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Purpose: Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process., Design: Systematic review and Delphi consensus process., Participants: Twenty-five international retinal specialists participated in the Delphi consensus survey., Methods: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists who voted on inclusion, exclusion, rephrasing, and addition of complications. Furthermore, surveys determined specifiers for the selected complications. This iterative process helped to refine the final classification system., Main Outcome Measures: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration., Results: After screening 18 229 articles, 130 complications were categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 complications (70%) after 3 rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 complications (52%) in the final list. A total of 14 complications (11%) met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds also were excluded from the final classification system after the Delphi process terminated. In addition, 47 of 75 proposed complication specifiers (63%) were included based on participant agreement., Conclusions: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare early anatomic outcomes following treatment with faricimab vs. aflibercept in a pooled analysis of the head-to-head dosing phase of the TENAYA/LUCERNE trials in neovascular age-related macular degeneration (nAMD)., Design: TENAYA/LUCERNE (NCT03823287/NCT03823300) were identical, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials., Participants: Aged ≥ 50 years with treatment-naïve nAMD., Methods: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) after 4 initial doses every 4 weeks (Q4W) or aflibercept 2.0 mg every 8 weeks (Q8W) after 3 initial doses given Q4W., Main Outcome Measures: Post hoc analyses comparing faricimab with aflibercept in terms of change in central subfield thickness (CST) from baseline and proportion of patients with an absence of subretinal (SRF) and intraretinal fluid (IRF) during initial 12-week head-to-head dosing phase, when both arms received 3 injections, and time to first absence of IRF and SRF., Results: 1329 patients were enrolled across TENAYA/LUCERNE (n = 665 faricimab; n = 664 aflibercept). There were greater (nominal P < 0.0001) reductions in adjusted mean CST from baseline with faricimab vs. aflibercept at weeks 4, 8, and 12, with comparable vision outcomes. At week 12, more patients (95% confidence interval) achieved an absence of SRF (87.9% [85.4%, 90.4%] vs. 79.0% [76.0%, 82.1%]) and both IRF and SRF (77.2% [74.0%, 80.4%] vs. 66.5% [62.9%, 70.0%]), but not IRF (88.4% [86.0%, 90.8%] vs. 85.0% [82.3%, 87.6%]), with faricimab vs. aflibercept, respectively. In patients with IRF and/or SRF at baseline (n = 581 faricimab; n = 591 aflibercept), the 75th percentile of time to first absence of IRF and SRF was reached at week 8 with faricimab and week 12 with aflibercept. At week 12, cumulative incidence of first-time absence of IRF and SRF was 85.5% (82.3%, 88.1%) with faricimab and 75.0% (71.3%, 78.3%) with aflibercept., Conclusions: Faricimab resulted in greater improvement in anatomic outcomes than aflibercept during the head-to-head dosing phase and a faster time to first absence of retinal fluid., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To evaluate the performance of a disease activity (DA) model developed to detect DA in participants with neovascular age-related macular degeneration (nAMD)., Design: Post hoc analysis., Participants: Patient dataset from the phase III HAWK and HARRIER (H&H) studies., Methods: An artificial intelligence (AI)-based DA model was developed to generate a DA score based on measurements of OCT images and other parameters collected from H&H study participants. Disease activity assessments were classified into 3 categories based on the extent of agreement between the DA model's scores and the H&H investigators' decisions: agreement ("easy"), disagreement ("noisy"), and close to the decision boundary ("difficult"). Then, a panel of 10 international retina specialists ("panelists") reviewed a sample of DA assessments of these 3 categories that contributed to the training of the final DA model. A panelists' majority vote on the reviewed cases was used to evaluate the accuracy, sensitivity, and specificity of the DA model., Main Outcome Measures: The DA model's performance in detecting DA compared with the DA assessments made by the investigators and panelists' majority vote., Results: A total of 4472 OCT DA assessments were used to develop the model; of these, panelists reviewed 425, categorized as "easy" (17.2%), "noisy" (20.5%), and "difficult" (62.4%). False-positive and false negative rates of the DA model's assessments decreased after changing the assessment in some cases reviewed by the panelists and retraining the DA model. Overall, the DA model achieved 80% accuracy. For "easy" cases, the DA model reached 96% accuracy and performed as well as the investigators (96% accuracy) and panelists (90% accuracy). For "noisy" cases, the DA model performed similarly to panelists and outperformed the investigators (84%, 86%, and 16% accuracies, respectively). The DA model also outperformed the investigators for "difficult" cases (74% and 53% accuracies, respectively) but underperformed the panelists (86% accuracy) owing to lower specificity. Subretinal and intraretinal fluids were the main clinical parameters driving the DA assessments made by the panelists., Conclusions: These results demonstrate the potential of using an AI-based DA model to optimize treatment decisions in the clinical setting and in detecting and monitoring DA in patients with nAMD., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Purpose: We assessed outcomes of eyes with neovascular age-related macular degeneration (nAMD) that switched from proactive (treat-and-extend) to reactive (pro re nata) treatment regimen after developing macular atrophy (MA) or submacular fibrosis (SMFi)., Methods: Data were collected from a retrospective analysis of a prospectively designed, multinational registry of "real-world" nAMD treatment outcomes. Eyes without MA or SMFi when starting treatment with a vascular endothelial growth factor inhibitor regimen that subsequently developed MA or SMFi were included., Results: Macular atrophy developed in 821 eyes and SMFi in 1,166 eyes. Seven percent of eyes that developed MA and 9% of those that developed SMFi were switched to reactive treatment. Vision was stable at 12 months for all eyes with MA and inactive SMFi. Active SMFi eyes that switched to reactive treatment had significant vision loss. No eyes that continued proactive treatment developed ≥15 letter loss, but 8% of all eyes that switched to a reactive regimen and 15% of active SMFi eyes did., Conclusion: Eyes that switch from proactive to reactive treatment after developing MA and inactive SMFi can have stable visual outcomes. Physicians should be aware of the risk of a significant loss of vision in eyes with active SMFi that switch to reactive treatment.

