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Objective: To investigate the relative effect of disorganization of the retinal inner layers (DRIL) and ellipsoid zone (EZ) loss on visual function in diabetic macular ischemia (DMI)., Design: Prospective cross-sectional observational study., Participants: Patients with stable treated proliferative diabetic retinopathy (PDR) without center-involved diabetic macular edema were recruited at the Moorfields Eye Hospital from December 2019 to November 2021. The main inclusion criteria were best-corrected visual acuity (BCVA) of ≥ 40 ETDRS letters (Snellen equivalent 20/160) with OCT angiography (OCTA) evidence of DMI in ≥ 1 eye., Methods: Each eligible eye of the recruited patients was assessed for BCVA, OCT, and OCTA metrics. The prespecified OCT parameters were DRIL and subfoveal EZ loss. Generalized estimating equations were used., Main Outcomes Measures: The frequency of DRIL and EZ loss, their relative contributions to vision loss, and their associations with microvascular alterations were evaluated., Results: A total of 125 eyes of 86 patients with PDR were enrolled; 104 (83%) eyes had a BCVA of ≥ 70 letters. Disorganization of the retinal inner layers was more prevalent than EZ loss (46% [58 eyes] vs. 19% [24 eyes]). On average, the presence of DRIL had a more pronounced impact on vision, retinal thickness, and microvascular parameters than EZ loss. After multivariable adjustment, the odds of coexisting DRIL increased by 12% with every letter decrease in BCVA; however, there was no statistically significant association of subfoveal EZ loss with BCVA. In eyes with DRIL in the absence of EZ loss, the BCVA declined significantly by 6.67 letters compared with eyes with no DRIL nor EZ loss (95% confidence interval [CI], -9.92 to -3.41; P < 0.001). However, if DRIL and EZ loss coexisted, the resultant BCVA was 13.22 letters less than eyes without these structural abnormalities (95% CI, -18.85 to -7.59; P < 0.001)., Conclusions: In patients with DMI with a Snellen visual acuity of 20/160 or better, eyes with DRIL were associated with more visual function loss and retinal blood circulation alterations than those with subfoveal EZ loss only., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment., Design: Clinical study evaluating diagnostic accuracy., Participants: Patients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments., Methods: In phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN)., Main Outcome Measures: Sensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA., Results: In eyes with persistent activity, the combination of 3 non-ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN., Conclusions: In nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the relationship of choroidal thickness with the early stages of age-related macular degeneration (AMD) and their disease features in a Japanese population., Design: Cross-sectional survey., Participants: A total of 1293 Japanese persons 65 to 86 years of age residing in the Saku area who underwent eye screening as part of the Japan Public Health Center-based Prospective Study., Methods: Comprehensive ophthalmic assessment included fundus photography, measurement of intraocular pressure, and determination of refractive status. OCT with enhanced depth imaging mode was performed and subfoveal choroidal thickness was assessed. Multinomial logistic regression models were used to assess the relationships of choroidal thickness with the early stages of AMD, namely early AMD and intermediate AMD, and their disease features, after adjustment for potential confounders., Main Outcome Measures: Relationship of choroidal thickness with early AMD, intermediate AMD, and their disease features., Results: Of 1293 potential participants, 901 (mean age, 73.2 years) had choroidal thickness data, fundus photographs of sufficient quality, and no concomitant retinal disease (including 5 with late AMD). Mean choroidal thickness was 246.1 μm, 15.1% had early AMD, and 9.0% had intermediate AMD. After adjustment for age, gender, and refractive status, choroidal thickness was associated positively with presence of intermediate AMD (for each 1- standard deviation [SD] μm increase: odds ratio [OR], 1.43; 95% confidence interval [CI], 1.13-1.81), whereas no significant association was found with presence of early AMD. Among intermediate AMD features, choroidal thickness was associated positively with presence of AMD pigmentary abnormalities (associated with at least medium drusen; for each 1-SD μm increase: OR, 2.21; 95% CI, 