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Longitudinal Assessment of Retinal Thinning in Adults With and Without Sickle Cell Retinopathy Using Spectral-Domain Optical Coherence Tomography.
Lim, JI, Niec, M, Sun, J, Cao, D
JAMA ophthalmology. 2021;(3):330-337
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Abstract
IMPORTANCE Determination of retinal thinning rates may help to identify patients who are at risk of progression of sickle cell retinopathy. OBJECTIVE To assess the rates of macular thinning in adults with and without sickle cell retinopathy using spectral-domain optical coherence tomography (OCT) and to identify ocular and systemic risk factors associated with retinal thinning. DESIGN, SETTING, AND PARTICIPANTS This longitudinal prospective case-control study enrolled adult participants from a university-based retina subspecialty clinic between February 11, 2009, and July 3, 2019. The study was designed in autumn 2008 and conducted from February 2, 2009, to July 3, 2020. Participants with sickle cell retinopathy (sickle cell group) were matched by age and race with participants without sickle cell retinopathy (control group). Participants received annual spectral-domain OCT and clinical examinations. Those with at least 1 year of follow-up by July 3, 2020, were included in the analysis. Data were analyzed from February 2, 2009, to July 3, 2020. MAIN OUTCOMES AND MEASURES The primary outcome was comparison of spectral-domain OCT measurements from early-treatment diabetic retinopathy study subfield rates of retinal thinning between eyes with and without sickle cell retinopathy and between different sickle cell hemoglobin subtypes. The secondary outcome was identification of ocular and systemic risk factors associated with rates of retinal thinning. RESULTS Among 370 adults (711 eyes) enrolled in the study, 310 participants (606 eyes) had sickle cell retinopathy, and 60 participants (105 eyes) did not. Of those, 175 of 310 participants (56.5%; 344 of 606 eyes [56.8%]; mean [SD] age, 37.8 [12.8] years; 126 women [72.0%]) in the sickle cell group and 31 of 60 participants (51.7%; 46 of 105 eyes [43.8%]; mean [SD] age, 59 [15.4] years; 22 women [71.0%]) in the control group had at least 1 year of clinical and spectral-domain OCT follow-up data from baseline. The mean (SD) follow-up was 53.7 (32.6) months for the sickle cell group and 54.6 (34.9) months for the control group. Rates of macular thinning in the sickle cell group were significantly higher than those in the control group for the inner nasal (difference, -1.18 μm per year; 95% CI, -1.71 to -0.65 μm per year), inner superior (difference, -1.03 μm per year; 95% CI, -1.78 to -0.29 μm per year), inner temporal (difference, -0.61 μm per year; 95% CI, -1.16 to -0.07 μm per year), and outer nasal (difference, -0.41 μm per year; 95% CI, -0.80 to -0.03 μm per year) quadrants. Patients with sickle cell hemoglobin SC and sickle cell hemoglobin β-thalassemia subtypes had higher rates of retinal thinning than those with the sickle cell hemoglobin SS subtype. Risk factors associated with greater rates of retinal thinning included participant age, stage of retinopathy, previous stroke, and presence of hypertension, acute chest syndrome, or diabetes. Hydroxyurea therapy was associated with decreased rates of retinal thinning and may be a protective factor. CONCLUSIONS AND RELEVANCE In this study, rates of retinal thinning were higher among participants with sickle cell retinopathy compared with those without sickle cell retinopathy, and thinning rates increased with participant age and stage of retinopathy. These findings suggest that identifying anatomic worsening of sickle cell maculopathy through spectral-domain OCT may be a useful parameter to evaluate the progression of sickle cell retinopathy.
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Goji Berry Intake Increases Macular Pigment Optical Density in Healthy Adults: A Randomized Pilot Trial.
