at 4 week inter-
IPL is commonly used to improve signs of photo- vals received 91.7% satisfaction [27].
aging. Structural components of the skin are Combination procedures, such as the use of
altered due to the accumulation of UV damage. In IPL with 1064 and 1320 nm Nd:YAG laser treat-
addition, the loss of elasticity due to normal aging ments [28, 29], microdermabrasion [30], and the
can be seen on the skin. Photorejuvenation through use of botulinum toxin A [31], may enhance pho-
the use of the IPL device has been described as a torejuvenation. Higher wavelengths from the
dynamic non-ablative process used to smooth the Nd:YAG laser can stimulate collagen formation
skin surface, reduce visible vessels, and reduce by significantly altering the dermis. IPL treat-
mottled pigmentation [23]. Thermal damage from ment followed immediately by a tri-chloro-acetic
the IPL device induces the formation of type 1 and acid (TCA) peel is especially effective for the
3 collagen fibers and reorganizes elastic fibers to treatment of pigment disturbances.
280 S. Iyengar et al.

Photodynamic Therapy (PDT) Similarly, IPL has been used to treat striae dis-
tensae, a type of scar characterized by linear
PDT uses IPL as a light source which stimu- bands of atrophic skin. In a study by Hernandez-­
lates severely photodamaged skin (as in pho- Perez et  al., there was a statistically significant
torejuvenation) and destroys pre-malignant improvement using IPL to treat abdominal striae
cells in actinic keratosis and basal cell carci- in 15 patients [36]. While there is no classical
nomas via activation of a photosensizer [32]. treatment for improving the appearance of stretch
Topical a­ dministration of 5-aminolevulinic acid marks, the authors suggest IPL could be a prom-
[5-ALA] or its methyl ester induces formation ising therapy.
of protoporphyrin IX which photosensitizes
the target area prior to IPL irradiation. The IPL
light leads to the production of activated oxy- Hair Removal
gen species within photodamaged cells, result-
ing in their destruction. The photosensitizer is Studies have shown IPL has very good results in
applied between 30  min and 3  h prior to IPL removing unwanted hair. Gold et al. reported an
irradiation. Indications for PDT include pho- average of 60% hair removal after one treatment
torejuvenation, precancer and nonmelanoma session and 3  month follow-up in 31 patients
skin cancer, such as actinic keratosis, superfi- with hypertrichosis [37]. Sadick et  al. reported
cial basal cell carcinoma, and Bowen’s disease. 76% hair removal using a filtered IPL system
Side effects include pain during irradiation, after a mean of 3.7 treatments in 34 patients with
erythema, edema, and crusting for up to a week, excess body hair [38]. From the study, 14 patients
and subsequent hyperpigmentation, especially followed up for more than 12 months and reported
in darker skin types. Depending on the photo- 83% hair removal in the end. Efficacy and hence
sensitizer used, treatment size, and lesion type, patients’ satisfaction of IPL hair removal varies
side effects may be more or less severe. In gen- according to the hair type, hair color, skin color,
eral, PDT is well tolerated and can be used to number of treatments, treatment settings, and
treat multiple areas simultaneously. operator. Black hairs on fair skin have the best
hair removal clearance with IPL [5, 39]. However
with increasing Fitzpatrick skin type, more side
Scars effects such as redness, crusting, and pigmenta-
tion changes may be seen [39–41]. Yellow discol-
There have been few studies examining the use of oration of the terminal hairs and paradoxical hair
IPL in the treatment of hypertrophic scarring. It growth in adjacent areas to the treated sites have
is hypothesized that IPL works by targeting mel- been noted as side effects of the IPL treatment
anin and vascular pigments which promote col- [42]. Effective home-treatment IPL devices have
lagen overgrowth [33]. Bellew et  al. compared recently been developed for hair management,
the efficacy of long PDL pulses with IPL on and a major part of optical hair treatments may
hypertrophic surgical scars [34]. Two treatments soon be carried out with these devices.
were performed 2 months apart. It was concluded
both treatments were equally effective in terms of
appearance, but there was less risk of developing Acne
purpura with IPL. Subjects reported IPL as more
painful than PDL.  Another study by Erol et  al. The use of light therapy for the treatment of acne
reported a 92.5% improvement in the clinical is increasing due to its safety and relative efficacy
appearance of hypertrophic or keloid scars after [43]. Acne is a chronic inflammatory disorder of
utilizing IPL in 109 patients [35]. There was a the pilosebaceous unit and is prevalent in more
reduction in the height, erythema, and hardness than 85% of adolescents. Bacterial proliferation
of the scars. of Propionibacterium and rupture of the come-
17  Intense Pulsed Light (IPL) 281

done provide the inflammatory appearance of 25% of cases. Few studies have surfaced which
acne. While traditional therapies include sys- examine the effect of IPL on the cutaneous mani-
temic and topical antibiotics, keratolytics and festation of sarcoidosis. A study by Hasegawa
retinoids, the issue of antibiotic resistance and et  al. treated a 60  year old female with facial
adverse side effects may result in under treat- plaques using topical ALA with IPL and later
ment, loss of patient compliance and undesired PDT [45]. Patients completed five sessions and at
results. It has been hypothesized that light 6 months had no signs of recurrence. Similarly,
decreases the amount of Propionibacterium and Rosende et  al. reports a case of a 54  year old
reduces the size of the pilosebaceous apparatus. female with manifestations on the extremities
More specifically, light causes photo-excitation and nose [46]. IPL treatment on the nose with a
of porphyrins present inside the bacteria, leading 590 nm cutoff filter and double pulse (initial total
to the release of free oxygen radicals which are dose 37 J/cm2) was delivered with a 20 ms delay
bactericidal to Propionibacterium. between pulses. Sessions were conducted over 2
Intense pulse light devices for acne treatment years with an increase in fluence at each visit.
release 400–1000  nm polychromatic high-­ Two year later, the patient was asymptomatic. It
intensity pulsed light that activates the porphyrin is postulated that the mechanism of action could
destruction of Propionibacterium [43]. The light be due to the destruction of abnormal blood ves-
also stimulates endogenous chromophores to sels, which are an important component of
indirectly reduce sebaceous gland activity by inflammatory dermatoses by delivering pro-­
damaging blood vessels supplying the gland. It is inflammatory cytokines to the skin [3].
postulated that IPL may also exert an anti-­
inflammatory effect by downregulating tumor
necrosis factor alpha (TNF-α) and upregulating Hidradenitis Suppurativa
transforming growth factor-beta1 (TGF-β).
Hidradenitis suppurativa is a chronic and suppu-
rative inflammation of apocrine glands, most
Seborrheic Keratosis commonly found in the axilla, inguinal folds,
perineum, genitalia, and periareolar region [44].
Seborrheic keratosis is a benign skin lesion of the Follicles are plugged by keratin leading to inflam-
epidermis which appears yellow-brown or dark-­ mation, abscess, and fistula formation. Factors
brown in color [44]. The use of IPL in ten patients such as obesity and hormone abnormalities have
with multiple seborrheic keratosis was studied. been linked to this condition. Highton et  al.
Results showed superficial and small seborrheic examined IPL treatment in 18 patients with
keratosis responded well to IPL compared to hidradenitis suppurativa over 4  weeks with ses-
larger and thicker lesions. Dermoscopy con- sions two times per week [47]. At the end of the
firmed the heat-induced change in lesion color study, patients reported a high degree of patient
from brown to grey immediately after treatment. satisfaction. More studies are needed to further
IPL filters with short cut-off wavelengths (400– examine the therapeutic efficacy of IPL in treat-
900 nm) should be chosen in order to act prefer- ing hidradenitis suppurativa.
entially on the epidermis and only treat the
superficial lesion [3].
Nail Psoriasis

Sarcoidosis Nails are a common manifestation found in up to

50% of patients with psoriasis [48]. Nails appear
Sarcoidosis is a multi-organ systemic disease of with “oil drop” discoloration, splinter hemor-
unknown origin characterized by non-caseous rhages, and onycholysis. While pulsed dye laser
granulomas [44]. Skin involvement occurs in has been used to successfully treat nail psoriasis,
282 S. Iyengar et al.

a study by Tawfik examined the effect of IPL as 4. US Food and Drug Administration DoHaHS. K150907
Trade/Device Name: Ellipse Nordlys Pre-market noti-
an additional treatment option for this condition. fication letter. 2015.
Twenty patients were treated with IPL every 5. Lask G, Eckhouse S, Slatkine M, Waldman A,
2 weeks for a maximum of 6 months. At the end Kreindel M, Gottfried V. The role of laser and intense
of the study, the nail bed showed a 71.2% light sources in photo-epilation: a comparative evalu-
ation. J Cutan Laser Ther. 1999;1(1):3–13.
improvement while the nail matrix improved 6. Goldman MP, Bennett RG. Treatment of telangiecta-
32.2%. The Nail Psoriasis Severity Index sia: a review. J Am Acad Dermatol. 1987;17(2 Pt 1):
(NAPSI) score also showed significant improve- 167–82.
ment post-treatment. IPL serves as a potential 7. Sommer A, Van Mierlo PL, Neumann HA, Kessels
AG. Red and blue telangiectasias. Differences in oxy-
promising treatment for nail psoriasis. More genation? Dermatol Surg. 1997;23(1):55–9.
studies, however, need to be performed to fully 8. Dover JS, Sadick NS, Goldman MP.  The role of
examine this relationship. lasers and light sources in the treatment of leg
veins. Dermatol Surg. 1999;25(4):328–35. discus-
sion 335–336
Conclusion
9. Redisch W, Pelzer RH. Localized vascular dilatations
Intense Pulsed Light is a non-coherent source of the human skin, capillary microscopy and related
of pulsed light with a bandwidth ranging studies. Am Heart J. 1949;37(1):106–13.
from 400 to 1200 nm. Indications for its use 10. Raulin C, Greve B, editors. Laser und IOL-­Technologie
in der Dermatologie and Aesthetischen Medizin. 1st
include treatment of leg vein telangiectasias, ed. Schattauer Stuttgart: New York; 2001.
hair removal, scarring, pigmentary alterations, 11. Ruiz-Esparza J, Goldman MP, Fitzpatrick RE, Lowe
photorejuvenation, and vascular lesions. The NJ, Behr KL.  Flash lamp-pumped dye laser treat-
advantages of IPL are its versatility, large ment of telangiectasia. J Dermatol Surg Oncol.
1993;19(11):1000–3.
treatment areas and non-­ablative nature. As 12. Podmore P.  Treatment of widespread generalized

the wavelength, spot size, and pulse duration congenital aberrant telangiectasia with a flashlight
can be widely adjusted, IPL targets skin chro- source. J Cutan Laser Ther. 2000;2(2):79–80.
mophores specific to the condition. Some sys- 13. Raulin C, Schroeter C, Maushagen-Schnaas E. Treatment
possibilities with a high-energy pulsed light source
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deeper chromophores. with intense pulsed light. J Cutan Laser Ther. 1999;
Several studies have demonstrated the effi- 1(2):95–100.
15. Schroeter CA, Neumann HA. An intense light source.
cacy of IPL in treating various conditions. The photoderm VL-flashlamp as a new treatment
Various trials have confirmed the efficacy of possibility for vascular skin lesions. Dermatol Surg.
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treatment stimulates production of type-1 collagen 38. Sadick NS, Weiss RA, Shea CR, Nagel H, Nicholson J,
and collagenase transcripts in papillary dermis fibro- Prieto VG.  Long-term photoepilation using a broad-­
blasts. Lasers Surg Med Abstr Suppl. 2001;13(33) spectrum intense pulsed light source. Arch Dermatol.
26. Negishi K, Tezuka Y, Kushikata N, Wakamatsu S.  2000;136(11):1336–40.
Photorejuvenation for Asian skin by intense pulsed 39. Fodor L, Menachem M, Ramon Y, et al. Hair removal
light. Dermatol Surg. 2001;27(7):627–31; discussion using intense pulsed light (EpiLight): patient satisfac-
632. tion, our experience, and literature review. Ann Plast
27. Huang YL, Liao YL, Lee SH, Hong HS.  Intense
Surg. 2005;54(1):8–14.
pulsed light for the treatment of facial freckles in 40. Raulin C, Greve B, Grema H.  IPL technology: a

Asian skin. Dermatol Surg. 2002;28(11):1007–12; review. Lasers Surg Med. 2003;32(2):78–87.
discussion 1012. 41. Moreno-Arias GA, Castelo-Branco C, Ferrando J. Side-
28. Goldberg DJ, Whitworth J.  Laser skin resurfacing effects after IPL photodepilation. Dermatol Surg.
with the Q-switched Nd:YAG laser. Dermatol Surg. 2002;28(12):1131–4.
1997;23(10):903–6; discussion 906–907. 42. Radmanesh M.  Temporary hair color change from
29. Fatemi A, Weiss MA, Weiss RA.  Short-term histo- black to blond after intense pulsed light hair removal
logic effects of nonablative resurfacing: results with therapy. Dermatol Surg. 2004;30(12 Pt 2):1521.
a dynamically cooled millisecond-domain 1320  nm 43. Pei S, Inamadar AC, Adya KA, Tsoukas MM. Light-­
Nd:YAG laser. Dermatol Surg. 2002;28(2):172–6. based therapies in acne treatment. Indian Dermatol
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The evaluation of aluminum oxide crystal microderm- 44. Piccolo D, Di Marcantonio D, Crisman G, et  al.

abrasion for photodamage. Dermatol Surg. 2001; Unconventional use of intense pulsed light. Biomed
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31. Fagien S, Brandt FS.  Primary and adjunctive use of 45. Hasegawa T, Suga Y, Mizuno Y, Haruna K, Ikeda S. 
botulinum toxin type A (Botox) in facial aesthetic Photodynamic therapy using intense pulsed light
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28(1):127–48. 564–5.
32. Ruiz-Rodriguez R, Sanz-Sánchez T, Córdoba S. Pho- 46. Rosende L, del Pozo J, de Andrés A, Pérez Varela L. 
todynamic photorejuvenation. Dermatol Surg. 2002; Intense pulsed light therapy for lupus pernio. Actas
28(8):742–44; discussion 744. Dermosifiliogr. 2012;103(1):71–3.
33. Hedelund L, Due E, Bjerring P, Wulf HC, Haedersdal M.  47. Highton L, Chan WY, Khwaja N, Laitung JK. Treat­
Skin rejuvenation using intense pulsed light: a ran- ment of hidradenitis suppurativa with intense pulsed
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 Current Status of Light-Emitting
Diode Phototherapy 18
in Dermatological Practice

R. Glen Calderhead

Abstract and Romans used the healing power of the sun,

Phototherapy in its broadest sense means any and it was still being actively used in Europe in
kind of treatment (from the Greek therapeia the eighteenth, nineteenth and early twentieth
‘curing, healing,’ from therapeuein ‘to cure, century, particularly red light therapy carried
treat.’) with any kind of light (from the Greek out with the patient placed in a room with red-
phos, photos ‘light’). The modern accepted tinted windows. One famous patient was King
definition of phototherapy, however, has George III of Great Britain and Northern
become accepted as: “the use of low incident Ireland who ruled from 1760 to 1801, popu-
levels of light energy to achieve an athermal larly though erroneously known as ‘Mad King
and atraumatic, but clinically useful, effect in George’. We now strongly suspect that he was
tissue”. Under its basic original definition, actually suffering from the blood disease por-
phototherapy is an ancient art because the old- phyria, so being shut in a room with red-draped
est light source in the world is the sun, and walls and red tinted windows to treat his
therapy with sunlight, or heliotherapy, has depression probably only served to make him
been in use for over 4000 years with the earli- even more mad, since porphyria is often asso-
est recorded use being by the Ancient Egyptians ciated with severe photosensitivity! Entities
(Giese, Living with our Sun’s ultraviolet rays, treated this way included the eruptive skin
Springer, New York, 1976). They would treat lesions of rubella and rubeola, and even ‘mel-
what was probably vitiligo by rubbing the ancholia’, as was the case with King George
affected area with a crushed herb similar to III, now recognised as clinical depression.
parsley, then expose the treated area to sun- Hippocrates, the Father of Medicine, certainly
light. The photosensitizing properties of the concurred with the latter application some two
parsley caused an intense photoreaction in the millennia before King George: Hippocrates
skin leading to a very nasty sunburn, which in prescribed sunlight for depressive patients and
turn hopefully led to the appearance of postin- believed that the Greeks were more naturally
flammatory secondary hyperpigmentation, or cheerier than their northern neighbors because
‘suntan’ thereby repigmenting the depig- of the greater exposure to the sun.
mented area. In their turn the Ancient Greeks
Keywords
R. G. Calderhead LED-LLLT · Photobiomodulation · Collagenesis
Research Division, VP Medicoscientific Affairs, · Elastinogenesis · Wound healing · Adenosine
Clinique L, Goyang-shi, Gyeonggi-Do, South Korea triphosphate · Mitochondrion
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 285

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_18
286 R. G. Calderhead

famous patient was King George III of Great

Box 18.1 Britain and Northern Ireland who ruled from
• Phototherapy is not new! It was being 1760 to 1801, popularly though erroneously
used more than 4000 years ago known as ‘Mad King George’. We now strongly
• Light-emitting diodes (LEDs) have suspect that he was actually suffering from the
attracted great interest as a photo- blood disease porphyria [2], so being shut in a
therapeutic source room with red-draped walls and red tinted win-
• An LED is not a laser, so although dows to treat his depression probably only served
LED energy is noncoherent it is to make him even more mad, since porphyria is
quasimonochromatic often associated with severe photosensitivity!
• LEDs are solid state and robust Entities treated this way included the eruptive
• LEDs are comparatively inexpensive skin lesions of rubella and rubeola, and even
‘melancholia’, as was the case with King George
III, now recognised as clinical depression.
Hippocrates, the Father of Medicine, certainly
Introduction concurred with the latter application some two
millennia before King George: Hippocrates pre-
History of Phototherapy scribed sunlight for depressive patients and
believed that the Greeks were more naturally
Phototherapy in its broadest sense means any cheerier than their northern neighbors because of
kind of treatment (from the Greek therapeia ‘cur- the greater exposure to the sun.
ing, healing,’ from therapeuein ‘to cure, treat.’) In the field of wavelength-specific photother-
with any kind of light (from the Greek phos, pho- apy research, red light therapy was examined at a
tos ‘light’). The modern accepted definition of cellular level under the newly-invented micro-
phototherapy, however, has become accepted as: scope by Fubini and colleagues in the late eigh-
“the use of low incident levels of light energy to teenth century [3], who were able to show that
achieve an athermal and atraumatic, but clinically visible red light, provided via lenses and filters
useful, effect in tissue”. Under its basic original from sunlight, selectively activated the respira-
definition, phototherapy is an ancient art because tory component of cellular mitochondria. There
the oldest light source in the world is the sun, and is nothing new under the sun. However, the sun is
therapy with sunlight, or heliotherapy, has been a fickle medical tool, particularly in northern
in use for over 4000  years with the earliest Europe, and modern phototherapy as we know it
recorded use being by the Ancient Egyptians [1]. started around the turn of the last century with
They would treat what was probably vitiligo by Finsen’s electric arc lamp-based system, giving
rubbing the affected area with a crushed herb phototherapy at the turn of a switch, independent
similar to parsley, then expose the treated area to of the sun [4]. However, apart from the use of
sunlight. The photosensitizing properties of the blue light therapy for neonatal bilirubinemia
parsley caused an intense photoreaction in the which continues to the present day, phototherapy
skin leading to a very nasty sunburn, which in was, in the majority of its applications, overtaken
turn hopefully led to the appearance of postin- in the first part of the twentieth century by better
flammatory secondary hyperpigmentation, or medication or improved treatment techniques.
‘suntan’ thereby repigmenting the depigmented The development of the first laser systems, a
area. In their turn the Ancient Greeks and Romans race which was narrowly won by Theodore
used the healing power of the sun, and it was still Maiman in 1960 with his flashlamp-pumped
being actively used in Europe in the eighteenth, ruby-based laser, next gave clinicians and
nineteenth and early twentieth century, particu- researchers a completely different and unique
larly red light therapy carried out with the patient light source to play with. In the 4 years between
placed in a room with red-tinted windows. One 1960 and 1964, the ruby laser was followed by
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 287

the argon, helium-neon (HeNe), neodymium: insulator. Simply explained, light-emitting semi-
yttrium-aluminum-garnet (Nd:YAG), solid state conductors or diodes consist of negative (N-type)
semiconductor laser (diode laser) and carbon and positive (P-type) materials, which are ‘doped’
dioxide (CO2) lasers all of which have remained with specific impurities to produce the desired
as workhorses in the medical field, and the HeNe wavelength. The n-area contains electrons in
laser (632.8 nm) has in fact provided a large bulk their ground or resting state, and the p-area con-
of the phototherapy literature over the last three tains positively charged ‘holes’, both of which
decades. As for light-emitting diodes (LEDs), the remain more or less stationary (Fig.  18.1a–c).
first light from a semiconductor was produced in When a direct current electric potential with the
1907 by the British experimenter H.  J. Round. correct polarity is applied to an LED, the elec-
Independently in the mid 1920s, noncoherent trons in the N-area are boosted to a higher energy
infrared light was produced from a semiconduc- state, and they and the holes in the P-area start to
tor (diode) by O-V Losev in Russia. These stud- move towards each other (Fig. 18.1d), meeting at
ies were published in Russia, Germany and the the N/P junction where the negatively-charged
UK, but their work was completely ignored in the electrons are attracted into the positively-charged
USA [5]. It was not till 1962 that the first practi- holes. The electrons then return to their resting
cal and commercially-available visible-spectrum energy state and, in doing so, emit their stored
(633 nm, red) LED was developed in the USA by energy in the form of a photon, a particle of light
Holonyak, regarded as the ‘Father of the LED’ energy (Fig.  18.1e). The wavelength emitted is
while working with the General Electric noncoherent, ideally very narrow-band, and
Company. In the next few years, LEDs delivering depends on both the materials from which the
other visible wavelengths were produced, with LED is constructed, the substrates, and the p-n
powers ten times or more that of Holonyak’s junction gap. Table 18.1 shows a list of the main
original LED.  For reasons which will be dis- substrates and associated colors. LEDs fall into
cussed later, these LEDs were really inappropri- two shapes: there is the older dome-type LED,
ate as therapeutic sources, although they were and the more recent, and currently more often
extremely bright and very cheap compared with used, “on board chip” (OBC) which is much
laser diodes, and it was not till the late 1990s that more compact and less expensive than the older
a new generation of extremely powerful, qua- dome type. They are also more efficient.
simonochromatic LEDs was developed by Figure 18.2 shows the anatomy of both types of
Whelan and colleagues as a spin-off from the LED. The dome types can be mounted on printed
National Aeronautic and Space Administration circuit boards (PCBs) at regular and precise dis-
(NASA) Space Medicine Program [6]. Unlike tances from each other to provide an LED array,
their cheap and cheerful predecessors, the so-­ whereas the OBC type is already part of the PCB,
called ‘NASA LEDs’ finally offered clinicians in other words, LED system manufacturers can
and researchers a new and truly practical thera- purchase preloaded PCBs in whatever configura-
peutic tool [7]. tion and size are available. Figure 18.3 shows an
example of both types from an actual array.
The surface of the PCB is very often coated to
The What and Why of LEDs reflect the wavelength of the LEDs mounted on
it. Some of the light energy emitted from the
 hat Is an LED?
W LED array will be reflected back off the stratum
Light-emitting diodes belong to the solid state corneum, or horny layer, of the skin, and a por-
device family known as semiconductors. These tion of the incident light which enters the skin
are devices which fall somewhere between an will be scattered backwards out of the skin. The
electrical conductor and an insulator, although reflective coating on the PCB captures these pho-
when no electrical current is applied to a semi- tons, the energy of which would otherwise be lost
conductor, it has almost the same properties as an into the air or could be absorbed by the PCB and
288 R. G. Calderhead

a b
Direction of motion Direction of motion

Electrons Ele Ele

ctro ctro
(– charge) de de

N-type material

Holes Direction of motion

(+ charge)

Direction of motion d Current flows through

this N/P junction
P-type material Direction of motion
c DEPLETION
ZONE
Electrons reach
higher energy level

Direction of motion

e – +

DC power
source
Electron is attracted to
positively-charged hole:
drops back to normal
energy level:
releases stored energy
as a photon (light energy)

Fig. 18.1  What is an LED and how can it produce light? called the N/P junction, and movement of both electrons
(a) An LED is basically composed of two materials, the and holes starts again, but with power applied the elec-
N-type or negative material and the P-type or positive trons move to a higher energy level from their ground or
material. The N-material contains negatively charged resting state. (e) As in b above, the N-electrons are
electrons which move as shown, and the P-material con- attracted to the P-holes, but in moving down through the
tains positively charged holes, which move in the opposite N/P junction they must return to their ground energy level,
direction. When the materials are apart and not connected and lose their extra stored energy in the form of a photon,
to any power source, movement continues, so both materi- the smallest packet of light energy. Unlike the situation in
als are conductors. (b) When the materials are sandwiched b, however, when power is applied this action continues
together, however, without any power applied to the elec- endlessly and no depletion layer is formed. The N- and
trodes attached to opposite ends, the negatively charged P-materials are ‘doped’ with other materials which deter-
electrons in the center of the chip are attracted to the mine the distance of the ‘fall’ between electrons and
holes, and form an area called the depletion layer as seen holes: the greater the distance the electrons have to fall,
in (c) and all movement ceases in both the N- and the higher is the energy level of the photons emitted.
P-materials: the chip is now an insulator. (d) Power is Photons with high energy levels have shorter wavelengths
applied to the electrodes, with the positive electrode or than those with lower energy levels, thus the wavelengths
anode at the origin of movement of the holes and the nega- of the emitted light are determined by the substrate mate-
tive electrode or cathode at the origin of movement of the rials and their doping. High quality N- and P-materials
electrons. Observing the polarity when connecting a and pure doping substances will give photons of very
direct current (DC) power source is extremely important. nearly the same wavelength, i.e., quasimonochromatic
Power flows through the junction between the materials, light
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 289

Table 18.1  Most common substrate combinations and

the colors they are capable of producing
Substrates Formula Colors produced
Aluminum (AlGaAs) Red, infrared
gallium
arsenide
Aluminum (AlGaP) Green
gallium
phosphide
Aluminum (AlGaInP) Green, yellow, orange,
gallium orange-red (all
indium high-intensity)
phosphide
Gallium (GaAsP) Yellow, orange,
arsenide orange-red, red
phosphide
Gallium (GaP) Green, yellow, red
phosphide
Gallium (GaN) Blue, green, pure green
nitride (emerald green): also
white (if it has an AlGaN Fig. 18.2  Anatomy of the older high-quality dome-type
Quantum Barrier, LED and the newer on board chip (OBC) type (inset box).
so-called ‘white light’ In the case of the dome type, the cathode is always shorter
LED) than the anode and there is a flat surface in the base of the
Indium (InGaN) Near ultraviolet, blue, LED by the cathode so polarity is clearly determined
gallium bluish-green when connecting to a DC power source or mounting on a
nitride printed circuit board (PCB). On top of the cathode post
and forming part of the negative electrode of the LED chip
is a parabolic reflector in which the chip itself is mounted
thus ensuring as much light as possible is directed for-
produce unwanted heat, and recycles them back wards, with a consistent angle of divergence, typically 60°
into the skin. This can significantly increase the steradian or less depending on the specifications of the
efficiency of an LED panel. The bodies of the lat- LED.  A fine wire connects the positive electrode of the
est generation of LEDs are designed to recycle chip to the anode post, thus completing the circuit. The
entire assembly is encapsulated in an optical quality clear
the photons the LEDs emit, thereby adding even plastic envelope, giving the final assembly its robust
more efficiency. As LED phototherapy uses low nature. In the OBC type, the chip comes premounted to
incident levels of power, even a small loss of that the PCB, but shares more or less the same anatomy as the
incident power could negatively affect the desired dome-type LED, with the chip mounted above the para-
bolic reflector. The OBC tye LEDs are much more com-
clinical result: higher efficiency of the LED pact than the dome type
panel, i.e. more light out for less electrical energy
in, is therefore the ideal.
collimating optics; and phase means that all of the
 hat Is the Difference Between LEDs
W photons march along together exactly equidistant
and Lasers or IPLs? from each other in time and in space. Laser diodes
The laser is a unique form of light energy, pos- do not have inherent collimation, but because they
sessing the three qualities of monochromaticity, are still true lasers, and therefore a so-called point
collimation and phase which make up the overall source, the light can be gathered and optically col-
property of ‘coherence’. Monochromaticity limated: the humble but ubiquitous laser pointer
means all the photons are of exactly the same works on this principle. Intense pulsed light is, on
wavelength or color; collimation means the built- the other hand, totally noncoherent, with a very
­in parallel quality of the beam superimposed by large range of polychromatic (multiwavelength)
the conditions of the laser resonator or by light from near infrared all the way down to blue;
290 R. G. Calderhead

and so can never be focused to a small point.

Laser energy can easily produce high photon
intensity per unit area, IPLs much less so, but pro-
vided LEDs are correctly arrayed, they are capa-
ble of almost laser-like incident intensities.
Figure  18.4 schematically illustrates the differ-
ences between lasers, IPLs and LEDs. In short,
LEDs for therapeutic applications must be qua-
simonochromatic, be capable of targeting wave-
length-specific cells or materials, have stable
output, and be able to deliver clinically useful
photon intensities.

 hy Use LEDs?
W
There are many excellent laser and intense
pulsed light (IPL) systems available to the der-
matologist. Why should LEDs be considered as
a viable alternative phototherapy source? If the
author had been asked this question before the
end of the 1990s, he would have been enjoying a
quiet chuckle. Up until Prof Harry Whelan and
his NASA colleagues in the Space Medicine
Laboratory developed the “NASA LED” in
1998, LEDs were cheap, bright and cheerful, but
not really suitable for clinical applications
because in addition to being highly divergent,
they had a waveband, rather than a wavelength
and therefore had extremely poor chromophore
selectivity. As discussed above, the NASA LED
offered quasichromaticity, i.e., the vast majority
of the photons were at the same wavelength, and
output powers some 5 orders of magnitude
Fig. 18.3  Close-up view of LEDs mounted on PCBs higher than the previous generation of LEDs.
from actual therapeutic systems, dome type in the upper
part of the figure and OBC type in the lower part. In both
This made LEDs for the first time a suitable pho-
types, Note the precise x-y spacing of the LEDs, and the totherapeutic light source (see Figs.  18.2 and
reflective backing into which they are mounted. The pur- 18.4 above). In addition to their output powers
pose of the reflective backing of the array is to capture and narrow-band output, the other reasons for
these photons and reflect them back into the skin, known
as ‘photon recycling’
using LEDs in clinical practice are efficiency
and price.
has no possibility of collimation with extreme The electricity-light conversion ratio of a
divergence; and has its vast variety of photons typical laser is very low, requiring hundreds or
totally out of phase. The new generation of LEDs, even thousands of watts in to give an output of
on the other hand, has an output plus or minus a a few watts. The same applies to IPL systems,
few nanometers of the rated wavelength, and so where the flashlamp has to be pumped with
these LEDs are classed as quasimonochromatic; enormous amounts of energy to provide poly-
some form of optical collimation can be imposed chromatic light, which may however be filtered
on the photons which are divergent but do have (cut-on or cut-off). Even when filtered, IPL
some directionality; however they are not in phase energy is ­ delivered over a waveband rather
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 291

a laser (e.g., HeNe)

b laser diode
10 a&b

Relative intensity
5

c IPL 0
10 c 400 700 1000
Wavelength (nm)
Relative intensity

0
400 700 1000
Wavelength (nm) 10
d
d
Relative intensity

LED

0
400 700 1000
Wavelength (nm)

Fig. 18.4  Comparison among the output characteristics pulse of broad-band polychromatic noncoherent light, so
of a laser, laser diode, intense pulsed light system and a the ‘magnifying glass’ would show a plethora of widely
new generation LED. (a) A laser emits all of its energy at divergent photons of many different wavelengths, but with
one precise wavelength, in a coherent beam, i.e., mono- the majority in the near infrared as seen from the spectro-
chromatic, collimated and with the photons all in phase gram. Because of the very broad waveband, the relative
both temporally and spatially. If a ‘special magnifying intensity at any given wavelength is low to very low. (d)
glass’ could view the beam, it would show the situation as The LED is somewhat similar to the laser diode, but the
seen in the figure. All of the energy is delivered at a pre- light is noncoherent, highly divergent and quasimono-
cise wavelength, as illustrated in the spectrogram, so the chromatic. The ‘magnifying glass’ shows plenty of pho-
relative intensity of the beam is extremely high. (b) A tons, mostly the same color (wavelength), with some
laser diode has all the characteristics of a laser, except that degree of directionality but without any of the phase and
the beam is divergent, without collimation. However, potential collimation associated with the laser diode. The
because it is a point source the beam can be collimated relative intensity is still very high, however, because the
with condensing optics. The magnified view of the beam vast majority of the photons are being delivered at the
shows a lower photon intensity than the laser, but the rela- nominal wavelength with a very narrow waveband of plus
tive intensity is still very high. (c) An IPL system emits a or minus a very few nanometers

than at a specific wavelength (cf. IPL output LEDs are much less expensive than even laser
with laser or LED output in Fig. 18.4). In the diodes. Depending on quality and wavelength,
case of LEDs, which are quasimonochromatic anywhere from 200 new-generation LEDs can
and therefore require no filtering, the conver- be purchased for the cost of a single laser
sion efficiency is very high so that very few diode.
watts of electrical current at a low voltage are The cost of laser and IPL systems is very high,
required to produce a clinically useful output. so a much cheaper LED-based system offers the
292 R. G. Calderhead

possibility to halt the ever-upward spiralling ‘set-it-and-forget-it’ microprocessor-­controlled

costs of health care for both the clinicians and technology, the clinician or their assistant simply
their patients. A further advantage is the solid sets the head up over the area to be treated fol-
state nature of LEDs. There are no filaments to be lowing the manufacturer’s recommendations,
heated up, and no flashlamps are required to pro- turns the system on, and he or she can then leave
duce light or to pump the laser medium: LEDs the patient for the requisite treatment time and
thus run much cooler than their extremely higher-­ attend to other patients or tasks. Moreover, in
powered cousins, so less is required in the way of most cases a suitably trained nurse or therapist
dedicated cooling systems, again helping to can carry out the treatment once the clinician has
reduce the cost. However, some cooling of LEDs prescribed it, because LED systems are much
is still required, especially when LEDs of the new more inherently safe for the patient than lasers or
OBC type are mounted in multiple arrays, IPLs. Figure 18.5 shows an example of one of the
because the driver circuits of the new type of new generation of well-designed, robust but ele-
LED generate heat, rather than the LEDs them- gant, mobile and very versatile LED photother-
selves, and the temperature of the PCBs increases: apy systems.
this is transferred to the OBC LEDs by conduc-
tion, and as the temperature of an LED
increases, its output will move away from the
rated wavelength. When wavelength cell- or
target-­ specificity is required, this could be a
major problem.
The solid state nature of LEDs also makes
them much more robust than either lasers or IPL
systems, so they tend to be able to take the some-
times not-so-gentle handling which is part of a
busy clinical practice without causing either out-
put power loss or alignment problems. LEDs can
be mounted in flat panel arrays, which may in
turn be joined together in a treatment head that
can be adjustable to fit the contour of the large
area of tissue being treated, whether it is the face,
an arm, the chest or back, or a leg. Compare this
potentially very large treatment area of some
hundreds of square centimeters with that of a
laser, usually a very few millimeters in diameter,
or that of an IPL treatment head, typically
1 cm × 3 cm, and the clinician-intensive nature of
the latter two is quickly evident when large areas
are to be treated such as the entire face. Multiple
shots are required, and the handpiece has to be
manually applied and controlled by the user. The Fig. 18.5  Example of a state-of-the-art FDA-cleared new
LED-based treatment head can be attached to an generation LED phototherapy system which offers a vari-
ety of wavelengths (830, 633 and 415  nm, alone or in
articulated arm to make individual adjustment dual-wavelength combinations) with a flexible put-and-­
even easier. stay hinged treatment array to match any body contour
Finally, if multiple wavelength-specific targets from flat (back or décolleté) to extremely curved (arm or
are to be treated, LED arrays with different wave- leg), and friction hinges in the arm allowing easy exten-
sion and positioning of the treatment head without the
lengths can be designed to be easily interchange- need for locking nuts. (HEALITE II, Lutronic Corporation,
able, controlled by the same base unit. With Goyang, South Korea, and Freemont, CA, USA)
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 293