There have been recent advances in basic research and clinical studies in polypoidal choroidal vasculopathy (PCV). A recent, large-scale, population-based study found systemic factors, such as male gender and smoking, were associated with PCV, and a recent systematic review reported plasma C-reactive protein, a systemic biomarker, was associated with PCV. Growing evidence points to an association between pachydrusen, recently proposed extracellular deposits associated with the thick choroid, and the risk of development of PCV. Many recent studies on diagnosis of PCV have focused on applying criteria from noninvasive multimodal retinal imaging without requirement of indocyanine green angiography. There have been attempts to develop deep learning models, a recent subset of artificial intelligence, for detecting PCV from different types of retinal imaging modality. Some of these deep learning models were found to have high performance when they were trained and tested on color retinal images with corresponding images from optical coherence tomography. The treatment of PCV is either a combination therapy using verteporfin photodynamic therapy and anti-vascular endothelial growth factor (VEGF), or anti-VEGF monotherapy, often used with a treat-and-extend regimen. New anti-VEGF agents may provide more durable treatment with similar efficacy, compared with existing anti-VEGF agents. It is not known if they can induce greater closure of polypoidal lesions, in which case, combination therapy may still be a mainstay. Recent evidence supports long-term follow-up of patients with PCV after treatment for early detection of recurrence, particularly in patients with incomplete closure of polypoidal lesions., (Copyright © 2023 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

