Papers by Christophe Baudouin
Advances in experimental medicine and biology, 2002
To investigate in impression cytology (IC) specimens the expression of inflammatory and apoptosis... more To investigate in impression cytology (IC) specimens the expression of inflammatory and apoptosis-related markers by conjunctival epithelial cells from patients with dry eye as a rationale for treatment with topical cyclosporine. Immunologic anomalies were identified at baseline, before treatment with the masked medication, in a homogeneous series of patients with dry eye syndrome, who were enrolled in a large European multicenter clinical trial (Cyclosporin A Dry Eye Study; Allergan, Irvine, CA). IC specimens were collected in 243 patients with moderate to severe keratoconjunctivitis sicca (KCS), with or without Sjogren's syndrome (SS). Fifty normal subjects were separately examined to provide normal control values. Specimens were analyzed in a masked manner by flow cytometry, using antibodies directed to markers of the immune system and/or apoptotic pathway: HLA DR, CD40, CD40 ligand, Fas, and APO2.7. Levels of expression were quantified, and results were compared with those obtained in the 50 normal patients. One hundred sixty-nine specimens were successfully interpreted at baseline, including 41% from patients with SS. A highly significant increase of HLA DR expression by conjunctival cells was found in KCS-affected eyes compared with normal eyes, which did not express this marker or did so very weakly. HLA DR expression in eyes with SS was significantly higher than in KCS-affected eyes without SS. Fas and APO2.7 were found at low levels in all normal and KCS-affected eyes. CD40 and CD40 ligand expressions were significantly increased in eyes with KCS compared with normal eyes. HLA DR, CD40 and Fas were found at significantly higher levels in the SS group than in the non-SS group. CONCLUSIONS. Conjunctival cells from patients with dry eye with moderate to severe KCS, with or without SS, overexpress inflammatory and apoptosis-related markers. Whether inflammation is a primary phenomenon in KCS or is the consequence of repetitive abrasion of the ocular surface after tear film deficiency remains to be determined. These data, nevertheless, support the use of immunomodulatory and/or anti-inflammatory drugs in the treatment of patients with KCS.
Stem cell research & therapy, 2015
Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure ... more Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies. Here, we investigated the potential of MSCs therapy in an glaucoma-like ocular hypertension (OHT) model and decipher in vitro the effects of MSCs on primary human trabecular meshwork cells. Ocular hypertension model was performed by cauterization of 3 episcleral veins (EVC) of Long-Evans male rat eyes. MSCs were isolated from rat bone marrow, amplified in vitro and tagged with quantum dot nanocrystals. Animals were distributed as 1) MSCs group receiving 5.10(5)cells/6μl Minimum Essential Medium and 2) MEM group receiving 6μl MEM (n = 10 each). Injections were performed into the anterior chamber of 20 days-hypertensive eyes and IOP was monitored twice...
Investigative ophthalmology & visual science, 2015
To analyze the correlation between photophobia and corneal crystal density in nephropathic cystin... more To analyze the correlation between photophobia and corneal crystal density in nephropathic cystinosis using in vivo confocal microscopy (IVCM) and anterior-segment optical coherence tomography (AS-OCT). Forty eyes of 20 patients with nephropathic cystinosis aged 7 to 37 years were included in this study. Ophthalmologic investigations included clinician-assessed and self-assessed evaluations of photophobia, slit-lamp biomicroscopy analysis, the depth of crystal deposition (DCD) and the central corneal thickness (CCT) in the central cornea measured with AS-OCT, and IVCM analysis of the crystal density score (IVCM-CysS), inflammatory cell density (IVCM-inf), and nerve damage (IVCM-N). Age, sex, intraleukocyte cystine concentrations (ICC), and the need for renal transplantation were also recorded. The average subjective and objective photophobia scores were 2.10 ± 1.28 and 1.70 ± 1.41, respectively. Using AS-OCT, the average percentage of crystal infiltration (OCT-CysP) and was 49.56 ± ...