1.42-3.42), whereas no significant association was found with presence of large drusen alone. In addition, among large drusen subtypes, choroidal thickness was associated positively with presence of pachydrusen (for each 1-SD μm increase: OR, 1.53; 95% CI, 1.10-2.13). Furthermore, exploratory analysis revealed that choroidal thickness was associated positively with presence of non-AMD pigmentary abnormalities (for each 1-SD μm increase: OR, 1.92; 95% CI, 1.31-2.18)., Conclusions: Choroidal thickness seems to be associated with the pathology of intermediate AMD and its features in Asians., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the systemic and ocular features of fellow eyes' association with nonexudative neovascularization (NV) based on OCT angiography (OCTA) and to identify longitudinal morphologic changes associated with progression to exudation., Design: Cohort study of contralateral eye in patients with neovascular age-related macular degeneration (nAMD) in 1 eye., Participants: Patients with nAMD in one eye were eligble for inclusion and enrolled between June 2015 and Jan 2017. The study eye was the contralateral eye that was free of nAMD with a minimum follow-up of 1 year., Methods: Progressive multimodal imaging was performed on both eyes. Nonexudative NV was detected on OCTA in the study eye and quantitative changes analyzed. Nonexudative NV eyes were divided into progression to exudation or not during a minimum of 12 months follow-up., Main Outcome Measures: Association between systemic and ocular characteristics with nonexudative NV were determined. Change in OCTA size, vessel density, and vessel length density were compared between visits as predictors of progression to exudation., Results: Among 229 study eyes, 21 (9.1%) had nonexudative NV detected on OCTA at baseline. Hyperlipidemia (adjusted odds ratio [AOR], 1.3; 95% confidence interval [CI], 1.10-3.20; P = 0.04), triglycerides (AOR, 2.84 per mmol/L; 95% CI, 1.06-4.35 per mmol/L; P = 0.02), and baseline lesion size in the presenting eye (AOR, 1.6 per 500 μm; 95% CI, 1.21-3.25 per 500 μm; P = 0.03) were associated significantly with nonexudative NV in the study eye. In the study eye nonexudative NV group, 8 (38%) progressed to exudation, with a mean time to exudation of 377 ± 138 days. The progressor group had larger baseline NV size (1834 ± 552.8 μm vs. 910 ± 461.7 μm; P < 0.01), higher increase in vessel density/year (8.3 ± 4.1%/year vs. 1.1 ± 2.5%/year; P ≤ 0.01), and higher increase in vessel length density/year (15.6 ± 10.6% vs. 1.9 ± 3.6%; P = 0.02). The change in lesion size per year was similar in both groups., Conclusions: Patients with nonexudative NV in the study eye had significant differences in ocular and systemic characteristics. More than a third of study eyes with nonexudative NV at baseline progressed to exudation, suggesting that close monitoring is essential. OCT angiography features associated with exudation include a larger baseline lesion size, increase in vessel density, and vessel length density., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of delaying anti-vascular endothelial growth factor (VEGF) treatment of active disease at any point during a patient's treatment journey on clinical outcomes in a real-world cohort of patients with neovascular age-related macular degeneration (nAMD)., Design: Longitudinal cohort study., Participants: Consecutive treatment-naive nAMD eyes commencing anti-VEGF monotherapy (bevacizumab, ranibizumab, or aflibercept) from January 2014 from a tertiary eye center in Singapore., Methods: We conducted a real-world study using registry data comparing delayed re-treatment (defined as not receiving treatment at 2 or more monitoring visits when disease was graded as active) versus timely re-treatment (defined as receiving treatment when disease was active)., Main Outcome Measures: The primary outcome was the change in visual acuity (VA) in the timely and delayed re-treatment groups at 12 months., Results: Data from 286 eyes were included and categorized into the timely (188 [66%]) or the delayed (98 ([34%]) group. The mean numbers of anti-VEGF injections over 12 months were similar: 5.6 (standard deviation [SD], 2.9) versus 4.9 (SD, 3.2; P = 0.11) for the timely and delayed groups, respectively. Timely treated patients showed larger gains in VA (6.4 letters [SD, 8.1 letters] vs. 1.2 letters [SD, 5.3 letters; P = 0.04), a higher proportion with VA of 6/12 or better (30% vs. 8%; P = 0.01), and greater reduction in OCT-measured central subfield thickness (135 μm [SD, 154 μm] vs. 87.8 μm [SD, 129 μm]; P = 