July 2024
Volume 13, Issue 7
Open Access
Retina  |   July 2024
Morphology, Fundus Autofluorescence, and Retinal Sensitivity of Photocoagulated Lesions in Proliferative Diabetic Retinopathy
Author Affiliations & Notes
  • Kentaro Nishida
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Ryo Kawasaki
    Department of Public Health, Osaka University Graduate School of Medicine, Suita, Japan
  • Yoko Fukushima
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
    Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan
  • Shizuka Takahashi
    Department of Ophthalmology, Higashiosaka City Medical Center, 3-4-5 Nishi-iwata, Higashi-Osaka, Osaka, Japan
  • Takashi Fujikado
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
  • Kohji Nishida
    Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan
    Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan
  • Correspondence: Kentaro Nishida, Department of Ophthalmology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, #E7, Suita 565-0871, Japan. e-mail: [email protected] 
Translational Vision Science & Technology July 2024, Vol.13, 1. doi:https://doi.org/10.1167/tvst.13.7.1
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      Kentaro Nishida, Ryo Kawasaki, Yoko Fukushima, Shizuka Takahashi, Takashi Fujikado, Kohji Nishida; Morphology, Fundus Autofluorescence, and Retinal Sensitivity of Photocoagulated Lesions in Proliferative Diabetic Retinopathy. Trans. Vis. Sci. Tech. 2024;13(7):1. https://doi.org/10.1167/tvst.13.7.1.

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Abstract

Purpose: To evaluate the relationships among morphology, fundus autofluorescence (FAF), and retinal sensitivity of photocoagulated lesions more than 1 year after panretinal photocoagulation in patients with proliferative diabetic retinopathy and good vision.

Methods: This retrospective cohort study included patients with proliferative diabetic retinopathy who had undergone panretinal photocoagulation more than 1 year ago. The photocoagulated lesions were classified according to FAF levels: group A, no FAF; group B, diffuse FAF; group C, white-dotted centers with diffuse FAF; group D, white-dotted centers without FAF; and group E, controls. The main outcome measures were FAF, retinal sensitivity, and morphology of the photocoagulated lesions.

Results: The median sensitivity values and number of photocoagulated lesions in groups A (n = 37), B (n = 39), C (n = 4), D (n = 15), and E (n = 39) were 0 dB, 18.0 dB, 13.9 dB, 0.3 dB, and 21.5 dB, respectively. EZ lines were absent in 93.5%, 18.1%, 50%, 93.3%, and 0% of lesions in groups A, B, C, D, and E, respectively. The inner retinal layer was damaged in 45.2%, 3.0%, 50%, 73.3%, and 0% lesions in groups A, B, C, D, and E, respectively. Statistically significant between-group differences were observed in the retinal sensitivities of the photocoagulated lesions, presence of EZ lines, and damage to the inner retinal layer (p < 0.05).

Conclusions: The photoreceptors in most photocoagulated lesions with diffuse FAF retain their morphology and function.

Translational Relevance: Using fundus autofluorescence, the damage to photoreceptors after panretinal photocoagulation in patients with diabetes can be estimated in a noninvasive manner. This process can help in determining the need for additional panretinal photocoagulation.