Li, X, Holt, RR, Keen, CL, Morse, LS, Yiu, G, Hackman, RM
Nutrients. 2021;(12)
Abstract
Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide. Macular pigment optical density (MPOD), a biomarker for AMD, is a non-invasive measure to assess risk. The macula xanthophyll pigments lutein (L) and zeaxanthin (Z) protect against blue light and provide oxidant defense, which can be indexed by MPOD. This study examined the effects of Z-rich goji berry intake on MPOD and skin carotenoids in healthy individuals. A randomized, unmasked, parallel-arm study was conducted with 27 participants, aged 45-65, who consumed either 28 g of goji berries or a supplement containing 6 mg L and 4 mg Z (LZ), five times weekly for 90 days. After 90 days, MPOD was significantly increased in the goji berry group at 0.25 and 1.75 retinal eccentricities (p = 0.029 and p = 0.044, respectively), while no changes were noted in the LZ group. Skin carotenoids were significantly increased in the goji berry group at day 45 (p = 0.025) and day 90 (p = 0.006), but not in the LZ group. Regular intake of goji berries in a healthy middle-aged population increases MPOD may help prevent or delay the development of AMD.
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Visual Acuity in Retinal Vein Occlusion, Diabetic, and Uveitic Macular Edema: Central Subfield Thickness and Ellipsoid Zone Analysis.
Ciulla, TA, Kapik, B, Grewal, DS, Ip, MS
Ophthalmology. Retina. 2021;(7):633-647
Abstract
PURPOSE This study assessed relationships between best-corrected visual acuity (BCVA), central subfield thickness (CST), and ellipsoid zone (EZ) integrity in macular edema (ME) patients. DESIGN Post hoc analysis of 6 clinical trials, which included verified diagnoses, protocol refractions, and reading center assessment of OCT images. PARTICIPANTS Participants (n = 1063) were diagnosed with ME from retinal vein occlusion (RVO), diabetic retinopathy (DR; diabetic macular edema, DME), or noninfectious uveitis (NIU). METHODS For CST, 2 clinical trials for each disorder were analyzed. For EZ, 3 studies across 2 disorders were analyzed. MAIN OUTCOME MEASURES Primary outcomes were correlations between BCVA and CST, and between BCVA and 4 central subfield EZ grades. RESULTS For baseline BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.56 (774 eyes; 95% confidence interval [CI], -0.61 to -0.51; P < 0.001); DME, -0.50 (91 eyes; 95% CI, -0.64 to -0.33; P < 0.001); and ME from NIU, -0.38 (198 eyes; 95% CI, -0.49 to -0.26; P < 0.001). Regarding change from baseline to 24 weeks for both BCVA and CST, Pearson correlation coefficients were: ME from RVO, -0.35 (95% CI, -0.43 to -0.27; P < 0.001); DME, -0.30 (95% CI, -0.48 to -0.09; P = 0.006); and ME from NIU, -0.42 (95% CI, -0.53 to -0.29; P < 0.001). Acute and chronic ME showed similar baseline and 24-week change linear correlations. With lower baseline CST, a trend of decreased baseline and 24-week change correlations was found. For central subfield EZ at baseline, mean BCVA progressively worsened with each of 4 EZ grades in 185 eyes with gradable EZ (DME, 41 eyes; NIU, 144 eyes; P ≤ 0.050 for all pairwise comparisons except between normal and questionably abnormal EZ grades). Eyes with normal baseline central subfield EZ showed greater 24-week change in BCVA than those with abnormal baseline EZ (15.00 letters vs. 8.16 letters; P = 0.0005, with baseline BCVA, CST, and age as covariates). CONCLUSIONS Despite these correlations, CST and EZ integrity, as graded herein, account for the minority of BCVA variation in patients with ME resulting from RVO, DR, and NIU.
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COMPARISON OF THE INTERNAL LIMITING MEMBRANE INSERTION TECHNIQUE AND THE INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE WITH VITRECTOMY TO TREAT MACULAR HOLE-ASSOCIATED RETINAL DETACHMENT.