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 evaluate the predictors of complete polypoidal lesion regression (CPREG) in polypoidal choroidal vasculopathy., Methods: Post hoc analysis of EVEREST II-a 24-month, multicenter, randomized, controlled clinical trial of 322 patients with polypoidal choroidal vasculopathy, randomized to receive ranibizumab with or without photodynamic therapy. Images of indocyanine green angiography (ICGA) were graded by a central reading center. Multiple logistic regression analysis with significant baseline predictors then was conducted to assess adjusted odds ratios for CPREG at month (M) 12., Results: Baseline ICGA characteristics were comparable between the treatment groups. Patients treated with combination therapy had higher odds of achieving CPREG at M12 (adjusted odds ratio = 4.64; 95% confidence interval, 2.85-7.55; P < 0.001) compared with those in the monotherapy group. Absence of polypoidal lesion pulsation on ICGA was also associated with CPREG at M12 (adjusted odds ratio = 2.62; 95% confidence interval, 1.32-5.21; P = 0.006). The presence of CPREG at M3 had higher odds of maintaining CPREG at M12 (adjusted odds ratio = 6.60; 95% confidence interval, 3.77-11.57; P < 0.001) compared with those with persistent polypoidal lesions., Conclusion: At M12, treatment with combination therapy was associated with higher probability of achieving CPREG than with ranibizumab monotherapy. The results contribute to the further understanding of the response of polypoidal lesions to treatment.

Purpose: To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD)., Methods: One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length., Results: Macular sensitivity reduced with increasing severity of MMD (β ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (β = -0.08, P < 0.001), with longer axial length (β = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (β = -2.16, P < 0.001) or worse MMD (β = -5.70, P < 0.001), and presence of macular posterior staphyloma (β ≤ -2.98, P < 0.001) or Fuchs spot (β = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (β = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62)., Conclusion: There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.

In central serous chorioretinopathy (CSC), the macula is detached because of fluid leakage at the level of the retinal pigment epithelium. The fluid appears to originate from choroidal vascular hyperpermeability, but the etiology for the fluid is controversial. The choroidal vascular findings as elucidated by recent optical coherence tomography (OCT) and wide-field indocyanine green (ICG) angiographic evaluation show eyes with CSC have many of the same venous patterns that are found in eyes following occlusion of the vortex veins or carotid cavernous sinus fistulas (CCSF). The eyes show delayed choroidal filling, dilated veins, intervortex venous anastomoses, and choroidal vascular hyperpermeability. While patients with occlusion of the vortex veins or CCSF have extraocular abnormalities accounting for the venous outflow problems, eyes with CSC appear to have venous outflow abnormalities as an intrinsic phenomenon. Control of venous outflow from the eye involves a Starling resistor effect, which appears to be abnormal in CSC. Similar choroidal vascular abnormalities have been found in peripapillary pachychoroid syndrome. However, peripapillary pachychoroid syndrome has intervortex venous anastomoses located in the peripapillary region while in CSC these are seen to be located in the macular region. Spaceflight associated neuro-ocular syndrome appears to share many of the pathophysiologic problems of abnormal venous outflow from the choroid along with a host of associated abnormalities. These diseases vary according to their underlying etiologies but are linked by the venous decompensation in the choroid that leads to significant vision loss. Choroidal venous overload provides a unifying concept and theory for an improved understanding of the pathophysiology and classification of a group of diseases to a greater extent than previous proposals., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess the impact of disease activity on clinical outcomes in a "real-world" cohort with neovascular age-related macular degeneration over 5 years., Methods: Data were obtained from the prospectively defined Fight Retinal Blindness! registry. Eyes were divided into tertiles based on the proportion of visits where choroidal neovascular lesion was active (low, moderate, and high) up until 5 years., Results: Data from 2,109 eyes were included. The adjusted mean (95% confidence interval) visual acuity change was -0.5 letters (-1.8 to 1.1), 1.8 letters (0.2 to 3.4), and -2.5 letters (-4.2 to -1.3) in the low, moderate, and high activity groups respectively, P < 0.001. Eyes in the low activity group were more likely to develop macular atrophy (56, 47 and 26% in the low, moderate, and high activity groups respectively, P < 0.001) but less likely to develop subretinal fibrosis (27, 35 and 42% in the low, moderate, and high activity groups respectively, P < 0.001)., Conclusion: Eyes with higher and lower levels of disease activity had poorer outcomes than eyes with moderate activity over 5 years, apparently because of the development of subretinal fibrosis or macular atrophy.