Basics of Light-Tissue Interaction wound healing or pain relief. If the incident

power is too high, heat will be the end product as
with the surgical laser. If a too-low photon inten-
Box 18.2 sity is delivered, there will be very little or no
• Light-emitting diodes deliver ather- reaction. The trick in LED phototherapy is to
mal and atraumatic cellular deliver just the right amount of photon intensity
photoactivation to achieve the desired clinical effect but in an
• “All light is absorbed in the first mil- athermal and atraumatic manner.
limeter of tissue”—FALSE!
• LEDs are a viable and valuable pho-
totherapeutic tool Photothermal and Athermal
• LEDs are capable of interesting light-­ Reactions
tissue interactions, provided certain
criteria are met. The most important Despite their very different output powers, lasers,
criteria are: IPLs and LEDs all depend on the ‘L’ which is
–– Wavelength. found in all their names, standing for ‘light’. It
Determines both the target and the could be said that they are all different facets of
depth at which the target can be the same coin, but even in photosurgery, photo-
reached therapy plays a very important role. If we con-
Quasimonochromaticity is essential sider the typical beam pattern of a surgical CO2
Wavelengths should be applied sepa- laser in tissue, we see the range of temperature-­
rately and not combined at the dependent bioeffects as illustrated schematically
same time in Fig.  18.6, ranging from carbonization above
–– Irradiance (power density). 200 °C, vaporization above 100 °C, through coag-
Gives suitably high intensity at all ulation around 60–85  °C, all the way down to
levels of target cells or materials photobiomodulation, which occurs atraumatically
Ensures sufficient athermal energy when there is no appreciable rise in the tissue tem-
transfer to raise targets’ action perature at the very perimeter of the treated area.
potentials These effects occur virtually simultaneously as
–– Dosimetry. the light energy propagates into the target tissue
Provided the wavelength and power with photon intensity decreasing with depth, and
density are appropriate, correct can be divided as shown into varying degrees of
dosage obtains the optimum effect photosurgical destruction and reversible photo-
with the shortest irradiation time damage, and athermal, atraumatic photobiomodu-
–– Temporal beam profile. lation. The photothermal and athermal zones are
Continuous wave would appear to be also shown in a typical CO2 laser specimen stained
more efficient for most cell types with hematoxylin and eosin (Fig. 18.6).
in  vivo, compared with ‘pulsed’ Photophysics tells us that each photon is a
(frequency modulated) light weightless packet of pure energy, with the energy
• Usually, cells should be targeted with measurable in electron volts (eV). Photobiology
only one LED wavelength at a time tells us that the photobiomodulation zone com-
• “Watts a joule”—the parameters prises cells which have absorbed the incident
must be appropriate photons, directly or indirectly transferred the
photon energy to the cells’ own energy stores in
an athermal and atraumatic manner, and have
The main purpose of using phototherapy is to become photoactivated. Photoactivated cells are
achieve some kind of clinical effect in the target associated with three reactions, one, two or all
tissue through the use of light energy, such as three of which may occur in photoactivated cells:
294 R. G. Calderhead

Phototherapy Carbonization & Burn-off

(>200°C)
TARGET TISSUE
Vaporization (>100°C)

Laser surgery
SR
N
al
rm
he
Coagulation (>60°C)

ot
ot
Ph

Protein Degradation (>55°C)

Protein Denaturation (>40°C)

ATHERMAL CELLULAR
PHOTOBIOACTIVATION

Fig. 18.6  Range of photothermal and athermal photobio- shows normal tissue architecture, even though some pho-
reactions in tissue following a typical surgical laser tons will have reached this layer and transferred their
impact, e.g., a CO2 laser. A hematoxylin and eosin stained energy to the cells in an athermal and atraumatic manner.
specimen of actual CO2 laser treated skin is also included Laser surgery involves all levels of bioreactions.
to show the typical histopathological changes for each of Photothermal nonablative skin rejuvenation (NSR) deliv-
the bioreactions: the epidermis has been totally vaporized ers controlled coagulative photothermal damage, with all
leaving a layer of carbon char above the coagulated der- the subsequent layers, whereas phototherapy only delivers
mis. The outermost layer, the photobioactivation layer, athermal and atraumatic photobioactivation

• if the cells are damaged or compromised, they nevi: all that was available then to him was a 1 ms
will repair themselves, or be repaired pulsed ruby laser and a C/W argon laser. In
• if the cells have a function, they will perform Fig.  18.7a can be seen a case of hemangioma
it more efficiently simplex (port wine stain) that had been somewhat
• if more of the cells are required for either of unsuccessfully treated previously with needle
the above, the cells will proliferate, or more electrolysis: the abnormal color was not removed,
will be recruited into the area through and the site of each needle application was
photochemotaxis marked with a small raised white scar. The argon
laser was used in Ohshiro’s zebra technique,
Laser surgery usually creates all the whereby linear areas 2  mm wide were treated
photothermally-­mediated zones mentioned, but leaving a 2 mm area of untreated tissue between
the importance of the photoactivation zone them [8]. As can be seen in Fig. 18.7b, not only
­cannot be stressed enough. It is the existence of did the argon laser treatment remove the port
this zone which sets laser surgery apart from any wine stain color, it also treated the abnormal con-
other thermally-dependent treatment, such as figuration in the form of the pinpoint scarring left
electrosurgery, or even athermal incision with the by the previous electrolysis treatment. Four to
conventional scalpel, and it is the photoactivated 6  weeks later, when the treated areas had com-
cells in this zone which provided the results that pletely healed, the untreated areas were then irra-
interested the early adopters of the surgical laser diated to complete the treatment. This was the
compared with the cold scalpel or electrosurgery, power of the “L” component of laser, the light,
namely equally good healing but with less inflam- aided by the photobioactivation zone, referred to
mation and much less postoperative pain. by Ohshiro as “simultaneous LLLT” [8].
Figure 18.7 demonstrates this in action, courtesy IPL systems, and the so-called nonablative
of Toshio Ohshiro MD PhD, a pioneer of laser lasers, produce areas of deliberate but controlled
surgery in Japan and worldwide. In the late coagulative damage beneath a cooled and intact
1970s, Ohshiro started using lasers in the treat- epidermis (Fig. 18.8), however they also produce
ment of vascular and melanin group anomaly the zone of simultaneous LLLT to help achieve
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 295

a b

Fig. 18.7  Illustration of how the “L” in laser, “light”, lesion was treated with Ohshiro’s zebra method (large
made it different from other surgical systems. (a) This open arrow shows the treated linear area). Normal skin
example of a hemangioma simplex lesion (port-wine color can be seen. In areas where hypertrophy existed,
stain) had been treated previously with needle electroly- these too have been treated successfully with heat plus
sis. The abnormal color of the lesion has not been light. The area between the black arrows shows an
removed, and small white hypertrophic scars can be seen untreated zone where the hypertrophic spots are clearly
where the needle was inserted. Heat only (electrothermal seen. (Courtesy of Prof Toshio Ohshiro MD PhD—Ref.
damage) was not successful in treating this lesion. (b) The [8], used with permission)

the desired effect of neocollagenesis and neoelas-or photophysical reaction. However, any such
tinogenesis through the wound healing process in reaction is not an automatic consequence of
the dermal extracellular matrix (ECM). LED-­ energy absorption. It may be converted swiftly
based phototherapy systems, on the other hand, into heat, as in the surgical and non-ablative
athermally and atraumatically induce only cellu- lasers or IPL systems, or re-emitted at a different
wavelength (fluorescence). The prime arbitrator
lar photobioactivation, but are still capable of ini-
tiating the wound healing process almost as of this ‘no absorption-no reaction’ precept is not
the output power of the incident light, but the
efficiently as IPLs and nonablative lasers, as will
be shown in detail in a later section. wavelength of the photons making up the beam,
and this comprises two important considerations:
wavelength specificity of the target, or the target
Wavelength and Its Importance chromophore; and the depth of the target. Based
on these two considerations, the wavelength must
The first law of photobiology, the Grotthuss-­ not only be appropriate for the chosen chromo-
Draper Law, states that only energy which is phore, but it must also penetrate deeply enough to
absorbed in a target can produce a photochemical reach enough of the target chromophores with a
296 R. G. Calderhead

Fig. 18.9  Photospectrogram of a human hand in vivo. The

generator, delivering uniform ‘white light’ at the waveband
shown on the x-axis, was placed above the hand and the sen-
sor below the hand. Optical density on the y-axis is shown in
logarithmic units. Penetration is shown on the right-hand
axis. The further down the curve reaches, the better the pen-
etration at that wavelength into living human tissue.
(Adapted from Smith KC: The Science of Photobiology.
1977. Plenum Press, New York, USA—Ref. [9])

millimeter of tissue’. Anyone who has shone a

Fig. 18.8  Theory behind photothermal nonablative skin
rejuvenation: the laser energy passes through the cooled
red laser pointer through their finger, transillumi-
epidermis without harming it, and delivers a controlled area nating the entire fingertip and completely visible
of coagulation in the typically elastotic dermis associated on the other side, has already disproved that
with photoaged skin. However, the photons do not stop statement. A totally different finding is seen with
there, and there are zones of protein denaturation and, most
importantly for the good result, athermal and atraumatic
green or yellow laser pointers, however, because
photoactivation around and beyond the controlled thermal of their poor scattering and penetration character-
damage. The photoactivated cells in the last of these three istics. Figure 18.9 is based on a transmission pho-
zones will assist with the wound healing process tospectrogram of a human hand captured in vivo
over the waveband from 500  nm (visible blue/
high enough photon density to induce the desired green) to 1100 nm in the near infrared [9]. The
reaction. In theory, a single photon can activate a photospectrometer generator was positioned
cell, but in actual practice multiple photon above the hand, delivering a ‘flat spectrum’ of
absorption is required to achieve the desired ‘white light’, and the recorder placed beneath it.
degree of reaction. The wavelength is shown along the x-axis, and
Phototherapy is athermal and atraumatic, the calculated optical density (OD) is on the
hence achieving selective photothermolysis is of y-axis, from lower ODs to higher. The higher the
no concern as it would be for surgical or other OD, the greater is the absorption of incident light,
photothermal applications. The penetration of and hence the lower the transmission, or penetra-
light into living tissue is, however, extremely tion depth into the tissue. It must also be remem-
important in phototherapy, and very frequently bered that the OD is not an arithmetic but a
displays characteristics which are often in dis- logarithmic progression, so that the difference
cord with results produced by mathematical between an OD of 3 and one of 8 is not simply 5,
models, a point frequently totally ignored by but 5 orders of magnitude, i.e. a factor of 10,000.
some researchers. A favorite, but photobiologi- From 500 to 595  nm (blue-green to yellow),
cally false, axiom beloved of phototherapy oppo- the OD was from 8.2 to approximately 7.6,
nents, is that ‘all light is absorbed within the first respectively, resulting in poor penetration. At
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 297

633 nm, the approximate wavelength of the HeNe around 610  nm visible orange-red and 860  nm
laser, the photobiological efficacy of which is near-infrared [12]. LED systems delivering
well recorded, the OD was approximately 4.5. In 633  nm or thereabout in the visible red and
other words, red light at 633 nm penetrated living 830 nm in the near infrared, and at high enough
human tissue by 3 orders of magnitude better photon densities were therefore developed, and
than yellow at 595 nm, because of the pigment-­ have been reported as having significant effects
specific absorption characteristics of the 2 on their target tissues at a good range of depths
­wavelengths. Visible yellow at 595 nm is at the well into the mid and deep reticular dermis, and
peak of the oxyhaemoglobin absorption curve, even into the muscle and bone. The usefulness of
and is also much more highly absorbed in epider- visible red and near IR LED phototherapy has
mal melanin than 633 nm, which is why the yel- already been reported in a wide range of medical
low light in the spectrogram did not transmit at specialties, including dermatology. Yellow light
all well into the tissue due to the competing chro- at 590–595  nm has also attracted attention, but
mophores of epidermal melanin and superficial the penetration properties of yellow light must be
dermal blood. Accordingly, cellular and other tar- carefully considered, as illustrated in vivo in
gets in the mid to deep reticular dermis are inac- Fig. 18.9. From the standpoint of photobiological
cessible to yellow light with sufficient photon theory, yellow light has very good potential spec-
intensities to achieve multiple photon absorption ificity in a number of subcellular targets such as
in the target cells. On the other hand, epidermal cytochrome-c oxidase, and superficial vascular-­
cellular targets such as the mother keratinocytes related targets, however its very poor penetration
in the stratum basale, or basal layer, are definitely into the intermediate and deeper dermis, where
accessible to 595 nm yellow light. cellular targets such as fibroblasts lie, limits the
The deepest penetration in this experiment practical efficacy of yellow light for these deeper
was achieved at 820–840 nm in the near infrared. targets. On the other hand, there are interesting
At this waveband, pigment is not a primary chro- targets in and around the basal layer of the epi-
mophore with the cell membrane, and flavonoids dermis which do react well to visible yellow
in it, as the major chromophore, and this 820– light, such as the mother keratinocytes, melano-
830 nm waveband coincides with the bottom of cytes and the epidermal Merkel cells, all of which
the water absorption curve. The most successful are rich in mitochondria and therefore contain
of the laser diode systems used in laser therapy as cytochrome-c oxidase, a major chromophore for
distinct to laser surgery, delivered a wavelength visible yellow light, and the source of intra- and
of 830  nm for this very reason [10], and was intercellular adenosine triphosphate (ATP) and
shown to penetrate living hands, and even bone, enhanced levels of cell-cell signaling compounds
very successfully [11]. After around 1000  nm, such as Ca2+ ions.
water absorption once again starts to play a sig- Blue light at around 415 nm has very interest-
nificant role, and in the curve in Fig. 18.9 the OD ing properties regarding the eradication of the
was seen to increase thereafter. In general, shorter bacterium Propionibacterium acnes (P. acnes)
visible wavelengths penetrate less than longer through endogenous photodynamic therapy
visible and near IR wavelengths, up to a given (PDT) although the photoreaction is different
waveband, depending on the absorbing from photoactivation and will be discussed later
chromophore. in the chapter. LED energy at 1072 nm has pro-
Following these findings, it made a great deal vided a convenient and easy-to-use LED irradia-
of sense to source LEDs for LED-based photo- tor for effective treatment of herpes simplex
therapy systems at wavelengths already tried, labialis in the home [13]. LED systems with
tested and proven in the more than three decades many other wavelengths have been produced,
of laser therapy application and research. gaily flashing or not, but basically these other
Furthermore, Karu has clearly shown that there is wavelengths have very little or no published work
a “tissue window” for phototherapy between to back up the claims of the manufacturers, and a
298 R. G. Calderhead

careful consideration of the wavelength/penetra- primary photoaction i.e., photochemical or pho-

tion ratio will rule out many of the shorter visible tophysical. Wavelength is thus probably the sin-
light wavelengths. “Any old LED will not do” is gle most important consideration in LED
an axiom which must be borne in mind by the phototherapy, because without absorption, there
dermatologist wishing to incorporate LED photo- can be no reaction.
therapy into his or her practice.
Finally, the different wavebands, visible light
and invisible infrared light, have different pri- Irradiance (Photon Intensity)
mary mechanisms even though the therapeutic
endpoint may be similar. Absorption of visible Light energy travels in the form of photons. It is
light photons at appropriate levels induces a pho- obvious that the more photons which are incident
tochemical reaction, and a primary photochemi- per unit area of tissue, the greater will be the
cal cascade occurs within the cell induced mainly bioeffect as the energy is transferred to the target
by cytochrome-c oxidase, the end enzyme of cells and the tissues. This incident photon inten-
respiratory chain of the mitochondria which, as sity is called the power density, or irradiance, of a
mentioned above, are the adenosine triphosphate beam of light. The power density (PD) is an
(ATP)-producing power-houses of the cell [14]. extremely important factor in laser surgery and
ATP is not just required to fuel cells, but the medicine, but taking second place to wavelength,
energy of the entire organism is based on ade- and is calculated using the following formula:
quate levels of ATP. Infrared photons, unlike vis-
OP
ible light, are primarily involved in photophysical PD =
TA
(W / cm 2)
reactions which occur mostly in the cellular
membrane, changing the rotational and vibra- where OP is the output power incident on the tar-
tional characteristics of the membrane molecules. get in watts (W) and TA is the irradiated target
Through subsequent activation of the various area in square centimeters (cm ). PD is usually
2

membrane-located transport mechanisms, such expressed in watts per square centimeter (W/cm )
2

as Na+/K+-ATPase (better known as the Na+/K+ or milliwatts (mW)/cm . It is the power density of
2

pump) and Ca+-ATPase (Ca+ pump) the cell per- a beam that will determine more than anything
meability is altered allowing in- and excellulation else (apart from wavelength) the magnitude of
of compounds. The chemical and osmotic bal- the bioeffect in the target tissue. Consider
ance in the cytosol are swiftly altered in turn Table 18.2, where a laser with a constant incident
increasing the energy requirements of the cell output power of 2 W targets tissue with a range of
and energy in the form of ATP is demanded from spot sizes from 100 μm to 1 cm. Simply changing
the mitochondria. This finally results in the the spot size, and thus the power density, can
induction of a secondary chemical ATP-­ have dramatically different effects on the target
producing cascade which gives more or less the tissue. Because the power density is worked out
same endpoint as the visible light photons, per unit area, calculated by the formula πr ,
2

namely cellular activation or proliferation [15]. where π is the constant pi, 3.142, and r is the
These photoreactions are illustrated schemati- radius (half the diameter) of the irradiated area,
cally in Fig. 18.10. we have to remember that there is an inverse
To sum up, the wavelength of a therapeutic square ratio between spot size and power density
source therefore has a double importance, namely for a constant output power. Doubling the spot
to ensure absorption of the incident photons by size will not cut the power density by one-half,
the target chromophores, and to be able to do so but by one quarter: increasing the spot size by a
at the depths at which these chromophores exist. factor of 10 will cut the power density by one-­
The waveband in which the wavelength of the hundredth, and vice-versa.
incident photons is located determines not only In LED phototherapy, it is therefore necessary
which part of the cell is the target, but also the to achieve a high enough incident photon intensity
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 299

BASIC REACTION
SIGNAL TRANSDUCTION
PHOTORECEPTION PHOTORESPONSE
AND AMPLIFICATION
a b
Visible red light Invisible near infrared light
Cell
membrane
1

3 Cytoplasm
5
2 2
1 4
4 6
3

5 7
Mitochondrion Nucleus

Same end result

Cell proliferation enhanced Cell function upregulated

Repair of injured/compromised cell

Fig. 18.10  Schematic depicting photoreception (absorp- ions and H+ dramatically increase. (4) This in turn upregu-
tion) of light in a cell, and the subsequent wavelength-­ lates intracellular signaling including mRNA production
specific response. The basic reaction as defined by Karu is from ribosomes on the rough endoplasmic reticulum, and
absorption, which is followed by signal transduction and finally (5) nuclear activity is also up regulated. (b) In the
amplification within the cytosol, and leads to the photore- case of near infrared light, the primary mechanism of
sponse involving the nucleus and membrane transport absorption is completely different (1) resulting in a photo-
mechanisms. (a) (1) Visible red light induces a primary physical reaction which changes the energy levels of the
photochemical cascade initiated in the mitochondrion, the cell membrane, in which near IR energy is absorbed. This
energy factory and cell power house, which results in kick-starts the Na2+K2+ and Ca2+K2+ pumps so that cyto-
increased levels of nicotinamide adenine dinucleotide plasmic levels of Ca2+ and H+ dramatically increase (2)
(NAD) extremely important in a wide range of redox and (4), prompting the mitochondrion to manufacture
(reduction-oxidation) reactions, one of the results of more ATP to fuel the increased energy requirement (3),
which is the generation of adenosine triphosphate (ATP) thereby raising cytoplasmic levels of ATP (4) which again
which is the ‘gasoline’ for the cell. (2) The increased lev- impacts on the transport mechanisms of the membrane not
els of cytoplasmic ATP fuel the membrane transport affected by the near IR light. Despite the totally different
pumps, the Na2+K2+ and Ca2+K2+ pumps (3) which induce pathways, the end result is however the same as in the case
extra- and intracellulation of messenger Ca2+ ions and pro- of visible light, namely further cyclic increased energy
tons (H+) which are elementary particles carrying a posi- levels in the cytoplasm (6) and upregulation of nuclear
tive electric charge, the flow of which is used to generate activity (6)
energy from ATP via ATPase. Cytoplasmic levels of Ca2+

to achieve the desired degree of multiple absorp- This was adapted by Ohshiro and Calderhead in
tion in the target cells, but not so high as to cause 1988 into the Arndt-Schultz curve to explain the
any degree of photothermally-mediated changes efficacy of LLLT (Fig. 18.11) [10, 16] from which
in the tissue architecture, in other words ideal it is clear that photon intensity should not be too
LED phototherapy should achieve athermal and weak (no reaction) or too strong (retardation or
atraumatic photoactivation of the target cells. The cell death) but must be adjusted to achieve maxi-
Arndt-Schultz law, first appearing in the mid- mum optimum photobiomodulation of the target
nineteenth century, states that weak stimuli excite cells or materials.
biologic behavior, stronger ones favor it, powerful A final note on intensity: one single LED,
ones arrest it and very powerful ones retard it. even one of the new generation of LEDs, when
300 R. G. Calderhead

Table 18.2  Illustration of the importance of altering the ever, as in the examples shown in Fig. 18.3, and
power density to achieve a complete range of bioeffects precisely positioned according to the angle of
from incision to photobiomodulation with a constant inci-
dent output power
divergence of the beam, the interaction where
the beams impact with each other gives an
Incident Spot size Power
power (∅, units density extremely intense photon density due to the phe-
(W) as given) (W/cm2) Bioeffect nomenon of photon interference. When this is
2 100 μm 25,000 Incision; excision combined with the excellent physical forward-,
2 200 μm 6250 Vaporization; deep lateral- and backward scattering characteristics
coagulation of red and near IR light, the result is that the
2 1 mm 250 Mild coagulation; highest photon intensity is beneath the surface of
protein denaturation
the skin, exactly where it should be to achieve
2 1 cm 2.5 Athermal, atraumatic
photobiomodulation the optimum therapeutic effect (Fig. 18.12b). If
the distance between the LEDs is too great, how-
ever, then the intensity will drop off dramatically
because of the lack of interaction between the
individual LED beams (Fig.  18.12c).
Furthermore, some LED system manufacturers
combine LEDs of different wavelengths, e.g.,
red and yellow, and then claim they are deliver-
ing ‘orange’ light (Fig.  18.12d) … incorrect!
The skin cells will not ‘see’ orange from a mix-
ture of red and yellow light as our eyes do, but
will react separately to the incident red photons
and yellow photons. Karu has pointed out that
there are many pairs of wavelengths which actu-
ally inhibit cellular activity when used together,
yet enhance activity when applied separately
[12]. Light energy represents information for
cells, and then they act on that information.
Imagine a cell receives receiving conflicting
Fig. 18.11 Ohshiro and Calderhead’s Arndt-Schultz
curve (1988) [10], based on the Arnd-Schultz law. From
information from two different wavelengths: one
stimulus strength A to B, no reaction occurs: the stimulus tells the cell to “turn right” and the other to “turn
is too weak. From B to C there is a sharp rise in bioeffect, left”. At best the cell will be confused and do
plateauing at C–D. This curve is based mostly on incident nothing. At worst, it will shut down partially or
power density (photon intensity), but the ideal combina-
tion of intensity and dose in phototherapy must therefore
completely. Unless there is a specific reason
be attained to reach the effect shown by the dark green based on photobiological knowledge, one wave-
shaded area, preferably as much as possible at the C–D length at a time should be the order of the day in
effect plateau. From point D onwards there is a sharp drop LED phototherapy.
in the effect, although it is still higher than normal until
point E. Strength B–E corresponds to the zone of athermal
As noted above, LEDs emit energy in a diver-
photobioactivation in Fig. 18.5 above. At stimulus strength gent manner thereby causing an exponential
E–F the bioeffect is gradually retarded, corresponding to drop in the available photon intensity the further
the protein denaturation/degradation zones in Fig.  18.5, the target is from the LED array. It is possible
and target death results from strength F–G corresponding
to the coagulation and vaporization zones in Fig. 18.5
using optics to maximize the output of an LED
array, and one manufacturer of an FDA-cleared
used on its own, will not achieve anywhere near LED system has overcome this by adding what
a clinically useful photon intensity in the target they term Optical Lens Array Technology, or
tissue (Fig.  18.12a). When multiple LEDs are OLAT™. An optically clear sheet embodying
mounted close together in a planar array, how- precisely-­placed mini-collimating lenses is fixed
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 301

a b c d

Fig. 18.12  Arrays of precisely spaced multiple LEDs are nomenon of photon interference. When this is coupled
required to achieve clinically useful photon densities in with the very strong forward and backward scattering
tissue. This illustration is modeled on the actual LED characteristics of red light, which is even stronger for near
array seen in Fig. 18.3 above, and is to scale. The distance IR energy, a zone of extremely high photon density,
from LEDs to the tissue is approximately 2.5 cm. (a) A greater even than the intensity at the LEDs themselves, is
single LED has insufficient photon intensity to achieve created under the surface of the target tissue. (c) If LEDs
any recordable clinical effect. (b) On the other hand, when are spaced too far apart, the photon intensity is sacrificed
LEDs with similar output characteristics are mounted a and is not clinically useful. (d) This is the case in treat-
precise distance apart to make use of the 60° divergence, ment heads with individual LEDs of different wave-
the beams will interact where they cross each other to pro- lengths, e.g., red and yellow, claimed as delivering
duce an extremely high photon intensity due to the phe- “orange” light … but not so!

a b c

Fig. 18.13  One example of how a manufacturer has era: note the loss of energy delivered to the target through
enhanced the beam intensity without increasing the output lateral scattering. (c) The same LED array at the same
power of the LEDs. (a) An optically clear sheet incorpo- LED irradiance but fitted with the optical lens array which
rating precisely placed semi-collimating lenses (optical can be seen on top of the LED array. A much higher pho-
lens array technology, OLAT™) is placed under the same ton intensity is concentrated and delivered to the target
schematic LED array as seen in Fig. 18.12b above. The with significantly less energy lost to lateral scatter.
divergence of each LED is decreased, thereby increasing (Photography courtesy of Medicoscientific Affairs,
the photon intensity within each beam. (b) A near-IR Lutronic Corporation, Goyang, South Korea: LED array
array (830 nm, 100 mW/cm2) is captured with an IR cam- from HEALITE II 830 nm LED phototherapy system)

in front of the LED arrays, each lens being in nomenon, but the photon intensity is now 30%
front of an LED in the array. The output from higher at any given plane in the LED beam pat-
each LED is therefore partially collimated to tern. Therefore, for the same irradiance, the pho-
reduce the angle of divergence by some 30%. ton intensity at the target has been increased to
This means that there are still intersecting beams allow for a more efficient irradiation of the target
to make use of the photon interference phe- tissue (Fig. 18.13).
302 R. G. Calderhead

Dosimetry greatest amount of energy in the table, 2000  J,

produced a phototherapeutic effect, whereas the
Up to this point in the section, the time for which smallest, 8 mJ (0.008 J), produced a photosurgi-
light of a given irradiance or power density is cal effect [17]. In an experiment performed
incident on a target has not been mentioned. 20  years ago by the author of this chapter, the
When treatment time comes into the therapeutic exposed rat knee joint, both encapsulated and
equation it quantifies the dose of light delivered. unencapsulated, was irradiated with a GaAlAs
When 1 W of power is incident on target tissue diode laser giving an incident power density of
for 1  s, the energy delivered is 1 joule (J). The 1  W/cm2. A range of doses was applied from
joule in itself is a particularly useless therapeutic 20 J/cm2 (20 s exposure) up to 1800 J/cm2 (30 min
parameter since it expresses only power over exposure). Tissue was examined macroscopically
time, and does not take into account the unit area and microscopically immediately after irradia-
of tissue being treated. The most important tion for any signs of damage: none was found.
parameter for the therapeutic dose in LED photo- The wounds were closed and followed up at dif-
therapy is the energy density (ED). ED is calcu- ferent time points over 2 weeks. No differences
lated as follows: were seen in coded specimens from each group at
all time points regarding morphological changes
OP ´ t
ED =
TA
(
J / cm 2 ) compared with the unirradiated control speci-
mens [18]. In pharmaceutical science, the medi-
where OP is the output power incident on the tar- cine must be correct before adjusting the dosage.
get in watts, t is the time in seconds and TA is the In phototherapy, the power density is analogous
irradiated area in cm2. ED is expressed in joules/ with the medicine, and the energy density is the
cm2 (J/cm2). However, too much is often made of dose. If the medicine is incorrect, i.e., a photon
the dose as the most important parameter in pho- intensity which is too low (no effect) or too high
totherapy, and criticism has been leveled at an (photothermal damage), no amount of playing
LED system that ‘the dose is too high’. In fact, as around with the dose will achieve the optimum
stated in the previous subsection, it is the power result [17].
density, rather than the energy density, which
more than anything else determines the bioreac-
tion, and this is illustrated in Table 18.3 where a Temporal Profile of the Beam
constant dose of approximately 25  J/cm2 can
achieve the entire gamut of bioeffects from pure The temporal profile of a beam of light energy sim-
athermal photobiomodulation to severe photode- ply means the output mode in which the light is
struction. The total uselessness of joules as a delivered to the target. There are two modes, con-
meaningful parameter is also illustrated: the tinuous wave (CW) and pulsed, with Q-switching

Table 18.3  This illustrates a variety of bioeffects (Δα) achieved with the same approximate energy density, or dose, of
25 J/cm2
P S∅ [a] (cm2) PD (W/cm2) t e ED (J/cm2) Δα
100 W 10.0 cm 78.6 1.3 20 s 2000 J 25 −
50 W 3.5 mm 0.1 500 100 ms 5 J 25 +
10 W 1.0 mm 0.0008 1250 20 ms 0.2 J 25 ++
1 W 200 μm 0.0003 3180 8 ms 8 mJ 25 +++
75 mW 3.0 mm 0.07 1.1 23 s 1.725 J 25 −
As can be seen from the table, the power density (PD) is the most important determinant of the bioeffect and the energy
density given alone is therefore not a real determinant of effect
Key to table: P: Incident power (units as shown), S∅: spot size diameter (units as shown), [a]: irradiated area, PD: power
densityt: exposure time (units as shown), E: energy (units as shown), ED: energy densityΔα: graded bioeffects (+++,
severe photodestruction; ++, medium photodestruction; +, mild and/or reversible photodestruction; −, bioactivation)
 18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 303

of a pulsed beam technology dramatically shorten- wavelength decreases, the frequency increases.
ing the pulse width and increasing the peak power Increased frequency is also positively associated
of pulsed beams. In CW, as the name suggests, with an increase in energy of the individual photons,
when the light source is activated the power reaches expressed as electron volts (ev), and for the previous
its maximum level, from mW up to 100 W or so, three wavelengths the respective photon energies
and stays there till the system is switched off are approximately 1.49, 1.96 and 2.99 ev. Photon
(Fig.  18.14a, left panel). An alternative to CW is energy determines the type of interaction between
when the beam is ‘gated’ to produce a train of the incident light and skin cells. For 830  nm, as
square waves: this is often incorrectly referred to as explained already, photophysical rotational and
‘pulsed’ light (Fig. 18.14a, right panel). Gating can vibrational changes occur in the electrons making
be accomplished by a mechanical shutter, or be up the cell membrane, whereas for visible light
achieved by simply switching the light source on there is a direct induction of an intracellular photo-
and off. The correct name for this process is ‘fre- chemical cascade. At very high ev values, such as
quency modulation’, because an exogenous fre- those associated with ultrashort wavelengths,
quency (the on-off sequence) is being superimposed namely X- and γ-radiation, the very large photon
on the inherent frequency of the beam which is pre- energies result in molecular disassociation of cells
determined by the wavelength, each wavelength with sufficient exposure, in other words the cells are
having a fixed frequency. For example, near infra- literally blown apart or “ionized”. These ultrashort
red at 830 nm, visible red at 633 nm and visible blue wavelengths are classed as ionizing radiation and
at 415  nm have ‘built in’ frequencies of approxi- are inherently extremely harmful to living tissue
mately 3.6  ×  108, 4.7  ×  108, and 7.2  ×  108  MHz, with a strong carcinogenic potential. LED-LLLT is
respectively. From this it can be seen that as the very much nonionizing radiation.