Zhu, K, Lei, B, Wong, W, Zhang, J, Guo, Y, Chen, H, Song, F, Chang, Q, Xu, G, Zhang, Y
Retina (Philadelphia, Pa.). 2021;(1):37-44
Abstract
PURPOSE To compare the anatomical and functional outcomes of macular hole (MH)-associated retinal detachment after vitrectomy with the internal limiting membrane (ILM) insertion technique or the inverted ILM flap technique. METHODS In this retrospective observational study, we reviewed the medical records of 49 eyes with MH-associated retinal detachment that underwent vitrectomy with the ILM insertion (26 eyes) or ILM flap (23 eyes) technique. RESULTS The MH closure rate at 12 months was greater in the ILM flap group versus the ILM insertion group (95% vs. 73%, respectively, P = 0.059). The postoperative best-corrected visual acuity (BCVA) at 12 months was significantly better in the ILM flap group (P = 0.014). All eyes (100%) showed an improvement in the BCVA of ≥0.3 logarithm of the minimum angle of resolution (15 Early Treatment Diabetic Retinopathy Study letters) in the ILM flap group versus 20 eyes (77%) in the ILM insertion group (P = 0.026). The preoperative BCVA and the ILM flap technique were significantly correlated with the postoperative BCVA (P = 0.028 and 0.027, respectively) and BCVA improvement (≥0.3 logarithm of the minimum angle of resolution [15 Early Treatment Diabetic Retinopathy Study letters]; P = 0.003 and 0.026, respectively). CONCLUSION The inverted ILM flap technique was more effective in improving the postoperative BCVA in patients with MH-associated retinal detachment when compared with the ILM insertion technique. The preoperative BCVA and the ILM flap technique were independent prognostic factors for visual outcomes in patients with MH-associated retinal detachment.
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Aqueous Cytokine Expression and Higher Order OCT Biomarkers: Assessment of the Anatomic-Biologic Bridge in the IMAGINE DME Study.
Abraham, JR, Wykoff, CC, Arepalli, S, Lunasco, L, Yu, HJ, Hu, M, Reese, J, Srivastava, SK, Brown, DM, Ehlers, JP
American journal of ophthalmology. 2021;:328-339
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PURPOSE To identify biomarkers for predicting response to anti-vascular endothelial growth factor (VEGF) therapy in diabetic macular edema (DME) and evaluate any links between cytokine expression and optical coherence tomography (OCT) phenotype. DESIGN The IMAGINE is a post hoc image analysis and cytokine expression assessment of the Efficacy & Safety Trial of Intravitreal Injections Combined With PRP for CSME Secondary to Diabetes Mellitus (DAVE) randomized clinical trial. METHODS Subjects were categorized as anatomical responders or nonresponders, and within the responder group as rebounders and non-rebounders based on quantitative, longitudinal OCT criteria. Retinal layer and fluid features were extracted using an OCT machine-learning augmented segmentation platform. Responders were further sub-classified by rapidity of response. Aqueous concentrations of 54 cytokines were measured at multiple timepoints. Expression was compared between responder groups and correlated with OCT imaging biomarkers. RESULTS Of the 24 eyes studied, 79% were anatomical responders with 38% super responders, 17% early responders, and 25% slow responders. Twenty-one percent were nonresponders. Super responders had increased baseline vascular endothelial growth factor (VEGF) (880.0 pg/mL vs 245.4 pg/mL; P = .012) and decreased monocyte chemotactic protein-1 (MCP-1) (513.3 pg/mL vs 809.5 pg/mL; P = .0.042) concentrations compared with nonresponders. Interleukin-6 (-24.9 pg/mL vs 442.8 pg/mL; P = .032) concentrations increased among nonresponders during therapy. VEGF concentrations correlated with central subfield thickness (r = 0.49; P = .01). Panmacular retinal volume correlated with increased interleuckin-6 (r = 0.47; P = .02) and decreased MCP-1 (r = -0.45; P = .03). Matrix metallopeptidase-1 correlated with subretinal fluid volume (r = 0.50; P = .01). CONCLUSIONS OCT imaging biomarkers correlated with both intraocular cytokines and responsiveness to anti-VEGF therapy, which indicated a possible link to underlying pathways and their relevance to DME prognosis. Baseline concentrations of VEGF and MCP-1 are associated with anatomic response to anti-VEGF therapy.