European Journal of Ophthalmology, 2015
To review methods of assessing bulbar redness, particularly with respect to the practicality of c... more To review methods of assessing bulbar redness, particularly with respect to the practicality of comparing different rating systems. The published literature was reviewed and discussed by a panel of experts and a narrative review prepared. Bulbar hyperemia is a common clinical sign and an important indicator of ocular disease. As bulbar hyperemia is a frequent side effect of topical glaucoma medications, accurate objective measurement is important to allow comparison of clinical studies. A number of different measurement systems have evolved to allow quantification of subjectively assessed redness to be rendered into a form that allows between-treatment comparisons and longitudinal changes in both clinical research and practice. Whereas widespread use of image-based rating scales has improved the assessment of bulbar redness in clinical practice and clinical research, these techniques are less than ideal. The scales are subject to an intrinsic subjectivity and are suboptimal in differentiating the physiologic phenomenon of bulbar hyperemia. There is also a degree of interobserver and intraobserver variation; in some studies, average variation in scores exceed half the extent of the whole scale. Moreover, a lack of interscale validation has led to confusion in comparing the results from clinical studies that use different scales. In a recent series of studies, cross-calibration between the various scales in use has been attempted. Whereas naive comparisons between the results obtained in studies using different bulbar redness scales can lead to erroneous conclusions, the tools exist to permit meaningful comparisons between rating systems and scales.
Investigative ophthalmology & visual science, Jan 3, 2015
Purpose:To evaluate the dynamic changes of optical quality in patients with dry eye disease (DED)... more Purpose:To evaluate the dynamic changes of optical quality in patients with dry eye disease (DED) using a double-pass system. Methods:Forty-eight patients with DED and 35 control subjects were included in this study. Each patient underwent an evaluation of the ocular surface using the Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), corneal and conjunctival staining (Oxford scale), and Schirmer I test. Using the tear film analysis program of the Optical Quality Analysis System (OQAS), the objective scatter index (OSI) was recorded every 0.5 s within a 20-s period with the subjects asked to blink freely. Several parameters were established to evaluate the dynamic alterations of optical quality and the effects of blinks: OSI standard deviation (SD), ΔOSI, ΔOSI/time, blinking change (BC), blinking frequency (BF), and tolerant limitation (TL). Results:DED patients had significant alterations of optical quality compared to control subjects. The ΔOSI, ΔOSI/time, BC, an...
Investigative ophthalmology & visual science, 2015
To evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) cyclocoagulation ... more To evaluate the safety and efficacy of high-intensity focused ultrasound (HIFU) cyclocoagulation in reducing intraocular pressure (IOP) in patients with refractory glaucoma by using a novel miniaturized delivery device (EyeOP1). We conducted a 12-month open-label multicenter prospective study (EyeMUST1 Study). Patients with primary (primary open-angle glaucoma [POAG]) or secondary refractory glaucoma were treated in two groups depending on the duration of each ultrasound shot (group 1: 4 seconds; group 2: 6 seconds). The primary efficacy outcome was based on IOP reduction at 6 and 12 months. Fifty-two patients were enrolled: 36 (69%) had POAG and 16 (31%) had secondary glaucoma. Group 1 (n = 24) and group 2 (n = 28) had similar demographics and baseline characteristics. In group 1, IOP was reduced from a mean preoperative value of 29.7 ± 7.7 mm Hg (n = 3.5 glaucoma medications) to a mean postoperative value of 21.3 ± 6.7 mm Hg (n = 3.5 glaucoma medications) and 20.1 ± 6.7 mm Hg (n =...
The British journal of ophthalmology, 2015
Demodex mites are implicated in several ocular surface diseases such as blepharitis, ocular rosac... more Demodex mites are implicated in several ocular surface diseases such as blepharitis, ocular rosacea and dry eye syndrome. Demodex eyelid infestation is classically diagnosed by analysing depilated eyelashes under the light microscope. The use of in vivo confocal microscopy (IVCM) could be an easy way to improve its diagnosis. The ability of IVCM to identify Demodex was evaluated and compared with the classic depilation method. Eight healthy subjects, 22 patients with dry eye syndrome without anterior blepharitis and 18 patients with anterior blepharitis were examined using lower eyelid IVCM (lash follicles and meibomian glands (MGs)). Twenty-five of the 48 subjects underwent both an IVCM examination and classic depilation to compare the two methods. Ex vivo Demodex obtained from lash depilation were also analysed using the confocal microscope. IVCM found 100% of the mite infestations among patients with anterior blepharitis, 60% among dry eye patients without blepharitis and 12% in ...
Ophthalmology, 2009
Objective: To analyze the corneas of patients with nephropathic cystinosis using in vivo confocal... more Objective: To analyze the corneas of patients with nephropathic cystinosis using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT).
