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窑Clinical Research窑

Effect of focal laser photocoagulation in eyes with mild

to moderate non-proliferative diabetic retinopathy

Department of Ophthalmology, Kim's Eye Hospital, INTRODUCTION

Myung-Gok Eye Research Institute, Konyang University
College of Medicine, Seoul 07301, Korea D iabetic retinopathy (DR) is a serious cause of visual
impairment in developed countries. The prevalence of
Correspondence to: Jung Il Han. Department of DR increases with the elapsed duration of diabetes, and
Ophthalmology, Kim's Eye Hospital, Myung-Gok Eye nearly all persons with type 1 diabetes, and more than 60%
Research Institute, Konyang University College of Medicine, of those with type 2 diabetes, have some level of retinopathy
Seoul 07301, Korea. [email protected] after 20y[1].
Received: 2016-03-16 Accepted: 2016-04-19 The earliest signs of DR are damage to the microvasculature,
and the formation of lesions such as hard exudates (HEs),
Abstract which are lipid leaks from the blood vessels [2]. Apperance of
HEs in macular area can be clue of the presence or previous
·AIM: To report the effect of focal laser photocoagulation existence of diabetic maculopathy [3]. Furthermore, large HE
on both the severity of hard exudates (HEs) and the rate
deposits are known to increase the risk of subretinal fibrosis [4]
of disease progression in eyes with mild to moderate
and Chew [5]
showed that size of HE were correlated
non-proliferative diabetic retinopathy (NPDR).
with later decreased of visual acuity over 5y.
· METHODS: We retrospectively reviewed the medical Focal laser photocoagulation is an effective treatment in
records of 33 patients (60 eyes) who had been diagnosed cases involving HEs; possibly because it leads to the closure
with mild to moderate NPDR between January 2006 and of microaneurysms and subsequent cessation of leakage into
December 2012. The patients were divided into 2 groups: the retinal space [6]. According to the result of the Early
Group A (38 eyes in 20 patients treated using focal laser Treatment Diabetic Retinopathy Study (ETDRS) for diabetic
photocoagulation) and Group B (treated without laser
macula edema (DME), focal laser photocoagulation is
photocoagulation). We also reviewed the best corrected
commonly used to treat DME with guide of fluorescein
visual acuity measurements, and the fundus photographs
angiography (FA) [7]. Characterization of diabetic
taken at both baseline and follow-up visits.
microaneurysms can be visualized using spectral-domain
· RESULTS: In Group A, HE severity grade had optical coherence tomography (OCT) [8]. On the other hand, a
decreased significantly from baseline to the final visit ( < study by Lovestam-Adrian and Agardh [9] found that when
0.05), but this was not the case in Group B ( =0.662). HEs are present, photocoagulation leads to a higher risk of
The cumulative probabilities of retinopathy progression both subretinal fibrosis and atrophic creep of the pigment
at 5y were 26% in Group A and 30% in Group B. Kaplan-
epithelium than when HEs are not present. This is
Meier survival curves showed no significant difference
particularly true when the HEs are subfoveally located.
between the groups with regard to retinopathy
Previous studies proved that the risk of development of
progression ( =0.805).
proliferative diabetic retinopathy (PDR) can be reduced by
· CONCLUSION: Focal laser photocoagulation reduced glycemic control [10]. Moreover, panretinal photocoagulation
the levels of HEs in eyes with mild to moderate NPDR. (PRP) in eyes with high-risk PDR can reduce the risk of
However, the treatment was not able to decelerate the severe visual loss compared with that of untreated eyes [11].
progression of DR. However, PRP is a destructive treatment procedure and it
· KEYWORDS: focal laser; diabetic retinopathy; retina; can cause adverse effects including complications of
non-proliferative diabetic retinopathy misdirected or excessive burns and despite of appropriate
DOI:10.18240/ijo.2016.10.12 treatment, visual loss can progress in nearly 5% of
individuals.
Jeong SH, Han JI, Cho SW, Lee DW, Kim CG, Lee TG, Kim JW. The purpose of the current study was to report the effects of
Effect of focal laser photocoagulation in eyes with mild to moderate focal laser photocoagulation on both HE severity and the rate
non-proliferative diabetic retinopathy. 2016;9 (10): of disease progression in eyes with mild to moderate
1439-1443 non-proliferative diabetic retinopathy (NPDR).
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Effect of focal laser photocoagulation

Figure 1 Standard photograph for grading hard exudates (HEs) Grade 1 (A): Total HE area less than 1/4 disc area; Grade 2 (B):
Total HE area more than 1/4 disc area, but less than 1 disc area; Grade 3 (C): Total HE area more than 1 disc area.