a b
Peak power Interpulse interval (in ms)
15
15 GW

Frequency modulated C/W beam

C/W beam (50% duty cycle)
Output power (GW)

80
Output power (mW)

Average power (in W)

0 0
on off Pulse width (in ns)

Time (s) Time (units as shown)

Fig. 18.14  Temporal profile of a beam of light. There are a 50% duty cycle is illustrated. When a laser beam is truly
two basic profiles, continuous wave (CW) (a) or pulsed pulsed, a tremendously high peak power, measured as
(b). In CW (a, left panel), the system is switched on, the high as gigawatts (GW) is released in an ultrashort pulse
light very rapidly reaches its maximum, and remains there interval, measured in nanoseconds (ns) (b, left panel). If a
till the system is switched off. This CW beam can be train of these pulses is emitted with a comparatively long
‘gated’ mechanically or electrically, i.e. rapidly switched interpulse interval of milliseconds (ms) (b, right panel),
on and off (a, right panel), which is often incorrectly then the target tissue ‘sees’ only the average power of the
referred to a ‘pulsing’. The correct name is frequency beam, measured in watts. This is called quasi-CW, also
modulation. This gives a series of rectangular waveforms: known as ‘superpulsing’ the beam
304 R. G. Calderhead

In a true pulsed beam, from a high-powered or there are two main mechanisms of action: photody-
Q-switched laser, an extremely high peak power is namic therapy (PDT) and athermal and atraumatic
reached in a spike-like waveform, with a very short photobiomodulation, which are totally different
pulsewidth, 1  ms or less or in the ­ nanosecond mechanisms of action.
domain for the Q-switched systems. The peak
power may be in mega- or even gigawatts
(Fig.  18.14b, left panel). If a train of such true Photodynamic Therapy (PDT)
pulses is delivered with a set interpulse interval
often orders of magnitude longer than the pulse PDT can be exogenous or endogenous, the better
width, then the target tissue ‘sees’ only the average known form of which is exogenous.
power of the beam, usually at CW output levels.
This is also referred to as ‘superpulsing’, or more Exogenous PDT
correctly, quasi-CW (Fig. 18.14b, right panel). No Exogenous PDT is typically defined as: “The
current therapeutic LED system is capable of deliv- use of a chemical, given orally, intravenously or
ering a true pulsed beam, although LED-LLLT topically (directly to the skin), that can be acti-
devices are available in which the LEDs are turned vated or energized by light to destroy a target
on and off to give flashes of energy in a range of tissue in which the chemical or substance has
frequencies which are superimposed on the fre- preferentially located. This activation causes
quency inherent to the wavelength of the emitted the formation of new molecules and free radi-
light. This is frequency modulation, but is often cals such as reactive oxygen species (ROS)
incorrectly referred to as “pulsing” the LEDs. which may also form other chemicals that, in
turn, may destroy the targeted material to a
varying extent, such as through ROS-mediated
Box 18.3 apoptosis of the photosensitized cells or closure
• LEDs are ideal for cellular photobio- of blood vessels feeding the target tissue.” PDT
modulation (low level light therapy, is another arm of phototherapy, and whilst
LLLT), an atraumatic and athermal exogenous PDT is thus still an athermal reac-
direct exchange of energy raising the tion, it is not atraumatic as deliberate induction
target’s action potential of apoptotic cell death is the main goal. The
• LEDs can be successfully used in pho- first main application for photodynamic therapy
todynamic therapy (PDT) was in the treatment of certain cancers, with
–– Exogenous PDT with such photosensitizers as hematoporphyrin
5-­aminolevulinic acid (5-ALA) for derivatives activated with low incident levels of
treatment of non-melanoma skin laser light, particularly with visible red light
cancers and severe photodamage. such as from the HeNe laser due to this wave-
–– - Endogenous PDT in porphyrins length’s better penetration than the shorter vis-
endogenous to Propionibacterium ible wavelengths in living human tissue [19].
acnes, for example, in the treatment This activated an oxygen-dependent phototoxic
of acne. cytocidal action within the cells containing the
agent, and the free radical singlet oxygen (1O2),
a short-lived product from the reaction between
an excited sensitizer molecule and oxygen,
 ED Phototherapy: Mechanisms
L played a very important part in the induction of
of Action cell death (apoptosis) and destruction of the
microvasculature feeding the tumor.
When light energy is incident on a target, the reac- One of the first applications for LED photo-
tion in the target following absorption is known as therapy was in fact PDT for non-melanoma skin
the mechanism of action. In LED phototherapy, cancers (NMSCs), such as basal cell carcinomas
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 305

a b c d

Fig. 18.15 Nonselective en bloc infiltration of skin by Pp appropriate wavelength activates the porphyrins to pro-
IX and Cp III of 5-ALA origin illustrated schematically. duce powerful but very short-acting reactive oxygen spe-
(a) Target lesion in superficial dermis. (b) 5-ALA oint- cies, such as singlet oxygen, and the affected skin cells die
ment applied topically to epidermis. (c) As 5-ALA pene- through oxidative-stress mediated apoptosis (induced cel-
trates en bloc into skin cells, it is transformed into Cp III lular destruction)
and Pp IX, photosensitizing porphyrins. (d) Light at an

and superficial squamous cell carcinomas, or

severe sun damage such as actinic keratosis with
the use of another exogenously-applied com-
pound, 5-aminolevulinic acid or 5-ALA in any
of its forms. This application continues to the
present with good success and robust long-last-
ing results [20, 21]. The topically applied 5-ALA
penetrates into the dermis under an occlusive
wrap, and is converted as part of the
mitochondrial-­based heme cycle into copropor-
phyrin III (Cp III), a member of the powerful
porphyrin photosensitizing family. When the
maximum amount of Cp III has been converted,
Fig. 18.16  Action spectra for coproporphyrin III and
the remainder of the 5-ALA is converted into
protoporphyrin IX. Note the extremely high peak at
another porphyrin, protoporphyrin IX (Pp IX). 415 nm, and the minor peak at 633 nm, visible red, par-
These two porphyrins become the specific tar- ticularly in Pp IX, which suggests the red wavelength for
gets of the LED energy at specific wavelengths, deeper activation of 5-ALA-induced porphyrins in PDT
for cutaneous lesions
and, following photoactivation, nonselectively
damage all of the superficial dermal tissue in
which they exist, as illustrated schematically in successfully. Another series of much smaller
Fig. 18.15. peaks is however seen from the yellow to the red
When a photoreaction is desired such as in waveband (the Q-band), the latter occurring at
5-ALA PDT for any purpose, an action spectrum around 633 nm, which was used in the early days
has to be run to investigate the action potential of of hematoporphyrin derivative PDT for other
a range of wavelengths in the target compound. cancer types as a much better-penetrating wave-
Figure 18.16 shows the absorption spectra of Pp length, thus giving a much deeper zone of por-
IX and Cp III.  There is a very large peak at phyrin activation and hence a deeper zone and
415 nm in the visible blue Soret band, but as will greater volume of controlled photodamage. Red
be remembered from the previous section on 633 nm LED-activated 5-ALA has been success-
wavelength, blue light has very poor penetrative fully used for NMLCs and actinic keratoses,
capability into the dermis, and so it would not photorejuvenation and inflammatory acne vul-
cause deep enough damage to treat NMSCs garis. These will be discussed in more detail
306 R. G. Calderhead

in the appropriate subsection on LED photother- fulfills the definition of phototherapy, namely
apy in clinical practice. direct cellular activation in an athermal and
atraumatic manner which has been the umbrella
Endogenous PDT mechanism of action long-associated with LLLT
Exogenous PDT as discussed above depends on (low level light therapy) over its 30-year-plus
an external photosensitizer, such as 5-ALA.  In history, whether with laser or non-laser sources.
endogenous PDT, the photosensitizer, or photo- Atraumatic and athermal LLLT thus differs
sensitizing substances, can be found occurring from PDT which actively seeks to damage the
naturally within the target cells or tissue. The target cells and tissues, although still in an
exogenous application of 5-ALA induces the athermal manner. As has already been discussed
synthesis of the porphyrins Pp IX and CP III in section “Wavelength and Its Importance” on
nonselectively in the tissues of the epidermis wavelength, near infrared and visible light have
and dermis under the area of application as different absorption targets (cell membrane and
already explained above. However, in the case subcellular organelles, respectively) but the end
of acne vulgaris the inflammatory acne lesions result is the same, and the energy level of the
are associated with the presence of their caus- cell is raised by both near IR and visible light of
ative bacterium, Propionibacterium acnes (P. appropriate wavelengths through direct absorp-
acnes). It has been well demonstrated that both tion of the incoming photon energy, which is
Pp IX and Cp III are endogenous to active P. then transferred to the receptor cell with no loss
acnes, and the more active is the bacterium, the through heat or luminescence. The main mecha-
higher the porphyrin concentration [22–24]. nism of action is connected with increased ade-
Referring again to Fig. 18.16, maximum photo- nosine triphosphate (ATP) production and
activation of both Pp IX and Cp III occurs at increased Ca2+ ion intra- and intercellular sig-
around 415 nm. Light at that wavelength, with a naling [26].
high enough photon intensity, could therefore Under photoactivation, three things can hap-
achieve activation of the porphyrins within the pen to the energized cell: if it is compromised
P. acnes, thereby selectively destroying or at or in some way damaged, the cell will heal
least severely damaging the P. acnes through much faster; if the cell is designed to perform
oxidative stress-induced apoptosis [25], but some specific function, such as fibroblast col-
without harming the surrounding skin cells. lagenesis and elastinogenesis, then the LLLT-
Endogenous PDT could therefore be applied in treated cell will perform these functions better
the light-only treatment of inflammatory P. and faster; finally, if the cell is designed to rep-
acnes lesions without the need for any exoge- licate, then it will replicate faster [14]. These
nous 5-ALA.  This will be discussed in more may happen singly, or in combination, and form
detail in the appropriate part of the following the basis of the three decades of LLLT literature
section. in which some, but not all, of the mechanisms
under the umbrella of photobiomodulation have
already been at least partly elucidated as sum-
Photobiomodulation marized in Table 18.4 and at a molecular level
in Table 18.5. In addition, in the past decade in
Basically the majority of the information in sec- particular, a good number of solid clinical and
tions “Introduction” and “Basics of Light-Tissue basic science papers have corroborated the pre-
Interaction” has been based on the concept of vious basic and clinical findings for LED pho-
photobiomodulation, also known as photoacti- totherapy, and some exciting new science on
vation therapy, and this approach completely LED-LLLT has been appearing in the last
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 307

Table 18.4  Summary of the major mechanisms associated with photobioactivation and LLLT
Mild thermal Biochemical (primary for visible
(<40 °C) light) Bioelectric Bioenergetic
↑ Nerve (Mitochondrial events) ↑ Electromotive action on ↑ Rotational and
conduction ↑ ATP production membrane bound ion transport vibrational changes to
↑ Release of nitric oxide (NO) mechanisms membrane molecule
↑ Very low levels of reactive oxygen electrons
species (ROS) (Primary for near-IR)
↑ Capillary ↑ Fibroblast ↑ Intracellular extra-cellular ion ↑ Stimulation of
dilatation proliferation → Collagen and elastin gradient changes acupuncture meridian
synthesis points
↑ Mast cell degranulation: cytokine, ↑ Depolarization of synaptic ↑ Increased
chemokine and trophic factor release cleft → closure of synaptic biophotonic activity
gate—pain control
↑ Macrophage activity (chemotaxis ↑ Activation of the dorsal horn
and internalization) → release of gate control mechanism → pain
FGF transmission slowed, pain control
increased
↑ Keratinocyte activity → cytokine
release in epidermis and dermis
↑ Opiate and nonopiate pain control
(endorphins, dynorphins and
enkephalins)
↑ RNA/DNA synthesis
↑ Enzyme production
↑ Superoxide dismutase (SOD)
production (mast cells)

Table 18.5  Molecular level activation by LLLT with appropriate LEDs (based on data from Gao X, Xing D. Molecular
mechanisms of cell proliferation induced by low power laser irradiation. J Biomedical Science. 2009 16:4 http://www.
ncbi.nlm.nih.gov/pmc/articles/PMC2644974/)
Classification Molecules LLLT-associated biological effects
Growth factors BNF, GDNF, FGF, bFGF, IGF-1, KGF, PDGF, Proliferation
TGF-β, VEGF Differentiation
Bone nodule formation
Interleukins IL-1α IL-2, IL-4,IL-6, IL-8 Proliferation
Migration
Immunological activation
Inflammatory PGE2, COX2, IL1β, TNF-α Acceleration/inhibition of inflammation
cytokines
Small molecules ATP, cGMP, ROS, CA2+, NO, H+ Normalization of cell function
Pain relief
Wound healing
Mediation of cellular activities
Migration
Angiogenesis

5 years. LED-LLLT can be used in combination exogenous or endogenous PDT in the treatment
with other conventional modalities to improve of inflammatory acne vulgaris. Once again, a
results and hasten healing time, and can also detailed discussion will be found in the follow-
offer a very interesting combination with either ing section.
308 R. G. Calderhead

clinical arena. However, a thorough understand-

Box 18.4 ings of the true capabilities, and indeed limita-
• LED-LLLT in the adjunctive combi- tions, of LED phototherapy in clinical practice is
nation approach is the key to clinical even more essential to go about amassing the
efficacy. required evidence-based medicine in the most
• LED-LLLT is not magic … it cannot efficient manner. A large number of LED-based
target everything as monotherapy. systems is commercially available now in the
• Based on the published peer-reviewed USA and world-wide, but a very, very small
literature, certain wavelengths can number has actually made it into the peer-­
accomplish different things in effec- reviewed literature with the vast majority of man-
tive LED-LLLT. ufacturers content to ride on the coat-tails of the
–– 633 nm has proved effective in 5-ALA companies who have done the actual work, both
PDT for non-melanoma skin cancers, basic science and controlled clinical trials, even
and has found applications in hair res- though the science of these bandwagon-jumping
toration and baldness prevention. systems is sketchy at best, and nonexistent or
–– Blue 415 nm endogenous PDT com- even erroneous at worst. Of particular concern
bined with red 633 or 830 nm LED-­ are the ‘look-alikes’ of far-east origin, particu-
LLLT applied sequentially has been larly China, based on proven systems but with
reported as a very effective light-only inferior quality LEDs which give neither the
therapy for moderate to severe acne rated wavelength, nor sufficient and stable output
vulgaris. power. Some of these systems mimic the free-­
–– Combined near infrared 833 and standing planar LED-based units, and others are
633  nm red LED-LLLT, applied small hand-held devices with a mesmerizing
sequentially, was reported as very array of pretty flashing multicolored LEDs,
effective in skin rejuvenation and all designed for the home-use market. These groups
aspects of wound healing, but more of ‘toy’ systems are doing more harm than good
recent literature suggests that 830 nm to the reputation of LED phototherapy, although
on its own is the key wavelength in one hopes that they are not visiting actual harm
these indications. on patients with ‘no effect’ hopefully being the
–– Visible yellow light (590  nm, worst that they achieve. The negative impact on
595  nm) has shown efficacy in the ‘good’ LED phototherapy has been and remains,
treatment of superficial conditions, however, very large. Hopefully this entire chapter
e.g., in the treatment of rosacea. will go some way to redressing that. Another
–– Adjunctive LED phototherapy will important point for anyone considering purchas-
complement any and all existing con- ing an LED phototherapy system is that some
ventional modalities which alter in LED system manufacturers claim that their LEDs
any way the architecture of the skin are ‘NASA technology’. This is totally mislead-
to achieve the desired clinical result. ing. Although the new generation of LEDs is
based on the ‘NASA LED’, they are not actual
NASA technology, and some of the LEDs thus
described are still of the previous generation:
 ED Phototherapy in Clinical
L caveat emptor! The reader must always bear in
Practice mind that with LED phototherapy, ‘any old LED
will NOT do’.
Good basic science is of course extremely impor- The treatment categories dealt with in this
tant to understand how LED-LLLT can be applied very important section are based on published lit-
in current dermatological practice, to help bolster erature, not so-called ‘white papers’, and so the
up evidence-based medicine from the practical reader can obtain the original articles from online
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 309

indexing sources such as PubMed, and see in in the treatment of NMSCs [27]. The lamp was
detail what has, and what has not, been scientifi- the brainchild of Dr. Colin Whitehurst, and it was
cally proven and clinically corroborated. The he who saw the potential for using the new gen-
author would like to point out that any suggested eration of LEDs which became available in 2000
treatment protocols are inserted only for example following Whelan’s work with the NASA Space
and guidance, and must not be taken as concrete. Medicine program referenced earlier. The new
Manufacturer’s recommendations are also only generation of LEDs emits quasimonochromatic
recommendations, and the reader should look to light and does not require filtering, plus the LEDs
the published literature or presentations from can be mounted in planar arrays to irradiate large
leaders in the field at leading national and inter- areas at the same time, such as the entire face. Dr
national congresses for more detailed and accu- Whitehurst then helped found Photo Therapeutics,
rate treatment protocols. It is the hope of the who built the first large-array 633 nm LED ther-
author that the reader will see the true possibili- apy source for LED PDT for the treatment on
ties of LED phototherapy to enhance his or her NMSCs with input from Prof Whelan. Large-­
clinical practice, and will moreover choose an scale clinical trials in the UK and elsewhere in
LED system based on the criteria which will Europe gave excellent results [28].
appear throughout the section, rather than on The basic protocol which has evolved for
hype, pretty flashing colors and pseudo-science. 633  nm LED PDT for NMSCs is as follows:
If the actual systems referenced seem to be please note that differences in LED systems and
extremely limited, that is because they are the photosensitizer do not make this an absolute pro-
only ones which have been published in the lit- tocol, and the recommendations of the manufac-
erature, and the author offers no apologies for turer of both the LED system being used and the
this. He can only demonstrate and present to the photosensitizer being applied must always be
reader what has been published on systems which studied and carefully followed. Following thor-
have met or exceeded the required criteria by the ough cleaning of the treatment area, 5-ALA of
relevant regulatory bodies. the appropriate strength (usually 20%) is applied,
and occluded with sterile cling film for the rec-
ommended incubation period (up to several
 on-melanoma Skin Cancers (NMSCs)
N hours, depending on the lesion being treated). At
and Actinic Keratosis the end of incubation, the occlusive dressing is
removed and any excess 5-ALA wiped off.
NMSCs, including Bowen’s disease and basal Activation of the porphyrins induced in the target
cell carcinoma, were the first entity to be treated tissue is then achieved with 633 nm light, with a
with LED PDT using specifically-designed dose usually around 45–90  J/cm2. This can be
633  nm LED-based system to activate 5-ALA, extremely painful, and some kind of forced air
and the pioneering company was Photo cooling may be applied during this phase for
Therapeutics (Fazeley UK and Carlsbad, CA) patient comfort. Following activation, the wound
with their Omnilux® PDT™ system. The is dressed, and the patient returns after 24 h for
Omnilux brand is currently owned by Radiency dressing removal and the situation is then fol-
Ltd., Hod Hasheron, Israel (parent company). lowed for 4–6  weeks. In a large percentage of
Having established that an effective activation lesions, recurrence is not a problem. Persistent
peak for the relevant porphyrins created from lesions are retreated till no recurrence is seen.
exogenous PDT existed at around 633 nm, a UK Figure  18.17 shows a typical example of the
company in 1996, working in tandem with the results of 633 nm LED PDT for an NMSC.
British Cancer Research Council, developed the In the case of actinic keratoses (AKs), which
Paterson Lamp, a filtered xenon-powered lamp are much more superficial than NMSCs, a much
which delivered most of its light energy at lower concentration of 5-ALA is applied with a
633 nm, to be used with exogenous 5-ALA PDT shorter incubation time. The protocol is otherwise
310 R. G. Calderhead

a b

Fig. 18.17  A basal cell carcinoma before (a) and 4 weeks used, Omnilux® PDT™, photographs courtesy of Colin
after 633 nm 5-ALA PDT (b) (20% 5-ALA, 5 h incuba- Morton MD, Falkirk, Scotland)
tion, 20 min activation at approximately 96 J/cm2. System

a b

Fig. 18.18 Actinic keratosis on the décolleté of a 20 min activation at approximately 96 J/cm2. Same system
45 year-old female before (a) and just over 6 weeks after as in Fig.  18.14, photographs courtesy of Colin Morton
633 nm 5-ALA PDT (b) (10% 5-ALA, 30 min incubation, MD, Falkirk, Scotland)

the same and the activation dose is still recom- and psychosomatically troublesome as the active
mended to be around 96  J/cm2. Figure  18.18 lesions, but more difficult to treat. It therefore
shows AK on the upper sternum of a female made sense to attack and eradicate acne while at
patient before and after 633 nm LED PDT. One the active stage, before scarring was an issue. In
treatment usually suffices for AKs. addition to the conventional approaches, LED
exogenous 5-ALA PDT with 633  nm and nar-
rowband blue light LED and non-LED sources at
Acne Vulgaris around 410–425 nm attracted attention with good
results, but with some downtime and pain associ-
Acne vulgaris still represents a major problem for ated with the activation stage of the photosensi-
the practicing dermatologist, despite advances in tizer [29–31]. The recurrence rate was, however,
clinical and medical therapy. Many approaches still rather high. The development of quasimono-
have been tried with varying degrees of success, chromatic LEDs at the peak wavelength of
but results are inconsistent, even in the same 415  nm offered a new approach, given the
regimen with the same patient. If untreated, or extremely high peak in the activation spectra of
treated improperly, active ace almost always Pp IX and Cp III, both of which porphyrins are
leads to unsightly acne scarring, as disfiguring endogenous to active P. acnes as already
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 311

discussed above. With a high enough photon of the different cellular and subcellular
intensity at 415  nm it would therefore theoreti- wavelength-­specific targets, and the quasimono-
cally be possible to activate the endogenous por- chromatic nature of LED therapy would assist in
phyrins in P. acnes selectively, thereby disabling precise targeting. In addition, applying the blue
or eradicating the P. acnes [32, 33]. On the other and red components together might actually go
hand, trying to activate porphyrins from exoge- some way to defeating the object of the exercise,
nously-applied 5-ALA PDT with narrow band as one of the effects of the red light is to try and
415  nm LED energy should be attempted with repair damaged cells, including the P. acnes tar-
extreme caution, as the activation process will be geted by the blue light.
both extremely painful and rather shallow owing Two clinical papers were published in 2007
to the physical characteristics of 415  nm light, using this sequential approach of 415  nm LED
with a prolonged downtime owing to the serious light-only therapy followed by 633 nm red LED
damage to the irradiated tissues. treatment, repeated over a 4-week period. One
In order to understand why the blue light ther- patient group was Caucasian [36] and the other
apy on its own was achieving good results but Asian [37], and both groups had a meaningful
with a still unacceptably high recurrence rate, the number of patients (>25) with a good selection of
etiology of acne must be considered. Acne is Burton grades 3–5, representing moderate to
often considered as an inflammatory disorder, severe inflammatory acne. The system used in
full stop, with colonization of blocked follicles both studies was the Omnilux (Radiancy, Israel)
by P. acnes as the main culprit. In fact, acne is with the blue™ (415 nm) and revive™ (633 nm)
multifactorial with major influences other than heads, and the same protocol was followed in
merely inflammation, such as hormonal and both the USA and Korea study centers. A two-­
­autoimmunological imbalances [34]. Acne is the week washout was imposed for anyone on oral
result of the establishment of a vicious circle set medication, and no other form of topical or ther-
up between P. acnes and some t-cells originally apy was allowed during the study and followup
homing into the site to help the defence system, period. A comedonal scrub was recommended
but ultimately converted by P. acnes to the black before each treatment session. The blue head was
side as ‘rogue t-cells’. Whereas 415 nm will pre- applied first for 20  min, followed at least 48  h
cisely target the P. acnes via the endogenous por- later by the red head. This was repeated for
phyrins and thereby remove one of the major 4  weeks. Assessments were performed at pre-
causes of the inflammation, the rogue t-cells and treatment baseline, at each of the 4 weeks during
any hormonal imbalance remain untreated by the treatment, and then at 4, 8 and 12 weeks after the
415  nm light, thus leaving the vicious circle final treatment session.
unbroken and paving the way for recurrence at The most interesting point in both studies was
some stage in the near future. If light-only ther- that the improvement obtained after the final
apy for acne were to work well and with robust treatment session, which ranged from 50% to
results, it would therefore be necessary to find 60% clearance of inflammatory lesions, contin-
another approach whereby the targets not dealt ued to improve up to 12  weeks after the final
with by the blue light could be attacked with treatment with no other therapeutic intervention,
another wavelength. A very interesting paper reaching from 83% to 90% clearance, and if
appeared from Papageorgiou and colleagues in extrapolated beyond the trial period would have
which they achieved excellent and long-lasting in many patients reached 100%, which from per-
results in acne treatment with a combination of sonal communication with the authors of both
filtered blue (415 nm) and red (660 nm) non-LED papers, it in fact did. Figure  18.19 is a graphic
light applied simultaneously [35]. It was then representation of the inflamed lesion reduction
suggested that sequential rather than simultane- curves of the two referenced papers.
ous application of blue and red light might have No secondary hyperpigmentation was seen in
an even better effect through selective targeting any patients in both studies, which is of particular
312 R. G. Calderhead

0
Goldberg & Russell (29)

Lee et al (30)
20
Clearance rates (% of lesions) Extrapolated clearance

40

60

80

100
0 1 2 3 4 4 8 12
Treatment weeks Follow-up weeks

Fig. 18.19  Inflammatory lesion clearance rates follow- (12 weeks from baseline). However, by extrapolating the
ing the blue/red combination LED phototherapy for acne clearance rates in both studies, which were clearly linear
adapted from the studies by Goldberg and Russell [29] in nature, the continued improvement is evident. No other
and Lee et  al. [30]. The Goldberg study had a 12-week therapy was used in either study. System used: Omnilux®,
follow-up after the final treatment, i.e. 16  weeks from Radiancy, Israel
baseline, whereas the Lee study had an 8-week follow-up

interest in the Asian skin type. In addition, over- severe side effects. The validity of the substitu-
all skin condition was subjectively assessed to tion of another LED wavelength to the current
have improved, and in the case of the Asian popu- protocol, namely near infrared at 830 nm with its
lation, skin lightening was objectively shown own unique cellular and tissue targets, in place of
across the population with an instrumental assay. the 633  nm visible red approach, is currently
Figure  18.20 shows examples of the treatment being assessed in ongoing clinical studies world-
efficacy courtesy of the authors of the papers. At wide, and the results are extremely promising
6  months after the final session, recurrences in probably owing to the specific cellular entities
both trial centers were extremely few and mild, targeted by 830 nm compared with those affected
easily treated with another regimen of the blue/ by 633 nm.
red LED therapy (David Goldberg and Celine SY
Lee, personal communication).
As with all approaches not involving exci- Skin Rejuvenation
sional surgery, there will always be a small per-
centage of patients in whom light-only LED Skin rejuvenation and antiageing have become
phototherapy for acne vulgaris will have disap- very ‘hot’ topics. Excessive skin exposure to
pointing results, but from the above studies the solar UVA and UVB brings about damaging mor-
overall efficacy is high enough to warrant apply- phological and metabolic changes in the epider-
ing this approach as the primary treatment of mis and dermal extracellular matrix (ECM),
choice. Sequential combination LED photother- combining with and accelerating the effects of
apy for acne can be combined with other topical chronological ageing and resulting in the lax, dull
approaches with even better results and improved and wrinkled appearance of ‘old’ skin. Oxidative
maintenance, provided none of these involves stressors such as singlet oxygen are photochemi-
any kind of photosensitizing agents, any of which cally generated following absorption of UV radi-
have the potential to create painful and possibly ation in the ECM and damage the matrix integrity
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 313

a b

c d

Fig. 18.20  Representative examples from the Goldberg the cheek and jaw line of a 19-year-old Korean male
and Lee studies on light-only combination blue/red LED patient from the Lee series, skin type IV. (d) Eight weeks
phototherapy for inflammatory acne. (a) Cystic acne at after the final treatment session (12 weeks from baseline).
baseline in a 21-year-old female, skin phototype II, from Good clearance with no secondary hyperpigmentation, a
the Goldberg and Russell series. (b) Six weeks after the major problem in the Asian skin. The remaining small
final treatment session (10  weeks from baseline). areas of redness will fade with time. Photographs courtesy
Excellent clearance and very good cosmesis. Photographs of SY Celine Lee MD
courtesy of Bruce Russell MD. (c) Inflammatory acne on

with elevated levels of the matrix metalloprotein- matrix; the viscosity and quality of the ECM
ases (MMPs) 1 and 2, formerly known as colla- ground substance glycosaminoglycans is
genase and gelatinase; elastotic damage to the reduced; and a chronic inflammatory infiltrate
underlying connective tissue occurs, with inter- can be identified. As this damage is caused by
stitial spaces appearing in a poorly-organized light, an elegant concept to use the power of light
314 R. G. Calderhead

to reverse the damage led to the application of facturers of the more recent second generation of
lasers, usually the CO2 or/and the Er:YAG, in fractional systems have returned to the original
what became known as ablative laser resurfacing. ablative wavelengths, the CO2 and the Er:YAG,
Although still regarded as the ‘gold standard’ in in addition to increasing the parameters of the
the rejuvenation of severely photoaged skin in nonablative fractional Er:glass systems, to
general and deep wrinkles in particular, the usu- deliver fractionated microbeams that visibly
ally severe side effects and a prolonged patient damage the both the epidermis and the dermis
downtime of up to several months associated with a recognizable amount of erythema and
with this approach drastically reduced its some edema post-treatment.
popularity. This in some way takes us back towards our
To attempt to overcome these problems, so-­ gold standard of ablative resurfacing, as once
called nonablative resurfacing was developed again heat deposition, combined with controlled
using specially adapted laser or intense pulse epidermal damage, becomes a pivotal consider-
light sources. The theory was to deliver a con- ation to achieve the ideal rejuvenation results on
trolled zone of deliberate photothermal damage a patient-by-patient basis [42]. This approach has
beneath an intact epidermis, so that the wound-­ been much more successful from the patient sat-
healing processes, including collagenesis and isfaction criterion, although at the cost of a little
remodeling, could occur under the undamaged downtime, because it is involving the epidermis
epidermis, thereby obtaining rejuvenation of the more than the previous nonablative and fractional
skin without any patient downtime and was pop- approaches.
ularized as the ‘lunch-break rejuvenation’. The In the meantime, other clinical researchers
theory was good, but in clinical practice patient were wondering if there was a role for LED pho-
satisfaction was very low, [38, 39] because the totherapy in skin rejuvenation, and the first
good dermal neocollagenesis seen in post-­ approach was to use a lower strength of topically-­
treatment histological analysis was not reflected applied low-strength 5-ALA activated with
in a ‘younger’ epidermis [40]. In an attempt to 633 nm LED in LED-PDT [43]. The results were
bridge this gap between ablative and pure nonab- good, but begged the question as to why more
lative rejuvenation, so-called fractionated or damage, and indeed some pain, should be
fractional technology was developed whereby inflicted to treat what was essentially compara-
many spots of almost grossly invisible epidermal tively mild skin damage. Another approach has
and dermal ‘microdamage’ were delivered via a been to deliver the 5-ALA at very low concentra-
scanner or ‘stamp-type’ head, all surrounded by tions (<2%) via liposomes and activate the target
normal epidermis and dermis to obtain swift tissue using intense pulsed light, achieving com-
reepithelialization and dermal wound healing plete quenching of the porphyrins and thus avoid-
[41]. Unfortunately, once again the clinical ing the side effect of residual photosensitivity
results of the first generation of nonablative frac- [44, 45]. Because of its totally noninvasive, ather-
tional lasers were not satisfactory to the majority mal and atraumatic nature, light-only LED pho-
of patients, with good dermal neocollagenesis totherapy for skin rejuvenation has also attracted
not being echoed in the epidermis. In both the attention first with a single wavelength system in
nonablative laser/IPL and the first generation of the visible yellow [46], but once again a sequen-
fractional nonablative technologies, the big tial combination technique, initially at least,
problem was that what the patient first sees when proved more effective than the single wavelength
looking in a mirror is the epidermis, not the der- just as was the case with LED phototherapy for
mis. It does not matter to the patient (or her acne [47, 48]. The wavelengths used for LED
friends) that her dermis is wonderfully better skin rejuvenation in the published literature were
organized if her epidermis remains unchanged, originally near IR at 830  nm applied first, fol-
what the author refers to as the SOE syndrome— lowed by 633  nm 72  h later, repeated over
‘same old epidermis’. Recognizing this, manu- 4  weeks. The rationale for using these wave-
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 315

lengths and the order in which they are applied clinical photography and subjective patient
are photobiologically based on the precepts of assessment, Dr Lee tested the results with pro-
the wound healing cycle, and will be covered in filometry and instrumental measurement of
some detail in the next subsection dedicated to skin melanin and elasticity. She also carried out
wound healing. Both of these wavelengths histological, immunohistochemical and bio-
involve the mother keratinocytes in the basal chemical assays. Dr Lee found that wrinkles
layer of the epidermis, however, in addition to the and skin elasticity were best improved in the
target dermal cells, with beneficial effects to both 830  nm-treated groups and a statistically sig-
the cellularity and organization of the epidermis, nificant improvement existed between the
but with no heat and no damage. treated and occluded sides in all of the experi-
Lee and colleagues, in the first and really mental groups, but not in the sham irradiated
detailed controlled study in the peer-reviewed group. Subjective patient satisfaction showed
literature, which was published in the very statistical significance between all the treated
prestigious Journal of Photochemistry and groups and the sham-irradiated group, but it
Photobiology (B), [49] compared LED skin was clear that a strong tend was shown in favor
rejuvenation in a total of 76 patients randomly of the 830  nm group compared with the
assigned to four groups: 830 nm LED therapy 830/633 nm and 633 nm groups. Figure 18.21
on its own, 633 nm LED therapy on its own, the compares the subjective patient “excellent” rat-
combination therapy with 830 and 633 nm and ings among the 633 nm, 830 nm + 633 nm and
a sham irradiated group. All patients were 830  nm groups from the final treatment ses-
treated hemifacially, so there was intrapatient sions through the 12-week assessment period.
as well as intergroup controls. In addition to For all groups, and interesting and clear