Introduction
Diabetic retinopathy (DR) is a common complication of diabetes, and its prevalence is expected to increase from 463 million in 2019 to 700 million in 2045.1 Furthermore, it is a leading cause of preventable blindness in the working-age population in many developed countries.2 
Dramatic improvements in the outcomes of DR have been observed since anti-vascular endothelial growth factor (VEGF) therapy was approved for the treatment of DR with or without diabetic macular edema.35 However, anti-VEGF therapy for DR without diabetic macular edema requires multiple injections and is costly, thus increasing the physical and economic burden.6,7 Previous clinical trials have demonstrated the beneficial effects of panretinal photocoagulation (PRP) in patients with proliferative DR (PDR).8,9 Further, a previous study reported that severe complications were fewer when PRP treatment was discontinued than when anti-VEGF injections were discontinued for patients with PDR.10 Thus, PRP remains the first-line treatment for PDR and neovascular glaucoma caused by severe retinal ischemia, including PDR. 
Fundus autofluorescence (FAF) imaging is a noninvasive imaging method that detects fluorophores accumulating in lipofuscin granules in retinal pigment epithelium (RPE) cells.11,12 FAF indicates the function of RPE cells; thus, several studies have investigated FAF of photocoagulated lesions. A previous study13 investigated FAF of photocoagulated lesions over time. The findings revealed hyperautofluorescence a few months after photocoagulation, which was caused by activation of abundant phagosomes and RPE in the adjacent areas. However, hypoautofluorescence was observed 1 year after photocoagulation; this was caused by complete RPE atrophy.13 Thus, FAF has been used to assess photocoagulated lesions in some patients,14 whereas optical coherence tomography (OCT) has been used to evaluate the morphology of photocoagulated lesions.15 
In previous studies, both morphology15 and FAF13 of photocoagulated lesions have been investigated immediately and approximately 1 year after photocoagulation. However, to our knowledge, no study has investigated FAF, morphology, and function at photocoagulated lesions more than 1 year after photocoagulation simultaneously, which can help to estimate the damage to photoreceptors in patients after PRP noninvasively and may help to determine additional PRP. 
Therefore, the aim of this study was to investigate the relationships among the morphology, FAF, and retinal sensitivity of photocoagulated lesions more than 1 year after PRP in patients with PDR. 
Methods
Participants
This retrospective study was performed in accordance with the tenets of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Osaka University Hospital, Suita, Japan (approval number: 16168-2). Patients with PDR who had undergone PRP more than 1 year ago and had visited Osaka University Hospital between April 2019 and October 2022 for follow-up visits were included. PRP was performed on the retina using a spot size of either 400 or 500 µm. One course of PRP and multiple PRP by different surgeons were included. The requirement for informed consent was waived because of the retrospective nature of the study. 
All patients had undergone ophthalmological examinations, including best-corrected visual acuity measurement, fundus photography, and FAF evaluation using the Optos 200Tx or Optos Silver Stone scanning laser ophthalmoscope (Optos plc, Dunfermline, Scotland, UK). Decimal visual acuity was converted to logarithm of the minimum angle of resolution units for analyses. Data regarding the type of diabetes and hemoglobin A1c levels were retrieved from medical records. 
Exclusion Criteria
The exclusion criteria were as follows: best-corrected visual acuity of less than 20/25; photocoagulation within the previous 1 year; active DR; anti-VEGF injection before the study; opaque media, including cataracts, vitreous hemorrhage, and other retinal diseases; severely ischemic photocoagulated lesions; severe photocoagulated lesions exposing the sclera; low-resolution images; and lack of reproducible data. 
Classification of FAF of the Photocoagulated Lesions
The lesions were classified by two graders (K.N. and Y. F., who are retina specialists) according to their FAF levels: group A, no FAF; group B, diffuse FAF; group C, white-dotted center with diffuse FAF in the background; group D, white-dotted center with no FAF in the background; and group E, controls (Fig. 1). In case of disagreement between the two graders, a third grader (S.T., who is a retina specialist) made the final decision. 
Figure 1.
 
Fundus photographs and FAF classification of the photocoagulated lesions. Fundus photographs (A and B) and FAF (C and D) of lesions after PRP in patients with PDR. Lesions with no FAF (black circle, C), lesions with diffuse FAF (white circle, C), lesions with white-dotted centers and diffuse FAF in the background (white-dotted circle, D), and lesions with white-dotted centers and no FAF in the background (black-dotted circle, D) are classified into groups A, B, C, and D, respectively. Schematic diagrams for groups A, B, C, and D are shown (E). FAF, fundus autofluorescence.
Figure 1.
 