Biologie Aujourd'hui, 2013
Second leading cause of blindness worldwide, glaucoma is an optic neuropathy related mainly but n... more Second leading cause of blindness worldwide, glaucoma is an optic neuropathy related mainly but not exclusively to an increase of intraocular pressure. Angle closure glaucoma is related to a blockade of aqueous humor to the trabecular meshwork, whereas open-angle glaucoma is a degeneration of the trabecular meshwork, the filter that allows aqueous outflow from the eye. Many improvements have been made in terms of diagnosis, follow-up and treatments, although the treatment of glaucoma is restricted to control intraocular pressure, in order to prevent optic nerve degeneration or to stop the progression of the disease toward blindness. The first line therapy is based on topical medications that are administered for the whole life span. Although globally efficient, these treatments, and most likely the preservative included in the excipient to prevent bottle contamination, induce side effects in the long-term that may impair the quality of life, patient compliance or directly induce ocular surface changes like inflammatory cytokine release, or tear film destruction, with further dry eye disease and chronic inflammation. A large body of evidence has been accumulated, showing that benzalkonium chloride, the preservative mainly used, is toxic over the long run and plays a role in such ocular surface impairment. Therefore efforts have been made in the last decade to eliminate or replace this compound, providing safer therapies to the patients. Furthermore, the identification of chemokines as playing a role in the trabecular degeneration has open new directions for treating glaucoma. The blockade of one receptor of CXCL12 has been experimentally shown not only to decrease intraocular pressure but also to prevent trabecular cell degeneration. This is an innovative concept that could allow development of new treatments, more specifically targeting the disease at its onset, rather than attempting to reduce its progression in its later stages.
Ophthalmology, 2014
To compare small incision lenticule extraction (SMILE) versus LASIK for post-refractive dry eye d... more To compare small incision lenticule extraction (SMILE) versus LASIK for post-refractive dry eye disease. Prospective, comparative, nonrandomized clinical study. Thirty patients scheduled for bilateral myopic SMILE and 30 age-, sex-, and refraction-matched patients scheduled for bilateral myopic LASIK were enrolled and followed for 6 months after the surgery. Complete evaluation of dry eye disease was performed at 1 and 6 months postoperatively, which included vision-related quality of life (Ocular Surface Disease Index [OSDI]), clinical examinations (tear film breakup time [TBUT], Schirmer I test, corneal staining), and tear osmolarity measurements, together with an overall severity score. Function and morphology of the corneal innervation were evaluated by corneal esthesiometry and subbasal nerve imaging using in vivo confocal microscopy (IVCM). Overall analysis of dry eye disease and corneal innervation. High incidence of mild to moderate dry eye disease was observed in both groups 1 month postoperatively, which remained significantly higher in the LASIK group than in the SMILE group 6 months after surgery (overall severity score [0-4]: 1.2±1.1 vs. 0.2±0.4, respectively, P < 0.01), leading to more frequent use of tear substitutes over the long term. Corneal sensitivity was better in SMILE than in LASIK eyes 1 month postoperatively (3.5±1.79 vs. 2.45±2.48, respectively, P < 0.01) and then recovered to statistically similar values at 6 months. Corneal nerve density, number of long fibers, and branchings as assessed by IVCM were significantly higher in the SMILE group compared with the LASIK group 1 and 6 months after surgery. Corneal sensitivity was negatively correlated with dry eye-related corneal damage (R² = 0.48, P < 0.01), and the long fiber nerve density was independently correlated with the OSDI score (R² = 0.50, P < 0.01) and the Schirmer test (R² = 0.21, P < 0.01) 6 months postoperatively. The SMILE procedure has a less pronounced impact on the ocular surface and corneal innervation compared with LASIK, further reducing the incidence of dry eye disease and subsequent degradation in quality of life after refractive surgery.