Fig. 18.21  Graphical comparison of only the “excellent’ interesting increase in satisfaction levels is seen during
result ratings by the LED rejuvenation trial subjects in the this 12-week period for all groups corresponding to the
630 nm, 830 nm plus 633 nm and 830 nm groups based on ongoing remodeling stage of the wound healing process.
data from the cited paper by Lee et al. [49]. Ratings start The patients who noted the greatest satisfaction, soonest,
from immediately after the final treatment session, then at were in the 830 nm group
4, 8 and 12 weeks thereafter with no further treatment. An
316 R. G. Calderhead

improvement was echoed in the patient satis- photoprotective effect against degradation of the
faction during that 12-week period: that newly-­formed extracellular matrix.
phenomenon can be explained by the remodel- This was an excellent and thorough study, and
ling process, continuing long after the final of the author recommends the reader to get hold of
the eight treatment sessions. However, based on it and read it, all 17 pages of it. It will go a long
a closer examination of the study data, the best way to convincing even the most skeptical of the
results were achieved not in the combination real efficacy of LED-LLLT for light-only skin
group but in the 830  nm group, and were rejuvenation, backed up with real science.
achieved fastest among the three groups. Figure 18.22 shows examples of the efficacy of
The clinical photography was backed up by light-only combination LED skin rejuvenation,
the histological findings for both collagenesis including histological findings from the Lee
and elastinogenesis, both of which were shown study demonstrating photorejuvenation of both
to take place in all dermal layers down to the the dermis and epidermis at only 2  weeks after
deep reticular dermis. No MMP activity was the final treatment session: as remodeling pro-
noted, and on the contrary the levels of tissue gressed, these histological results would have
inhibitors of MMPs (TIMPs) 1 and 2 were sig- become even better in conjunction with the
nificantly elevated in all treatment groups, but steady improvement in patient satisfaction in the
with a strong but nonsignificant trend noted for 12-week follow-up after the final treatment ses-
the 830 nm group over the others, suggesting a sion, as noted above.

a b c d

e f g h

Fig. 18.22  Representative examples of combination near organized stratum corneum. (f) Histology at only 2 weeks
IR/red light-only LED skin rejuvenation. (a) A 29-year-­ after the final treatment session. Note the much better-­
old female, skin type II, at baseline: note the mild rosacea organized dermal collagen, extending down into the
on her cheek. (b) The result at 6 weeks after the final treat- deeper reticular dermis, and the highly visible Grenz layer
ment session (10 weeks from baseline). Smoothing of the running under and attached to the basement membrane at
periocular wrinkles can be seen, with overall better skin the dermoepidermal junction. The epidermis is much
tone. The rosacea has almost gone. Photographs courtesy thicker with good cellularity and a very well-delineated
of Bruce Russell MD [40]. (c) Baseline findings in a stratum corneum. (Hematoxylin and eosin, original mag-
26-year-old Korean female, skin type IV. (d) Result nification ×100). The same improvement could be seen in
12  weeks after the final treatment session. Excellent the elastin content comparing baseline (g) with the find-
removal of the fine ‘crow’s feet’ wrinkles and overall ings 2  weeks after the final treatment (h) (Verhoeff van
improvement and lightening of the skin tone. (e) Giesen, original magnification ×200). Photographs and
Histological findings at baseline, showing a typical elas- photomicrographs courtesy of SY Celine Lee MD [42].
totic dermis under a thinned epidermis with a highly dis- System used: Omnilux®, Radiancy, Israel
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 317

The important point to be taken from these Wound Healing

findings is the that epidermis also showed
improved morphology and not just the dermis, Wound healing underpins all applications of LED
thus avoiding the SOE (same old epidermis) syn- phototherapy involving photoactivation therapy
drome which was the major problem with photo- (PaT), and plays a major role in obtaining good
thermal nonablative skin rejuvenation. As with cosmetic results in combination LED PDT/PaT
LED phototherapy for acne, adjunctive comple- for the treatment of acne, and in LED skin rejuve-
mentary treatment and maintenance techniques nation, in addition to the treatment of traumatic
with high quality creams and sera will certainly or post-surgical wounds themselves. A brief
improve the good results consistently shown for overview of the wound healing process is there-
light-only LED skin rejuvenation in these stud- fore warranted. Three distinct phases make up the
ies. The role of protective daily maintenance with wound healing process, namely inflammation,
a UVA/B sunblock of at least SPF 50 should also proliferation and remodeling, and although they
be considered. are distinguished by their timing and cellular
More discussion on the 830 nm/633 nm LED components, there is always some degree of
combination has appeared in Viewpoint 3 overlap between them.
(Trelles, Mordon and Calderhead) and Comment
3 (Goldberg) in an article on redressing  he Three Stages of Wound Healing
T
UV-mediated skin damage in Volume 17 of Inflammation is often regarded as a major prob-
Experimental Dermatology [50]. However, lem, but in the wound healing process it is abso-
although Lee concluded that the combination of lutely essential that inflammation occurs before
the 830 and 633  nm was optimum, if we read proceeding into the proliferative phase.
between the lines of the study it is clear that Inflammation only becomes a problem when it is
830  nm on its own was extremely interesting out of control, such as the end product of the
(Fig.  18.21), which was backed up by a 2011 vicious circle instigated by P. acnes and rogue
article by Kim and Calderhead on the efficacy of t-cells in acne vulgaris.
LED-LLLT [51], and by a 2013 wound-healing In the inflammatory phase, from wounding
study by Min and Goo [52]. Although LED pho- until about day 3–5, mast cells (already present
totherapy has a well-proven role in stand-alone or recruited through chemotaxis), macrophages
indications, especially for wound healing (already present, recruited or differentiated from
whether traumatic, delayed or iatrogenic, the monocytes or pericytes) and neutrophils
adjunctive role of LED phototherapy is perhaps (recruited or differentiated from hematopoietic
even more exciting and is the way of the future. stem cells) peak in the wound and surrounding
Adjunctive LED low level light therapy (LED- tissue. The macrophages ensure that all debris
LLLT) for the aesthetic dermatologist and plas- and detritus from the wound are removed through
tic surgeon, especially at 830 nm, has been well engulfment and internalization, and the leuko-
argued recently in articles appearing in 2015 cytes are the first line of defence of the autoim-
and 2016, respectively, in Laser Therapy [53] mune system against invading pathogens. When
and Clinics in Plastic Surgery [54]. they are at work, the macrophages release an
The wavelengths and systems that have been important trophic factor, fibroblast growth factor
reported in the six studies cited above are 595 nm (FGF), and leukocytes are associated with TGFα
(Gentlewaves®, Light Bioscience, VA, USA) [39], and β (transformational growth factor).
the 830  nm/633  nm combination (Omnilux® Connective tissue mast cells are granule-filled
plus™ and revive™, respectively: formerly Photo cells differentiated from CD34-expressing bone
Therapeutics, Fazeley, UK & Carlsbad, CA, USA, marrow precursors which circulate in the ECM
currently Radiancy, Ltd, Israel) [40–43] and the till they mature in situ, found normally around
new generation 830  nm HEALITE II (Lutronic capillaries and arterioles. In fact, the mast cell
Corporation, Goyang South Korea) [51–54]. was first described and named by the German
318 R. G. Calderhead

physiologist Paul Ehrilch in the latter part of the fibroblasts and endotheliocytes gradually returns
1800s. Mistakenly believing that the purpose of by day 20–22 to the pre-wound baseline, leaving
the granules was to nourish the ECM, he called the ECM in a regenerated state with newly formed
the cells ‘mastzellen’, (German for ‘feeding but somewhat haphazardly arranged clumps of
cells’), giving us our Anglicized version. Their collagen and elastin fibers, a fresh supply of gly-
part in the wound healing process is to release cosaminoglycans and well-vascularized.
their granules into the ECM. Although the gran- In the final and much longer stage of the
ules released first are proinflammatory, the later wound healing process, remodeling, which starts
granules contain antiinflammatory chemokines around day 19–23, these new fibers and struc-
and cytokines, chemotactic factors to recruit tures gradually mature and are slowly reorga-
more wound-healing cells to the area, and a mix nized into better alignment to give a strong,
of trophic factors. In the final degranulation, the flexible and plump ECM under an epidermis
most powerful antioxidant endogenous to our firmed and tightened by the Grenz layer of colla-
bodies, superoxide dismutase (SOD), is depos- gen fibers running under and attached to the der-
ited into the ECM to help protect against future moepidermal junction basement membrane.
UV exposure-related oxidative stress. The com- After the proliferative phase there are too many
bined efforts of all the inflammatory stage cells fibroblasts in the ECM. One method by which the
with their different but interlocking functions body reduces the number is through transforma-
thus leave the ECM in an ideal and favorable con- tion of some of the fibroblasts to a cell of great
dition for the proliferative stage cells. importance, namely the myofibroblast, which is
In the proliferative stage, from around day 4 to simply a fibroblast that has grown smooth mus-
day 21, the inflammatory stage cells decrease in cles (myo, Greek for muscle) at each end of its
number and fibroblasts and endotheliocytes peak. longitudinal axes. These tufts of muscles are fit-
Fibroblasts, (already in the area or differentiated ted with small barbs which hook onto the newly-­
from pericytes), are an extremely important mul- formed collagen fibres and exert force on them to
tifunctional cell. They are not only responsible for bring the fibers into good linear alignment. Once
synthesizing collagen to replace damaged ECM their task is completed, myofibroblasts go into
collagen fibers, but they also produce new elastin apoptosis, programmed cell death. If there are
to form elastic fibers and additionally manufac- still too many fibroblasts, some more will be
ture the ground substance, the glycoproteinous induced to dedifferentiate into quiescent fibro-
viscous gel-like liquid which lubricates and cytes, a kind of unipotent stem cell, which join
hydrates the ECM, and which also facilitates the stem cell pool in the dermis to replace fibro-
intercellular signaling and oxygen transport to blasts as they age. The remodeling process can
ECM components from arteries. It is also the take up to 6 months, or even longer, to complete,
fibroblasts’ task to maintain ECM morphological and this is important when thinking of patient
integrity through constantly monitoring the state education regarding when they can anticipate the
of the collagen and elastic fibers, lying along final optimal appearance of their treated tissue,
which they can often be seen. In this respect, the taking the findings of Fig. 18.22 above into con-
quality of both proliferative wound repair and the sideration. Figure  18.23 illustrates in schematic
final wound appearance rests firmly on the back form the time course of the wound healing pro-
of the fibroblast. Endotheliocytes (already present cess, showing the peaks and lows of the cells
in the wound or differentiated from endothelial associated with each of the three phases.
progenitor cells), clump together to start the neo-
vasculogenesis process, culminating in the repair  he Influence of Different Wavelengths
T
of damaged blood vessels and production of new of Light on the Wound Healing Cells
blood vessels to oxygenate the newly-­ forming When we consider LED phototherapy, it is very
ECM and provide essential nutrients. From a peak tempting to go ahead and invent ‘new’ wave-
at around day 12–18, the increased number of lengths for ‘new’ photoprocesses. It must never
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 319

Inflammation
Proliferation
Remodelling

Mast Macrophage
cell Myofibroblast
Relative total number of cells
Fibroblast

Leukocyte Endotheliocyte

Fibrocyte

Monocyte

0 3 20 100
Approximate time (days)

Fig. 18.23  Schematic illustration of the cell cycles and endotheliocytes, increase in number, and then as remodel-
numbers during the three phases of wound healing. ing starts, gradually decrease. In the case of fibroblasts,
During inflammation, which occurs from day zero to day some remain as active fibroblasts, but some transform into
3–5, the inflammatory cells (leukocytes, mast cells and myofibroblasts, literally fibroblasts with muscles, whose
macrophages) increase in number, peak and then return to task is to ensure good linear alignment of the new colla-
baseline levels. During proliferation, the collagen-­ gen fibres. It should be noted that the phases overlap, with
producing cells, fibroblasts, and neovascularization cells, no clear border between each

be forgotten that the original LLLT, low level the Introduction, the effect of red light specifically
laser therapy, has a rich and well-documented on subcellular organelles was first published by
history which extends back over almost the last Fubini and colleagues in the late eighteenth cen-
four decades, so by examining this wealth of pub- tury! [3]. The last three decades, however, have
lished literature it should be possible not to have added tremendously to the knowledge regarding
to reinvent the wheel all over again. Sadly, red light and skin cells. It was reported that
because the US Food and Drug Administration 632.8 nm red light from the HeNe laser induced
did not grant 510(k) approval to a laser therapy fibroblast monosheet formation in vitro faster and
system in the process erroneously called ‘bios- with much better alignment, almost double the
timulation’ until 2002, there is not a lot to be speed of the unirradiated controls [55].
found in the US literature until more recently. Furthermore, in the same study, a ‘wound’ created
However, those early US papers which are there, in the monosheet was repaired much faster in the
have been quietly forgotten, probably on the prin- HeNe-irradiated groups. More recent in vivo work
ciple that if one doesn’t understand it, one simply with 633 nm LED energy in human subjects dem-
ignores it. onstrated dramatic fibroplasic changes in speci-
A great deal of literature exists on red light-­cell mens from irradiated subjects compared with
reactions, because the mainstay light source of the unirradiated controls [56]. Tiina Karu, probably
early pre-LED investigators was the HeNe laser, the most well-known living photobiologist, has
delivering 632.8  nm, basically the same as the produced an enormous amount of work in her
633 nm of current array-based LED systems, also lifetime on the effects of low incident levels of
in continuous wave (C/W) rather than frequency light on cells and their organelles. She confirmed
modulated as discussed already. As mentioned in the much earlier work by Fubini and further iden-
320 R. G. Calderhead

tified the specific target for 633  nm light as the keratinocytes to release a large amount of cyto-
cytochrome-c oxidase resident at the end of the kines which drop down into the dermis to assist
mitochondrial respiratory chain [57]. She also with the dermal wound healing processes, so
showed that coherent light was not essential to much so that keratinocytes have been nicknamed
achieve effects in vivo, provided the photon inten- ‘cytocytes’ [64]. Additionally, the photoactivated
sity at the target was high enough. keratinocytes can improve the cellularity and
Mast cells have been stimulated in vitro and in organization of the epidermal strata through rais-
vivo to degranulate when irradiated with 633 nm ing the levels of extracellular ATP and the signal-
light, and much faster than when unirradiated: ing elements Ca2+ and H+, and obtaining a better
stimulation with 830 nm speeds up degranulation organized stratum corneum [64].
even more [58, 59]. The author and colleagues If the wound healing cells, including epidermal
have shown that, 48  h after a single irradiation keratinocytes, are examined for increased wave-
with 830 nm LED energy, mast cells in the fore- length-specific action potential based on the last
arms of healthy human subjects had 40–60% 30 years of both LLLT and non-laser light source
degranulated compared with specimens from literature, the wavelengths which have the most
unirradiated controls, where no degranulation verified and published results at a ­cellular and sub-
was seen at all [60]. In the same study, indepen- cellular level are 633 and 830  nm in the near
dently performed cell counts per field averaged IR. Near IR at 830 has excellent results in activat-
over many samples showed a significant increase ing the activity levels of the inflammatory stage
in the mast cells, macrophages and even neutro- cells, mast cells, macrophages and neutrophils,
phils recruited into the irradiated area, compared fibroblasts and in addition to epidermal keratino-
with baseline and the unirradiated control arm cytes. On the other hand, red light at 633 nm com-
(Table 18.6). Near IR energy at 830 nm has been pared with 595  nm yellow is excellent for
demonstrated to induce macrophages to perform photoactivating fibroblasts in vivo, due to its supe-
their chemotactic, phagocytic and internalizing rior penetrating powers, in addition to epidermal
functions better and faster, while releasing almost keratinocytes. With athermal and atraumatic LED-
30-fold the amount of fibroblast growth factor LLLT at these wavelengths, especially 830  nm,
(FGF) compared with unirradiated controls [61], there is no physical wound, but exactly the same
and the same is true for the attack and phagocytic clinical response is achieved as seen after any
functions of neutrophils [62, 63]. examples of the nonablative or even ablative
The epidermal basal layer keratinocyte is too approach involving frank photothermal damage.
often forgotten in LED phototherapy, but research Why is the 830 nm effective for skin rejuve-
has shown that 590, 633 and 830 nm noncoherent nation as monotherapy, as seen in the Lee et al.
light both in vitro and in vivo can activate the study [49]? Though this indication is not wound

Table 18.6  Numbers of mast cells, macrophages and neutrophils averaged per field (TEM, ×50,000) showing the aver-
aged value of at least eight fields per subject. (Based on data from Ref. [58])
Mast cells Macrophages Leukocytes
Patient No. Pre Post Control Pre Post Control Pre Post Control
1 1.5 5.5 1.25 0 6.0 0 0 3.35 0
2 1.5 6.75 1.5 0 8.25 0.25 0 4.0 0
3 1.0 7.0 1.25 0.5 6.75 0.25 0 4.5 0
4 0.5 4.75 0.5 0.25 5.0 0.25 0 4.0 0
5 1.0 8.0 1.0 0.75 7.75 0.5 0 4.25 0
6 1.5 7.25 1.5 1.0 7.0 0.75 0 4.5 0
7 1.25 7.0 1.5 0.5 7.5 0.75 0 3.75 0
8 0.5 6.25 0.5 0.75 6.5 0.5 0 4.0 0
The bold text indicates the significant cell count increase in the specimens from the treated arm compared with baseline
and the control arm
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 321

healing per se, it depends on inducing the (see Fig. 18.21) [49], as was also the case in the
wound healing process to clear wrinkles and acne studies already mentioned [36, 37].
tighten up skin. The 830  nm energy degranu- The same principle for LED-LLLT with
lates the mast cells, dumping a load of proin- 830 nm applies to frank wound healing, whether
flammatory substances into normal tissue, such it is accidental or iatrogenic trauma. Burns, for
as heparin, trypsin, histamine and bradykinin. example, are an ideal injury for LED photother-
This gives the tissue the impression that it has apy, because of the noncontact and hands-free
been ‘wounded’, even though there is actually application, and the large area of the treatment
no wound because of the athermal and atrau- heads. In a recent study, the 830  nm/633  nm
matic action of LED phototherapy. Macrophages combination produced excellent results in large
are also photoactivated, helping to give a clean area burns, as illustrated in Fig.  18.24 [65]. As
ECM ‘seeded’ with FGF, with some TGF mentioned already above, ablative laser resur-
released from neutrophils recruited into the facing lost popularity due to the potential of seri-
area by the degranulating mast cells. Because ous side effects, especially edema and prolonged
the inflammatory stage has been established erythema, leading to prolonged patient down-
especially by this mast cell-mediated ‘quasi- time. The wound left following laser ablative
wounding’, the tissue has no option but to pro- resurfacing is simply a full facial burn. In a
ceed into the next stages of the wound repair recent publication Trelles and co-workers used
process, starting with proliferation. When this 830 nm LED therapy following laser ablation of
830 nm irradiation is repeated over eight times the face with a combined Er:YAG/CO2 laser sys-
over 4 weeks, separated each week by 2–3 days, tem [66]. There were two groups of patients,
the dermal cells (and epidermal keratinocytes) 30  in each group. The experimental group
are upregulated in a step-wise manner and received the LED therapy following laser abla-
maintained in the inflammatory/proliferative tive treatment, and the control group received
stages. After the final treatment session the sham treatment from the standby setting of the
remodeling is allowed to start, and this explains system. The average healing times (full reepithe-
why the best results are not seen at this immedi- lization and resolution of erythema) for the con-
ately post-­treatment stage, but later on at 4, 8 trol and experimental groups were 13 weeks and
and 12 weeks or more after the final treatment 6 weeks respectively. The extent of post-procedure

a b

Fig. 18.24  A 39-year-old male patient with severe full tially applied as usual, a resting period of 4  weeks, and
facial electric spark burn injury before (a) and (b) three then another 4-week regimen. Photographs courtesy of
months after the final treatment with combination Prof Jin-wang Kim MD PhD, Burns Center, Haelym
830 nm/633 nm LED phototherapy. One full 4 week ses- University School of Medicine, Seoul, Korea. System
sion was performed with the wavelengths being sequen- used: Omnilux®, Radiancy, Israel
322 R. G. Calderhead

Fig. 18.25  Results of a controlled study on LED photo- all significantly reduced in the group which received
therapy after full face ablative Er:YAG/CO2 resurfacing, 830 nm LED phototherapy (based on data from Ref. [64])
30 patients per group. Healing was better than one half of System used: Omnilux®, Radiancy, Israel
the time compared with the controls, and sequelae were

pain, bruising and erythema was significantly and acute herpes zoster ophthalmicus [70].
less for the LED-­ treated group (Fig.  18.25), Additionally, 830 nm LED treatment has cleared
whereas improvement in the skin condition was irritant contact dermatitis and dissecting follicu-
much more clearly seen in the LED-treated litis of the scalp [51].
group, with a satisfaction index (SI) of 89% Long-term nonhealing ulcers which healed
compared with 51% for the control group. The following low incident levels of red light (HeNe
SI was calculated by adding only the number of laser, 633 nm) comprised the first topic to appear
‘excellent’ and ‘very good’ scores from a stan- in the literature from the Godfather of photother-
dardized 5-element scoring system, and express- apy, the late Prof. Endre Mester of Semmelweis
ing the result as a percentage of the total University, Budapest, Hungary, with a patient
population. Healing following upper blepharo- population of over 1000, and started all the con-
plasty and periocular laser resurfacing in a hemi- troversy surrounding LLLT in the early 1970s
facial study was reported to be cut by one-­half to [71]. Very interestingly, Mester reported that
one-third following LED therapy at 633 nm, and ulcers on the limb contralateral to the one treated
the improvement was subjectively rated as two- also eventually healed, although more slowly
to fourfold better compared with the unirradiated than the irradiated wounds. This was the first
side [67]. LED-LLLT following Er:YAG laser report on the systemic theory in phototherapy,
ablation of deep and extensive plantar warts whereby photoproducts created in the irradiated
roughly halved the healing time, cut the postop- tissue were carried systemically through the body
erative pain by at least one-tenth and gave less to have an effect wherever they were required. A
than 6% recurrence rate in 121 cases [68]. The 2012 study has shown the systemic effect in
study by Min and Goo already mentioned above mouse and rat models, whereby standardized
using 830  nm LED-LLLT showed excellent dorsal wounds were created with a fractional CO2
healing of a variety of difficult wounds, some laser. Only the abdomens of the animals were
of which were compromised with bacterial or irradiated with 830  nm LED-LLLT, and at the
viral infection (Fig.  18.26) [52]. As for more 6-day assessment point the indirectly LED-­LLLT
difficult targets, LED-LLLT has shown excel- treated wounds were significantly better healed
lent and lasting results in treating psoriasis [69], than the unirradiated controls [72]. A study with
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 323

a b e f

c d g h

Fig. 18.26  830 nm LED-LLLT in the control of inflam- treated elsewhere. Numbness and slight palsy also
mation and infection. (a) Fifty-two y.o. male with post-­ reported. (f) Improved condition after 1 week of five daily
filler ischemic ulcerative tissue necrosis, inflammation 830  nm LED-LLLT sessions. HS lesions are resolving
and severe pain. (b) Two weeks post escharotomy without with significant reduction in swelling and removal of
flap and LED-LLLT sessions every other day. Pain was palsy with return of sensation. Pain has been totally con-
controlled post 3 Tx. (c) Findings at 3 weeks post base- trolled. (g) Almost complete improvement, including HS
line. Wound closure continues with good granulation tis- infection, at 2  weeks post-baseline, treating every other
sue formation. (d) Final condition 6 weeks post-baseline day. (h) Final excellent result 3 weeks post-baseline with
and 1 week after the final Tx. Further improvement can be no HS recurrence in a 3-month follow-up. Clinical pho-
expected. (e) Fifty-four-year-old female with swollen lips, tography courtesy PK Min MD. System used: HEALITE
fever, severe pain, herpes simplex (HS) and bacterial II 830 nm, Lutronic, South Korea
infection following an illegal lip tattoo, unsuccessfully

830  nm on recalcitrant crural ulcers showed not only brings in oxygen and nutrients, but
accelerated healing [73]. Near IR 830  nm does establishes a higher oxygen tension in the treated
not only work in soft tissue wounds, but also in area which can establish gradients between the
bone where it accelerates the union of fractures, wound at the surrounding tissue, used as ‘super-­
even in the case of delayed union healing, replac- highways’ by the reparative cells [78]. In the case
ing the usual poorly-organized callus with better- of bony tissues, 830  nm has been shown to
quality bone so that the remodeling stage is much increase the metabolism of osteoblasts [79], and
shorter [74, 75]. to upregulate some of the genetic pathways lead-
Some of the mechanisms behind the efficacy ing to better differentiation of new, active osteo-
of LED phototherapy-accelerated wound healing blasts from mesenchymal cells [80].
have already been at least partly elucidated, such In conclusion, the application of LED-LLLT,
as the wavelength-specific activation of the der- either 830  nm followed by 633  nm, or particu-
mal and epidermal cells associated with the three larly more recently, 830 nm on its own, has been
phases of wound healing. in a chapter of her lat- shown to enhance all aspects of wound healing,
est book (Ten Lectures on Basic Science of Laser always provided the incident irradiance (power
Phototherapy. 2007, Prima Books AB, density, photon intensity) is sufficiently high and
Grängesberg, Sweden), Karu has suggested that an appropriate dose is given. In addition to the
the latency effect of phototherapy in cells actu- excellent and growing reputation of LED photo-
ally continues in subsequent generations of the therapy as a stand-alone light-only therapy, this
irradiated cells which is an important consider- means that LED-LLLT has proved to be an ideal
ation in skin rejuvenation [76]. Another impor- adjunctive therapy to any of the conventional
tant mechanism involves improvement of blood approaches seen in dermatological practice and
flow following irradiation with 830 nm, and this this is perhaps the most exciting aspect of LED
has been shown to positively impact on flap sur- phototherapy in the future [53, 54]. No matter
vival in the rat model [77]. Improved blood flow how the aesthetic and cosmetic dermatologist
324 R. G. Calderhead

alters the epidermal or dermal morphology of his cerebral trauma [81–83]. With these reports,
or her patient, be it through microdermabrasion, taken together with the already well-proven
ablative and nonablative skin rejuvenation, frac- effect of 830 nm on improving blood flow and its
tional technology or conventional surgery, the ability to pass through the skull and measure
addition of an appropriate LED phototherapy blood flow and cerebral a­ ctivity in vivo in a non-
regimen will help to improve already good results invasive manner [84, 85], the indication of LED-
but at a very reasonable cost, thus improving the LLLT transcranially for the treatment of simple
satisfaction rates of both the clinician and the senile dementia, but not Alzheimer’s, merits
patient. Many clinics in Australia now buy an some deep thought. The more we can find for
830 nm LED system and add 830 nm LED-LLLT LED-LLLT to do, the more ideas will appear.
as an adjunct to anything done to their patients,
but at no cost to the patient. This value-added
treatment has resulted in excellent results, happy Box 18.5
patients and an ever-increasing number of patient • LED-LLLT is intrinsically safe
referrals, hence happy clinicians as well. • Eye protection sometimes required
against potential optical hazards
• LED-LLLT is essentially side effect
Other Clinical Indications free
• Few contraindications exist, but sen-
The indications already discussed have been sible precautions should be taken
well-researched, and are being reported in the –– Patient history must be checked for
literature. Some other applications exist which any photosensitivity-related diseases
are very much at the experimental stage, but or conditions.
which should be mentioned to prepare the reader –– Drugs, ointments and even cosmetics
for what’s coming in the not-too-distant future being used by the patient must be
and for which LED phototherapy is proving very checked for photosensitizing elements.
interesting. At this stage the author cannot go
into details, because of the early stage of the
clinical and related basic science experiments,
but the reader should watch for articles on the Safety with LEDs
potential use of LED phototherapy in combina-
tion with platelet-rich plasma (PRP) for wound Surgical lasers and even intense pulsed light sys-
healing and for skin rejuvenation. PRP is well-­ tems are by their very nature designed to create
established as a valid method in wound healing thermal damage and are thus subject to stringent
to speed up the process and give good cosmesis safety codes to prevent accidental irradiation of
or in recalcitrant healing situations. Knowing tissue, other than the planned target tissues.
how cell-­specific certain LED wavelengths are, Because LEDs are incapable of creating photo-
the obvious step is to combine the two approaches thermal damage in tissues, the same stringent
to achieve even better results, even faster. Some codes regarding accidental irradiation of tissue
studies are currently well underway in Tokyo, do not apply. However, as all of the LED systems
and the results in a split-face study with 830 nm discussed above operate in the visible and near
vs. unirradiated indicate that this will be a field infrared waveband, there is a potential for opti-
to watch closely (Junichiro Kubota MD PhD, cal damage, as the eye is capable of gathering
personal communication and as yet unpublished this waveband and focusing the light onto the
data). Another emerging field is the transcranial retina at the back of the eye, particularly the
indication of LED-LLLT, usually at 830 nm or a macula and fovea, the area responsible for visual
similar near-­ IR wavelength, for post-stroke acuity. This will be looked at in a little more
patients, and those who have suffered severe detail below.
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 325

Most LED phototherapy systems are run from  ptical Hazards with LED
O
conventional mains electricity, and so present Phototherapy
potential hazards in common with any other such
mains-driven equipment as, for example, DVD As already mentioned above, any LED system
players and television sets. Common sense dic- operating in the visible to near-infrared wave-
tates the safe handling of this group of equip- band emits light which the human eye can gather,
ment, leading to the following guidelines: and focus onto the back of the retina as illustrated
in Fig.  18.27. If the incident power density is
DO NOT connect or disconnect the mains plug great enough, permanent damage to the fovea
with wet or damp hands could occur leading to uncorrectable loss of
DO NOT pull the plug from the mains socket visual acuity. For example, an incident power
using the power cable density from a laser source of as low as 75 mW
DO NOT place any containers with liquid in focused to a 50 μm spot produces a power density
them on top of the unit (e.g., coffee mugs) to of over 3800 W/cm2, perfectly capable of severely
prevent damage from accidental spillage. If damaging target biological tissue. However, a set
such spillage should occur immediately turn of values has been established for the maximum
off the system and have it serviced before permissible exposure, or MPE, to light at a range
using it again. of wavelengths, and these values are significantly
DO NOT attempt to perform and unauthorized lower for LEDs compared with laser sources,
servicing of the system which involves open- because lasers emit coherent light, and LEDs
ing up the case and/or defeating any emit a divergent beam of noncoherent light. If an
interlocks. LED phototherapy system has been indepen-
DO connect the mains cable to the system before dently tested to deliver light below the MPE for
plugging the mains plug into the socket its nominal wavelength, then even prolonged
DO check that the power to the wall socket is off direct viewing of the beam is theoretically safe.
before inserting the mains cable plug In clinical practice, however, visible light LED
DO switch off the wall socket before removing arrays are extremely bright, even when below the
the mains plug MPE for their wavelength, so some form of eye
protection is usually a good idea if only for patient
Apart from these rather obvious points, common comfort. Small, opaque eye cups held in place
sense should prevent any electrical-related dam- with an elasticated cord are popular, which will
age to therapist or patient. still allow the light to reach the periocular region

Focused spot at fovea = 50 mm dia.