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Relationship of Topographic Distribution of Geographic Atrophy to Visual Acuity in Nonexudative Age-Related Macular Degeneration.
Shen, LL, Sun, M, Ahluwalia, A, Young, BK, Park, MM, Toth, CA, Lad, EM, Del Priore, LV
Ophthalmology. Retina. 2021;(8):761-774
Abstract
PURPOSE To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA. DESIGN Retrospective analysis of a multicenter, prospective, randomized controlled trial. PARTICIPANTS The Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. METHODS We manually delineated GA on 1654 fundus photographs of 365 eyes. We measured GA areas in 9 subfields on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and correlated them with VA via a mixed-effects model. We determined the optimal diameter for the central zone by varying the diameter from 0 to 10 mm until the highest r2 between GA area in the central zone and VA was achieved. We estimated the VA decline rate over 8 years using a linear mixed model. MAIN OUTCOME MEASURES Geographic atrophy area in macular subfields and VA. RESULTS The percentage of area affected by GA declined as a function of retinal eccentricity. GA area was higher in the temporal than the nasal region (1.30 ± 1.75 mm2 vs. 1.10 ± 1.62 mm2; P = 0.005) and in the superior than the inferior region (1.26 ± 1.73 mm2 vs. 1.03 ± 1.53 mm2; P < 0.001). Total GA area correlated poorly with VA (r2 = 0.07). Among GA areas in 9 subfields, only GA area in the central zone was associated independently with VA (P < 0.001). We determined 1 mm as the optimal diameter for the central zone in which GA area correlated best with VA (r2 = 0.45). On average, full GA coverage of the central 1-mm diameter zone corresponded to 34.8 letters' decline in VA. The VA decline rate was comparable between eyes with initial noncentral and central GA before GA covered the entire central 1-mm diameter zone (2.7 letters/year vs. 2.8 letters/year; P = 0.94). CONCLUSIONS The prevalence of GA varies significantly across different macular regions. Although total GA area was associated poorly with VA, GA area in the central 1-mm diameter zone was correlated significantly with VA and may serve as a surrogate endpoint in clinical trials.
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Outcomes by Baseline Choroidal Neovascularization Features in Age-Related Macular Degeneration: A Post Hoc Analysis of the VIEW Studies.
Steinle, NC, Du, W, Gibson, A, Saroj, N
Ophthalmology. Retina. 2021;(2):141-150
Abstract
PURPOSE To assess the influence of baseline choroidal neovascularization (CNV) features on visual change and fluid resolution after anti-vascular endothelial growth factor (VEGF) treatment of eyes with neovascular age-related macular degeneration (nAMD). DESIGN Post hoc analysis of 52-week data from the phase 3 Vascular Endothelial Growth Factor VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) Studies (VIEW) 1 and 2 clinical trials. PARTICIPANTS One thousand eight hundred four patients with nAMD. METHODS Integrated data from VIEW 1 and 2 of 1804 eyes receiving intravitreal aflibercept injections (IAIs) 2 mg every 4 weeks, IAIs 2 mg every 8 weeks after 3 initial monthly doses, and ranibizumab every 4 weeks with documented baseline CNV type, total area, and leakage area were analyzed. Time to an event and cumulative incidence were evaluated by Kaplan-Meier analysis, and relative risks were estimated using proportional hazards analysis. MAIN OUTCOMES MEASURES Cumulative incidence of time to first sustained vision gain of 15 or more Early Treatment Diabetic Retinopathy Study letters, vision loss of more than 5 Early Treatment Diabetic Retinopathy Study letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by OCT with respect to CNV type, total CNV, and leakage area. RESULTS Eyes with predominantly classic CNV (mean best-corrected visual acuity [BCVA], 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of 15 letters or more than eyes with occult CNV (mean BCVA, 57.9 letters at baseline; P < 0.01). Eyes with occult CNV at baseline showed higher incidence rates of first sustained absence of retinal fluid and of intraretinal fluid than eyes with predominantly classic CNV (both P < 0.01). With increasing baseline CNV total area and leakage area, the incidence rate of first sustained gain of 15 letters or more decreased. CONCLUSIONS This post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area, and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD after anti-VEGF treatment.