SUBJECTS AND METHODS burns and which directly treated leaking microaneurysms.
From January 2006 to December 2012, 60 eyes of 33 Based on modification of a hierarchical DR progression
patients with mild to modereate NPDR were included in the algorithm proposed by Bressler [12]
, the progression of
study. The study was approved by the Medical Ethics DR was defined as including any of the following: 1) cases
Committee of Kim's eye Hospital of Konyang University and that had progressed from NPDR to PDR wherein no PDR
adhered to the provisions of the Declaration of Helsinki for had been identified at baseline on the basis of fundus
research involving human subjects. All the patients involved photographs, 2) additional cases of DR that had been treated
in the study gave written informed consent after thorough using PRP during follow-up period, and which were not
discussion on the potential benefits and risks of focal laser defined under criterion 1) above, and 3) additional cases
photocoagulation. wherein vitreous hemorrhage had occurred during follow-up
One or both of the participants' eyes had to meet the period, and which were not defined under either criterion 1)
following criteria to qualify for enrolment in this study: 1) or 2) above.
best-corrected Snellen visual acuity 逸0.8, 2) no definitive Clinically significant macular edema (CSME) was defined
retinal thickening at the macular center upon clinical when any of following criteria were met: 1) retinal
examination, 3) presence of HEs at the posterior pole, and 4) thickening at or within either 500 滋m or 1/3 disc diameter of
mild to moderate NPDR. the macular center, 2) HEs at or within 500 滋m of the macular
The patients were divided into 2 groups: Group A included center, combined with adjacent retinal thickening, 3) a
patients who had been treated using focal laser thickened retinal area at least 1 disc area in size, any part of
photocoagulation, Group B included patients who had been which was located within 1 disc area of the foveal center.
treated without laser photocoagulation. We reviewed both Statistical Analysis The demographics and clinical
the best corrected visual acuity measurements and the fundus characteristics of the patients [age, duration of diabetes, and
photographs of the central 30毅 , which were taken at the logarithm of the minimum angle of resolution (logMAR)
baseline and follow-up visits. Furthermore, OCT visual acuity] were analyzed using the independent -test.
measurements were reviewed when macular edema had Significance of sex and systemic hypertension were
developed or was suspected. Photographs were evaluated in evaluated using Fisher's exact test. Changes in HE severity
a masked fashion independently by two authors. were analyzed using the Wilcoxon signed-rank test.
We excluded patients with a history of eye injury, previous Cumulative probabilities of DR progression at each biannual
vitreoretinal surgery, glaucoma, or uveitis. Additionally, we visit up to 60mo were analyzed in each treatment group
excluded eyes that were administered any intravitreal steroid using Kaplan-Meier methods. Statistical analyses were
or anti-vascular endothelial growth factor (VEGF) injections performed using the commercially available software
in either the 6-month period before laser photocoagulation or package SPSS ver. 22.0 for Windows (SPSS Sciences,
during the follow-up period. In such cases, we also excluded Chicago, IL, USA). A -value of <0.05 was considered
the contralateral eyes. statistically significant.
HEs were graded using standard photographs (Figure 1) as RESULTS
follows: 1) Grade 1: total area less than 1/4 disc area (Figure A total 60 eyes of 33 patients were included in the analysis
1A); 2) Grade 2: total area more than 1/4 disc area, but less assigned to groups based on whether they had received laser
than 1 disc area (Figure 1B); 3) Grade 3: total area more therapy (Group A, =38) or not (Group B, =22). Of these
than 1 disc area (Figure 1C). patients, 17 were men (51.5% ) and 16 were women
Laser photocoagulation was performed using the following (48.5% ). Their mean age was 62.1y (range: 44-76y). The
parameters: spot size, 100-130 滋m; duration, 100ms; and average follow-up period was 51.4mo. The clinical and
power, 70-150 mW. The laser burn intensity was adjusted to demographic characteristics of both groups at baseline and at
achieve a gray-white burn that was less intense than PRP 5y are summarized in Table 1.
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Table 1 Demographic and clinical characteristics of the patients in Groups A and B

Parameters Group A Group B P
No. of eyes 38 22
Age (a) 61.5±7.96 63.0±6.77 0.580
Sex 0.481
M 9 8
F 11 5
Systemic hypertension 4 6 0.139
Duration of diabetes (a) 5.14±9.65 7.4±13.9 0.059
Visual acuity (logMAR, baseline) 0.05±0.08 0.05±0.05 0.841
Visual acuity (logMAR, at 5-year follow up) 0.14±0.21 0.04±0.08 0.078
Group A: Treated with focal laser photocoagulation: Group B: Treated without laser photocoagulation.