Purpose: To describe pulsatile filling of dilated choroidal veins in the watershed zones and propose an alteration in choroidal perfusion pressure., Methods: Retrospective review of original and digital subtraction indocyanine green angiography., Results: We observed pulsating blood flow within choroidal vein segments in the posterior pole in 14 eyes (diagnosis of polypoidal choroidal vasculopathy, central serous chorioretinopathy, or neovascular age-related macular degeneration). Pulsating dye front was observed in single or multiple large choroidal vein(s) in a location that is ordinarily a watershed zone between the segmental areas of venous drainage, and vessels proximal and distal were often dilated. The pulsatile venous segments filled more slowly than the neighboring veins. In digital subtraction indocyanine green angiography, the dye front advanced in an incremental fashion or oscillated in a back-and-forth manner during several cardiac cycles during the filling of these larger choroidal veins. With indocyanine green angiography, we observed dilated choroidal veins that violated the macula watershed zone, localized bulbous dilations, and arteriole-over-vein crossings with apparent compression., Conclusion: These novel observations suggest the pressure gradient for flow in the affected veins varied from low gradients when the filling was slow to high gradients when the filling was faster. The vessels violated the physiological watershed zone and seem to function as anastomoses between the ordinarily segmented venous drainage of the choroid. The dilated segments may result in pooling of venous blood as part of venous outflow abnormalities that may be operative in these diseases.

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.)

Myopia is an emerging public health issue with potentially significant economic and social impact, especially in East Asia. However, many uncertainties about myopia and its clinical management remain. The International Myopia Summit workgroup was convened by the Singapore Eye Research Institute, the WHO Regional Office for the Western Pacific and the International Agency for the Prevention of Blindness in 2019. The aim of this workgroup was to summarise available evidence, identify gaps or unmet needs and provide consensus on future directions for clinical research in myopia. In this review, among the many 'controversies in myopia' discussed, we highlight three main areas of consensus. First, development of interventions for the prevention of axial elongation and pathologic myopia is needed, which may require a multifaceted approach targeting the Bruch's membrane, choroid and/or sclera. Second, clinical myopia management requires co-operation between optometrists and ophthalmologists to provide patients with holistic care and a tailored approach that balances risks and benefits of treatment by using optical and pharmacological interventions. Third, current diagnostic technologies to detect myopic complications may be improved through collaboration between clinicians, researchers and industry. There is an unmet need to develop new imaging modalities for both structural and functional analyses and to establish normative databases for myopic eyes. In conclusion, the workgroup's call to action advocated for a paradigm shift towards a collaborative approach in the holistic clinical management of myopia., Competing Interests: Competing interests: Jost B Jonas: Advisory Board Novartis; Patent holder with Biocompatibles UK (Farnham, Surrey, UK) (Treatment of eye diseases using encapsulated cells encoding and secreting neuroprotective factor and/or anti-angiogenic factor; Patent number: 20120263794), and Europäische Patentanmeldung 16 720 043.5 and Patent application US 2019 0085065 A1 Agents for use in the therapeutic or prophylactic treatment of myopia or hyperopia)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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 evaluate the choroidal vascular patterns of patients with pachychoroid-related diseases in eyes images with wide-field indocyanine green angiography., Methods: Retrospective study of wide-field indocyanine green angiographic images of patients with pachychoroid, peripapillary pachychoroid syndrome, central serous chorioretinopathy, and pachychoroid-associated neovascularization that were evaluated for anastomoses between vortex vein systems, which are ordinarily separated by a watershed zone., Results: There were 21 subjects with a mean age of 57.4 years and 15 were male. Among the 42 eyes evaluated, central serous chorioretinopathy was found in 24 eyes (57.1%), peripapillary pachychoroid syndrome in 5 (11.9%), pachychoroid associated neovascularization in 7 (16.7%), and pachychoroid in 6 (14.3%). Every eye showed anastomosis between the superonasal, superotemporal, and inferotemporal vortex vein systems. The inferonasal vortex vein system was less likely to demonstrate anastomosis except for peripapillary pachychoroid syndrome, which showed anastomosis in all eyes. The anastomotic connections were prominent in the central macula in the central serous chorioretinopathy and pachychoroid-associated neovascularization cases, and around the nerve in the peripapillary pachychoroid syndrome cases. Although the large choroidal veins were particularly prominent in the neovascular cases, the number was fewer in the macular region than in other pachychoroid-related diseases in this series. Compared with a control group of nine eyes, the inferotemporal-superotemporal-superonasal anastomotic connections were more common in the case group (P < 0.001) and inferonasal quadrant (P = 0.023 right eye; P = 0.01, left eye)., Conclusion: Intervortex venous anastomosis is common in pachychoroid, central serous chorioretinopathy, peripapillary pachychoroid syndrome, and pachychoroid-associated neovascularization. This finding has important implications concerning pathogenesis and classification of disease.