Power density at fovea ≈ 3,820 W/cm2

λ = 670 nm ∼ 904 nm

75 mW, pupillary opening 1 cm

Power Density at cornea:
approx. 590 mW/cm2

Fig. 18.27  Schematic illustration of how a low incident the fovea. Although noncoherent and uncollimated LEDs
power of 75 mW from a laser beam is capable of being are significantly more intrinsically safe, the importance of
focused by the unaccommodated eye into a very small appropriate protective eyewear should always be consid-
spot, with damaging power densities, right in the center of ered. Common sense should be applied
326 R. G. Calderhead

in the case of LED phototherapy for skin rejuve- tem’s having gone through the due regulatory
nation. However, if the system delivers light process to obtain what is known as a 510(k)
which is over the MPE, then protective eyewear approval showing significant equivalence to
becomes mandatory for the patient, and also for another system with prior approval based on
any ancillary staff spending any length of time in which, and only on which, can that device be
the treatment room to help protect their eyes legally sold in the USA for clinical use. 510(k)
against diffuse reflection from the target tissue. approvals for existing LED systems can be
For shorter visible wavelengths such as the blue searched for on the FDA website (www.fda.gov/
waveband, the inherent photon energy of the light cdrh/510khome.html), and the systems already
is approximately one-third as high again as visible mentioned by name earlier in this chapter all hold
red light even though the incident power density such clearance.
is the same, as discussed above, and so has greater
potential for optical damage. Appropriate eye-
wear is necessary in this case. Side Effects
The ‘blink reflex’ is nature’s way of helping us
protect our own eyes against an over-bright visi- Once again, the inherently ‘safe’ output of LED
ble light source, but near-IR light cannot be systems helps to keep unwanted side effects to a
‘seen’ by the human eye and so the blink reflex is minimum, but with any kind of phototherapy
not triggered by energy in this invisible wave- there is always the outside chance of triggering
band. Near-IR is still gathered and focused by the such a side effect. These are almost 100%
unaccommodated eye just as visible light is, how- photosensitivity-­related, so a careful history of
ever, so suitable protective eyewear is thus man- the patient must always be taken to identify the
datory for LED systems delivering energy in the existence of pre-existing photosensitivity issues.
near-IR waveband above the rated MPE for the For example, if a patient reports that he or she
wavelength being used. regularly comes out in an itchy rash when
Clinician goggles or glasses are obviously not exposed to terrestrial sunlight, LED photother-
opaque, so they have to be specifically sourced apy, especially in the visible light waveband,
with an appropriate optical density for the wave- should not be given. Some skin types, such as the
length of the system. Eyewear designed for red Asian skin, are incredibly sensitive to epidermal
light will not protect adequately against IR or vis- inflammation caused by other wavelengths
ible blue light, for example. The eyes of the despite being very resilient to UV skin damage.
patient, and indeed anyone with the patient in the Particularly in the Asian skin, secondary hyper-
treatment room during LED therapy, must be pigmentation (PIH) can occur without any appar-
assiduously protected even though LEDs are ent physical insult, and a carefully-taken history
often discounted as inherently ‘safe’, compared will show if the patient is predisposed to this very
with a surgical laser or IPL. It is better to err on upsetting side effect. A very small proportion of
the side of caution! patients treated with LED therapy have reported
Finally, national and federal regulatory agen- post-treatment headaches of varying magnitudes,
cies, such as the US Food and Drug Administration all of which have resolved spontaneously. No
(FDA), issue approvals of systems for specific reason has been elucidated for this, and treatment
applications for which they have been proved with mild analgesics has been found to speed up
‘safe and effective’. Although some manufactur- the resolution of the headache. Almost all of
ers have received such approvals, they are few those so afflicted have been undergoing LED
and far between. Some less than truthful manu- phototherapy for facial skin rejuvenation, but
factures will claim FDA approval, when in fact interestingly only a very few have actually
all they hold is a letter from FDA recognizing stopped turning up for their treatments. The main
that their LED system is a nonsignificant risk point is to take a very careful and thorough
device, or NSRD. This is NOT the same as a sys- patient history to identify the potential of any
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 327

LED therapy-related problems, but they are very energy in a favorable in vitro environment will
much extremely few and far between. For longer replicate at a much faster rate than control cells.
sessions of LED phototherapy, for example in However the in vitro environment is totally dif-
facial skin rejuvenation, the main “side effect” is ferent to the living body, where the cancer cell
that the patients tend to fall asleep during the is seen as an out-and-out enemy by the autoim-
treatment and ‘wake up’ feeling great! mune system, and is in a very unfavorable envi-
ronment surrounded by potential killer cells. As
mentioned above, the very first application of
Contraindications red LED PDT phototherapy was in the treat-
ment of skin cancers, and application of low
Leading on from the previous subsection, any incident levels of light have been shown to
kind of endogenous or exogenous photosensitiv- cause regression or even complete removal of
ity is a contraindication to LED phototherapy. aggressive tumors in animal models [86], and
Patients with any form of porphyria, for example, induce significantly prolonged survival times in
should never be treated with LEDs. Those whose terminally-ill cancer patients [87]. Furthermore,
history includes solar-mediated eruptions are low incident levels of light energy have been
likewise not good subjects. The careful derma- shown to boost the autoimmune system. Once
tologist should also ascertain what the patients again, however, discretion should be used in the
are putting on their skins prior to an LED therapy case of a patient with a cancerous condition
session. Ointments or creams containing known who is seeking LED phototherapy for some-
photosensitizers such as coumarins or porphyrins thing else at a site distant from the cancer, such
must be discontinued at least 2 weeks before any as skin rejuvenation. As a final note, in the more
LED treatment. Some oral drugs, e.g., amioda- than four decades since the laser and other light
rone for cardiac arrhythmia sufferers, strongly sources have been used in medicine and sur-
photosensitize patients to UV and visible light: gery, not one case of iatrogenic, phototherapy-­
LED phototherapy in such patients is contraindi- linked cancer has been reported in the
cated. Even some perfumes contain recognized literature.
photosensitizers. The application or ingestion of In short, LED phototherapy systems from
photosensitizing drugs including systemic reti- reputable manufacturers are inherently safe,
noids and the recent use of topical retinoic acid provided they are used according to the manu-
should also be carefully considered, and some facturer’s recommendations regarding eye pro-
acne treatments such as Roaccutane® (isotreti- tection, and approved treatment protocols.
noin) are all contraindications. LED-LLLT systems are basically side-effect
Other potential, possibly more ‘emotional’ free, apart from the beneficial side effects, and
contraindications include patients who are preg- will give continue to deliver side-effect free
nant or lactating, although these are not as abso- therapy provided the list of contraindications
lute as the in the previous paragraph and if the discussed above, and always provided by
LED therapy is not being delivered over the responsible manufacturers, is carefully applied,
womb as in the case of facial skin rejuvenation in addition to the taking of a careful patient his-
for example, then it can be given at the discretion tory. However, as already said, not any old LED
of the treating clinician, and with the informed system will do, and the careful dermatologist
consent of the patient. In fact, possible benefits must ensure that the system has appropriate
may well accrue to both the mother and fetus quasimonochromatic wavelengths, appropriate
from the systemic nature of blood-borne benefi- photon intensities over a sufficiently large area,
cial photoproducts. has a proven track record in the published litera-
The most emotional contraindication is for ture and has marketing approval from regulatory
patients with some form of cancer. It is true that bodies such as CE marking and US FDA
cancer cells irradiated with visible/near-IR clearance.
328 R. G. Calderhead

ATP production, although in practical clinical

Box 18.6 application this waveband is extremely lim-
• ‘New’ LED wavelengths not likely, ited by its poor penetration into the dermis due
but possible to absorption in the biological pigments mela-
• Further technical advances may nin and hemoglobin, which are its preferential
increase the scope of LED-LLLT chromophores. However, this waveband also
• Potential for LED-LLLT in the home has potential in the treatment of inflammatory
and OTC market rosacea and other very superficial entities. In
• LED-LLLT is safe, effective, easily addition, the epidermal keratinocytes and
applied, side effect-free and well-­ Merkel cells also present an interesting target
tolerated by all patients. as a form of dermal preconditioning when vis-
• Effective as a stand-alone light ther- ible yellow treatment is followed by 830 nm.
apy, LED-LLLT will also prove even One FDA-cleared LED system (HEALITE
more invaluable in adjunctive ther- II™, Lutronic, Goyang, South Korea and
apy to complement all existing modal- Freemont, CA, USA) uses the combination of
ities in dermatological practice. a period of irradiation with 595 nm-only ultra-­
low-­level light therapy followed by the appro-
priate dose of 830  nm near-IR energy as the
main treatment beam. The advantage of this
LED Phototherapy: Quo Vadis? lies in the fact that the yellow component con-
tinues to operate while the 830  nm beam is
There is no doubt that LED phototherapy has active. Although there is no longer a clinical
come a very long way in less than two decades, utility, the visible yellow light shows that the
with the ‘NASA LED’ being introduced in 1998. system is operating, a real benefit for the
The big question now is, where can it go? I patient as they can see that something is hap-
believe the answer depends on three main areas: pening, not the case where the invisible near-
wavelength; other technical developments; and ­IR at 830 nm is used on its own.
applications. • Visible red light from 620 to 680 nm, with a
‘best case’ at 633  nm because of the minor
absorption peak in the action spectrum of the
New Wavelengths porphyrins associated with exogenous 5-ALA
PDT, the major peak in the absorption spec-
It is possible that a ‘new’ (and useful) wavelength trum of cytochrome c oxidase, and its deep
will be ‘discovered’, but unlikely. Having said penetration into living skin. 633  nm is an
that, at the time of writing 1072 nm LED photo- excellent wavelength to activate fibroblasts in
therapy has attracted a great deal of attention in vivo even in the deeper dermis. It is also
the treatment of herpes simplex labialis, or cold attracting attention in hair loss and hair resto-
sores as mentioned above. Apart from that, The ration. This wavelength also has a tremendous
current main wavelengths are: published database, because it is the same as
the HeNe laser (632.8 nm).
• Soret band short wavelength visible blue light, • Near infrared at 830  nm, because it has the
with the optimum peak at 415 nm, the peak of deepest penetration of any wavelength due to
the action spectrum of the porphyrins endog- its being at the bottom of the water absorption
enous to P. acnes and created in skin treated curve, and has a well-proven track record as
with 5-ALA. the most useful laser therapy wavelength in
• Visible yellow at 590–595 nm, at a peak of the near infrared diode laser therapy for musculo-
action spectrum of cytochrome c oxidase in skeletal and neurogenic pain, enhancement of
the mitochondrial redox chain to instigate local blood and lymphatic flow, and wound
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 329

healing. This wavelength as delivered by acted in coordination with the photoabsorption

LEDs now has a good body of literature show- effects to give excellent bone healing, even in the
ing preferential effects in degranulation of case of slow union fractures [74]. No LED photo-
mast cells, photoactivation of neutrophils and therapy system is capable of delivering a true
macrophage cells with associated release of pulsed beam, and simply modulating a continu-
trophic factors, and enhanced remodeling in ous wave beam of tens or even hundreds of mil-
the wound healing process. liwatts per square centimeter will not produce the
same effect as the very tightly delivered, narrow
There are now many LED devices currently pulse-width true pulsed diode laser beam, so this
available that have wavelengths the same or very wavelength is also not an appropriate one for an
near to those given above, but we have to remem- LED system, given that one of the main advan-
ber that in many cases an action spectrum peak tages of LED arrays is the ability to irradiate a
has very narrow shoulders, so a difference of large area of tissue rather than a very small treat-
even 5 nm from the peak can in some cases dra- ment target. In all of the wavelengths bulleted
matically lower the action potential. There are above, and in their clinical application, the tar-
other wavelengths which have been proved use- gets are not precise points, and the ability to irra-
ful in the laser therapy literature, in particular diate a large tissue mass is an advantage. Despite
780 nm for neurological applications and 904 nm the present and future claims, I do not believe
for dental and other hard tissues, including bone. that we will see a ‘new’ and clinically proven
In the case of neurological indications, such as wavelength for light-only LED phototherapy in
repairing transected or crushed nerves, the punc- the near future.
tal nature of laser energy with its extremely high
photon intensity delivered within the very small
treatment area is essential to the treatment tech- New Technical Developments
nique: it is impossible to concentrate LED energy
from an array onto such a small spot, so LED sys- LED technology is constantly evolving, as seen in
tems at this wavelength would simply not have the current transition from the individually board-
the same effect as a laser diode-based handpiece mounted dome-type LED to the latest generation
(coherent LD-LLLT vs. noncoherent LED-­ of ‘on-board’ chips which are actually part of the
LLLT). In the case of 904 nm in hard tissue, the circuit board. There has been speculation about
laser systems used were based on a GaAs (gal- developing whole-body LED arrays, particularly
lium arsenide) laser diode. GaAs laser diodes are in the sports medicine and sports clinic environ-
capable of generating peak power outputs in the ment, so that athletes could have a complete LED
range of 15–45 W, but cannot be operated in con- ‘photobath’ after a strenuous workout to help relax
tinuous wave because of the tremendous heat overused muscles and dissipate lactic acidosis,
they generate and the need to provide a dedicated thereby enabling total retention of tonus in a delib-
cooling system. The GaAs laser diode is there- erate overtraining program to reach absolute peak
fore operated in a true pulsed mode, with pulse power and stamina. The application of such whole-
widths in nanoseconds and interpulse intervals of body arrays in the spa and beauty market would
milliseconds, so the average power seen by the also be very interesting. Some systems already
tissue is in milliwatts, usually 3 orders of magni- exist. The problem with such large arrays of good
tude less than the peak power: a 15 W peak power quality LEDs is heat. LEDs do not in themselves
would this give an average power at the tissue of generate a lot of heat because they are solid state,
15 mW. However, these ultrashort pulses create but when mounted in arrays they require on-board
effects in tissue other than photoabsorption, such driver circuitry, and this does generate a fair
as photoosmotic and photoacoustic effects. In amount of heat which must be dissipated other-
hard tissues such as bone, it was therefore pro- wise overheating of the LEDs will result in move-
posed that a physical resonance was set up which ment away from their rated wavelength, in addition
330 R. G. Calderhead

to shortening of their useful life. Efficient cooling ately selected LEDs are concerned. There are
of the circuit boards is thus essential and this is not already a large number of very pretty colored,
an easy matter even with the current size of arrays, happily twinkling LED-based systems being
to the extent that the method of cooling has actu- touted as suitable for home use, however the vast
ally been patented in some systems. In order to majority of them are mere toys, especially the
cool the number of large arrays which would be ones with multicolored LEDs, and the poor user
necessary for a whole-body LED generator would might as well stand in front of their christmas
require a dedicated and powerful cooling system, tree lights as use these systems. This does not
and this raises the dual problem of developing an mean that responsible manufacturers have not
appropriate method of extracting heat, whether it been researching correct combinations of appro-
was based on air- or water-based cooling, and priate wavelengths and intensities in
where the heat extracted from the LED arrays ergonomically-­ designed hand-held self-con-
would go. In a small treatment room, the heat tained units which will be safe and effective for
build-up could be very noticeable, as was the case home use: some indeed have. These units have
in the first generation of large surgical laser sys- become available in a number of ways: for pre-
tems. The development of on-board chips has scription by a dermatologist or other specialist as
gone some way to solving this problem, and the a maintenance program for their in-office LED
emergence of electrostatic cooling systems which treatment regimen; as an over-the-counter prod-
could be built directly into or onto the LED boards uct from chemists or pharmacists with product-
is very interesting. This is a field which will be related training; or from reputable self-health
very interesting to watch. mail-order companies. The author is aware of
Another area for development may well be in one company who has two such self-contained
the optics of the LEDs themselves. Currently hand-held products, one blue/red for treatment
LEDs deliver a divergent beam, typically in the of acne, and one infrared/red for skin rejuvena-
region of 60°–120° steradian. It is the deliberate tion, which have achieved FDA 510(k) clear-
overlapping of these divergent beams that causes ance. Despite their size, they have the same high
the phenomenon of photon interference, which, quality LEDs delivering the same intensity in
coupled with scattering of light in target tissue, mW/cm2 as the medical versions of the systems
allows LED arrays to deliver very useful photon based on LED arrays. When used for the recom-
intensities over large areas of tissue. As men- mended time they will thus deliver exactly the
tioned already, corrective collimating optics have same dose as their much larger cousins. Naturally
already been used in one system to reduce the they cover a very much smaller area than the
angle of divergence of LEDS in an array, thereby full-sized planar arrays, but because of their
giving a higher photon intensity for the same irra- lightweight nature, it is anticipated that the user
diance at the LED.  However, LEDs are nonco- will be able to watch TV or listen to music while
herent, so it is extremely challenging to collimate irradiating the target area one bit at a time, and
the beam of light from an LED completely, unlike they will be absolutely ideal for a maintenance
the case of the laser diode in the ubiquitous laser program following office or clinic treatment
pointer. Likewise, focusing an LED to a very with the full-sized systems. Home use LED-
small point, as can be achieved with a laser LLLT is therefore yet another area to be watched
source, is impossible, and the most efficient with great interest.
focusing lens would produce simply a very small
inverted image of the LED.  Semi-collimation
would appear to be the limit for altering the beam Applications: Combination Is Key
of energy from an LED, unless there are advances
in chip technology. The applications for light-only LED photother-
The final area is the home market, which is tied apy continue to grow in a pan-speciality manner,
into the previous subsections as far as appropri- so that a large range of clinicians is finding useful
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 331

applications for LED phototherapy of appropri-

ate wavelength and incident photon intensity. Box 18.7
However, as with lasers, a saturation point will • LED phototherapy is here to stay!
be reached. This can be combatted by using • ‘Any old LED’ will NOT fit the bill!
LED phototherapy in combination with exist- • When considering buying an LED
ing conventional surgical and nonsurgical system, ask the right questions!
approaches to achieve even better results. A per- • Combination treatment is the key!
fect example where this is happening is full face
laser ablative resurfacing. Initially hailed as a
superb approach to rejuvenating severely photo-
 onclusions (And Questions
C
aged skin, in recent years it has declined dra-
You Should Ask)
matically in popularity because of potential side
effects such as scarring, unpleasant-looking
LED phototherapy is certainly here to stay, but
sequelae and a very long downtime before the
unfortunately the medicoscientific waters are
patient can once again return to work or to soci-
being muddied by a number of manufacturers
ety. However, everyone agrees it is still the ‘gold
who have jumped on the LED bandwagon, mak-
standard’, particularly for deep wrinkles and
ing extravagant claims and barefacedly using the
severe photodamage. Some reports have now
data amassed by those companies who have been
appeared on the use of LED phototherapy
responsible enough to go through regulatory
together with ablative laser resurfacing. The
approvals, such as FDA 510(k) clearances, as if
controlled study already discussed above by
the data were their own. Statements such as ‘….
Trelles et  al. is an excellent example which
uses NASA technology ….’ are common, but
compared two groups of full-face ablative resur-
totally misleading. The current generation of
facing patients [56]: one group was also treated
LEDs actually exceeds the 1990s NASA technol-
with LED phototherapy, and the control group
ogy as far as output power and quasimonochro-
was not, but otherwise the resurfacing and
maticity are concerned, and in fact have
wound care regimens were exactly the same.
absolutely nothing to do with NASA! Even worse
The healing time in the LED-treated group was
than these manufacturers are the companies
cut by more than one-half, postoperative pain
which import ‘lookalikes’ from the Eastern
was cut by more than 70% and the erythema
block. They may be cheap, but they are certainly
cleared in less than 7 weeks compared with up
not cheerful, and the heart of an LED system is
to 4–6 months.
the quality and pedigree of the LEDs used in its
LED phototherapy can and does offer even
arrays: you get what you pay for. To make sure
better results in any case where the dermatologist
you get what you actually want, i.e., an LED pho-
has in some way altered the epidermal and der-
totherapy system that will actually do something
mal architecture of his or her patient, whether it is
that you want it to do, and make you and your
as mild as an epidermal powder peel, through
patients happy, please see the following, which
chemical peels to nonablative resurfacing with
will not only summarize the main points of the
lasers or IPL systems, fractional laser and non-­
chapter but will also reinforce my favorite maxim
laser approaches, like microneedling radiofre-
which is; ‘Any old LED will NOT do’.
quency, and full-face ablative resurfacing. The
adjunctive application of LED phototherapy will,
I believe, drive its acceptance even more strongly  aveat Emptor (Let the Buyer
C
than its use as a stand-alone modality, and the Beware!)
major advantage of LED-based systems is their
very competitive pricing in addition to their por- When considering purchasing an LED-based
tability and versatility. Combination therapy is phototherapy system for his or her practice, the
the key [53, 54]. wise dermatologist should always ask the manu-
332 R. G. Calderhead

facturer or salesperson the following questions While on the subject of wavelength, some
(and take a written note of verified or verifiable manufacturers offer all the colors of the rainbow
answers!). in the one system, in one particular system
mounted in a semicircular bar which scans over
 hat Regulatory Approvals Does
W the face with the claim that ‘blue is for serenity,
the System Have? green is for inner peace, yellow is for well-being,
This means appropriate FDA 510(k) approvals in and red is for relaxation’. In fact, this manufac-
the USA (no LED system has yet got full premar- turer is not offering phototherapy, but ‘chromo-
keting approval, PMA), Health Canada in therapy’ also known as ‘colorology’ which is an
Canada, TGA in Australia, Ministry of Health, alternative medical approach based on ‘chakras’
Labour and Welfare (Kohseishou) in Japan, and their associated colors to achieve balance in
appropriate CE marking for medical devices in an unbalanced system [88]. As with reflexology,
Europe, and so on. It does not mean having the origin of the approach is Russian, as is a great
‘NASA technology LED’s’ or ‘Approved by the deal of the literature, but chromotherapy has a
FDA’, the latter of which usually simply means a large following. The methods and English lan-
letter from FDA recognizing that the system is a guage studies used to prove that it works, how-
nonsignificant risk device (NSR) or minimal risk ever, have been severely criticized [89]. In
device (MSR). This is not an approval to market, addition, as Karu and colleagues have well-­
but is simply a guide based on which the institu- demonstrated, the intermingling of wavelengths
tional review board (IRB) of a research center way well include some which cancel each other
can classify the system when it does take part in out thus having no effect, or indeed downregulate
a properly structured study. cellular activity compared to the wavelengths
applied individually [12]. The fact that the light is
 hat Is (Are) the Wavelength(s)?
W scanned over the face should sound another
As has been said many times, wavelength is the warning bell, since this dramatically lowers the
most important single factor when attempting to dose, even if the photon intensity were high
achieve a photoreaction: no absorption, no reac- enough (which it is not). The answer? Keep to
tion. Some targets can respond to a fairly broad well-proven wavelengths, applied singly and
waveband of 30–100 nm or so, but most of the with a suitable period (48–72 h) allowed between
targets in LED phototherapy are much more applications to allow the targeted cells to respond
specific. Ask what the nominal wavelength of to the information they have received.
the system is, and what is the deviation either
side. For example, the Omnilux revive™ and  hat Is the Intensity?
W
HEALITE II mentioned elsewhere in this chap- You are looking for an answer here in mW/cm2
ter have LED arrays with a nominal wavelength, (milliwatts per square centimeter) of the entire
with the range of ±5–7  nm. That means that array, not the ‘lumens’ of an individual LED or
93–95% of the photons are at the rated wave- indeed the whole array, nor should you be told
length and will therefore optimally target that the system is “very bright”. If in doubt about
wavelength-­specific chromophores at that wave- this parameter and its paramount importance,
length such as 633  nm for cytochrome c oxi- next to wavelength, please re-review section
dase, and 415 nm for the porphyrins Cp III and “Irradiance (Photon Intensity)” above on photon
Pp IX endogenous to P. acnes. Visible red at density, another way of saying ‘intensity’. A
670 nm, for example, will still have some effect good range, depending on wavelength, would be
on cytochrome c oxidase, but that wavelength anywhere from 40 mW/cm2 up to 150 mW/cm2,
just misses the boat as far as peak efficiency of although the higher the intensity, the more prob-
exogenous porphyrin activation is concerned for lems will exist in keeping the LED array cool
ALA PDT, where 633 nm is the wavelength of enough to avoid discomfort to the patient and a
choice. drift away from the LED nominal wavelength. If
18  Current Status of Light-Emitting Diode Phototherapy in Dermatological Practice 333

this range seems low compared with a diode laser manufacturer will have arrived at by conducting
therapy system, for example, always bear in mind dose-ranging response-related studies. If the rec-
that the better LED systems cover a large area of ommended dose is, for example, 120 J/cm2 over
tissue, for example some offer an active array 20  min, increasing the irradiation time by
area of 220 cm2, unlike the laser therapy system 10–30 min will not get a 50% better effect, but on
which usually irradiates a spot of only a few mm the other hand, cutting the time down by half to
in diameter per ‘shot’. 10 min may well give a result well below 50% of
If you get an answer in joules, ignore it … bet- that achieved at the recommended time. If an
ter still, laugh loudly. If you get an answer in LED-LLLT system supports arrays with different
joules per square centimeter (J/cm2), that’s better, wavelengths, the manufacturer may well have
but it is actually the answer to the next question! standardized the treatment time to the same for
The incident intensity or power density is each of the heads, but the dose will almost always
extremely important, because a higher power be different for each wavelength, simply because
density enables a shorter irradiation time, and it of a combination of LED characteristics, wave-
has been reported for a continuous wave system length/tissue interactions and the individual pho-
that shorter irradiation times with a higher inten- ton energy associated with each wavelength.
sity got significantly better results in first passage
human gingival fibroblast proliferation in vitro  ow Should the LED Energy
H
compared with longer irradiation times at a lower Be Delivered?
intensity, even though the dose (in J/cm2) was the The answer here will be ‘in continuous wave (or
same [90]. Of course, the Arndt-Schultz curve CW)’, which is good; or ‘frequency modulated
must always be remembered (section “Irradiance (also known as photomodulated)’ which is not so
(Photon Intensity)” above), and the upper limit of good; or ‘pulsed’, which is actually the incorrect
photoactivation must never be exceeded or a pho- way of saying the second answer and is totally
tothermal reaction will occur. wrong! Light at a given wavelength already con-
tains its own frequency, as discussed in section
 hat Is the Recommended Dose?
W “Temporal Profile of the Beam” above, and light
This is where the J/cm2 unit should be the correct represents ‘information’ to cellular targets.
answer, but NOT the dreaded joule. If you see a Imposing a secondary frequency on that primary
joule running around an LED system, kill it. As frequency can not only disrupt the flow of infor-
discussed above, the joule is simply a unit of mation, it also cuts down on the dose since there
energy and has no significance whatever on the is no light incident on the target cells when the
clinical effect in a prescribed area of target tissue. source is switched off. It is true that cells have a
Correlate the dose with the recommended irradi- ‘dark reaction’ time as shown by Karu [91], but
ation time. As a matter of interest, if you cannot it occurs well after irradiation, and not in the
find out the intensity from the manufacturer, by short off-duty interval in a frequency modulated
dividing the dose (J/cm2) by the irradiation time beam cycle. Figure  18.28 is by an independent
(in seconds), you will end up with the intensity in research group, Almeida-Lopes and colleagues
W/cm2 (or mW/cm2). at the University of Sao Paulo, Brazil, who
For this category, there is no ‘correct’ dose for reported the data on power density in Ref. [90]
an LED-LLLT system, although it should cer- above, and shows the growth pattern of first pas-
tainly be no lower than 20  J/cm2 depending on sage human gingival fibroblasts exposed in vitro
the wavelength. If the intensity or power density to 640 nm at several frequencies and continuous
is correct, then it is almost impossible to over- wave (CW), with constant incident power den-
dose. Overdosing is not recommended, however, sity and dose as ascertained in earlier studies.
simply because it wastes time and will not often There was a significant difference seen between
produce dramatically better results than the the group of frequencies and the unirradiated
recommended dose, which the responsible controls (p  >  0.01 for all), with the higher
 334 R. G. Calderhead

70 Incident radiant flux (dose): 2.25 J/cm2 can produce to look like a genuine publication,
Incident power: 56 mW although they may actually contain good data, or
60 λ = 640 nm
Cell count x 1000

50 Continuous wave articles from the commercially-oriented medical

180 Hz
120 Hz ‡ press unless they are also in turn backed up by
40
60 Hz ‘real’ papers. All of the referenced works in this
30 10 Hz
Control chapter are either from peer-reviewed PubMed
20
listed journals, or books from reputable publish-
10 ers. Also, make very sure that the articles offered
0 by the manufacturer/salesperson are on their
0 2 4 6
specific system and wavelength(s). Very often
­
Time (Days)
articles on approved systems by another manu-
Fig. 18.28 An in vitro experiment to assess the effects of facturer will be cited as ‘proof’ that their (unap-
various frequencies in frequency modulated beams com- proved) system works, even though sometimes
pared with a continuous wave beam and an unirradiated
control on the cell proliferation of first passage pooled
the intensity, dose or even wavelength is not the
human gingival fibroblasts. The dose was kept constant at same as in the published articles.
2.25 J/cm2. All of the frequencies were statistically signifi-
cantly better at increasing proliferation (§, p  <  0.01 for
all). The CW beam, however, was significantly more effi-
cient than both the control and the frequency modulated
Finally ….
beams (‡, p  <  0.001 and §, p  <  0.01, respectively). The
results represent the averaged data from ten repeated Despite the moaning of the sceptics, LED photo-
experiments. (Used with the permission of Pra. Lucianatherapy has definitely arrived, has been proven to
Almeida-Lopes, personal communication, data as yet
unpublished)
work in many areas, and is finding a rapidly
increasing number of applications both within
frequencies inducing better cell proliferation, and outside dermatology. LED-LLLT systems
but the continuous wave beam induced greatest are comparatively inexpensive and robust, LED-­
and most significant proliferation compared with LLLT itself is easy to administer, safe, effective,
both the unirradiated controls (p < 0.001) and the pain free (in fact it can be used to treat pain),
frequency modulated beams (p  <  0.01). The side-effect free, well-tolerated by patients of all
experiment was repeated ten times and the ages from infants to centenarians, and minimally
results averaged. (Data and graph reproduced contraindicated. It offers the possibility of a
with the permission of Pra. Luciana Almeida- stand-alone noninvasive phototherapy method,
Lopes, as yet unpublished data). Cells, espe- but when used together with any of the methods
cially first passage human gingival fibroblasts, currently used by the dermatologist to alter his or
seem to prefer CW to frequency modulated her patient’s skin, already good results can be
energy. expected to become even better. LED photother-
apy will not turn a poor dermatologist into a good
What Has Been Published one, but it will help the good dermatologist to
on the System/Technology? become even better, with happier patients. And
What you are looking for here are papers by rep- finally, please remember, above all, not any old
utable authors published in the indexed and peer-­ LED will do the job!
reviewed literature, or at least in well-established
and peer-reviewed journals (15 or more volumes)
which have not yet been indexed by MedLine References
and/or PubMed but which do none-the-less have
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 Laser and Light for Wound Healing
Stimulation 19
Ehsan Azimi, Navid Bouzari, and Keyvan Nouri

Abstract wounds however, are more challenging. The

Understanding wound healing is critical for incidence of chronic wounds in the United
health care professionals mainly because of States is approximately five to seven million
the enormous burden of chronic wounds on per year (Sen et  al., Wound Repair Regen
society. In addition, in many medical special- 17(6):763–771, 2009) and the annual costs
ties, creating wounds for diagnostic and thera- for management of these wounds is greater
peutic purposes is part of a physician’s daily than $20 billion.
practice.
Acute wounds are usually closed using Keywords
sutures, staples, or other methods of wound Wound healing · Chronic wounds · Tissue
closure. Conventional modalities include welding · Tissue soldering · Helium-neon
maintenance of a moist wound bed, and pre- lasers · Gallium-arsenide (GaAs) lasers ·
vention of infection. Although acute wounds Gallium-aluminum-arsenide (GaAlAs) lasers
are not challenging in most settings, they · Nd:YAG lasers · Carbon dioxide lasers ·
may influence the hospital stay or expenses Ruby lasers · Krypton lasers · Argon dye lasers
related to medical procedures. Chronic

E. Azimi
Department of Dermatology, Cutaneous Biology
Research Center, Massachusetts General Hospital,
Charlestown, MA, USA
N. Bouzari
South Shore Skin Center, Plymouth, MA, USA
e-mail: [email protected]
K. Nouri (*)
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 339

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_19
340 E. Azimi et al.

Summary Box Current hypotheses are: stimulation of

• Cutaneous wound healing is divided Ca influx and mitosis rate, increased
into three phases: the inflammatory expression of Heat-Shock-Proteins (e.g.
phase, the proliferative phase, and the HSP70 and HSP47), increased expres-
remodeling phase sion of growth factors such as TGF-β,
• The wound healing process can be alteration of mitochondrial activity and
applied to both acute and chronic increased ATP synthesis, augmented
wounds. Acute wounds are generally formation of mRNA and protein secre-
less than 8 weeks, and usually result in a tion, enhancement of fibroblast and
sustained restoration of anatomic and keratinocyte proliferation and migra-
functional integrity. Chronic wounds are tion, angiogenesis, improvement of
defined as wounds that have failed to phagocytosis, and increased rate of
proceed through the usual stepwise transformation of fibroblasts into
fashion. Lasers are used for healing of myofibroblasts.
both acute and chronic wounds.
• The main techniques of laser-assisted
wound closure of acute wounds are:
simple tissue welding, tissue soldering, Introduction
dye-enhanced tissue welding, and addi-
tion of growth factors. Understanding the wound healing is critical for
• The potential advantages of laser- health care professionals mainly because of the
assisted tissue bonding over conven- enormous burden of chronic wounds on society.
tional methods include increased In addition, in many medical specialties, creating
immediate wound strength, fluid-tight wounds for diagnostic and therapeutic purposes
closure, decreased operative repair time, is part of physician daily practice.
reduced probability of infection and Acute wounds are usually closed using sutures,
bleeding, and improved cosmetic staples, or other methods of wound closure.
results. However, lasers have disadvan- Conventional modalities include maintenance of a
tages such as their high cost, risk of moist wound bed, and prevention of infection.
dehiscence, risk of thermal damage, and Although acute wounds are not challenging in
inconsistency of the results. most settings, they may influence the hospital stay
• The exact mechanism involved in laser- or expenses related to medical procedures. Chronic
assisted wound closure is not com- wounds however, are more challenging. The inci-
pletely understood. The heat produced dence of chronic wounds in the United States is
by laser energy in the tissue causes col- approximately five to seven million per year [1]
lagen fibers to loose their triple helix and the annual costs for management of these
structure and become fused, intertwined, wounds is greater than $20 billion [2, 3]. Accurate
swollen, and dissolved. diagnosis is the key, and can be clinically made in
• Different lasers for treating chronic less than 75% of cases [4]. Treatment usually con-
wounds include helium-neon, gallium- sists of debridement of necrotic tissue, mainte-
arsenide (GaAs), gallium-aluminum- nance of a moist wound bed, and control of
arsenide (GaAlAs), Nd:YAG, carbon infection. Unfortunately, despite many progresses,
dioxide, ruby, krypton, and argon dye treating chronic wounds is still challenging.
lasers Laser and light based technologies have
• The exact mechanism of action of low recently emerged as alternative therapies for
intensity laser therapy is not known. wound healing. A variety of lasers and light
sources have been introduced as a non-invasive
19  Laser and Light for Wound Healing Stimulation 341

tool for chronic wound healing as well as an observed, which mediates tissue repair and even-
alternative method of closure of surgical wounds. tually the reestablishment of the barrier function
This chapter will discuss the role of this new of the skin. Tissue repair is divided into three
technology in wound healing. phases: the inflammatory phase, the proliferative
phase, and the remodeling phase [5] (Fig. 19.1).