In Group A, HE severity had decreased significantly between

the baseline and final visits ( <0.05), but this was not the
cases in Group B ( =0.662; Figure 2). The mean changes
in HE severity between baseline and 5y were -0.39 in Group
A 0.05 in Group B ( <0.05).
Progression of retinopathy was partitioned into a stepwise
hierarchy of criteria in order to meet the outcome definition
or treatment of each criterion (Table 2). Nine of 38 eyes in
Group A and 6 of 22 eyes in Group B progressed to PDR.
The need for PRP was the most common evidence of
progression to PDR in both groups.
Throughout the 5-year follow-up period, the cumulative
probabilities of DR progression in Group A were 12% up to
3y, 18% up to 4y, and 26% up to 5y. The corresponding Figure 2 Changes in HE severity during a 5-year follow-up.
values in Group B were 9% , 19% , and 30% , respectively.
However, the Kaplan-Meier survival curves showed no
significant difference between the groups with regard to in
DR progression ( =0.805; Figure 3).
Two of the 38 eyes in Group A and 1 of the 22 eyes in
Group B developed CSME. This did not constitute a
statistical difference ( =0.698).
DISCUSSION
Macular HEs in cases of DR have previously been shown to
increase the risk of visual impairment and developing of
subretinal fibrosis[5,13].
Previous study involving HE patients have shown that laser
photocoagulation can decrease the retinal area covered by
HEs during the first 6mo, but HE increases again between 6
and 12mo [14]. Therefore, a follow-up period of 12mo is not
sufficient to draw any conclusions regarding the long-term
efficacy of laser photocoagulation. In the present study, we
found that HEs decreased significantly in severity between Figure 3 Cumulative probability of DR progression by
12mo and 5y in patients with mild to moderate NPDR ( < treatment group defined as change from NPDR to PDR,
0.05). treatment using PRP, or occurrence of vitreous hemorrhage.
Many factors can influence the severity of HEs such as,
anemia, higher blood pressure, proteinuria, glycated reported strict control of serum cholesterol levels can reduce
hemoglobin (HbA1c), intravenous insulin use, and peripheral the degree of HEs[16].
vascular disease [15]. Moreover, medical treatment can also The positive effect of laser photocoagulation has been well
decrease the level of HEs, and a previous study have known for many decades in eyes with macular edema, and it
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Effect of focal laser photocoagulation

Table 2 Participants progressing to proliferative diabetic retinopathy by treatment group up to 5y

1-year 2-year 3-year 4-year 5-year
Progression category
Group A Group B Group A Group B Group A Group B Group A Group B Group A Group B
(n=38) (n=22) (n=38) (n=22) (n=38) (n=22) (n=38) (n=22) (n=38) (n=22)
Total cases that progressed from
1 0 0 2 0 0 0 0 2 0 0
NPDR to PDR
Received PRP laser (not counted
0 2 2 0 0 0 2 0 1 1
in row above)
Reported vitreous hemorrhage
0 0 0 0 0 0 0 0 2 1
(not counted in 2 rows above)
Total with progression to PDR 0 2 4 0 0 0 2 2 3 2
Data shown are total/additional numbers of patients (not counted in preceding rows). NPDR: Non-proliferative diabetic retinopathy; PDR:
Proliferative diabetic retinopathy; PRP: Panretinal photocoagulation. 1Documented on fundus photographs.

still remains as a widely used modality for exudative DME [7]. irregular follow-up intervals and treatment decision
However, it is not without limitations and controversy, as depending on the physician's discretion rather than on a
one clinical study showed that during the three-year given protocol may have resulted in the final outcome.
follow-up, the 10 letter decline of visual acuity was observed Another limitation of this study was that HE severities were
in 12% of the eyes [17]. In this study, focal laser assessed using estimated values based on disc area, and the
photocoagulation for the treatment of HE was not effective changes of HE area could not be calculated with the
in the prevention of macular edema in eyes with mild to objective measurements.
moderate NPDR ( =0.698) during the 5-year follow up In summary, focal laser photocoagulation reduced HE
period. severity in eyes with mild to moderate NPDR. However, the
The previous studies also have reported the effectiveness of same focal laser photocoagulation was not able to prevent
intravitreal triamcinolone (IVTA) for the reduction of the HE DME or slow DR progression. Therefore, we suggest that
and DME. Larsson [18]
showed that a single 4-mg focal laser photocoagulation can be an option for HE.
injection of IVTA reduced HE deposition and improved ACKNOWLEDGEMENTS
visual acuity within 3mo. IVTA can induce regression of Conflicts of Interest: Jeong SH, None; Han JI, None;
macular edema by reducing breakdown of the blood-retina Cho SW, None; Lee DW, None; Kim CG, None; Lee TG,
barrier in patients with diabetes [19]. Additionally, it was more None; Kim JW, None.
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栽藻造押8629原愿圆圆源缘员苑圆 8629-82210956 耘皂葬蚤造押ijopress岳员远猿援糟燥皂
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