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 examine the relationship between macular microvasculature parameters and functional changes in persons with diabetic retinopathy (DR)., Methods: Cross-sectional study of 76 eyes with varying levels of DR. Optical coherence tomography angiography (OCTA) quantified superficial and deep perifoveal vessel densities and foveal avascular zone areas. Retinal sensitivity was measured using microperimetry. Optical coherence tomography angiography parameters and retinal sensitivity were correlated., Results: Deep perifoveal vessel density decreased with increasing severity of DR (adjusted mean 51.93 vs. 49.89 vs. 47.96, P-trend = 0.005). Superficial and deep foveal avascular zone area increased with increasing DR severity (adjusted mean: 235.0 µm vs. 303.4 µm vs. 400.9 µm, P-trend = 0.003 [superficial]; 333.1 µm vs. 513.3 µm vs. 530.2 µm, P-trend = 0.001 [deep]). Retinal sensitivity decreased with increasing DR severity (adjusted mean: 25.12 dB vs. 22.34 dB vs. 20.67 dB, P-trend = 0.003). Retinal sensitivity correlated positively with deep perifoveal vessel density (Pearson's ρ = 0.276, P = 0.020) and inversely with superficial foveal avascular zone area (Pearson's ρ = -0.333, P = 0.010)., Conclusion: Alterations in retinal microvasculature can be observed with OCTA with increasing severity of DR. These changes are correlated with reduced retinal sensitivity. Optical coherence tomography angiography is useful to detect and quantify the microvasculature properties of eyes with diabetic macular ischemia.