Transactions of the American Ophthalmological Society, 2012
Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunc... more Long-term antiglaucomatous drug administration may cause irritation, dry eye, allergy, subconjunctival fibrosis, or increased risk of glaucoma surgery failure, potentially due to the preservative benzalkonium chloride (BAK), whose toxic, proinflammatory, and detergent effects have extensively been shown experimentally. We hypothesize that BAK also influences trabecular meshwork (TM) degeneration. Trabecular specimens were examined using immunohistology and reverse transcriptase-polymerase chain reaction. A trabecular cell line was stimulated by BAK and examined for apoptosis, oxidative stress, fractalkine and SDF-1 expression, and modulation of their receptors. An experimental model was developed with BAK subconjunctival injections to induce TM degeneration. Mass spectrometry (MS) imaging assessed BAK penetration after repeated instillations in rabbit eyes. Trabecular specimens showed extremely low densities of trabecular cells and presence of cells expressing fractalkine and fracta...
Toxicology in Vitro, 2010
Purpose: To test a new multiple endpoint analysis (MEA) including occludin gene expression for sc... more Purpose: To test a new multiple endpoint analysis (MEA) including occludin gene expression for screening the ocular irritation potential of tear substitutes on human corneal epithelium (HCE), an in vitro model proposed to limit the use of animal testing in pre-clinical studies. Methods: Four chemically-preserved and two non chemically-preserved tear substitutes were tested after acute (24 h, 24 h + 24 h post incubation) and repeated applications (for 72 h) and compared to the positive control, benzalkonium chloride (BAK) at 0.1% and 0.01%, by assessing complementary parameters. Cellular viability was evaluated using MTT, histomorphologic analysis was performed on H&E stained vertical sections, IL-8 release was measured by ELISA, and occludin gene expression was quantified using qRT-PCR. Results: Cellular viability was moderately reduced by Perborate and Polyquad-preserved tear substitutes and dramatically reduced by BAK and by Thiomersal Ò and Oxyd Ò preserved tear substitutes. Thiomersal Ò also increased IL-8 release. Occludin expression profiles were modified by the four chemically-preserved tear substitutes and by the mechanically-preserved Comod Ò , but not by the mechanically-preserved Abak Ò . The behavior of BAK and tear substitutes led us to propose a prediction model for the classification of different levels of irritants, mainly based on the occludin transcriptional study. Conclusion: The versatility and sensitivity of the HCE model allowed the modeling of cumulative effects that may approach conditions obtained after long term application of tear substitutes. Thus, the modified MEA proposed in this study represents a valuable tool for in vitro eye irritation assessment with the power to detect mild irritants and subclinical eye irritant potential.
Radiation Physics and Chemistry, 2005
ABSTRACT
Progress in Retinal and Eye Research, 2009
In the cornea, the epithelium and the underlying stroma are separated by the basement membrane an... more In the cornea, the epithelium and the underlying stroma are separated by the basement membrane and Bowman's layer. The disruption of these anatomical barriers during wound healing represents a key step which initiates tissue remodeling through the modification of the epithelial-stromal interactions (ESI). Diffusible cytokines are generally viewed as central modulators in the bidirectional communication between these epithelial and stromal compartments and their implication in all stages of the wound healing process has been an active area of research for many years. Our studies which aimed to explore mechanisms of matrix degradation in pathological corneal wound healing have shown that EMMPRIN, a glycoprotein expressed on corneal epithelial cell surface, can induce matrix metalloproteinase (MMP) production and myofibroblasts differentiation after direct interaction with corneal fibroblasts. EMMPRIN appears therefore as a potential mediator of ESI by direct cell-cell contact which represents a new mechanism for dysregulated MMPs' induction observed in corneal ulcerations. These direct epithelial-stromal interactions (direct-ESI) can occur when delayed epithelial healing prevents regeneration of the basement membrane and allows the two cell types to come into close proximity. We propose that prevention of these interactions through inhibition of EMMPRIN may represent a promising therapeutic strategy in the inhibition of MMP induction in ulceration.
Ophthalmology, 2008
Objective: To characterize and understand, at the cellular level, the aqueous humor pathways afte... more Objective: To characterize and understand, at the cellular level, the aqueous humor pathways after filtering surgery, using in vivo confocal microscopy and impression cytology (IC).