Fundus photographs and FAF classification of the photocoagulated lesions. Fundus photographs (A and B) and FAF (C and D) of lesions after PRP in patients with PDR. Lesions with no FAF (black circle, C), lesions with diffuse FAF (white circle, C), lesions with white-dotted centers and diffuse FAF in the background (white-dotted circle, D), and lesions with white-dotted centers and no FAF in the background (black-dotted circle, D) are classified into groups A, B, C, and D, respectively. Schematic diagrams for groups A, B, C, and D are shown (E). FAF, fundus autofluorescence.
Retinal Sensitivity and Circulation of the Photocoagulated Lesions
The retinal sensitivity of the photocoagulated lesions was evaluated using microperimetry (MP-3; NIDEK Co., Ltd., Gamagori, Aichi, Japan), which was performed more than twice using the Goldman Ⅲ stimulus size. The scores at the center of each photocoagulated lesion were averaged and defined as the retinal sensitivity of the photocoagulated lesion (Fig. 2). 
Figure 2.
 
Retinal circulation and sensitivity of the photocoagulated lesions. FAF (A) and OCT angiography (B) of three photocoagulated lesions (group A, black circle; group B, white circle) (A) are evaluated in one patient. OCT angiography does not reveal severe ischemia in the three photocoagulated lesions (white circle) (B). Microperimetry scores at each point around the center of the photocoagulated lesions are shown (C, D). Microperimetry was performed more than twice a day (C) on 2 or more days (D). The scores at the center of each photocoagulated lesion (white circle) are consistent. The values are averaged and defined as the retinal sensitivity of each photocoagulated lesion. Group A, lesions with no FAF; group B, lesions with diffuse FAF.
Figure 2.
 
Retinal circulation and sensitivity of the photocoagulated lesions. FAF (A) and OCT angiography (B) of three photocoagulated lesions (group A, black circle; group B, white circle) (A) are evaluated in one patient. OCT angiography does not reveal severe ischemia in the three photocoagulated lesions (white circle) (B). Microperimetry scores at each point around the center of the photocoagulated lesions are shown (C, D). Microperimetry was performed more than twice a day (C) on 2 or more days (D). The scores at the center of each photocoagulated lesion (white circle) are consistent. The values are averaged and defined as the retinal sensitivity of each photocoagulated lesion. Group A, lesions with no FAF; group B, lesions with diffuse FAF.
The retinal circulation around the photocoagulated lesions was evaluated using OCT angiography (Angioplex Elite 9000; Carl Zeiss Meditec, Inc., Dublin, CA) (Fig. 2B). 
Morphological Changes in the Photocoagulated Lesions
OCT (Spectralis, Heidelberg Engineering, Heidelberg, Germany) was performed to evaluate the morphological changes in the photocoagulated lesions. Multiple OCT slices were acquired, and the OCT image closest to the center of the photocoagulated lesion was selected for further evaluation. Two graders evaluated the presence of the ellipsoid zone (EZ) line and damage to the inner retinal layer (INL) (Fig. 3). In case of disagreement between the two graders, a third grader made the final decision. 
Figure 3.
 
Morphological changes in the photocoagulated lesions. Fundus photographs (A) and FAF (B) of two photocoagulated lesions (group A, black circle; group B, white circle). These lesions were evaluated using OCT (C). One lesion remains on the EZ line and has an intact INL (white arrows). The EZ line is absent in one lesion, which also shows INL damage (black arrows, D). Group A, lesions with no FAF; group B, lesions with diffuse FAF.
Figure 3.
 