Purpose: Although there have been many population-based studies of age-related macular degeneration (AMD), only limited information is available in Asia on the epidemiology of geographic atrophy (GA). We aimed to determine the prevalence and patterns of GA through an analysis of multiple studies conducted within the Asian Eye Epidemiology Consortium (AEEC)., Design: Cross-sectional meta-analyses., Participants: A total of 97 213 individuals aged 40 years and older., Methods: Data from 22 population-based studies from countries belonging to the AEEC were included. In all studies, AMD was defined on the basis of standardized grading systems. Geographic atrophy was defined as an area of pallor in the fundus with visibility of the underlying choroidal blood vessels and sharply defined borders. Random-effects meta-analysis was performed to estimate overall and age-, gender-, and region-specific pooled prevalence of GA., Main Outcome Measures: Prevalence of GA per 1000 persons., Results: The mean age was 60.8 ± 10.0 years, and 42 673 (43.9%) were male. Overall, a total of 223 individuals (0.2%) had GA. The pooled overall prevalence of GA was 1.57 per 1000 persons (95% confidence interval [CI], 1.04-2.10), which was 3 times less than that of neovascular AMD of 5.20 per 1000 persons (95% CI, 3.97-6.43). Compared with those aged 50 to 59 years, the prevalence of GA increased from 0.34 per 1000 persons (95% CI, 0.07-0.62) to 2.90 per 1000 persons (95% CI, 1.55-4.25) in those aged ≥70 years. The GA prevalence per 1000 persons was similar between urban (2.22; 95% CI, 1.22-3.23) and rural residents (1.33; 95% CI, 0.70-1.96). Geographic atrophy was more prevalent in South Asia (based on studies from India and Nepal, 3.82 per 1000 persons; 95% CI, 1.72-5.93) compared with East Asia (based on studies from China, Korea, Hong Kong, Taiwan, and Japan, and the Singapore Chinese Eye Study, 0.76 per 1000 persons; 95% CI, 0.31-1.22, P = 0.005)., Conclusions: Geographic atrophy is uncommon in Asian populations compared with those of European ancestry. Even within Asia, geographic differences in GA prevalence were seen. The findings of this meta-analysis suggest that better dissection of risk factors in the Asian population for GA may provide insights into the biological pathways that drive these late-stage manifestations, thus suggesting better targets for prevention., (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 assess the 1-year effectiveness, safety, and treatment patterns of ranibizumab in patients with myopic choroidal neovascularization (mCNV) enrolled in the LUMINOUS study., Methods: This 5-year, prospective, multicenter, observational, study enrolled 30,138 patients across all approved ranibizumab indications from outpatient ophthalmology clinics. 297 consenting patients (≥18 years) with mCNV who were treatment-naïve or prior-treated with ranibizumab or other ocular treatments were enrolled, and treated with ranibizumab according to the local product label. The main outcomes are visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters or equivalent), adverse events during the study, and treatment exposure over 1 year. Results are presented by prior treatment status of the study eye and injection frequency., Results: Of the 297 mCNV patients recruited in the study, 108 were treatment-naïve and 175 were prior ranibizumab-treated. At baseline, the mean age of patients was 57.6 years, and 59.0 years and 80.6% and 65.7% were female in the treatment-naïve and prior ranibizumab-treated groups, respectively. Most were Caucasian (treatment-naïve, 88.9%; prior ranibizumab-treated, 86.9%). The mean (±standard deviation [SD]) VA letter changes to 1 year were +9.7 (±17.99) from 49.5 (±20.51) and +1.5 (±13.15) from 58.5 (±19.79) and these were achieved with a mean (SD) of 3.0 (±1.58) and 2.6 (±2.33) injections in the treatment-naïve and prior ranibizumab-treated groups, respectively. Presented by injection frequencies 1-2, 3-4 and ≥5 injections in Year 1, the mean (SD) VA changes were +15.0 (±14.70), +7.7 (±19.91) and -0.7 (±16.05) in treatment-naïve patients and +1.5 (±14.57), +3.1 (±11.53) and -3.6 (±11.97) in prior ranibizumab-treated patients, respectively. The safety profile was comparable with previous ranibizumab studies., Conclusions: Ranibizumab treatment for mCNV showed robust VA gains in treatment-naïve patients and VA maintenance in prior ranibizumab-treated patients in a clinical practice setting, consisting mainly of Caucasians. No new safety signals were observed during the study., Competing Interests: Mr. Hamilton is a consultant for Allergan, Bayer Healthcare, Novartis Pharmaceuticals, and Roche; receives grants from Bayer Healthcare, Novartis Pharmaceuticals and Roche; receives lecture fees from Allergan, Roche, Bayer Healthcare, and Novartis Pharmaceuticals Drs Clemens and Dunger-Baldauf are employees and shareholders of Novartis Pharma AG, Basel, Switzerland. Dr. Minnella is a consultant for Theà Laboratoire and receives travel and meeting grant from Allergan, Bayer Healthcare, Novartis Pharmaceutical, Theà Laboratoire Dr Lai is a Consultant for Allergan, Bayer Healthcare, Boehringer Ingelheim, Genentech, Novartis Pharmaceuticals, and Roche; receives grants from Bayer Healthcare, Novartis Pharmaceuticals and Roche; receives lecture fees from Allergan, Bausch & Lomb, Bayer Healthcare, and Novartis Pharmaceuticals. Dr Dai receives research grants and non-financial support from Novartis. Dr. Sakamoto is a Consultant for Bayer Healthcare, Novartis Pharmaceuticals, Roche, Bausch & Lomb, Senju and Santen; receives grants from Bayer Healthcare, Santen, Otsuka Pharmaceuticals, Novartis Pharmaceuticals, and Senju; receives lecture fees from Bausch & Lomb, Bayer Healthcare, and Novartis Pharmaceuticals, Santen, and Senju. Dr Cheung receives consulting fees from Bayer, Novartis and Boehringer-Ingelheim, Roche. Dr Ngah receives research grants for the study and lecture fees from Bayer, Novartis and Allergan. Prof Dr Holz receives grants from Bayer, Centervue, Genentech/Roche, Heidelberg Engineering, Novartis, and Zeiss, and is a consultant for Acucela, Alcon, Bayer, Boehringer-Ingelheim, Galimedix, Genentech, Heidelberg Engineering, Lin-Bioscience, Novartis, Roche, and Zeiss. These competing interests of the authors does not alter their adherence to PLOS ONE policies on sharing data and materials.