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EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The ARIES Study: A Randomized Clinical Trial.
Mitchell, P, Holz, FG, Hykin, P, Midena, E, Souied, E, Allmeier, H, Lambrou, G, Schmelter, T, Wolf, S, ,
Retina (Philadelphia, Pa.). 2021;(9):1911-1920
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Abstract
BACKGROUND/PURPOSE Treating neovascular age-related macular degeneration with intravitreal aflibercept treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether intravitreal aflibercept early-start T&E was noninferior to late-start T&E. METHODS A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with the best-corrected visual acuity 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2 mg intravitreal aflibercept at Week (W) 0, W4, W8, and W16. At W16, patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: the best-corrected visual acuity change from randomization to W104. RESULTS Two-hundred seventy-one patients were randomized. The mean (SD) best-corrected visual acuity at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. The mean (SD) best-corrected visual acuity change (W16-104) was -2.1 (11.4) versus -0.4 (8.4) letters (early-T&E vs. late-T&E; least-squares mean difference: -2.0; 95% confidence interval: -4.75 to 0.71; P = 0.0162 for noninferior); +4.3 (13.4) versus +7.9 (11.9) letters (W0-104). The mean (SD) number of injections was 12.0 (2.3) versus 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained best-corrected visual acuity; the mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. The last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients. CONCLUSION Outcomes were similar between patients with neovascular age-related macular degeneration treated with an intravitreal aflibercept early-T&E or late-T&E regimen after initial dosing, with one injection difference over 2 years. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02581891 https://clinicaltrials.gov/ct2/show/NCT02581891. Supplemental Digital Contents (files 1 http://links.lww.com/IAE/B419).
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Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration.
Khurana, RN, Kunimoto, D, Yoon, YH, Wykoff, CC, Chang, A, Maturi, RK, Agostini, H, Souied, E, Chow, DR, Lotery, AJ, et al
Ophthalmology. 2021;(7):1027-1038
Abstract
PURPOSE To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). DESIGN Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. PARTICIPANTS The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. METHODS At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). MAIN OUTCOME MEASURES Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). RESULTS For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 μm, -146 μm, and -142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. CONCLUSIONS Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.
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The Relationship Between Keratoconus Stage and the Thickness of the Retinal Layers.
Özsaygılı, C, Yıldırım, Y
Turkish journal of ophthalmology. 2021;(2):75-82
Abstract
OBJECTIVES To examine the relationship between keratoconus (KC) stage and the thickness of the retinal layers. MATERIALS AND METHODS Retinal layer thicknesses were compared between 85 eyes of 85 KC patients and 40 eyes of 40 controls similar in age, sex, and axial length. KC patients were staged as stage 1, 2, or 3 according to the Amsler-Krumeich staging system, and segmentation of the retinal layers was performed with spectral domain optical coherence tomography automatic segmentation program. The thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE) in the central 1 mm Early Treatment Diabetic Retinopathy Study subfield was analyzed. RESULTS There was no significant difference between the control and KC groups in the segmentation of the RNFL, GCL, IPL, or OPL (p=0.306; p=0.661; p=0.893, p=0.664, respectively). The INL differed significantly between control and stage 2 KC, control and stage 3 KC, stage 1 and 2 KC, and stage 2 and 3 KC, increasing in thickness with higher stage (p=0.004; p=0.005: p=0.001; p=0.002, respectively). The RPE also differed significantly between control and stage 2 KC, control and stage 3 KC, stage 1 and 2 KC, and stage 2 and 3 KC, showing decreased thickness with higher stage (p=0.03; p=0.001; p=0.001; p<0.001, respectively). The ONL also thinned as stage increased, but the results were not statistically significant (p=0.051). CONCLUSION More advanced KC stage was associated with increased thickness of the INL layer, where the neuroglial cell bodies are located, and decreased thickness in the outer retinal layers, especially the RPE.