Morphological changes in the photocoagulated lesions. Fundus photographs (A) and FAF (B) of two photocoagulated lesions (group A, black circle; group B, white circle). These lesions were evaluated using OCT (C). One lesion remains on the EZ line and has an intact INL (white arrows). The EZ line is absent in one lesion, which also shows INL damage (black arrows, D). Group A, lesions with no FAF; group B, lesions with diffuse FAF.
Statistical Analyses
The Wilcoxon test was used to evaluate the retinal sensitivity of the photocoagulated lesions. A mixed model was used to evaluate random effects. Fisher's exact test was used to evaluate the presence of the EZ line and damage to INL in the photocoagulated lesions. All statistical analyses were performed using JMP Pro 17 statistics software (JMP Statistical Discovery LLC, Cary, NC) and p value of less than 0.05 was considered statistically significant. 
Results
Eleven male and eight female patients with a mean age of 62.5 ± 10.2 years were included. The mean best-corrected visual acuity was 1.02, and the mean hemoglobin A1c level was 7.4% ± 0.9%. Approximately 15.8% of patients had type 1 diabetes, and the mean duration of diabetes was 25.9 years (Table 1). 
Table 1.
 
Demographic Data of Study Patients
Table 1.
 
Demographic Data of Study Patients
The total number of lesions evaluated via microperimetry were 37, 39, 4, 15, and 39 in groups A, B, C, D, and E, respectively. The total number of lesions evaluated via OCT was 31, 33, 4, 15, and 33 in groups A, B, C, D, and E, respectively. Table 2 presents the distribution of lesions in each patient group. The median sensitivities of the photocoagulated lesions in groups A, B, C, D, and E were 0 dB (interquartile range [IQR] 0–0 dB), 18.0 dB (IQR, 14.0–19.7 dB), 13.9 dB (IQR, 9.9–16.0 dB), 0.3 dB (IQR, 0–5.3 dB), and 21.5 dB (IQR, 20.0–23.9 dB), respectively, with significant between-group differences (p < 0.0001). Excluding groups A and D and groups B and C, each pair of groups showed statistically significant differences (p < 0.005) (Fig. 4). The patients’ random effect on retinal sensitivity was statistically significant (Wald p < 0.05), and the fixed effect between group E and each of the remaining groups, except for group C (p = 0.166), was statistically significant (p < 0.0001). 
Table 2.
 
Distribution of Lesions in Each Patient Group
Table 2.
 
Distribution of Lesions in Each Patient Group
Figure 4.
 
Retinal sensitivity of the photocoagulated lesions. The median sensitivities of the photocoagulated lesions in groups A, B, C, D, and E were 0 dB (IQR, 0–0 dB), 18.0 dB (IQR, 14.0–19.7 dB), 13.9 dB (IQR, 9.9–16.0 dB), 0.3 dB (IQR, 0–5.3 dB), and 21.5 dB (IQR, 20.0–23.9 dB), respectively, with significant between-group differences (p < 0.0001). Excluding groups A and D and groups B and C, each pair of groups showed statistically significant differences (p < 0.005). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 4.
 
Retinal sensitivity of the photocoagulated lesions. The median sensitivities of the photocoagulated lesions in groups A, B, C, D, and E were 0 dB (IQR, 0–0 dB), 18.0 dB (IQR, 14.0–19.7 dB), 13.9 dB (IQR, 9.9–16.0 dB), 0.3 dB (IQR, 0–5.3 dB), and 21.5 dB (IQR, 20.0–23.9 dB), respectively, with significant between-group differences (p < 0.0001). Excluding groups A and D and groups B and C, each pair of groups showed statistically significant differences (p < 0.005). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
The EZ line was absent in 29 (93.5%), 6 (18.1%), 2 (50%), 14 (93.3%), and 0 (0%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05) (Fig. 5). Damage to the INL was observed in 14 (45.2%), 1 (3.0%), 2 (50%), 11 (73.3%), and 0 (%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05) (Fig. 6). 
Figure 5.
 
Morphological changes in the EZ line in photocoagulated lesions. The EZ line is absent in 29 (93.5%), 6 (18.1%), 2 (50%), 14 (93.3%), and 0 (0%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 5.
 
Morphological changes in the EZ line in photocoagulated lesions. The EZ line is absent in 29 (93.5%), 6 (18.1%), 2 (50%), 14 (93.3%), and 0 (0%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 6.
 
Morphological changes in the INL of the photocoagulated lesions. Damage to INL is observed in 14 (45.2%), 1 (3.0%), 2 (50%), 11 (73.3%), and 0 (%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 6.
 