Wound Healing
Inflammatory Phase
Understanding the process of wound repair is a
prerequisite to maximizing our knowledge The initial event in tissue injury is the damage to
regarding the use of lasers for wound healing. endothelial cells and blood vessels. This causes
Cutaneous wound healing involves the complex extravasation of blood into the wound and colla-
interaction of several types of cells, their cyto- gen exposure which leads to blood clotting,
kines or mediators, and the extracellular matrix. platelet aggregation and activation, as well as
After cutaneous injury a cascade of events is migration of neutrophils and monocytes (and

PDGF Platelet
EGF
TGF-β Neutrophil
IGF-1
Serotonin Macrophage
Fibrinogen
Tissue injury ADP
Epithelial cell
TXA2
Fibroblast
Phagocytose bacteria
and matrix proteins
Blood extravasation PDGF
FGF
TGF-β
TGF-α
VEGF
Angiogenesis

Inflammatory phase IL-1 Activin

TGF-β TGF-α
Migration and proliferation

IL-6 KGF
PDGF HB-EGF
Migration and proliferation GM-CSF

Proliferative phase
Collagenase,
hyaluronidase Collagen III degradation

Collagen remodeling

Collagen I synthesis

Remodeling phase
0 Minutes to hours Day 1 Day 7 Day 14 Months

Fig. 19.1  Phases of wound healing: The inflammatory ing collagen III by collagen I. IL interleukin, KGF kerati-
phase starts within minutes after tissue injury with extrav- nocyte growth factor, FGF fibroblast growth factor, VEGF
asation of blood followed by activation of platelets, mono- vascular endothelial growth factor, PDGF platelet-derived
cytes and macrophages, release of mediators and growth factor, EGF epidermal growth factor, HB-EGF
cytokines. These cytokines induce the proliferative phase heparin binding EGF, TGF-α transforming growth factor-
by activating keratinocyte and fibroblast proliferation and alfa, TGF-β transforming growth factor-beta, IGF-1 insu-
migration, as well as release of a variety of growth factors lin-like growth factor-1, GM-CSF granulocyte-macrophage
involve in angiogenesis and granulation tissue formation. colony stimulating factor, ADP adenosine diphosphate,
The last phase of wound healing is remodeling via replac- TXA2 thromboxane A2
342 E. Azimi et al.

subsequently macrophages) to the site of injury. the normal skin ratio of 4:1 for type I collagen to
Activated platelets release a variety of mediators type III collagen is present. In addition, the com-
(Fig. 19.1) which initiate the wound healing cas- position of other matrix material such as water,
cade by attracting and activating fibroblasts, fibronectin, hyaluronic acid, and proteoglycans
endothelial cells and macrophages. Neutrophils, changes over the period of a year or more [5, 9].
once in the wound environment, phagocytose
bacteria and matrix proteins. Later in the inflam-
matory phase, monocytes and macrophages Acute vs. Chronic Ulcers
become the dominant figures, and release a vari-
ety of cytokines, inducing epithelial cell migra- The wound healing process can be applied to
tion and proliferation as well as matrix production both acute and chronic wounds. Acute wounds
[5, 6]. are generally less than 8 weeks, and usually result
in a sustained restoration of anatomic and func-
tional integrity. Chronic wounds are defined as
Proliferative Phase wounds that have failed to proceed through the
usual stepwise fashion. As a result, the healing
This phase involves the creation of a permeability process is prolonged and incomplete, with lack of
barrier as well as the establishment of an appro- restoration of integrity [10]. A large number of
priate blood supply and reinforcement of the factors can impede wound healing and may pre-
injured tissue. Keratinocytes and fibroblasts pro- dispose a patient to the development of chronic
liferate and migrate to the wound bed. Fibroblast wound. These include both local factors (wound
proliferation and migration are modulated by infection, tissue hypoxia, repeated trauma, the
PDGF, EGF, TGF-α, TGF-β and presence of debris and necrotic tissue), and sys-
FGF.  Macrophages play a key role in initiating temic causes (diabetes mellitus, malnutrition,
fibroblast proliferation and migration. When the immunodeficiency, and the use of certain medi-
number of macrophages begins to diminish, cations) [11–13].
fibroblasts and keratinocytes are the main source
of the growth factors. The interplay of keratino-
cytes with fibroblasts gradually shifts the micro- Lasers for Wound Healing
environment away from an inflammatory to a
synthesis-driven granulation tissue. The use of laser energy for wound healing was
In the granulation tissue, mesenchymal cells proposed more than 35 years ago [14]. It was first
are maximally activated, cells proliferate, and suggested for bonding skin incisions, and termed
synthesize huge amounts of extracellular matrix “laser welding”. Interest in the efficacy of lasers
which supports the developing capillary loops. as a noninvasive tool for treatment of all types of
Keratinocytes proliferate and migrate over the wounds soon grew among researchers in both ani-
provisional matrix of the underlying granulation mal models [15, 16] and clinical studies [17, 18].
tissue, eventually closing the defect [5, 7, 8]. The concept that surgeons can replace their scal-
pels and tedious suturing techniques with a sim-
ple, non-operator-dependent, safe, and rapid
Remodeling Phase technique, has inspired many investigators to
experiment on different laser systems [19]. The
In this phase, remodeling of the collagen into a areas of research can be divided in two major
more organized structure occurs in order to groups: lasers to augment the healing of acute
increase the wound’s tensile strength. The type wounds (tissue welding, tissue soldering, etc. see
III collagen of the granulation tissue is replaced below), and lasers for chronic wound (e.g. low
by type I collagen through a tightly controlled intensity laser devices, see below). Although these
synthesis of new collagen and lysis of old until two groups of lasers share many similarities, there
19  Laser and Light for Wound Healing Stimulation 343

are differences in their mechanism of action, laser Table 19.1 Lasers commonly used in acute wound
systems, laser parameters, etc. which will be dis- healing
cussed in this chapter. Technique Laser System + Solder/dye
Tissue welding CO2
Argon
Lasers for Acute Wounds Nd:YAG
Diode
Tissue soldering Diode + Albumin-genipin
Interest for tissue welding for closure of acute Diode + Methylene blue
wounds first came out of early experiences with Diode + albumin
the use of electrocautery energy [20]. Later, laser Diode + fibrinogen
energy was introduced for vascular anastomosis CO2 + Albumin
and then for other type of acute wounds. After the Nd:YAG + albumin
introduction of laser-assisted wound closure, it Argon + fibrinogen
was rapidly evident that welding of skin was dif- Dye-enhanced Alexandrite + indocyanine green
ficult. In fact, the initial tensile strength of the Argon + fluorescein isothiocyanate
Diode + indocyanine green
wound was weak compared with conventional
Diode + gold nanoshells
sutures in the first few days post incision [15, 21,
22]. However, the wound healing process was
generally accelerated, and the cosmetic aspect of tensile strength during the first few days; (2)
the scar was improved. In order to enhance the noticeable thermal damage; (3) inconsistency of
tensile strength and minimize the thermal dam- the results [19].
age, various improvements have been suggested. Tissue Soldering: Laser-assisted tissue solder-
The main techniques are simple tissue welding, ing uses an additional component known as a
tissue soldering, dye-enhanced tissue welding, “solder” for better wound closure. The solder
and addition of growth factors (Table 19.1). (bovine albumin, human albumin, blood etc.)
Tissue Welding: The first method introduced absorbs the laser energy, coagulates, and as a
for laser-assisted wound closure was “tissue result, enhances the tensile strength while mini-
welding”. The principle of laser-assisted tissue mizing the thermal damage of the surrounding
welding is based on the heat produced by the tissue [19, 28]. Laser-assisted tissue soldering
laser irradiation. The increased temperature in has been carried out using two types of lasers:
the skin causes collagen denaturation and the lasers such as Nd:YAG and GaAs, whose radia-
crosslinking of fibrils [23]. It is crucial to esti- tion penetrates deep into tissue [29]; and lasers
mate the optimal photonic energy that is to be such as CO2, whose radiation is highly absorbed
delivered to tissue. In this respect, major deter- by surface tissue [21]. A variety of solders have
mining factors are laser wavelength, power, also been studied (Table  19.1). Albumin as a
exposure time, and mode of operations (continu- ­solder, was introduced in 1988, and showed to be
ous wave or pulsed). For this reason, various promising in the following studies with CO2,
types of laser systems were investigated diode and Nd:YAG lasers [15, 30–32]. Other sol-
(Table 19.1) [15, 24–26]. The first successful use ders such as fibrinogen [33], Albumin-genipin
of a laser in tissue welding was in 1979 when [34], and methylene blue [35] have also been
ND:YAG was used to repair incisions made in suggested. Again, the major drawback of this
blood vessels of a rat [27]. Later, tissue welding technique was the weak tensile strength of the
was successfully performed for skin closure as repairs due to the decreased solubility of the par-
well as for anastomosis of other tissues [15]. tially denatured solder. To overcome this prob-
Despite progresses made in tissue welding, sur- lem, “2-layer” soldering was developed. In
geons still do not embrace this new laser technol- “2-layer” soldering, the layer in contact with tis-
ogy. The main reasons can be summarized in sue absorbs the laser and bonds to tissue while
three main drawbacks of laser welding: (1) low the second layer provides cohesive strength and
344 E. Azimi et al.

flexibility. The main limitation of this method is ative to maintain a predetermined tissue tempera-
lack of flexibility of bonded tissue [36]. ture in order to prevent thermal degradation of
Dye-enhanced tissue welding: The concept of growth factors [40].
using a topical tissue-staining dye to facilitate
selective delivery of laser energy by the target tis-
sue has been postulated to improve tissue weld-  asers vs. Conventional Methods
L
ing. A nontoxic dye that is strongly absorbed by a of Acute Wound Closure
specific laser wavelength can serve to confine
photon absorption and the resultant thermal Conventional techniques for tissue bonding
energy to the weld site. A variety of combinations (sutures, staples, and adhesives) are highly reliable
of dyes and lasers have been studied with vari- procedures that have proven themselves over the
able success rates [17, 33, 37, 38]. It seems that years to be good clinical practice. Sutures have
combination of indocyanine green with either been successfully used for centuries. They are
pulsed alexandrite or pulsed diode laser is supe- inexpensive, flexible, reliable, and readily avail-
rior to other dye-enhanced tissue welding tech- able [15]. However, they are not the perfect tech-
niques. Nonetheless, it is worth noting that very nique due to several reasons (Table  19.2). Since
limited clinical data have been available yet that sutures cause trauma to the skin, and i­ntroduce
confirm the clinical value of dye-enhanced tissue foreign body, they can result in inflammation,
welding. granuloma formation, and scarring. Many techni-
Nanoshells are a new class of nanoparticles cal factors such as position on the needle in the
consisting of a dielectric core surrounded by a holder, the slope of the tissue at needle entrance,
thin metal shell. Use of gold nanoshells in con- suture spacing, knot tension, and choice of suture
junction with near Infrared light has recently material can affect wound healing [25, 41]. Staples
been suggested as a means of dye-enhanced tis- are another mean of wound closure which share
sue welding. Application of lasers at wavelengths many common characteristics with sutures.
within the near infrared, the region between However, they are faster and more uniform than
approximately 650 and 900  nm, where tissue sutures. Their main disadvantage is that they come
components have minimal absorption, decreases in predetermined size which precludes their use in
the chance of widespread thermal damage and some anatomical sites. Adhesives are clean, fast,
improves penetration depth [39]. The use of non-operator-dependant, painless method of
nanoshells has several advantages over indocya- wound closure. They are an excellent “no needle”
nine green. For example, the small size of alternative in pediatric patients. However, for most
nanoshells reduces diffusion from the site of applications, they have not been able to provide
treatment and concentrates heating at the inter- adequate strength [15, 42, 43].
face to be welded. Also they are less photosensi- As shown in detail in this chapter, laser-
tive hydrolytically sensitive and susceptible to assisted tissue bonding can transcend the limita-
photobleaching in the presence of light compar- tions of conventional methods in many aspects.
ing to indocyanine green. Their potential advantages over conventional
Addition of Growth factors: Attempts have methods include increased immediate wound
been made to use recombinant growth factors, as strength, fluid-tight closure, decreased operative
an adjunct to laser-assisted tissue soldering to repair time, reduced probability of infection and
accelerate wound healing. A variety of growth bleeding, and improved cosmetic results.
factors such as HB-EGF, FGF, TGF-β, etc. have However, there have been several obstacles
been studied. The result of an animal study by which prevented physicians from using laser
Poppas and colleagues showed that addition of welding clinically. These included collateral ther-
TGF-β to the solder (albumin in their study) mal injuries, inconsistency of the results, and a
increases the tensile strength of the wound by lack of understanding of the exact mechanism by
more than 50%. Using this technique, it is imper- which laser irradiation induces tissue bonding. In
19  Laser and Light for Wound Healing Stimulation 345

Table 19.2  Advantages and disadvantages of different methods of wound closure

Advantage Disadvantage
Suture Reliable Cause trauma to the tissue
Flexible Time consuming
Inexpensive Operator dependant
Available Introduce foreign body
No immediate watertight closure
Risk of needle-stick
Risk of infection (due to lack of sealing)
Need suture removal
Staple Reliable Cause trauma to the tissue
Available Inflexible (predetermined size)
Relatively quick Introduce foreign body
Not operator dependant No immediate watertight closure
Risk of needle-stick
Risk of infection (due to lack of sealing)
Need staple removal
Adhesive Immediate watertight closure Expensive (controversial)
Painless Does not provide hemostasis
No trauma to tissue Introduce foreign body
“No needle” procedure (Possible) need for subcutaneous sutures
Less risk of infection Risk of tissue reactivity
No need for removal Not flexible (comparing to sutures)
Fast
Laser Immediate watertight closure Expensive
Better scar Not readily available
“No needle” procedure Foreign body (Soldering, dye-enhanced)
Less risk of infection Risk of dehiscence
No need for removal Complicated (many parameters to consider)
Fast Risk of thermal damage
Dynamic effects (may increase growth Inconsistent results
factors)

addition, there are many parameters that need to Mechanism of Laser-Assisted Wound
be optimized in the welding process. These Bonding
parameters include wavelength, fluence, pulse
duration, repetition rate, irradiation time, spot The exact mechanism involved in laser-assisted
size, and solder selection. Indeed, the parameter wound closure is not completely understood.
window for optimum tissue bonding is very Nonetheless, what is commonly believed is that
small. All parameters should be chosen appropri- tissue bonding occurs mainly due to the thermal
ately to provide enough heat for denaturation and effect of laser. The heat produced by laser energy
crosslinking of collagen fibers, but not to the in the tissue causes collagen fibers to loose their
level of tissue necrosis and sloughing of wound triple helix structure and become fused, inter-
edges. What makes the use of laser even more twined, swollen, and dissolved. This generates a
complicated is the fact that energy levels and coagulum that serves both as a coating for sealing
exposure times that may work very well with cer- the wound and as a sophisticated scaffold for re-
tain tissues may not be the best for other situa- colonization of cells, as in the case of re-epitheli-
tions [15, 19]. As we discuss later in this chapter, alization [26, 44, 45]. Other theories have been
several thermal feedback systems have been sug- postulated, as to say Helmsworth and colleagues
gested to overcome the above limitations. believe that welding effect is the result of reorga-
346 E. Azimi et al.

nization of intramolecular disulfide bonds of of the light, their absorption by tissue compo-
laminin, type IV collagen, and entactin rather nents is minimal; hence, they may need to be
than covalent bonds of type I collagen [46]. used in conjunction with exogenous absorbers
Despite the controversies, it seems that collagen to induce welding. Due to its water and melanin
plays a major role although bonding is most absorption coefficient values [47], Nd:YAG
likely dependant on extracellular proteins rather (1064 nm) is another infrared laser used in tis-
than collagen alone. sue welding. Like many of the near infrared
lasers, Nd:YAG laser needs to be used with sol-
ders for optimal welding. It should be noted
 aser Systems and Parameters
L that most of our knowledge about lasers used
for Optimal Wound Bonding for wound bonding is on either in-vitro or ani-
mal studies. Therefore, the optimal laser sys-
In order to achieve a reliable tensile strength, it tems and parameters for human wound closure
is crucial to estimate the optimal photonic yet to be determined.
energy that is to be delivered to tissue. In this
respect, major determining factors are laser
wavelength, power, exposure time, and mode of Lasers for Chronic Wounds
operations (continuous wave or pulsed). For
this reason, various types of laser systems were Laser irradiation was introduced as a noninva-
investigated [15, 25]. CO2 was one of the first sive therapeutic modality for acceleration of
lasers employed for wound bonding because of wound healing in the late 1960s, and has since
its availability. However, it is a poor choice of been used for the treatment of a variety of
wavelength and unlikely to yield a reliable high chronic ulcers [49]. Different laser systems such
strength bonds. Due to the high absorption at as helium-neon, gallium-arsenide (GaAs), gal-
the surface, the outermost tissue layers are lium-aluminum-arsenide (GaAlAs), Nd:YAG,
“overcooked,” whereas the deeper layers are carbon dioxide, ruby, krypton, and argon dye
hardly affected at all. Therefore, the tempera- lasers have been studied [50, 51]. Despite differ-
ture in dermis is not high enough for collagen ences in wavelengths, the common characteristic
alteration and fusion. If the energy is increased of all these lasers is that they all employ low
to achieve the suitable temperature in dermis, energy for wound healing. This method of ther-
the surface will burn. Increasing the pulse dura- apy has been known as low-intensity, low-power,
tion will also result in producing a large zone of or low-level laser therapy. It has been suggested
thermal damage. Like CO2 laser, holmium:YAG to increase the speed, quality and tensile strength
(Ho:YAG) has a high absorption by water, of tissue repair, resolve inflammation and pro-
hence causes thermal injury at the surface. To vide pain relief. The use of low intensity laser
overcome this problem, these lasers need to be therapy is not limited to wound healing; and it
used under a temperature-controlled system. has been used in odontological, rehabilitative,
Near Infrared lasers (650–900  nm) such as and other medical specialties. The basic princi-
diode lasers are also becoming more popular in ple of laser therapy is that low intensity laser
welding studies. While the wavelengths radiation has the capability to alter cellular
between 780 and 850 nm have the advantage of behavior in the absence of significant heating.
less absorption by water, their relatively high Previous works have been focused on three
absorption by melanin prevents their deeper areas: in-vitro studies on molecular and cellular
penetration [47, 48]. Recently, 980-nm diode function, animal studies, and human trials.
was suggested as a better wavelength for wound Unfortunately, the clinical data is mostly anec-
closure due to its better absorption by water and dotal, poorly controlled, and more variable than
less absorption by melanin comparing to other might be desired. The in-vitro and animal studies
infrared lasers [48]. In general, although near are less arguable, and provide most of the scien-
infrared lasers would allow deeper penetration tific rationale of laser therapy.
19  Laser and Light for Wound Healing Stimulation 347

Table 19.3  Commonly used lasers for different types of that depending on the applied dose, wavelength,
chronic ulcers irradiation time, and also the conditions of the
Type of treated tissue, different positive and negative bio-
chronic Laser type and Energy (J/ logical answers can be achieved.
ulcer wavelength cm2) Resulta
Venous 810 nm 4.0 Not effective
GaA1As
660–950 nm 12.0 Effective Mechanism of Laser-Assisted
GaA1As Wound Healing
904 nm GaAs 1.0 Effective
632.8 nm 4.0 Effective The exact mechanism of action of low intensity
HeNe
laser therapy is not completely understood.
810 nm diode 4.0 Effective
Pressure 904 nm GaAs 1.0 Effective
Currently there is no accepted theory to explain the
830 nm diode 5.0 Effective mechanism of low-intensity lasers, and this lack of
Diabetic 670 nm diode 18 and 36 Not effective knowledge complicates the evaluation of conflict-
with 36 J/cm2 ing reports in the literature. Another limitation is
632.8 nm 1.0, 4.0, Effective with the lack of ideal models of chronic wounds. Most
HeNe 4.8, 5.0, all except of the studies have been conducted on surgically
10.0, and 16 J/cm2
16.0 excised skin. These wound models excluded com-
904 nm GaAs 1.0 Effective mon problems associated with delayed healing,
830 nm diode 5.0 Effective such as ischemia, infection, and necrotic debris.
a
The results given are based on authors’ conclusion. Not What makes the data even more confusing is that a
all the studies are well controlled randomized trials variety of laser parameters such as wavelength, flu-
ence, and time of treatment onset can influence the
Lasers have been used for healing of a variety biologic effects of low intensity lasers.
of chronic wounds such as pressure ulcers, The suggested mechanisms at molecular level
venous ulcers, and diabetic ulcers [Table 19.3]. are stimulation of Ca influx and mitosis rate,
The first implication of lasers for pressure ulcers increased expression of Heat-Shock-Proteins
was to use them as a surgical tool for debride- (HSP70 is overexpressed in the laser-induced
ment. Controlled trials on CO2 laser versus con- thermal damage zone and HSP47 is expressed
ventional debridement showed less bleeding, less during the recovery phase [62]), increased expres-
infection, and shorter hospital stay with the use sion of growth factors such as TGF-β, alteration
of CO2 laser [52, 53]. Later, low intensity lasers of mitochondrial activity and increased ATP syn-
such as diode and GaAs were attempted. While thesis, augmented formation of mRNA and pro-
some reports found impressive wound healing tein secretion. On the cellular level laser-induced
outcomes, some others showed no advantages changes are enhancement of fibroblast and kerati-
[54–56]. There is insufficient evidence to suggest nocyte proliferation and migration, angiogenesis,
a benefit of treating venous ulcers with low- improvement of phagocytosis, and increased rate
intensity laser therapy. Most of the data are anec- of transformation of fibroblasts into myofibro-
dotal, and there is only one small randomized blasts (Fig.  19.2) [62–70]. Some of the animal
controlled trial suggesting the therapeutic benefit studies on laser-assisted wound healing are in
of laser therapy for venous ulcers [57]. Low accordance of molecular and cellular studies,
intensity laser therapy has been shown by various showing decreased inflammatory period,
studies to be effective in the treatment of diabetic increased collagen and granulation tissue in the
wound healing [58]. Some of the suggested wound bed, increased tensile strength, and faster
advantages of this method are increased micro- epithelialization [55, 71, 72]. However, repeated
circulation, increased speed of healing, improved experiments on many of the above in-vitro and
wound epithelialization, increased granulation animal models have failed to verify these benefits.
tissue formation, and increased collagen deposi- These conflicting reports may partly be explained
tion [59–61]. However, some authors emphasize by considering discordance among the laser types
348 E. Azimi et al.

PDGF Platelet
EGF
TGF-β Neutrophil
IGF-1
Serotonin Macrophage
Fibrinogen
Tissue injury ADP
Epithelial cell
TXA2
Fibroblast
Phagocytose bacteria
and matrix proteins
Blood extravasation PDGF
FGF
TGF-β
TGF-α
VEGF
Angiogenesis

Inflammatory phase IL-1 Activin

TGF-β TGF-α
Migration and proliferation

Laser IL-6 KGF

PDGF HB-EGF
Migration and proliferation GM-CSF

Proliferative phase
Collagenase,
hyaluronidase Collagen III degradation

Collagen remodeling

Collagen I synthesis

Remodeling phase
0 Minutes to hours Day 1 Day 7 Day 14 Months

Fig. 19.2  The molecular and cellular effects of low keratinocytes. At molecular level, they increase FGF,
intensity lasers on chronic wounds: Lasers mainly affect TGF-β, VEGF, IL-6, and PDGF. IL interleukin, FGF
inflammatory and proliferative phases of wound healing. fibroblast growth factor, VEGF vascular endothelial
At cellular level, lasers improve phagocytosis, enhance growth factor, PDGF platelet-derived growth factor, TGF-
angiogenesis, and increase proliferation of fibroblasts and β transforming growth factor-beta

used, the parameters selected, and the wound A clinical practice guideline (2006 revision). J Foot
models chosen. In summary, to better understand Ankle Surg. 2006;45(5 Suppl):S1–66.
4. de Araujo T, Valencia I, Federman DG, Kirsner
the role of low intensity lasers in healing of RS.  Managing the patient with venous ulcers. Ann
chronic wounds, well-controlled studies that cor- Intern Med. 2003;138(4):326–34.
relate cellular effects [55] and biologic processes 5. Bolognia J, Jorizzo JL, Rapini RP.  Dermatology.
are needed. In the absence of such studies, the lit- London: Mosby; 2003.
6. Clark RA, Ghosh K, Tonnesen MG.  Tissue engi-
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of lasers in wound healing at this time. 2007;127(5):1018–29.
7. Werner S, Krieg T, Smola H. Keratinocyte-fibroblast
interactions in wound healing. J Invest Dermatol.
2007;127(5):998–1008.
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 Lasers in Hair Growth and Hair
Transplantation 20
Nicole E. Rogers, Marc R. Avram,
Isabella Camacho, and Ali Rajabi-Estarabadi

Abstract • Results from hair transplantation are consis-

Results from hair transplantation are consis- tently natural
tently natural. • Demand for the procedure has increased
Demand for the procedure has increased significantly
significantly. • Lasers have been implemented in the field of
Lasers have been implemented in the field hair transplantation to create recipient sites
of hair transplantation to create recipient sites and enhance hair growth
and enhance hair growth.

Keywords Introduction
Hair growth · Hair transplantation · Lasers
Lasers have been an exciting new technology in
the field of hair loss and hair transplantation.
Since the theory of selective photothermolysis
was introduced in 1983 by Anderson and Parrish
[1], there has been a virtual explosion of laser
applications, ranging from hair removal to facial
rejuvenation to treatment of unwanted blood ves-
sels. One area that is still early in its development
is lasers for hair loss and hair transplantation.
This is especially exciting because a relatively
N. E. Rogers (*) limited number of treatment options exist for
Hair Restoration of the South, Metairie, LA, USA treating hair loss. FDA-approved medical treat-
M. R. Avram ments for hair loss include topical minoxidil and
Department of Dermatology, Weill Cornell Medical oral finasteride. The minoxidil 5% foam was
Center, New York, NY, USA
recently approved for once daily use in women.
I. Camacho Some women can benefit from birth control pills,
School of Medicine, Georgetown University,
oral spironolactone or finasteride (off-label in
Washington, DC, USA
pre-menopausal women due to risks of
A. Rajabi-Estarabadi
teratogenicity).
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine, The field of hair transplantation has under-
Miami, FL, USA gone a significant transformation during the

© Springer International Publishing AG, part of Springer Nature 2018 351

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_20
352 N. E. Rogers et al.

Fig. 20.3  Patient 2: before hair transplantation

Fig. 20.1  Patient 1: before hair transplantation

Fig. 20.4  Patient 2: after 900 grafts

were treated in 2014 worldwide for hair resto-

ration. In the United States, 112,409 surgical
hair restoration procedures were performed in
2014, compared to 88,304 surgical hair restora-
Fig. 20.2  Patient 1: after 1000 grafts tion procedures performed in 2012, showing a
27% increase [2].
last 10–15 years. With the advent of follicular This chapter will focus on the two major laser
unit transplantation, patients achieve far better applications affecting the hair: (1) laser-assisted
results than they could with the original unnatu- creation of recipient sites in hair transplantation,
ral punch grafts (Figs.  20.1, 20.2, 20.3 and and (2) the use of low-level-laser therapy to
20.4). This cosmetic revolution has resulted in increase hair growth. Both applications have
an ever-­increasing demand for the procedure. faced considerable controversy within the laser
According to the International Society of Hair and hair transplant community. We attempt to
Restoration Surgery, practice census results provide a balanced perspective of each so that
from 2015 estimated that about 358,109 surgi- their roles may be fairly assessed and possibly
cal patients and 697,372 non-­surgical patients even implemented.
20  Lasers in Hair Growth and Hair Transplantation 353

Hair Transplantation

In addition to medical therapy, hair transplanta-

tion can provide even more dramatic and perma-
nent results. The field of hair transplantation has
evolved considerably over the last few decades as
large ‘pluggy’ punch grafts have been replaced
with tiny 1–4 hair follicular unit grafts. Nowadays
patients can expect very natural-looking results
(Fig.  20.5a, b). Hairs are harvested from the
occipital donor area either as an elliptical strip,
and then separated into individual grafts using
magnification, or they are manually or roboti-
cally harvested individually using 0.8–1  mm
punches (follicular unit extraction, Fig.  20.6).
Then, the grafts are placed back into pinpoint
slits created in the areas of thinning. The body’s
natural clotting factors act as a glue to hold the
grafts in place. Most hair transplant doctors use
steel blades or needles to create recipient sites.
Fig. 20.6  Harvesting of single follicular units using
manual extraction process
a
Over a week’s time small scabs form around the
grafts, and after 2–6 weeks the grafts will enter a
resting telogen phase and shed. By 6–9  months
the hairs start growing in and by 12–18 months,
patients can expect their full results.
In using needles to create recipient sites, phy-
sicians face several challenges. The foremost
among these is hemostasis. As each new recipient
site is created, bleeding makes graft placement
difficult and time-consuming. Heavy drinkers or
patients on aspirin or blood-thinning supple-
b
ments may present even more of a challenge.
Grafts may pop out and require replacement.
This challenge prevents many interested derma-
tologic surgeons from entering the field.

Lasers in Hair Transplantation

• Recipient sites for hair transplantation are

usually made with needles
• Difficulties with hemostasis called for the use
of CO2 lasers for recipient site creation
Fig. 20.5 (a) Male patient before hair transplant surgery.
(b) Same patient 9  months after hair surgery (1050 1–4 • In 1996, the FDA approved lasers for use in
hair grafts) hair transplantation
354 N. E. Rogers et al.

The first application of lasers in hair trans- sealing off of blood led to limited graft ‘take’
plant surgery was for the creation of recipient and frequent graft fallout [5]. By adjusting the
sites in areas of thinning hair. CO2 lasers of the laser’s energy down slightly, there was an
10,600 nm wavelength were developed for abla- increase in “biological glue” that kept future
tive resurfacing of the face and skin. They were grafts from falling out.
used to create incisions several millimeters deep Subsequent studies confirmed the ability to
where the hair grafts could be placed. The goal make recipient sites with excellent hemostasis
was to create recipient sites with better hemosta- and growth of transplanted hair (Figs.  20.7 and
sis because the CO2 laser would stop bleeding 20.8) [5, 6]. These studies led to FDA approval of
instantly [3]. Also because the alopecic skin lasers for hair transplantation in 1996 [7–9]. FDA
would be vaporized, there would be less risk of approval resulted in a worldwide interest and use
graft compression and greater density (hairs per of lasers to create recipient sites. Yet, today very
square cm) could be achieved [4]. few hair surgeons use laser to make recipient
Carbon dioxide lasers were introduced in the sites. What happened?
mid-1960s. They were popularized in the 1970s in
dermatologic surgery because of their ability to
vaporize tissue and seal blood vessels. The prob-
lem with continuous wave carbon dioxide lasers
was the peripheral non-specific spread of heat,
resulting in widespread scarring of the skin. In the
1990s, the concept of selective photothermolysis
was applied to carbon dioxide lasers. By limiting
the exposure time of the laser to less than one-half
of the thermal relaxation time of the surrounding
tissue, there was a significant reduction in lateral
thermal damage. This allowed CO2 lasers to
vaporize tissue with excellent hemostasis and no Fig. 20.7  Laser recipient sites versus steel created sites
scarring. Pulsed CO2 lasers were introduced to
treat dermatoheliosis and acne scarring with dra-
matic results.
The problems of bleeding and popping of
grafts at recipient sites remained. The investiga-
tion of handpieces for creating recipient sites in
pulsed CO2 lasers was begun in the mid-1990s to
over come this problem. High energy pulsed CO2
lasers would vaporize tissue and seal dermal ves-
sels with excellent hemostasis.
Initial studies found that average graft hair
counts were greater in laser-created sites in four
of the ten patients, and looked more natural [3].
They also found that there was less bleeding in
the laser-created sites, and that the associated
grafts required less handling. Despite extensive
research by highly experienced hair transplant
surgeons, the long-term implementation of
lasers for hair transplant surgery was limited. Fig. 20.8  Physician making CO2 laser assisted recipient
This was because in some cases the complete sites
20  Lasers in Hair Growth and Hair Transplantation 355

• Lasers have a minor role in hair To overcome the lateral tissue necrosis associ-
transplantation ated with CO2 lasers, clinicians have tried to use
• Steel needles can provide closer site creation, holmium:YAG or erbium:YAG lasers instead of
with less lateral damage, resulting in greater traditional CO2 lasers for recipient site creation.
density and less post-surgical hemorrhagic Histologic studies of the Ho:YAG (λ = 2120 nm)
crusting demonstrated no advantage over traditional CO2
[4]. It created jagged, irregular-shaped channels
Some clinicians and investigators reported with even larger zones of thermal injury. The
superficial de-epithelialization surrounding the Er:YAG (λ  =  2940  nm) has shown promising
sites. This led to greater and longer-lasting results in creating recipient sites for both andro-
crusts post-operatively. Delayed hair growth of genetic alopecia [13] and cicatricial alopecia
2–6  weeks was also observed [5]. The chief [14]. Its use in a 2-year clinical trial produced
obstacle over time was density. There was sig- greater than 95% yield of 1–4-hair follicular units
nificant collateral damage to the surrounding with no reported side effects [15]. However, its
tissues, which affected the growth of existing use has been limited by the lack of hemostasis
pigmented terminal hair follicles. Histologic and the inability to create sites deep enough with
studies of laser-­created site showed a minimum single pulse (Fig. 20.10).
of 20–50 μm of lateral thermal damage through There have been newer studies showing the ben-
the dermis (Fig.  20.9). Although lasers were efits of using ablative carbon dioxide (CO2) frac-
able to create excellent hemostasis and growth tional laser therapy. In one of the most recent
of transplanted hair, it did not allow for close studies, it has been shown that combining hair
placement of recipient sites among existing hair growth factors with ablative CO2 fractional laser
follicles. Nineteen gauge needles could more therapy is more beneficial than using hair growth
safely create closely spaced sites than pulsed factor alone for male androgenetic alopecia (MAA).
CO2 lasers. If the recipient sites were created After six treatment sessions involving 27 patients in
too close together, poor growth, telogen efflu- a randomized half-split study, 93% of patients in the
vium, or complete skin necrosis could occur. combined group showed improvement compared to
Add to these problems the expense of the laser 67% of patients in the growth factor group.
purchase and maintenance, the risk of damage Discomfort due to treatment resolved in 2–3 days in
to water-containing organs such as the cornea, all patients, with the most common side effect being
as well as the associated learning curve, and the post-treatment erythema [16]. Another study deter-
technique has largely fallen out of favor mined that ablative CO2 fractional lasers induce hair
[10–12].