0.04) at 12 months. A longer delay between detection of active disease and re-treatment was associated with poorer vision outcomes (0.02-letter decrease/day; P = 0.03; R 2  = 0.29)., Conclusions: Although it has been established that adequate numbers of injections are required for favorable outcomes, timely re-treatment of active disease also is important. This should be emphasized to patients to ensure optimal outcomes in real-world clinical settings., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12 and 24 months in routine clinical practice., Design: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness!, Participants: Treatment-naïve eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5 mg], aflibercept [2 mg], or bevacizumab [1 mg]) with at least 3 injections from December 2013 through December 31, 2018, and at least 12 months of follow-up., Methods: Intraocular pressure was measured at each clinical visit for all eyes as part of routine practice., Main Outcome Measures: The primary outcome was the mean change in IOP (in millimeters of mercury) at 12 months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up., Results: We identified 3429 treatment-naïve eyes (395 receiving bevacizumab, 1138 receiving aflibercept, and 1896 receiving ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean IOP change was -0.5 mmHg (95% confidence interval CI, -0.6 to -0.3 mmHg) at 12 months and -0.4 mmHg (95% CI, -0.6 to -0.3 mmHg) at 24 months, whereas the proportions of clinically significant IOP increases were 5.6% and 8.8%, respectively. A lower mean IOP change and fewer IOP elevations at 12 and 24 months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (P ≤ 0.01 for both comparisons at each time point and outcome). Eyes with pre-existing glaucoma demonstrated more IOP increases over 12 and 24 months (odds ratio [OR], 2.2 [95% CI, 1.2-3.8; P = 0.012] and 2.1 [95% CI, 1.1-3.8; P = 0.025], respectively)., Conclusions: Mean IOP did not change significantly from baseline to 12 and 24 months in eyes receiving VEGF inhibitors, whereas clinically significant IOP elevations occurred in a small proportion of eyes. Aflibercept was associated with fewer clinically significant IOP elevations, whereas eyes with pre-existing glaucoma were at a higher risk., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the 12-month real-world visual and disease activity outcomes of eyes with polypoidal choroidal vasculopathy (PCV) treated with a combination of photodynamic therapy (PDT) and anti-vascular endothelial growth factor (VEGF) injections (combination group) versus those eyes treated with anti-VEGF monotherapy alone with rescue PDT being used as required (monotherapy group)., Design: Database comparative observational study., Participants: Eyes with PCV as graded in the Fight Retinal Blindness! database from Australia, New Zealand, Singapore, and Switzerland., Methods: Clinical information from a multisite, international registry of neovascular age-related macular degeneration was analyzed with an intention-to-treat approach., Main Outcome Measures: Primary outcome measure was the change in visual acuity in logMAR letters over 12 months between the two groups analyzed with intention-to-treat approach., Results: Forty-one and 152 eyes received combination therapy and anti-VEGF monotherapy, respectively. All anti-VEGF agents were pooled, and bevacizumab represented 66.1% of injections administered. The adjusted mean change in visual acuity between the combination group and monotherapy group at 12 months was +16.9 letters (95% confidence interval [CI], 10.6-23.3 letters) and +8.2 letters (95% CI, 5.2-11.3 letters), respectively (P = 0.02). Proportion of inactive lesions and mean time to inactivity was 85.3% and 80.7 days (95% CI, 62.8-98.5 days), respectively, in the combination group compared with 76.8% and 150.4 days (95% CI, 132.8-168.0 days), respectively, in the monotherapy group (P = 0.01). The mean number of injections of anti-VEGF agent between the combination and monotherapy groups was 4.3 injections (95% CI, 3.6-5.2 injections) and 6.4 injections (95% CI, 5.9-6.9 injections), respectively (P = 0.01)., Conclusions: The real-world outcomes for treatment of PCV showed larger gains in vision, higher proportion of inactive lesions, quicker time to inactivity, and fewer injections administered in the combination group compared with the monotherapy group. These findings are consistent with current evidence reporting the advantages of combination therapy for PCV., (Copyright © 2018 American Academy of Ophthalmology. All rights reserved.)