Purpose: We sought to evaluate longer-term efficacy and safety of intravitreal aflibercept monotherapy (IAI) vs IAI plus rescue photodynamic therapy (rPDT) in patients with polypoidal choroidal vasculopathy (PCV)., Design: This was a prospective multicenter, double-masked, sham-controlled randomized clinical study across 62 centers., Methods: In this phase 3b/4 study, patients with PCV with best-corrected visual acuity of 73-24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent) received IAI 2 mg every 4 weeks until week 12, when they were randomized 1:1 to receive IAI or IAI plus rPDT if rescue criteria were met. Patients not requiring rescue received IAI every 8 weeks; those requiring rescue received IAI every 4 weeks plus sham/active PDT. At week 52 (the primary endpoint), IAI was noninferior to IAI plus rPDT. After week 52, treatment intervals could be extended beyond 8 weeks at the investigators' discretion. Noninferiority of IAI vs IAI plus rPDT for mean best-corrected visual acuity change from baseline to week 96 was evaluated., Results: Over 96 weeks, 54 patients (17.0%) met rescue criteria. At week 96, IAI was noninferior to IAI plus rPDT in terms of Early Treatment Diabetic Retinopathy Study letters gained (+10.7 vs +9.1, P = .48). Proportions of patients with complete polyp regression (33.1% vs 29.1%) or without active polyps (82.1% vs 85.6%) were similar. In year 2, the mean number of injections was 4.6 in both arms. No new safety signals were observed., Conclusion: IAI monotherapy was noninferior to IAI with rescue PDT up to 96 weeks, and functional and anatomical improvements achieved at 52 weeks were maintained. Few patients required rescue PDT, which provided no additional visual benefit., (Copyright © 2019. Published by Elsevier Inc.)

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.)

A structurally and functionally intact choroid tissue is vitally important for the retina function. Although central retinal artery is responsible to supply the inner retina, choroidal vein network is responsible for the remaining one-third of the external part. Abnormal choroidal blood flow leads to photoreceptor dysfunction and photoreceptor death in the retina, and the choroid has vital roles in the pathophysiology of many diseases such as central serous chorioretinopathy, age-related macular degeneration, pathologic myopia, Vogt-Koyanagi-Harada disease. Biomarkers of choroidal diseases can be identified in various imaging modalities that visualize the choroid. Indocyanine green angiography enables the visualization of choroid veins under the retinal pigment epithelium and choroidal blood flow. New insights into a precise structural and functional analysis of the choroid have been possible, thanks to recent progress in retinal imaging based on enhanced depth imaging (EDI) and swept-source optical coherence tomography (SS-OCT) technologies. Long-wavelength SS-OCT enables the choroid and the choroid-sclera interface to be imaged at greater depth and to quantify choroidal thickness profiles throughout a volume scan, thus exposing the morphology of intermediate and large choroidal vessels. Finally, OCT angiography allows a dye-free evaluation of the blood flow in the choriocapillaris and in the choroid. We hereby review different imaging findings of choroidal diseases that can be used as biomarkers of activity and response to the treatment., Competing Interests: There are no conflicts of interest