Morphological changes in the INL of the photocoagulated lesions. Damage to INL is observed in 14 (45.2%), 1 (3.0%), 2 (50%), 11 (73.3%), and 0 (%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Discussion
The present study revealed that photoreceptors in most photocoagulated lesions with diffuse FAF retained some retinal sensitivity and the morphology of the EZ line and INL more than 1 year after PRP for PDR. To our knowledge, this study is the first to suggest that some photoreceptors are preserved and functional in most photocoagulated lesions with diffuse FAF. 
It is unclear whether photocoagulated lesions with diffuse FAF contain photoreceptors. Animal experiments have evaluated the regeneration of photoreceptors after photocoagulation.15,16 These studies evaluated the damage to the RPE–photoreceptor junction in the lesions caused by a 100-ms pulse in rabbit retina and revealed that the RPE–photoreceptor junction in the representative intense burnt lesions became shorter. Moreover, the area of the lesion was decreased to 36% of the initial lesion size at 4 months. A previous study hypothesized that photoreceptor regeneration after photocoagulation can be attributed to two factors: lateral photoreceptor migration, which replaces the initial cell loss, and the recovery of damaged outer segments.15 RPE plays a crucial role in maintaining the regenerated photoreceptors once photoreceptor regeneration occurs. FAF is an indicator of lipofuscin production by RPE. Therefore, the photocoagulated lesions with diffuse FAF (group B) had RPE and could maintain the regenerated photoreceptors. Moreover, these lesions had some retinal sensitivity and an EZ line. In contrast, lesions with no FAF (group A) had thick pigmentation owing to scarring or no RPE. Thus, these lesions have almost no retinal sensitivity, and most lack an EZ line. Furthermore, two-fifths of these lesions showed INL damage. 
Hyperfluorescence with a dotted center was observed in groups C and D. A previous study reported that lesions showing this pattern were observed 6 months after photocoagulation and indicated RPE aggregation.17 Another previous study13 reported that lesions showing hyperfluorescence with a dotted center darkened over time, although some photocoagulated lesions retained the pattern 14 months after photocoagulation. At the time of evaluation in the present study, more than 1 year had passed since photocoagulation; however, some lesions had retained their hyperfluorescence with dotted centers. Lesions with this pattern and no FAF in the background (group D) had significantly lower retinal sensitivity than did those in group C (p < 0.005). These group D lesions seemed to progress to the stage with no FAF (group A) over time. The lesions showing hyperfluorescence with dotted centers and diffuse FAF in the background (group C) exhibited some retinal sensitivity. These group C lesions seemed to progress to the stage with diffuse FAF (group B) over time. No statistically significant differences were observed between groups C and D in terms of morphological changes. This may be attributed to the small number of patients in these groups, given the rarity of their condition wherein slow progression of FAF was observed. 
The random effect of the patients on retinal sensitivity was statistically significant (Wald p < 0.05) and may be attributed to the variability in the distribution of lesions among patients, similarities between the photocoagulated lesions in the same patient, and limitation of the area where microperimetry could be performed with accuracy and reproducibility. However, the fixed effect between group E and each of the remaining groups, except group C (p = 0.166), which had a small number of cases, was statistically significant (p < 0.0001), and the difference in retinal sensitivity between those groups was considered significant. 
Some patients had lesions with varying FAF in the same eye; the reasons for these differences remain unclear. If photocoagulation was performed under different conditions, such differences could be explained easily. In real-world clinical practice, even if photocoagulation is performed for the same duration with the same power, differences in burn strengths could be observed in the lesions immediately after photocoagulation. This finding may be attributed to the presence of media opacities such as cataracts, vitreous hemorrhage,18 and retinal edema, which are not uniform in the same eye. Eye movements can also affect the burn strength of each photocoagulated lesion. Therefore, retinal damage caused under the same conditions, with the same power and duration, could change, and the regeneration of photoreceptors may occur in some photocoagulated lesions. Moreover, the burn strength and retinal damage of photocoagulated lesions vary with changes in patients, surgeons, or laser delivery systems. PRP is widely used worldwide; however, retinal conditions after PRP appear to be different. 
One hypothesis regarding the mechanism underlying the efficacy of PRP for PDR is that it decreases the number of photoreceptors consuming a large amount of oxygen in the outer retina and improves hypoxia in the inner retina by inducing oxygen transport from the choriocapillaris.19,20 However, photocoagulated lesions with diffuse FAF seem to have photoreceptors from this study, and photocoagulated lesions with diffuse FAF after PRP may be less effective at the aspect of photoreceptor destruction. FAF of photocoagulated lesions after PRP can indicate the preservation of photoreceptor noninvasively; thus, they can help to determine the need for additional PRP for the severe ischemic diseases, such as refractory neovascular glaucoma cases. 
This study has some limitations. Because this study was retrospective, it was not possible to evaluate the burn strength immediately after photocoagulation and laser delivery. Prospective studies must be conducted in the future to validate these findings. 
In conclusion, the study findings suggest that photoreceptors in most photocoagulated lesions with diffuse autofluorescence retain their morphology and function. Using FAF, the damage to photoreceptors after PRP can be estimated in a noninvasive manner in patients with diabetes; this process can help to determine the need for additional PRP. 
Acknowledgments
Supported by JSPS KAKENHI Grant Number 21K12809. We would like to extend our special thanks to certified orthoptists at Osaka University Hospital for their valuable advice and precise ophthalmological examinations especially Suzuka Doi, Misa Morota, Rio Nakai, and Ayano Nakamichi. Medical writing and editing support were provided by Editage. 
Data Availability Statements: The data supporting the findings of this study are available from the corresponding author upon reasonable request. 
Disclosure: K. Nishida, None; R. Kawasaki, None; Y. Fukushima, None; S. Takahashi, None; T. Fujikado, None; K. Nishida, None 
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Figure 1.
 