Molecular Genetics and Metabolism, 2014
To establish the safety and efficacy of a new gel formulation of cysteamine hydrochloride (CH) ey... more To establish the safety and efficacy of a new gel formulation of cysteamine hydrochloride (CH) eye drops, for the treatment of corneal complications of nephropathic cystinosis. Open label dose response clinical trial. Eight patients with infantile nephropathic cystinosis including 4 children, 3 adolescents, and 1 adult (mean age at inclusion, 12.1 ± 4.6 years) treated with CH 0.1% eye drops. Patients were treated, in both eyes, with the control CH 0.1% eye drop formulation on average 4 times daily for one month and then switched to Cystadrops® at the same dose frequency. Based on clinical ocular findings, the dose regimen was adapted at D30 and D90 in order to decrease the frequency of instillation. After D90, this dose frequency was maintained, except in cases of crystal density worsening. Patients had a follow-up visit every 6 months during 48 months. Safety assessment consisted of adverse event and serious adverse event monitoring and recording at each visit. For the efficacy study, the primary endpoint was the corneal cystine crystal density measured with an in vivo confocal microscopy (IVCM) score. All patients completed the study. During the 4-year study period, neither serious adverse events nor significant adverse events related to the study drug were reported. After switching to Cystadrops®, the IVCM total score decreased from baseline to D90 by a mean of 28.6 ± 17.5% (p<0.001). From D90 to M48, the IVCM total score remained stable and significantly decreased as compared to that at D1 despite a reduced dose regimen from D90. At M48, the mean IVCM total score was 8.13 ± 4.15, decreased by a mean 29.9 ± 26.29% from D1 (p = 0.001), with a reduced number of instillations compared to that at D1. The IVCM total score and photophobia were significantly correlated (p = 0.04). This study provides evidence that Cystadrops® gel is superior to the CH 0.1% formulation in terms of efficacy and has a good safety profile over a long follow-up period.
Journal of Neuroimmunology, 2007
Tumor necrosis factor-alpha (TNF) has been implicated in retinal ganglion cells (RGC) degeneratio... more Tumor necrosis factor-alpha (TNF) has been implicated in retinal ganglion cells (RGC) degeneration in glaucoma. Atypical protein kinase C (PKC) ζ is involved in cell protection against various stresses. The aim of this study was to investigate the potential proapoptotic effects of intravitreal injections of TNF with or without PKCζ specific inhibitor on the rat retina. TNF was injected in the vitreous of rat eyes alone or in combination with specific PKCζ inhibitor. PKCζ and NF-κB were studied by immunohistochemistry and western-blotting analysis on retina, and apoptosis quantified by the TUNEL assay. While low basal PKCζ was observed in the control eyes, TNF induced intense expression of PKCζ mostly in bipolar cells processes. PKCζ staining became nuclear when TNF was coinjected with PKCζ inhibitor. TNF alone did not induce apoptosis in the retina. Coinjection of the PKCζ-specific inhibitor and TNF, however, induced apoptosis in the inner nuclear and ganglion cell layers. The PKCζ-specific inhibitor unmasks retinal cells to TNF cytotoxicity showing a link between the proapoptotic effects of TNF and the antiapoptotic PKCζ signaling pathway.
Journal of Cataract & Refractive Surgery, 2009
PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to analyze the in vivo arc... more PURPOSE: To use anterior segment optical coherence tomography (AS-OCT) to analyze the in vivo architecture of clear corneal incisions after phacoemulsification using different techniques.
European Journal of Ophthalmology, 2012
Purpose. To determine the prevalence of ocular surface diseases and identify risk factors in a po... more Purpose. To determine the prevalence of ocular surface diseases and identify risk factors in a population of patients receiving antiglaucomatous eyedrops over the long term. Methods. An observational cross-sectional study was designed to investigate ocular surface signs and symptoms using simple clinical tools. An ocular surface disease intensity score was calculated based on 10 questions regarding ocular surface symptoms and signs with a 4-grade scale. Patients were classified into 3 groups (A, B, and C) according to this total score. A multinomial logistic regression was performed in order to identify risk factors for surface disease. Results. In an overall population of 516 patients, 49% belonged to group A, 30% to group B, and 21% to group C. The multivariate analysis showed that the following factors were correlated with the severity of ocular surface disease: patient age, number of daily eyedrops, past topical treatment changes for ocular intolerance (found in the history of 40% of the patients), intraocular pressure (found to be significantly higher in patients with more severe ocular surface disease), and glaucoma severity. Conclusions. Patients treated for primary open-angle glaucoma or ocular hypertension often have ocular surface diseases, more often and more severely in older patients receiving more drugs and presenting with more severe glaucoma. These high prevalence values might therefore have consequences on the burden of the disease in terms of adherence to treatment and quality of life.
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Papers by Christophe Baudouin