Fig. 20.9  Pathology showing CO2 laser assisted recipient

sites for hair transplantation Fig. 20.10 CO2 laser and Erbium laser
356 N. E. Rogers et al.

growth by the activation of the Wnt10b/β-catenin • Formation of smoke plume containing possi-
pathway in  vivo, with results indicating that the bly infectious disease
10 mJ/spot and 300 spots/cm2 setting was the most • Potential for igniting a fire with concomitant
effective dosage [17]. According to this study, after oxygen use with sedation
using an ablative CO2 fractional laser, the wound
healing process results in progression into the ana- There are also risks inherent in the CO2 laser
gen phase of the hair follicle cycle, thus, increasing because it targets water as its primary chromo-
hair growth. phore. Laser operators must be aware of the pos-
Using lasers for hair transplantation can be sibility of damaging organs high in water content,
helpful for novices to the field, in controlling such as the cornea. There is also the formation of
bleeding and reducing time to place the grafts. a smoke plume, which could contain bacteria,
However, it may take more time to create sites viral DNA, or viable cells. The high voltage of a
with an appropriate angle and spacing. CO2 laser may pose an electrical hazard by ignit-
Recipient sites cannot be made too close ing tissue, oxygen, or volatile solvents used in
together due to the dermal necrosis. If they are hair products. As seen in (Table 20.1), there are
too closely made, widespread necrosis of the as many advantages as there are disadvantages to
scalp may occur. It is unclear whether the using lasers for hair transplantation.
vaporization of tissue by laser creates enough More recent methods include robotic technol-
density to outweigh this requirement. ogy that is now being used to harvest individual
Ultimately, one must consider factors like the follicular grafts from the back of the scalp, and
cost of the laser and whether this technique is this may soon be applied to the creation of recip-
superior to current standard of practice. It may ient sites as well [23]. Table 20.2 includes a list
be hard for an expensive, complex laser to beat of different tools that presently used most fre-
the ease and economy of using needles or steel quently for the creation of recipient sites
blades, especially when bleeding is not a sig- (Fig. 20.11).
nificant problem for the experienced hair trans-
plant surgeon.
Perhaps novel fractional ablative devices will Lasers in Hair Growth
be able to create recipient sites as close as #19
and #20 gauge needles without the increased risk • LLLT (Low Level Light Therapy) has been
of necrosis. Creating a fractional ablative hand- further studied in randomized, controlled tri-
piece with a scanner would allow recipient sites als showing beneficial results
to be created quicker, with better hemostasis • Devices are sold without a prescription,
leading to reduced operating time for patient and through direct-to-consumer marketing
physician.
The application of lasers for hair growth is
• CO2 ablative lasers have FDA approval for based on the rare observation of hair growth in
hair transplantation. patients after laser hair removal. This ‘paradoxi-
• Not used in hair transplants due to density. cal hypertrichosis’ has been reported following
• If laser transplant is performed, spacing too treatment with the long-pulsed Nd:Yag laser
close will result in telogen effluvium. (755  nm) [24], the diode laser (810  nm) [25],
• Fractional ablative lasers may allow greater and with intense pulsed light (650–1200  nm)
density in the future. [26–28]. Endre Mester, a Hungarian physician,
was the first to observe in the 1960s that mice
Risks Inherent in CO2 Laser Usage treated with lasers designed to prevent cancer
actually regrew hair in half the time of mice not
• Damage to water-containing organs, such as exposed to laser treatment [29]. He shaved off
the cornea their dorsal hair and divided the mice into
20  Lasers in Hair Growth and Hair Transplantation 357

Table 20.1  Pros and cons of lasers in hair transplantation

Pros of lasers in hair transplantation
1. Improved hemostasis because blood vessels are sealed by laser
2. Reduced time to plant grafts
3. May be easier for beginner hair transplant doctors, as well as their assistants
4. Nerve endings, like blood vessels, are sealed with theoretical reduction in pain [3]
5. May achieve higher density because tissue is vaporized, not just pushed apart [4]
6. Less graft compression, again because alopecic skin measuring 1–2 mm wide is vaporized [3]
7. Less handling of the graft itself, because the laser-prepared sites are wider (1–2 mm) than scalpel created sites.
8. Don’t have to constantly sharpen 1–2 mm trephines [3]
9. Less risk of cobblestoning (from graft elevation) or pitting (from graft depression) because there is a constant
depth of laser-created site [3]
10. Use of less epinephrine [10]
11. Shorter operative time, which translates to less patient discomfort and less staff frustration [18]
12. Lower risk of cyst formation as a result of tissue left behind [19]
Cons of lasers in hair transplantation
1. Expense of laser, required office space, and maintenance [20, 21]
2. May fray epithelial edges and cause superficial de-epithelialization [5]
3. Greater postoperative crusting [4, 22]
4. Delayed (2–6 weeks) regrowth of transplanted follicles [5]
5. Risk of telogen effluvium from heat of laser—may thin sites with existing hair
6. Increased risk of secondary infection [5]
7. Risk of injury to adjacent hair follicles in recipient area [5]
8. May achieve lower density because cannot place so close as to risk necrosis [20, 21]
9. Longer operating time, because of difficulty creating site at the appropriate angle [5]
10. Persistent erythema [22]
11. Learning curve associated with using laser [5]
12. Plume may contain noxious and carcinogenic chemicals

Table 20.2  Traditional tools for recipient site creation control and treatment groups, the latter receiv-
Traditional needles: 17 g (4 hair FU’s), 18 g (3 hair ing a low-powered ruby laser therapy (694 nm).
FU’s), 19 g (2 hair FU’s) or 20 g (1 hair FU’s) He found no evidence of cancer in the mice, but
Chisel blades (custom cut) did observe that the laser-treated group had
Spear point blade faster hair regrowth. This was the origin of “bio-
Minde blade stimulation” using “cold laser” or “soft laser”
No-core needles
therapy administered at lower powers of
1–500  mW.  Higher powered lasers, emitting
1–10  W, are used to clear blood vessels or
hyperpigmentation.
Several other parameters are involved in
administering LLLT.  Wavelengths of 600–
700 nm are used to treat superficial tissues, while
780–950 nm wavelengths are used for deeper tis-
sues. There is a biphasic dose response curve, in
which the central distribution, 700–770 nm is not
considered to have as much activity. The dose of
energy is comparable to regular laser use,
between 1 and 20 J, but it is delivered in a much
Fig. 20.11  Instruments presently used to create recipient slower way (Power = J/s = watts).
sites Basic Science of LLLT
358 N. E. Rogers et al.

• Stimulates the mitochondrial transport chain intermembranous space. These protons enter
• Enhances ATP production back into the mitochondrial matrix through chan-
• Stimulates wound healing nels in the ATP synthase enzyme complex. This
• Reduces inflammation entry is coupled to ATP synthesis from ADP and
• Improves neurologic damage, such as with phosphate (Pi) (Fig. 20.13).
stroke LLLT has been found to increase the activity
• Improves musculoskeletal and joint pain of Complex II and Complex IV in particular [34].
This was demonstrated in a controlled study of
The use of LLLT is based on several scientific wounds treated with AsGa (gallium arsenate,
papers showing that it can increase ATP levels in 904 nm) low-level laser. This study also showed
tissues by stimulating the mitochondrial transport a clinical improvement in the rate of wound heal-
system [30–32]. To fully understand this we must ing after LLLT.  Another study using the same
briefly review the structure and mechanisms of laser but at a slightly different wavelength
ATP synthesis in mitochondria. These intracellu- (808 nm) showed enhancement of ATP ­production
lar organelles are considered to be the power- in human neuronal cells in culture [30]. This sup-
houses of the cell. They have an outer membrane ports the observation that LLLT can help in the
and an inner membrane, which has numerous setting of neurologic damage following strokes
infoldings or cristae. Between these two mem- [35, 36]. Its ability to repair neurologically dam-
branes there is an intramembranous space. The aged tissue may be a function of inhibiting nitric
very center of the mitochondria is called the oxide synthase and upregulating the expression
matrix (Fig. 20.12). of transforming growth factor-beta 1 [37].
The respiratory chain has five major com- It appears that low-level-lasers can help not
plexes that shuttle electrons from the intramem- only with neurologic damage but also with neu-
branous space into the matrix. These include rogenic pain and musculoskeletal complaints.
NADH dehydrogenase (Complex I), ATP succi- Peer-reviewed studies found it helpful in treating
nate dehydrogenase (Complex II), cytochrome c low back pain [38], temporomandibular joint dis-
reductase (Complex III), cytochrome c oxidase orders [39], and rheumatoid arthritis patients
(Complex IV), ATP synthase (Complex V) and with carpal tunnel syndrome [40]. In fact, the
two freely diffusible molecules ubiquinone and MicroLight 830 is a low level laser, which
cytochrome c that shuttle electrons from one received 510K medical device clearance by the
complex to the next [33]. By transferring elec- FDA in 2002 for the treatment of carpal tunnel
trons centrally, a proton gradient is built up in the syndrome. Some chiropractors and practitioners
of holistic medicine attest to its usefulness in
Outer membrane
treating patients with other chronic disorders like
fibromyalgia [41, 42]. They liken it to acupunc-
Intramembranous space ture, in providing a noninvasive treatment where
other options have failed. As mentioned above,
Inner membrane
LLLT can improve wound healing.
One study showed that the helium neon laser,
Matrix at a wavelength of 633 nm, was effective in stim-
Cristae * ulating the cellular responses of wounded fibro-
blasts and promoting cell migration [43]. Another
* study looking at LLLT for wound healing in dia-
betic rats found faster healing in the treatment
group, again with an optimum wavelength of
633 nm [44].
Perhaps most important is the evidence that
Fig. 20.12  Structure of mitochondria LLLT can reduce levels of inflammation in the
20  Lasers in Hair Growth and Hair Transplantation 359

Intermembrane
4H+ space 4H+ 2H+

+ + + + + + + + Cyto C2+ + + + + + + H+
e
QH2
e
I e III
Q
II
IV

NADH2 Fumarate Cyto C3+ 1/2O2+2e-

Succinate
NAD-
Mitochondrial
matrix H2O

ATP ADP+Pi

Fig. 20.13  Structure of the mitochondrial transport chain (Reprinted from Hamblin MR, Demidova TN. Mechanisms
of low level light therapy. Proc SPIE. 2006;6140:614001 [33], with permission from the SPIE)

tissues. It was found to reduce the levels of TNF-­ [48]. He observed that strips of smooth muscle
alpha in rats treated with a 650  nm  Ga-Al-As from intestinal tissue would alternately contract
laser [45]. It has also been found to reduce levels and relax as he cast a shadow or allowed UV light
of serum prostaglandin E2 in rats with zymosan-­ to shine on it, respectively. Years later he won the
induced arthritis that underwent illumination Nobel prize for identifying that UV light acti-
with 810 nm laser [46]. The authors also observed vates the release of nitric oxide from vascular
a reduction in joint swelling that was comparable smooth muscle cells [49]. This photo-activated
to treatment with dexamethasone. Finally, levels vasodilation may allow increased blood supply to
of COX-2 mRNA expression are also reduced in nearby hair follicles. If so, this would be similar
patients treated with LLLT [47]. to minoxidil’s proposed effect of vasodilation on
These results suggest that LLLT may be use- the follicles.
ful in treating autoimmune and other disorders
based on inflammation, where primary treat-
ments have failed. Hair disorders such as lichen LLLT Products
planopilaris and alopecia areata may even bene-
fit. Androgenetic alopecia, which is not an The application of low-level light therapy (LLLT)
inflammatory process, may improve more from for male and female hair loss began shortly after
increased energy and ATP created by the laser. the turn of the century with only manufacturer
Studies are lacking to directly link the production data. A laser comb delivery of LLLT was FDA
of ATP with the enhancement of hair growth. cleared for treatment of male pattern hair loss in
However, there are many drugs whose mecha- 2007, but with mixed reviews among physicians
nism of action is still unclear. It would be a shame [22, 50]. The devices were marketed directly to
to omit a helpful treatment from our armamen- consumers via the internet, television, and other
tarium simply because we do not yet understand print advertisements. Soon, however, hair loss
it. Hopefully more studies will soon bring this to specialists began to offer chair-type devices in
light. their offices and sold helmets, hats, and brushes
One possible explanation for the effect of light and combs that contained the low-level light
on hair follicles is photo-relaxation, a concept technology. In 2011 the same laser comb device
proposed by Dr. Robert Furchgott in the 1950s was cleared for treatment of female pattern hair
360 N. E. Rogers et al.

Table 20.3  Low-level light therapy devices everything but later its makers were charged with
Hairmax LaserComb™ libel and misbranding [54].
Sunetics® Laser Hair Brush and Clinical unit Some other names in the industry of LLLT for
Revage® 670 laser (chair unit) hair growth are Sunetics® International, located
Spencer Forrest X5 (Handheld) Hair Laser™ in Las Vegas, NV [55] and the Revage 670® laser
LaserCap® (via physicians only) [56]. The Sunetics product comes either as a
iGrow® Hair laser System brush ($200–400) or as a freestanding machine
Capillus® (via physicians only)
for total scalp treatments ($39,900). It uses a
650  nm wavelength at a fluence of 5  mW.  It is
loss as well [51]. Since the last edition of this marketed especially among hair transplant offices
book, there has been a further increase in the to increase the quality/quantity of the donor area,
number of commercially available LLLT devices to reduce the pain and to speed wound healing
(Table 20.3). after transplant, and to prevent or reduce hair loss
The Hairmax Lasercomb™ has been one of from post-transplant shock. It also is sold as an
the most publicized products on the market. It option for men and women who do not want to
was developed and patented by Lexington undergo a hair transplant procedure and haven’t
International in 2000. Although the exact improved with minoxidil or finasteride. The
wavelength and other parameters are kept con- Revage 670® is a chair-based laser that uses rota-
fidential, the manufacturers do reveal that it tional phototherapy containing 30 diodes that
uses a diode laser operating in the red portion rotate 180° around the scalp. It is given as in-­
of the visible color spectrum [52]. It gives off a office treatments 2×/week for 6 weeks then once
monochromatic, collimated laser energy. It is weekly for 16 weeks. Each treatment session is
indicated to promote hair growth in males with 30 min each.
androgenetic alopecia who have Norwood The first study investigating low-level light
Hamilton Classifications of Ia to V and therapy for hair loss was published in 2003 in a
Fitzpatrick skin types I to IV.  Reports of the non-peer-reviewed journal [57]. It was sup-
data they submitted to the FDA are positive, ported by the manufacturers of HairMax
showing increased hair counts among almost LaserComb™. It enrolled 35 patients with
all patients in their four-site study. However, androgenetic alopecia (AGA). Twenty-eight
they have chosen to keep the specifics of this males and seven females were given a handheld
data proprietary. And although the trials were laser comb to use at home for 6 full months,
done only in men, they market the product to combing the hair for 5–10 min daily. They found
women as well. The FDA approved it in that overall, for men and women there was a
January 2007 after the company filed a 510(k) 93.5% increase in hair counts in both temporal
notice, requesting that it be registered as a and vertex sites. Tensile strength of individual
medical device. hairs also increased by 78.9%.
One caveat is that FDA approval of medical Another independent study was performed by
devices is far less rigorous than it is for standard the authors in 2008 using the Sunetics® clinical
pharmaceutical drugs. This labeling indicates unit (hood) device. Participants received 20-min
that the FDA has reviewed the product and found treatment sessions twice weekly for 3–6 months.
it to be safe and ‘substantially equivalent’ to Trichoscopy showed a decrease in the number of
predicate devices already on the market. The vellus hairs, increase in the number of terminal
most similar predicate device is the TerraQuant, a hairs, and an increase in shaft diameter, however
handheld LLLT device emitting 60–90 W within the study was limited by a small patient popula-
the 600–900  nm wavelength for treatment of tion (n = 7) and the results were not statistically
musculoskeletal pain [53]. Other such devices significant [58].
include the Violet Ray device, which was manu- In 2009, the first of several randomized con-
factured in the 1950s as a treatment for nearly trolled trials was published. It was supported by
20  Lasers in Hair Growth and Hair Transplantation 361

the manufacturers of HairMax LaserComb™. institutions. All trials were registered at www.
This was a multi-center sham-device controlled clinicaltrials.gov as well as the Institutional
study that did demonstrate statistically significant Review Boards for each participating author. A
improvements in hair growth in men over a sham total of 128 male and 141 female subjects with
device [59]. AGA were randomized to receive either a laser
In 2013, several more randomized, controlled comb (1 of 3 models) or a sham device (emitting
trials were published. One study tested the Oaze, white light), to apply to the scalp three times
a helmet-type device emitting LEDs with wave- weekly for 26  weeks. The subjects and site
lengths of 630, 650 and 660  nm. Forty Korean investigators remained blinded as to the type of
subjects with AGA were enrolled and received device and the analysis of the digital photo-
either an active or sham device to use at home for graphs was also blinded.
18 min daily. A tattoo was used to mark the area Overall, 103 males and 122 females com-
of study within the frontal or vertex area, and pleted the study. The female patients had an
phototrichogram analysis was performed at base- increase in mean terminal hair count from base-
line, 12 weeks, and 24 weeks. After 24 weeks of line of 20.2, 20.6, and 18.4 hairs per cm2 in the
treatment, the active group showed statistically 9-beam, 12-beam, 7-beam devices compared
significantly greater hair density than the sham-­ with 2.9 (p  <  0.0001), 3.0 (p  <  0.0001), 1.6
device group. (p = 0.0017) hairs/cm2 in sham-treated patients.
Another randomized, placebo-controlled Among male patients, the mean terminal hair
trial was performed in 2013 also using a helmet- count increased by 20.9 and 25.7 hairs per cm2
type device called the “TOPHAT655” (investi- for the 9- and 12-beam devices compared with
gational version of the iGrow [60]). It contained 9.4 (p = 0.0249) and 9.4 (p = 0.0028) hairs per
twenty-­one 5 mW lasers (655 ± 5 nm), and 30 cm2 with the sham-devices. Also, a higher per-
LEDs (655  ±  20  nm). Forty-four males (age centage of the patients in the active treatment
18–48) with androgenetic alopecia were group reported improvement in overall hair loss
enrolled and 41 completed the study (22 active, condition, thickness, and fullness in self-­
19 placebo). Areas of thinning were trimmed to assessment than did the sham-treated individu-
3 mm, tattooed, and photographed. The control als (Figs. 20.14 and 20.15).
group was given an identical device with incan-
descent lights that were painted red. Patients
used the devices at home for 25 min per treat-  LLT Mechanisms of Action for Hair
L
ment on alternating days for 16 weeks (total of Growth in Nutshell
60 treatments). Statistical analysis was blinded.
After deleting one outlier (placebo group) data Originally, LLLT was hypothesized to grow
point, the investigators found a 35% increase in hair by increasing mitochondrial signaling to
the number of hairs in the treatment group com- ultimately increase ATP levels in tissues [32,
pared with the sham-device group (P = 0.003). 33, 63]. Since then, it has been suggested that
No distinction was made between vellus and ter- LLLT has similar (but not clearly delineated)
minal hairs, and the diameter of the hairs was effects as minoxidil on the hair follicle [64].
not measured. No females were included in the These mechanistic overlaps may include a
study, but according to the author a second man- release of nitric oxide, [65] localized vasodila-
uscript showing similar results for women is in tion [66], or the opening of potassium channels
press [61]. [67]. LLLT may also work by activating NF-kB
A very recent study was a second multi-cen- signaling with subsequent anti-apoptotic effects
ter, randomized, sham-device controlled double-­ [68]. There is fairly good evidence that LLLT
blind study using the HairMax Lasercomb™ can increase levels of vascular endothelial
[62]. The authors included well-respected growth factor (VEGF) resulting in more rapid
experts in hair loss at major academic angiogenesis [69–71]. It appears to do so via
362 N. E. Rogers et al.

Fig. 20.14  Clinical results before and 26  weeks after treatment with HairMax Lasercomb™ (photos courtesy of
Lexington International, LLC)

the ERK/Sp1 signally pathway [72]. Whether

this has more of an effect on hair growth or
wound healing is uncertain.
Recently, the role of LLLT in hair growth
was evaluated in C3H/HeJ mice, leading to the
conclusion that LLLT induces the anagen phase
of hair follicles, thus promoting hair regrowth
by initiating the Wnt10b/β-catenin pathway
[73]. In this study, the LLLT group expressed a
significantly higher level of Wnt10b and
β-catenin on the second day than the control
group according to both the western blot and
PCR results. Wnt signaling, especially Wnt10b
expression, is necessary for hair follicle devel-
opment by activating bulge stem cells towards
hair formation [74, 75]. Activation of the
Wnt10b/β-catenin pathway has been seen to
result in regeneration of hair follicles [76].
Based on a recent evidence-based review on
LLLT devices for treating alopecia, it was found
Fig. 20.15  Microscopic results before and 26  weeks that FDA-cleared devices are effective for
after treatment with HairMax Lasercomb™ (photos cour- patients with pattern hair loss, with low inci-
tesy of Lexington International, LLC) dence of adverse effects [77].
20  Lasers in Hair Growth and Hair Transplantation 363

Lasers for Wound Healing then it may not be enough to warrant its wide-
spread use. Presently, the authors recommend
There have been a significant number of publica- using laser therapy as an adjunct to medical
tions investigating the role of LLLT for treating therapy if optimal results are not happening
wounds. Most of it has been limited to in vitro or with minoxidil and/or finasteride.
mouse models, and do not thoroughly differenti- No matter how we implement lasers to treat
ate between photothermal, photochemical, or patients with hair loss, we must first identify
photomechanical effects [78]. A 635  nm laser the etiology. Frequently conditions such as
was found to stimulate wound contraction in sus- lichen planopilaris or alopecia areata may
ceptible mouse strains [79]. It was found to present in a way that mimics androgenetic alo-
increase levels of basic fibroblast growth factor pecia. We should be sure that the patients
(bFGF) and insulin-like growth factor-1 (IGF-1) undergo medical evaluation and biopsy where
with greater statistical significance than was seen necessary. This crucial step may be left out
in control groups [80]. Based on these studies, when treatments such as LLLT are available
LLLT may have a role in the post-operative directly to the public without a prescription.
period following hair transplantation. Most Consumers should be protected from buying
patients experience scabbing over the grafted expensive items that may not be applicable or
area that can last for 1–2  weeks after surgery. aggressive enough for their type of hair loss.
They may also have discomfort in the donor area Likewise, physicians should be open to the
for 1–3  days after surgery. The use of LLLT in use of such devices where other options have
treating the grafted and/or donor areas after hair failed, so long as reproducible studies can
transplantation may be an area of future study. demonstrate their safety and efficacy.
More human clinical trials are needed.

Conclusion References
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 Photobiomodulation and Hair
Growth 21
Molly B. Hirt and Ronda S. Farah

Abstract Keywords
Since the initial Food and Drug Administration Photobiomodulation (PBM) · Hair growth ·
clearance of the first photobiomodulation Alopecia · Androgenetic alopecia (AGA) ·
device for androgenetic alopecia in 2007, the Laser · Low-level laser therapy (LLLT) ·
market for these devices has rapidly expanded. Light-emitting diodes
Sixteen unique devices are currently available
to consumers with varying designs, treatment
durations and frequency. While the precise
mechanism for hair growth stimulation Abbreviations
remains to be elucidated, current evidence
suggests the laser light alters hair cycle dura- FDA Food and Drug Administration
tion to promote the anagen growth phase. LED Light-emitting diodes
Photobiomodulation devices have an excellent mW Milliwatts
safety profile with pruritus and skin dryness nm Nanometer
reported to be the most common side effects. PBM Photobiomodulation
Overall, research has demonstrated clinical PRP Platelet rich plasma
efficacy of these devices, including random- RCT Randomized control trial
ized controlled studies. As photobiomodula- UBM Ultrasound bio-macroscopic
tion continues to emerge as a treatment
modality for androgenetic alopecia, additional
information on the most effective light
sources, precise light wavelength, treatment Background
schedule, and effectiveness on various hair
diseases is still needed. Photobiomodulation (PBM) involves the use of
low-level red or near infrared light to stimulate a
photochemical reaction. The treatment of tissue
M. B. Hirt · R. S. Farah (*) with low energy light, resulting in a therapeutic
Department of Dermatology, University of
response is termed PBM therapy [1, 2]. This type
Minnesota, Minneapolis, MN, USA
e-mail: [email protected], [email protected]; of therapy has also been referred to as low level
[email protected] laser (light) therapy or photobiostimulation

© Springer International Publishing AG, part of Springer Nature 2018 367

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_21
368 M. B. Hirt and R. S. Farah

t­ herapy and has been recently become widely uti- factor induction and cell-signaling, therefore
lized for the management of androgenetic alope- modifying gene expression along with cell
cia (AGA) [1, 2]. The initial discovery was made migration, proliferation and metabolism [2, 21,
by Dr. Endre Mester in 1967 when he serendipi- 23–28]. With regards to its use for hair growth,
tously discovered that mice irradiated with low-­ it has been hypothesized to stimulate bulge
powered lasers experienced increased hair stem cells within the hair follicle and aid in the
regrowth [3, 4]. Since that time, the market for transition of the follicles from telogen to ana-
PBM devices for the management of alopecia has gen [2, 29]. It is also thought to extend anagen,
rapidly expanded. inhibit early transition to catagen, and acceler-
Many of the available designed PBM devices ate hair growth [2, 29].
have been focused on AGA, as it is the most com-
mon of the alopecias in both sexes [5–8]. AGA
not only results in physical changes and hair thin- Photobiomodulation Device
ning of the scalp, it has also been associated with Characteristics
psychological issues such as reduced quality of
life and poor body image, making the develop- PBM devices may contain exclusively diode
ment of treatment options imperative [9–11]. lasers or lasers combined with light-emitting
Treatments for AGA include finasteride, topical diodes (LEDs). Lasers emit coherent, monochro-
minoxidil, and for women, spironolactone may matic light, whereas LEDs emit non-coherent
be recommended. These treatments can be effec- light with a wider range of wavelengths [2]. The
tive, however, they may be associated with local continuous laser light has previously been
or systemic side effects. Hair transplantation may thought to be imperative for PBM efficacy.
be offered, especially for extensive disease, how- However, the use of LEDs has challenged this
ever, this is often costly and involves downtime. theory, and whether diode lasers or LEDs are
More recently, platelet rich plasma (PRP) therapy more clinically efficacious remains to be deter-
has been proposed as a treatment option, though mined [2]. Wavelengths of these devices range
large randomized controlled trials supporting use from 500 to 1000 nanometers (nm) to encom-
are lacking. To date, none of these devices have pass the red or near-infrared spectrum of light
been Food and Drug Administration (FDA) [2]. Amongst the PBM devices currently avail-
cleared for the management of other non-­ able on the market, the total number of lasers
cicatricial or cicatricial alopecias. and/or LEDs ranges from 7 to 272 diodes [30–
45]. The total power for each device ranges
between  approximately 35 milliwatts (mW) to
Mechanism 1360  mW.  The iGrow® and iRestore® are the
only devices currently incorporating both laser
The exact mechanism of PBM therapy is diodes and LEDs into their design. Marketed
unknown and remains to be elucidated. devices may emit light in a continuous or pulsed
However, preliminary work has found PBM fashion. Of note, the most efficacious wave-
encourages tissue regeneration, alleviates pain, length, power, treatment time and frequency for
and decreases inflammation, making it applica- these devices to stimulate hair growth remains to
ble to medical fields ranging from dentistry and be elucidated.
pain to acupuncture and dermatology [2, 12– In 2007, the FDA cleared the first PBM device
19]. At the cellular level, it has been proposed for the treatment of AGA [46]. The affordability,
that PBM changes adenosine triphosphate pro- non-invasive nature, and convenient at home or
duction in the mitochondria [2, 20, 21]. The office-based treatment options have sparked
anti-inflammatory properties are postulated to patient interest in use of the PBM devices when
decrease pro-­inflammatory cytokines [2, 13, compared to procedures such as hair transplanta-
22]. PBM is also thought to effect transcription tion. According to the FDA 510(k) Premarket
21  Photobiomodulation and Hair Growth 369

Notification database, there are currently 16 trolled trials, PBM was found to significantly
PBM devices marketed for home-use in the increase hair regrowth [50]. In 2017, Afifi et al.
United States (Table 21.1) [47]. The cost of each completed a systematic review of 11 studies, 5 of
device ranges from approximately $295 to $3000, which were randomized sham-controlled trials
often based on the number of diodes and shape of [51]. Hair counts or density were used as objec-
the device [30–45]. Available device shapes tive measurements. Other evaluated items in sev-
include combs, helmets, caps, or headbands. eral studies included the following: patient
Treatment time also varies based on the chosen satisfaction, hair shaft diameter, tensile strength
device and ranges from 90 seconds three time per and hair thickness. Hair thickness and tensile
week to 36 minutes every other day. Response to strength improved in two of four studies evalu-
use of these PBM devices may take 3–4 months ated [51].
of continued use, and the response is expected to Published randomized controlled trials (RCT)
continue throughout the first 6–12 months of use exist for HairMax®, iGrow®, and Capillus® PBM
[30–45, 48]. The longest duration of treatment devices. HairMax® LaserComb has conducted
reported in the literature is 26  weeks [48–50]. the largest studies evaluating the effectiveness of
LaserCap® is currently the only device company PBM devices in treating AGA. In 2009, the first
which limits sales to authorized physicians. All multicenter, double-blind RCT evaluated the
other device companies offer their devices HairMax® LaserComb as compared to a sham
directly to consumers. device in males with AGA [49]. Subjects assigned
to the HairMax® LaserComb in a 26-week study
period demonstrated a statistically significant
PBM in the Home and Office increase in mean hair density when compared to
controls. Subsequently in 2014, Jimenez et  al.
Consumers may purchase most of the available published a multicenter, double-blind RCT com-
PBM devices for home use. Two devices that paring the effectiveness of the HairMax®
have been available for office-based treatments LaserComb to a sham device in the treatment of
are the Capillus272 Office Pro® and the Sunetics AGA including both men and women [48].
Clinical Laser® [30, 31]. Office-based devices are Subjects randomized to the HairMax® LaserComb
desirable for patients that would like to trial the device achieved a statistically significant increase
device prior to purchasing for home use. in density of terminal hair fibers when compared
Anecdotally, physicians have reported using to subjects treated with the sham device.
PBM after PRP in the office setting. However, In 2013, Lanzafame et  al. evaluated the effi-
long-term studies on the efficacy of this tech- cacy of the iGrow®, a device with a combination
nique are lacking. More recently, PBM device of lasers and LEDs, in male subjects with AGA
sales have been expanded from the consumers and reported a 35% increase in post-treatment
and physicians to hair salons. The remaining hair counts compared to controls using a sham-­
devices on the market are designed for home use device [52]. Subsequently in 2014, Lanzafame
(Table 21.1). et al. reported a 37% increase in post-treatment
hair counts in female subjects using the iGrow®
device [53]. The most recently published study
Available Data was conducted by Friedman et al. in 2017. In this
study female AGA patients were randomized to
As PBM continues to emerge as a treatment for the Capillus® 272 device or a sham-device treat-
AGA, research within the field continues to ment. Subjects used the devices every other day
expand. In 2016, Zarei et al. reviewed 21 studies for a total of 17  weeks. Subjects assigned the
(2 in vitro, 7 animal, and 12 clinical) to evaluate Capillus® 272 device demonstrated a 51%
the effectiveness of PBM in treating various types increase in hair counts as compared to the sham
of alopecia [50]. In all but two small, uncon- device [54].
370 M. B. Hirt and R. S. Farah

Table 21.1  Summary of clinical studies evaluating device efficacy for treatment of androgenetic alopecia
Peer-
Studies Study type Device Subjects Treatment Results reviewed
Capillus Yes Double blind, Handi-Dome 44 F 30 min Statistically Yes
(1) sham Laser (272 Eevery other significant 51% Friedman
device- diode model) day for increase in et al. [54]
controlled 17 weeks terminal hair count
multicenter versus sham-
RCT treated group
HairMax Yes Prospective HairMax 28 M 5–10 min Total hair counts Yes
(5) cohort study LaserComb 7F every other increased by Satino
day for 93.5% and total et al. [57]
24 weeks hair tensile
strength increased
by 78.9%
Double blind, HairMax 110 M 15 min Mean terminal hair Yes
sham LaserComb 3 days/week density increased Leavitt
device- for 26 weeks by 19.8 hairs/cm2 et al. [49]
controlled, versus 7.6 hairs/
multicenter cm2 decrease in
RCT sham-treated
group
Device-treated
patients reported
overall
improvement in
hair health and
quality versus
sham-treated
group
Investigator’s
subjective global
assessment of hair
growth was not
significantly
different between
groups
Case report HairMax 2 M 7.5 min No significant Yes
LaserComb 3 days/week change in hair Rushton
for 26 weeks counts (total, et al. [58]
vellus, anagen,
telogen) or hair
thickness
Retrospective HairMax 11 M 8, 11 or Global Yes
cohort study LaserComb (7, 21 F 15 min photographic Munck
9 or 12 diode 3 days/ assessment of hair et al. [59]
model) weekfor growth showed 8
8–48 weeks patients with
significant
improvement, 20
with moderate
improvement and
4 with no
improvement
21  Photobiomodulation and Hair Growth 371

Table 21.1 (continued)
Double blind, HairMax 128 M 8, 11 or Overall, terminal Yes
sham LaserComb (7, 141 F 15 min hair density Jimenez
device- 9 or 12 diode 3 days/week increased by 15.27 et al. [44,
controlled, model) for 16 weeks hairs/cm2 48]
multicenter compared to
RCT sham-treated
group
Higher percentage
of device-treated
patients reported
improvement in
hair loss, but this
did not always
reach statistical
significance
iGrow Yes Double blind, TOPHAT655 41 M 25 min Statistically Yes
(2) sham (iGrow) every other significant 35% Lanzafame
device- day for increase of in et al. [52]
controlled 16 weeks terminal hair count
RCT versus sham-
treated group
Double blind, TOPHAT655 42 F 25 min Statistically Yes
sham (iGrow) every other significant 37% Lanzafame
device- day for increase of in et al. [53]
controlled 16 weeks terminal hair count
RCT versus sham-
treated group
iRestore Yes Double blind, iRestore 18 M 25 min Pending, study in N/A
(1) sham 18 F 3 days/week progress
device- for 17 weeks
controlled
RCT
LaserCap Yes Case series LaserCap 7F 30–60 min Improvement in No
(2) 3–4 days/ hair volume and
week shine
for
3–6 months
Case series LaserCap 1 M 30 min Improvement in No
2F every other hair volume and
day for shine
6 months
NutraStim No N/A N/A N/A N/A N/A N/A
Theradome Yes Double blind, Theradome™ 80 M 20 min Pending, study in N/A
(1) sham LH80 PRO 2 days/week progress
device- for 26 weeks
controlled
multicenter
RCT
RCT randomized-controlled trial, M male, F female, N/A not applicable

In May 2017, Esmat et al. published a study hair loss [55]. The outcomes were measured
comparing the efficacy of the iGrow® device to using folliscope and ultrasound bio-macroscopic
topical minoxidil 5% as well as the combination (UBM) techniques. This preliminary investiga-
of both therapies in treatment for female pattern tion suggested that use of a combination PBM
372 M. B. Hirt and R. S. Farah

with minoxidil could accelerate hair density Conclusion and Future Directions

when compared to either modality used alone.
Limitations of this study include the use of a fol- Evidence suggests that PBM is a safe and effec-
liscope and UBM techniques for evaluation as tive treatment option for patients with
these have not been used frequently for this type AGA. Therefore, it may be an effective alterna-
of assessment in the past [55]. tive treatment for patients who are unresponsive
to medical management or do not wish to undergo
surgical procedures or take medications to treat
Safety Profile their disease. Further studies are needed to exam-
ine the effectiveness of PBM devices in the treat-
One of the benefits of the PBM devices for the ment of other types of alopecia (i.e. telogen
treatment of AGA is their outstanding safety pro- effluvium, lichen planopilaris, frontal fibrosing
file. The most common side effects reported in the alopecia, etc.) and varying types including thick,
large multicenter study involving 269 subjects thin, curly and straight hair. Research focused on
were pruritus (2.5%) and dry skin (5.1%) [48]. the development of topical and oral treatment
Other less common side effects of using these protocols in conjunction with PBM should con-
devices are irritation, scalp tenderness, mild urti- tinue to be pursued [55].
caria, redness, acne, and a warm sensation [48]. There are numerous devices on the market,
The primary concern with use of laser devices is making it difficult for the physician and patient to
the risk of retinal damage as a result of laser light navigate. Currently, it is unknown if one device
exposure [56]. To the authors’ knowledge, no offers more clinical benefit over another. A head-­
reports of ocular damage from PBM devices are to-­
head comparison of FDA-cleared PBM
reported. As a means to further prevent this risk, devices was initiated in 2016 and results have not
many of the devices currently on the market con- yet been reported. Each device has unique design
tain a built-in safety feature to help prevent acci- features. In addition, these devices vary in terms
dental eye exposure. Data on use in pregnant and of cost, total power output, frequency of use, and
lactating patients are lacking. treatment time. Wavelengths of these devices are
similar, though optimal treatment wavelength is
unknown. Further research into device specifica-
Clinical Pearls tions such wavelength, dosimetry, frequency of
use, duration of treatment, and optimal light
Clinical experiences with these devices may lead source is needed to determine the most effective
dermatologists to find that cost is a barrier for treatment modality for patients with AGA. Each
their use. In these situations, combs are the least of these factors is important for patients when
expensive and may be considered. Other issues considering a PBM device. Physicians should
encountered in clinic are varying hair thickness, understand PBM and remain informed and armed
texture and curl. Some clinicians may lean with information regarding devices on the mar-
towards using a device with teeth so as to part ket. As this arena continues to expand, questions
thick hair and possibly deliver more light to the regarding PBM will likely become more com-
target. Anecdotally, compliance is also an issue, monplace in the office setting.
even with extensive counseling from a seasoned
clinician. In these situations one may consider a
cap or helmet shaped device which is hands free. References
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 Reflectance Confocal Microscopy
in Oncological Dermatology 22
Pablo Fernández-Crehuet Serrano,
Gonzalo Segurado-Miravalles,
and Salvador González

Abstract optical plane in focus (confocal) is detected.