Fundus photographs and FAF classification of the photocoagulated lesions. Fundus photographs (A and B) and FAF (C and D) of lesions after PRP in patients with PDR. Lesions with no FAF (black circle, C), lesions with diffuse FAF (white circle, C), lesions with white-dotted centers and diffuse FAF in the background (white-dotted circle, D), and lesions with white-dotted centers and no FAF in the background (black-dotted circle, D) are classified into groups A, B, C, and D, respectively. Schematic diagrams for groups A, B, C, and D are shown (E). FAF, fundus autofluorescence.
Figure 1.
 
Fundus photographs and FAF classification of the photocoagulated lesions. Fundus photographs (A and B) and FAF (C and D) of lesions after PRP in patients with PDR. Lesions with no FAF (black circle, C), lesions with diffuse FAF (white circle, C), lesions with white-dotted centers and diffuse FAF in the background (white-dotted circle, D), and lesions with white-dotted centers and no FAF in the background (black-dotted circle, D) are classified into groups A, B, C, and D, respectively. Schematic diagrams for groups A, B, C, and D are shown (E). FAF, fundus autofluorescence.
Figure 2.
 
Retinal circulation and sensitivity of the photocoagulated lesions. FAF (A) and OCT angiography (B) of three photocoagulated lesions (group A, black circle; group B, white circle) (A) are evaluated in one patient. OCT angiography does not reveal severe ischemia in the three photocoagulated lesions (white circle) (B). Microperimetry scores at each point around the center of the photocoagulated lesions are shown (C, D). Microperimetry was performed more than twice a day (C) on 2 or more days (D). The scores at the center of each photocoagulated lesion (white circle) are consistent. The values are averaged and defined as the retinal sensitivity of each photocoagulated lesion. Group A, lesions with no FAF; group B, lesions with diffuse FAF.
Figure 2.
 
Retinal circulation and sensitivity of the photocoagulated lesions. FAF (A) and OCT angiography (B) of three photocoagulated lesions (group A, black circle; group B, white circle) (A) are evaluated in one patient. OCT angiography does not reveal severe ischemia in the three photocoagulated lesions (white circle) (B). Microperimetry scores at each point around the center of the photocoagulated lesions are shown (C, D). Microperimetry was performed more than twice a day (C) on 2 or more days (D). The scores at the center of each photocoagulated lesion (white circle) are consistent. The values are averaged and defined as the retinal sensitivity of each photocoagulated lesion. Group A, lesions with no FAF; group B, lesions with diffuse FAF.
Figure 3.
 
Morphological changes in the photocoagulated lesions. Fundus photographs (A) and FAF (B) of two photocoagulated lesions (group A, black circle; group B, white circle). These lesions were evaluated using OCT (C). One lesion remains on the EZ line and has an intact INL (white arrows). The EZ line is absent in one lesion, which also shows INL damage (black arrows, D). Group A, lesions with no FAF; group B, lesions with diffuse FAF.
Figure 3.
 
Morphological changes in the photocoagulated lesions. Fundus photographs (A) and FAF (B) of two photocoagulated lesions (group A, black circle; group B, white circle). These lesions were evaluated using OCT (C). One lesion remains on the EZ line and has an intact INL (white arrows). The EZ line is absent in one lesion, which also shows INL damage (black arrows, D). Group A, lesions with no FAF; group B, lesions with diffuse FAF.
Figure 4.
 
Retinal sensitivity of the photocoagulated lesions. The median sensitivities of the photocoagulated lesions in groups A, B, C, D, and E were 0 dB (IQR, 0–0 dB), 18.0 dB (IQR, 14.0–19.7 dB), 13.9 dB (IQR, 9.9–16.0 dB), 0.3 dB (IQR, 0–5.3 dB), and 21.5 dB (IQR, 20.0–23.9 dB), respectively, with significant between-group differences (p < 0.0001). Excluding groups A and D and groups B and C, each pair of groups showed statistically significant differences (p < 0.005). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 4.
 
Retinal sensitivity of the photocoagulated lesions. The median sensitivities of the photocoagulated lesions in groups A, B, C, D, and E were 0 dB (IQR, 0–0 dB), 18.0 dB (IQR, 14.0–19.7 dB), 13.9 dB (IQR, 9.9–16.0 dB), 0.3 dB (IQR, 0–5.3 dB), and 21.5 dB (IQR, 20.0–23.9 dB), respectively, with significant between-group differences (p < 0.0001). Excluding groups A and D and groups B and C, each pair of groups showed statistically significant differences (p < 0.005). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 5.
 
Morphological changes in the EZ line in photocoagulated lesions. The EZ line is absent in 29 (93.5%), 6 (18.1%), 2 (50%), 14 (93.3%), and 0 (0%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 5.
 
Morphological changes in the EZ line in photocoagulated lesions. The EZ line is absent in 29 (93.5%), 6 (18.1%), 2 (50%), 14 (93.3%), and 0 (0%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 6.
 
Morphological changes in the INL of the photocoagulated lesions. Damage to INL is observed in 14 (45.2%), 1 (3.0%), 2 (50%), 11 (73.3%), and 0 (%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Figure 6.
 
Morphological changes in the INL of the photocoagulated lesions. Damage to INL is observed in 14 (45.2%), 1 (3.0%), 2 (50%), 11 (73.3%), and 0 (%) lesions in groups A, B, C, D, and E, respectively, with statistically significant between-group differences (p < 0.05). Group A, lesions with no FAF; group B, lesions with diffuse FAF; group C, lesions with white-dotted centers and diffuse FAF in the background; group D, lesions with white-dotted centers and no FAF in the background; group E, controls.
Table 1.
 
Demographic Data of Study Patients
Table 1.
 
Demographic Data of Study Patients
Table 2.
 
Distribution of Lesions in Each Patient Group
Table 2.
 
Distribution of Lesions in Each Patient Group
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