Imaging techniques capable of non-invasive, Similar to dermoscopy images, real time
high-resolution, skin imaging in vivo have been images obtained by RCM are oriented horizon-
the focus of recent attention in the dermatology tal to skin surface (optical transversal sections).
field. These efforts are directed to improve the Melanin provides strong contrast because of its
diagnostic accuracy of skin cancer, especially high refractive index (1.7) relative to the sur-
cutaneous melanoma. Reflectance-mode con- rounding epidermis; the melanosome size,
focal microscopy (RCM) allows real time non- ­similar to the near-infrared wavelengths (800–
invasive histological imaging with cytological 1064  nm), produces strong back scattering of
detail comparable to conventional histology of the beam. Thus, cells containing melanin, such
the skin when exploring cutaneous structures as pigmented keratinocytes, melanocytes, or
between the stratum corneum and the upper melanophages, appear very bright when illumi-
reticular dermis. RCM consists of a light source nated in this manner. Similarly, other organelles
for illumination of a small spot within translu- or cytoplasmic granules provide good contrast
cent tissue; and a point detector that detects (albeit less intense than melanin), resulting in
back-­scattered and reflected light though a pin- good imaging of cells containing them, such as
hole. The pinhole prevents out-of-focus light Langerhans cells, lymphocytes, or cytoplasmic
from reaching the detector; as a result, only the granules in keratinocytes at the stratum granu-
losum. Major confocal imaging criteria of pig-
mented lesions such as benign and malignant
P. F.-C. Serrano
Department of Dermatology, melanocytic tumors have been established.
Alto Guadalquivir Hospital, Andújar, Jaén, Spain RCM imaging criteria of other skin cancers
G. Segurado-Miravalles such as basal cell carcinoma, squamous cell
Department of Dermatology, Ramón y Cajal Hospital, carcinoma, oral cavity neoplasm, and mycosis
Madrid, Spain fungoides have also been evaluated. RCM
S. González (*) shows promise for: (1) guidance during biopsy
Department of Medicine and Medical Specialities, collection; (2) monitoring histological architec-
Alcalá University, Madrid, Spain tural changes or dynamic process such as
Dermatology Service, Memorial Sloan-Kettering inflammatory response or capillary flow; (3)
Cancer Center, New York, NY, USA histological correlation with dermoscopic fea-
Hospital Ramón y Cajal, Alcala University, tures; (4) monitoring of the response of a given
Madrid, Spain lesion to treatment; and (5) demarcation of the
e-mail: [email protected]

© Springer International Publishing AG, part of Springer Nature 2018 375

K. Nouri (ed.), Lasers in Dermatology and Medicine, https://doi.org/10.1007/978-3-319-76118-3_22
376 P. F.-C. Serrano et al.

extension of a lesion before proceeding to inva- required the development of light source and
sive treatments such as surgical excisions. The computerization technologies to enable realiza-
main limitation of RCM is its relatively low tion of tissue imaging in  vivo. Since the 1980s
penetration through the dermis; currently, a several research groups have demonstrated the
maximum depth of 250–300  μm can be use of tandem scanning confocal microscopy for
achieved, preventing imaging of structures imaging human and animal tissue in  vivo [10–
located in deep dermis and hypodermis. The 13]. Confocal scanning laser microscopy for
main challenge is the interpretation of images. imaging human skin in vivo was first reported in
Specific photographic atlas, courses and devel- 1995 [8]. In vivo RCM offers several important
opment of teledermatology may solve this advantages over conventional histology. Imaging
problem. is painless and non-invasive, causing no tissue
damage. The skin is not altered in any by pro-
Keywords cessing (fixation, sectioning, and mounting) or
Confocal microscopy · Melanoma · Nevi staining, minimizing artifact or disruption of the
Basal cell carcinoma · Actinic keratoses native structure in the tissue. The data, collected
Squamous cell carcinoma · Bowen disease in real time, is faster than routine histology, and
the skin site can be repeatedly imaged over time
to evaluate dynamic changes such as tissue
growth, wound healing, lesion progression or
Introduction response to therapy [14–18]. Conventional his-
tology only demonstrates tissue morphology at
Dermatology is a medical speciality in which one time point.
diagnosis is frequently based exclusively on The principle of reflectance confocal micros-
clinical examination. Recent advances in imag- copy involves the use of a point source of light
ing techniques provide the potential for non- that illuminates a small spot within translucent
invasive high-resolution skin imaging in  vivo. tissue. The reflected light (reflectance) is then
These can overcome some of the disadvantages imaged onto a detector after passing through a
of the conventional biopsy and histologic analy- small pinhole. The pinhole prevents out-of-focus
sis. Such advances include dermoscopy [1], light from reaching the detector. This means that
optical coherence tomography [2], high-fre- only the region of a specimen that is in focus
quency ultrasound [3], magnetic resonance (confocal) is detected. To create an image of the
imaging [4], fluorescence-­ mode confocal whole plane of the sample being studied, the
microscopy [5], and reflectance-mode confocal point source beam is scanned. This enables a vir-
microscopy (RCM). Of these, confocal micros- tual sectioning of a thin horizontal tissue plane
copy is the technique with more possible appli- in  vivo. The ability to optically section a tissue
cations, offering real time non-invasive enables intact tissue to be imaged without the
microscopic images with the highest resolution need to physically section the tissue as is the case
imaging comparable to routine histology when with conventional histology, allowing the physi-
exploring cutaneous structures between stratum cal structure of the tissue to be preserved. The
corneum and reticular dermis [6–8]. resolution provided by RCM depends on the pin-
hole size, the numerical aperture of the objective
lens, and the wavelength used. Lasers of different
Principles of Reflectance-Mode wavelengths may be used as the light source for
Confocal Microscopy RCM. Longer wavelengths penetrate deeper into
the skin but provide less lateral resolution. Back-­
The confocal scanning microscope was invented scattering of light occurs due to local variations
by Marvin Minsky while working as postdoctoral of the refractive index within the tissue as well as
fellow at Harvard in 1955 [9]. However, it when the scattering structure has a size similar to
22  Reflectance Confocal Microscopy in Oncological Dermatology 377

the illuminating wavelength. Near-infrared wave- contain the water or the gel interface when imag-
lengths (800–1064  nm) produce strong back-­ ing. This device consists of a metal ring that is
scattering from melanosomes, despite melanin fixed to the patient’s skin with adhesive, and is
absorption at this wavelength, because they have coupled to the microscope housing with a magnet
a high refractive index relative to the surrounding during imaging. It has a concave shape to hold
epidermis and have a size similar to the illumi- the immersion medium. By moving the objective
nating wavelength [14]. This means that cells lens in the “z” stage (vertical) with respect to the
containing melanin, such as basal keratinocytes skin surface, it is possible to image at different
and melanocytes, image brightly. horizontal levels within the tissue since the focal
New microscopes use a single optical fibre that plane is progressively moved deeper. Images can
is common to both the illumination optical path be grabbed to produce static pictures of horizon-
and the detection optical path. This single-­mode tal skin sections as well as recorded on videotape
optical fibre acts as a spatial filter which rejects (20–30  Hz) to produce movies to demonstrate
the out-of-focus information collected by the dynamics events such as blood flow [8, 14–18].
objective lens. This system simplifies the opto-
mechanical complexity by eliminating the bulky
optical components and confocal apertures (pin-  eflectance Confocal Microscopy
R
holes) associated with conventional confocal Findings of Normal Skin
implementations. This fibre-optic approach has
enabled miniaturization of the confocal scanner Confocal microscopy offers a new view of the skin,
into a hand-held device that provides the flexibil- both in terms of orientation and image content,
ity and mobility necessary for current clinical use. with two principal differences from routine histol-
The commercially available RCM has a wave- ogy. First, the image obtained is horizontal or en
length of 830 nm and 30× objective lens of NA face (horizontal) rather than vertical sections that
0.9, which provides a lateral resolution of approx- are normally obtained from routine histology.
imately 1  μm and an axial resolution (section Second is that this image is in a gray-scale (bright-
thickness) of 3–5 μm [14]. With this system, it is scale) similar to radiographs. The field of view with
possible to image normal skin to a depth of 200– RCM varies with different microscopes, but is gen-
250 μm [14]. This is sufficient for imaging epi- erally 250–500  μm across [14]. The level being
dermis and upper dermis (papillary dermis and imaged can be ascertained by the morphologic
upper reticular dermis). Imaging deeper layers appearance of tissue at a given depth or by measur-
within the skin can also be achieved by using ing the depth of section, using a micrometer
greater laser power, but the laser power used in attached to the “z” stage of the objective lens.
the commercially available device is less than Image contrast is produced by differences in the
30  mW and causes no tissue damage or eye refractive indices of the varying tissue and cell
injury. Water immersion lenses are used since the structures. Melanin-containing structures (melano-
refractive index of water (1.33) is close to that of somes, melanocytes, melanophages, and pig-
epidermis (1.34) and this minimizes spherical mented keratinocytes, among others) have the
aberrations caused when the light passes through highest refractivity, followed by keratin-containing
the tissue-air interface [14]. It is also possible to structures, such as the stratum corneum, the infun-
use water-based gels as immersion media, par- dibulum, and the hair follicle. Nuclei, air, and
ticularly if imaging a scaly or hyperkeratotic serum exhibit minimum reflectivity [19].
lesion since the gel settles between disrupted cor- Microscopic structures similar in size to the wave-
neocytes, reducing irregularities in refraction. length of the incident light display the highest
Gel is also useful if imaging a skin site that is not refractive indices. The maximum imaging depth
particularly flat, since the gel doesn’t run off of that has been achieved to date with RCM is approx-
the skin in the same way water can. A skin con- imately 300 μm [14] although this may increase as
tact device is used to reduce motion artefact and the technique continues its development.
378 P. F.-C. Serrano et al.

When imaging the skin in real time starting sites appears generally brighter because of what
from the surface and progressing deeper, the appears to be more pigment at the basal layer.
most superficial images obtained are of the stra- Sun-exposed skin also demonstrated thicker and
tum corneum. This produces very bright images more fissured or wrinkled stratum corneum, more
because the refractive difference at the interface randomly arranged and irregularly shaped dermal
between the immersion medium (water at 1.33) papillae, and clumping of the dermal reticulated
and stratum corneum (1.54) results in a large pattern, consistent with collagen and elastic
amount of back-scattered light. Low laser fluen- fibers. Variation in the density of keratinocytes is
cies help to minimize this. The morphologic also apparent, with sun-protected sites showing a
appearance is that anucleated polygonal corneo- greater density than sun-exposed sites. The palms
cytes measuring 30–40 μm in size, and grouped and soles of feet are notable for having an
in “islands” separated by skin folds, which appear extremely thick stratum corneum and a greater
very dark. The next layer seen is the stratum number of eccrine ducts.
granulosum consisting of 2–4 layers of cells
measuring 25–35 μm in size with a thickness of
between 3 and 10 cells, depending on the ana-  eflectance Confocal Microscopy
R
tomic location. These cells have the nuclei as of Non-melanocytic Neoplastic Skin
dark central ovals within the cell, surrounded by Lesions
bright grainy cytoplasm due to the presence of
bright multiple structures (0.1–1.0 μm) that cor- RCM characterization of neoplastic lesions is an
respond to keratohyalin granules. The granulo- important area for research, with the potential to
cytes have clear outlines that form the aid in the non-invasive diagnosis and manage-
characteristic confocal finding known as the hon- ment of a variety of skin cancers. With the advent
eycomb pattern. The spinous layer has between 5 of newer, less invasive, or topical therapies, it is
to 10 layers of 15–25 μm in size cells, which have desirable to use a non-invasive diagnostic tool
a dark oval central area (the nucleus) and clearly that can allow high resolution, accurate identifi-
demarcated outlines that together with the stra- cation of tumor subtypes and tumor margins, and
tum granulosum form the characteristic honey- response to treatment.
comb pattern. The deepest layer of epidermis, the
basal layer, is seen as a bright clusters of cells
measuring about 7–10 μm [20]. The suprapapil- Basal Cell Carcinoma (Fig. 22.1)
lary epidermal plate at the dermo-epidermal
junction is apparent as rings of bright basal cells Basal Cell Carcinomas (BCC) are the commonest
surrounding a dark dermal papillae, which often skin tumors in man, and RCM characteristics of
show a central area of blood flow consistent with BCC have been well defined [22]. As with histol-
papillary dermal vascular loops. The papillary ogy, the different subtypes of BCC share certain
dermis can be seen to consist of a network of confocal patterns that make it relatively easy to
reticulated fibers and small blood vessels. We can reach a diagnosis. They include the presence of
also observe eccrine ducts, with appear as bright islands of monomorphic tumor cells (Fig. 22.1b)
centrally hollow structures that spiral through that are elongated in shape and have nuclei ori-
epidermis and dermis, and hair shafts with pilo-­ ented along the same axis, producing a polarized
sebaceous units. These appear as whorled cen- appearance (basaloid nuclei). This polarized cell
trally hollow structures with elliptical elongated pattern persists through the thickness of the epi-
cells at the circumference and a central refractile dermis, with loss of the normal progressive size
long hair shaft. difference of differentiating epidermal cells, loss
The appearance of normal skin varies accord- of the normal honeycomb pattern, and loss of der-
ing to the skin site and skin colour being imaged mal papillae architecture. The presence of pleo-
[21]. Skin from sun-exposed or darkly pigmented morphism and architectural disorder of the
22  Reflectance Confocal Microscopy in Oncological Dermatology 379

overlying epidermis is indicative of actinic dam- ture was first described by Ravinobitz and co-
age or consequence of the tumor. In addition, workers and was described in detail [19]. Small
RCM images show numerous dark, round spaces bright structures corresponding to inflammatory
or branching (arborizing) lines, containing mov- cells can also be seen in the dermis.
ing cells with different levels of refractivity. This All these observations allow defining a num-
phenomenon corresponds to leukocyte trafficking ber of criteria to establish a successful diagnosis
[23]. It is also possible to visualize inflammatory of BCC using RCM. As the number of criteria is
cell infiltrate among the tumor cells. Imaging is higher, the specificity increased. A retrospective,
obtained at video-rate (30 frames per s), allowing multicentric study from 152 lesions [25] has
high temporal resolution (33  ms per frame) for shown that the presence of at least two of these
visualizing dynamic process such as leukocyte criteria has a sensitivity of 100% for the diagno-
rolling and adhesion on the endothelium. Another sis of BCC. The presence of two or more criteria
relatively common finding is a dark area sur- was found to be 100% sensitive and 53.6% spe-
rounding aggregates of tumor cells, probably due cific for the diagnosis of BCC, while four or more
to mucin deposits. This feature corresponds to the RCM criteria presented 95.7% specificity and
characteristic clefting (separation of tumor 82.9% of sensitivity.
islands from the surrounding stroma) seen on his- In a published large prospective study, Guitera
tology (Fig.  22.1c). Ulrich et  al. presented 13 et  al. [26] analyzed 710 consecutive equivocal
cases of BCC (including the three main histologic lesions by RCM. The lesions included 216 mela-
subtypes) and found good linear correlation nomas, 266 nevi, 119 BCCs, 67 pigmented facial
between dark areas seen by RCM and peritumoral macules, and 42 lesions classified as other skin
mucin thickness [24]. The stroma sometimes tumors. They studied 50% of the lesions (chosen
appears brighter than the tumor islands, which are randomly) by multivariate analysis and identified
darker than usual (hyporeflective) (Fig. 22.1b, d) eight independently significant diagnostic features
and are referred to as dark silhouettes. This fea- for BCC, with a sensitivity of 97.1% and a speci-

250 mm 100 mm

a b c 150 mm d

Fig. 22.1  Basal cell carcinoma. (a) Dermoscopy reveals shows a defined lobulated tumor island (asterisk) with
spoke-wheel areas and concentric blue-gray structures. peripheral palisading of nuclei (yellow arrowheads),
(b) RCM mosaic (1.5 × 1.5 mm) at the upper dermis level subtle peritumoral dark cleft-like space, and a refractile
revealing tumor nodules (asterisks) of weak to moderate surrounding fibrotic stroma (s). (d) RCM view
refractility. The bright stroma delineates individual tumor (0.5 × 0.650 mm) shows a collection of tumoral islands
islands. Red and blue rectangles correspond to magnified (asterisks) surrounded by brigt stroma (s). Small aggre-
images labeled c and d. (c) RCM view (0.250 × 0.5 mm) gate of melanophages (red arrows) is also noted
380 P. F.-C. Serrano et al.

ficity of 93.4%. Five of the factors were positive: connected to epidermis were absent. Finally, the
polarized elongated structures in the superficial presence of cords connected to epidermis in the
layer, linear telangiectasia-like horizontal ves- absence of clefting was associated with a higher
sels, compact nests of hyporeflective cells, odds of superficial BCC [30].
peripheral palisading, and a new concept called
epidermal shadowing, which they described as a
large dark featureless area disrupting the epider- Actinic Keratoses (Fig. 22.2)
mis due to en face clefting of the underlying
tumor nests. The three negative features were the Actinic keratoses (AK) are keratinocytic dyspla-
atypical honeycomb pattern, nonvisible papillae, sias that can develop into squamous cell carcino-
and cerebriform nests. A recently published sys- mas (SCC). RCM features of AK include
tematic review of diagnostic accuracy of RCM in irregular hyperkeratosis, and parakeratosis
BCC estimated a sensitivity of 97% and a speci- (Fig. 22.2b), architectural disarray (Fig. 22.2c),
ficity of 93% of RCM in diagnosing BCC, this epidermal cell nuclear enlargement with pleo-
supports outcomes of Guitera et al. [26, 27]. morphism (Fig. 22.2c), and round vascular loops
RCM has been employed in different studies frequently surrounded by solar elastosis
that describe the main features of different histo- (Fig.  22.2d). The pattern of architectural disar-
logical subtypes of BCC which is important in ray does not involve the full thickness of the epi-
order to determine the therapeutics and prognosis dermis [31]. Pellacani et  al. found good
of the tumor [28]. Infiltrative BCC is visualized concordance between the keratinocyte atypia
as ill-defined invading structures composed of visualized with RCM and histopathology [32]. A
very polarized cells that penetrate and deform the recently published study stated that photodam-
dermis, while nodular BCC reveals well-defined aged skin and AK are part of a disease contin-
tumor islands with peripheral palisading sur- uum, due to the almost constant presence of
rounded by dark areas [29]. In this regard, Longo keratinocyte pleomorphism and architectural
et al. analyzed 88 BCC and correlated confocal disruption in RCM images of photodamaged
features and BCC subtype. Nodular BCC was skin, although less severe than in AK [33].
more likely if clefting was present and cords con- Ulrich and co-workers [34] evaluated the sen-
nected to epidermis were absent. On the other sitivity of RCM in the diagnosis of AKs. They
hand, infiltrative BCC was the most common estimate this parameter in 97.7% (a total of 44
diagnosis if tumor islands, big or small, and cords AKs were included in this study).

se
a
se

b 100 mm c 100 mm d 100 mm

Fig. 22.2  Actinic keratosis. Skin cancerization. (a) tinocyte disarray (red dashed circle). (c) RCM image
RCM image (0.5 × 0.5 mm) at the level of stratum cor- (0.5 × 0.5 mm) of the upper dermis level displaying solar
neum with hyperkeratinization and parakeratosis. (b) elastosis (se) and round blood vessels (dashed red
RCM image (0.5 × 0.5 mm) at the spinous layer with kera- circles)
22  Reflectance Confocal Microscopy in Oncological Dermatology 381

The most important limiting factor of RCM is tional histology. Other features observed were
the shallow depth penetration of the illuminating parakeratosis, multinucleated cells, and solar
wavelength, which prevents accurate visualiza- elastosis.
tion of the dermo-epidermal junction in particu-
larly hyperkeratotic lesions. This has traditionally
limited the capability of RCM to distinguish AK Squamous Cell Carcinoma (Fig. 22.3)
from SCC.  Nevertheless new research in this
field conducted by Peppelman et  al. states that In 2009, Rishpon et al. [40] published a study of
the presence of architectural disarray in the stra- the confocal characteristics of 38 clinically sus-
tum spinosum and granulosum in combination pected SCC lesions that were subsequently con-
with dermal nest-like structures strongly suggests firmed by histology. The features identified were
a SCC instead of an AK [35]. an atypical honeycomb or disarranged pattern in
Pigmented AKs usually constitute a diagnos- the epidermis (Fig. 22.3d), large round cells with
tic challenge, in this way Moscarella et al. [36] nuclear atypia in the stratum spinosum and stra-
found the presence of epidermal changes (atypi- tum granulosum (Fig.  22.3d), and round and
cal keratinocytes, parakeratosis and scaling), polymorphous blood vessels crossing the dermal
increased epidermal thickness, bright and small, papillae (Fig. 22.3e). RCM images of the stratum
dermal papillae with enlarged interpapillary corneum typically reveal bright amorphous struc-
space and intraepidermal dendritic cells as the tures that correspond to the presence of crusts on
main RCM features of pigmented AK. the tumor surface and polygonal nucleated cells
with a bright rim around a dark nucleus (para-
keratosis) (Fig. 22.3c). Hyperkeratosis and acan-
Bowen Disease thosis permitting, RCM may also show increased
dermal vasculature and solar elastosis as well as
Bowen disease (BD) is an in situ squamous cell tumor islands in the case of invasive SCC [35].
carcinoma (SCC) histologically characterized by As above mentioned, the presence of architec-
proliferation of atypical pleomorphic keratino- tural disarray in stratum spinosum and granulo-
cytes throughout the epidermis. Dyskeratosis, sum in conjunction with nest-like structures in
mitosis, and multinucleated cells are very dermis is associated with a correct diagnosis of
­common findings [37]. Clinically, it can be mis- SCC in 88.5% of cases when discriminating
diagnosed as non-melanoma skin cancer or cer- between SCC and AK [35].
tain inflammatory skin conditions, such as
eczema and psoriasis [38]. Ulrich et  al. [39]
recently published a study of the confocal fea- Mycosis Fungoides
tures of ten BD lesions and described their cor-
relation with routine histologic features. The At the patch stage of mycosis fungoides (MF),
most common confocal findings were disruption changes are often subtle; consequently diagnosis
of the stratum corneum, an atypical honeycomb at this early phase with confocal microscopy may
pattern in the epidermis with a greater degree of be difficult. The most important confocal features
architectural disorder and cellular atypia than in include hyporefractivity of dermal papillary rings
AK, S-shaped blood vessels in the center of the and small, weakly refractive round cells located
dermal papillae, and two types of characteristic in the spinous layer, which correlate to the inter-
targetoid cells. The first type of cells was mor- face changes and exocytosis, respectively. In the
phologically large cells with a dark center, a plaque phase of MF, the visualization of typical
bright rim, and a dark halo, and the second type confocal features of MF may be easier. Some
were large cells with a bright center and a dark small, lightly refractive cells appear in the spi-
halo. The cells are thought to correspond to the nous layer correlating to epidermotropism of
different degrees of dyskeratosis seen by conven- lymphocytes, which sometimes are grouped and
382 P. F.-C. Serrano et al.

a c

150 mm

200 mm
d

150 mm

b 150 mm

Fig. 22.3  Squamous Cell Carcinoma. (a) Dermoscopy image (0.5 × 0.5 mm) shows impetiginized stratum cor-
displays a nodular lesion with irregular and polymophous neum with inflammatory cells (yellow asterisks), atypical
vessels and whitish opaque areas. (b) Slight oblique RCM nucleated corneocytes (red arrow) and hyperkeratosis
submosaic (1.5  ×  1.5  mm) at dermo epidermal junction (hk). (d) RCM image (0.5 × 0.5 mm) at suprabasal epider-
reveals keratinocyte disarray, exocytosis and polymor- mal layer displays keratinocyte disarray (kd). (e) RCM
phous vessels (red arrowheads). In the upper portion image (0.5 × 0.5 mm) at the upper dermis shows the pres-
hyperkeratotic areas (hk) may be visualized. (c) RCM ence of polymorphous vessels (red arrowheads)

located inside dark spaces within the epidermis Recently, a study published by Mancebo and
corresponding to Pautrier microabscesses on his- co-workers [41] showed a very good correlation
topathology. These vesicle-like spaces have to be between RCM and histopathology regarding the
distinguished from those seen in acute eczema by presence of epidermal lymphocytes and detection
the absence of parakeratosis and spongiosis and of melanophages in the dermis. Pautrier collec-
the presence of other MF characteristic confocal tion had fair agreement (kappa 0.32), with Pautrier
features. In tumor-type MF, the hyporefractive collection more commonly visualized on RCM
papillary rings and the infiltration of small lightly (76% vs 59%). They also claimed that lesions
refractive cells in the epidermis are frequently with Pautrier collection identified by RCM were
visualized in confocal images, while the vesicle-­ significantly more likely to show TCR clonality.
like spaces are rarely detected. Inside papillary
dermis, highly refractive cells of small to medium
size are observed and blood vessels may show a Pigmented Lesions
well-circumscribed thickened wall [29]. RCM
may be a real-time guide for optimal biopsy site Early detection of melanoma is essential, and still
selection in patients with multiple lesions sug- one of the most challenging problems in clinical
gestive of MF. dermatology. The need for improved diagnostic
22  Reflectance Confocal Microscopy in Oncological Dermatology 383

a c

250 mm

500 mm 250 mm
b

Fig. 22.4  Pigmented seborrheic keratoses. (a) like openings and well-defined, intensely bright, rounded
Dermoscopy reveals a star-shaped lesion with sharply cir- areas (red arrows) corresponding to millium cysts. (c)
cumscribed and moth-eaten edges, also containing a cen- RCM image (0.5 × 0.5 mm) within the mosaic b displays
tral hyperpigmented area with millium-like cists. (b) irregular dermal papillae in size and shape with curved,
RCM Mosaic (3  ×  3  mm) at dermo-epidermal junction invaginated borders (asterisks). (d) RCM image
displays geographic dermal papillae and opening full of (0.5 × 0.5 mm) (red dashed line)
keratin material (red asterisks) corresponding to comedo-­

accuracy in melanocytic skin tumors with non-­ as melanoma. On RCM, we can see epidermal pro-
invasively methods has led to the development liferation without keratinocytic disarray and long,
and investigation of new imaging tools such as parallel, geographic dermal papillae (Fig. 22.4b, d),
high-resolution ultrasound, optical coherence which are well delimited by high bright rings of
tomography, spectroscopy and RCM. RCM is the basal keratinocytes (edge papillae). This architec-
most promising for non-invasively examining ture pattern has interpretation as benign pattern.
skin structures at a level that allows cellular details Additionally comedo-like openings filled with
and, such as dermoscopy, it may be useful for dif- keratin (Fig. 22.4c) and millium cists (Fig. 22.4b)
ferential diagnosis between pigmented lesions. are visualized. In the case of clonal seborrheic ker-
atosis, a clod pattern resembling melanocytic
Seborrheic Keratosis (Fig. 22.4) lesions may also be visualized [42].
Seborrheic keratosis is a common benign epider-
mal proliferation. Sometimes this tumor can be Dermatofibroma (Fig. 22.5)
pigmented and then it may be important in the dif- Dermatofibroma (DF) is a common benign der-
ferential diagnosis with melanocytic lesions such mal proliferation of histiocytes that can arise at
384 P. F.-C. Serrano et al.

Fig. 22.5  Dermatofibroma. (a) Dermoscopy shows a rings within the complete lesional área. Central portion
brown, pigmented network with central scar-like área. (b) shows partly homogeneus and dense collagen bundles
RCM mosaic (5,5 × 5 mm) at dermo-epidermal junction (yellow asterisks). At the periphery, the lesion displays
demonstrates increased density of bright dermal papillary elongated dermal papillae (red dashed circle)

any age and equally in male and female, but is focal microscopy examination of DF because
more typically seen in young adult women. spindle fibroblast-like cells, histiocytes and scle-
Darkly pigmented lesions can simulate dysplastic rotic stroma are too deep, in the reticular dermis.
nevi or melanoma. Reflectance confocal micro- Although there are not specific images in DF
scopic examination of DF shows the presence of examination using reflectance confocal micros-
a normal epidermis with homogeneously bright copy, we consider that this technique may be a
papillary rings and refractile keratinocytes above useful tool in differential diagnosis with others
the dermo-epidermal junction (Fig. 22.5b) corre- cutaneous tumors, particularly when DF is darkly
sponding histologically to the pigmentation of pigmented and it simulates melanocytic lesions.
the basal layer. Moreover, the dermis presents
high refractile, thick collagen bundle correspond- Angioma
ing to the sclerotic stroma of the tumor Angioma is a vascular tumor that consist in
(Fig. 22.5b). We have not specific images on con- numerous and dilated blood vessels. RCM shows
22  Reflectance Confocal Microscopy in Oncological Dermatology 385

dilated, tortuous blood vessels located at superfi- to the cleft-like separation of Paget cells from the
cial dermis. As RCM can obtain real time images epidermis that is seen on histology and is possibly
we visualize blood flow in these vessels [17]. due to mucin secreted by these cells or to intercel-
lular fluid. While mucin appears hyporeflective in
 igmented Basal Cell Carcinoma
P RCM images, Paget cells are frequently seen as
Pigmented BCC is a clinical and histologic vari- hyperreflective, probably due to the reflection of
ant of BCC that may at times be difficult to clini- light from the secretory granules and to the prom-
cally distinguish from benign pigmented lesions inent Golgi apparatus and numerous free ribo-
and melanoma. Agero and co-workers have char- somes that these cells contain. An atypical or
acterized pigmented BCC with RCM [43]. The disarrayed honeycomb pattern indicating disrup-
features include the same characteristics previ- tion of the epidermis is seen in many cases. The
ously mentioned for BCC. Melanin pigment was blood vessels are generally abundant, small, and
not uniformly distributed throughout the tumor vertically oriented, a typical finding for skin in the
cords. The variable amounts of melanin present, anogenital region. Considering the non-specific-
together with the melanin distribution within the ity of the clinical manifestations of PD and the
tumor nests, determined the variability in bright- fact that this disease can mimic a range of inflam-
ness of tumor nest visualized on matory, allergic, and infectious conditions, RCM
RCM.  Contributing to the pigmentation of the may facilitate earlier diagnosis and faster initia-
tumor is melanin pigment in benign epidermal tion of appropriate treatment [47]. It can also be
keratinocytes, in tumor cells of BCC, in melano- useful for selecting the most appropriate biopsy
cytes interspersed among the tumor cells, and in site and for mapping out margins prior to treat-
melanophages in papillary dermis. Melanin and ment [48, 49].
melanosomes provide strong contrast with the
surrounding edematous or mucinous dermal Melanocytic Nevi (Figs. 22.6 and 22.7)
stroma of BCCs under RCM. RCM is particularly well suited to the imaging of
melanocytic lesions, since the large amount of
 igmented Mammary Paget Disease
P melanin they contain provides very good con-
RCM has also been used to study Paget disease trast. Accurate characterization of the features of
(PD), probably because it has proven to