Pathologic myopia is a leading cause of visual impairment. Development of myopic choroidal neovascularization (CNV) is one of the most common complications that leads to central vision loss in patients with pathologic myopia. If left untreated, it can cause scarring with expanding macular atrophy leading to irreversible visual loss in a period as short as 5 years. Advancements in multimodal imaging technology have furthered our understanding of the condition; however, further studies are necessary to extend its utility in the diagnosis of myopic CNV. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has become the standard-of-care and the recommended first-line treatment option for myopic CNV. Long-term studies have demonstrated that early treatment of confirmed myopic CNV cases with an intravitreal anti-VEGF agent is useful to avoid late-stage complications. This strategy has also been shown to achieve visual outcome improvements for up to 4 years and visual stabilization up to 6 years. This review article provides an overview of the current knowledge on myopic CNV and discusses recent updates in the diagnosis and management of the condition. Furthermore, treatment recommendations are provided based on the authors' expert opinions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To characterize and compare morphologic and vascular features of the choroid in patients with typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) and to determine if PCV subtypes can be identified based on these choroidal features., Methods: Choroidal features of patients with AMD and PCV recruited from the prospectively planned Asian AMD Phenotyping Study were analyzed. Patients underwent choroidal imaging using spectral-domain optical coherence tomography with enhanced depth imaging. Raw optical coherence tomographic images were loaded on a custom-written application on MATLAB that enabled delineation for detailed morphologic and vascular analyses, including the curvature of the choroid-sclera interface, number of inflection points, choroidal thickness and choroidal vascular area within the macular (6 mm centered on fovea) and foveal (1.5 mm centered on fovea) regions. An inflection point represents the contour of the choroid-sclera interface, with >1 point signaling irregular shape., Results: A total of 156 eyes of 156 patients (78 affected eyes of 78 patients with typical AMD and 78 affected eyes of 78 patients with PCV) were analyzed. Eyes with PCV had thicker baseline choroidal thickness and greater choroidal vascular area compared with those with typical AMD (P < 0.05); these differences were no longer significant after adjusting for age and hypertension (P > 0.05). Typical PCV subtype with choroidal thickness of ≥257 μm had significantly greater choroidal vascular area at macular (mean difference = 0.054 mm; P < 0.001) and foveal (mean difference = 0.199 mm; P < 0.001) regions compared with eyes with typical AMD. However, eyes with PCV without thick choroid had similar choroidal vascular area as eyes with typical AMD., Conclusion: Based on the choroidal vascular features, two subtypes of PCV can be classified: typical PCV with increased choroid vascularity and polypoidal choroidal neovascularization with low choroidal vascularity. These data provide further understanding of different AMD and PCV subtypes.

Spectral domain optical coherence tomography (SD-OCT) is fast becoming the current standard of care for the detection and assessment of diabetic macular edema. With the application of SD-OCT for imaging of retinal microstructure and measurement of retinal thickness, new information regarding disease characteristics has been gathered, which was unrecognized previously. Retinal thickness measurements on SD-OCT have also been used for deciding the management and monitoring of the disease. Since its development, OCT has enhanced the understanding of retinal anatomical changes in diabetic retinopathy. Several authors have used SD-OCT to classify diabetic macular edema with the purpose of correlating the pathophysiology with disease severity. The classification systems have helped monitor the treatment efficacy and provide prognostic information on the treatment outcome. The following review article summarizes these classifications.

We investigated the relationship of visual impairment (VI) and age-related eye diseases with mortality in a prospective, population-based cohort study of 3,280 Malay adults aged 40-80 years between 2004-2006. Participants underwent a full ophthalmic examination and standardized lens and fundus photographic grading. Visual acuity was measured using logMAR chart. VI was defined as presenting (PVA) and best-corrected (BCVA) visual acuity worse than 0.30 logMAR in the better-seeing eye. Participants were linked with mortality records until 2012. During follow-up (median 7.24 years), 398 (12.2%) persons died. In Cox proportional-hazards models adjusting for relevant factors, participants with VI (PVA) had higher all-cause mortality (hazard ratio[HR], 1.57; 95% confidence interval[CI], 1.25-1.96) and cardiovascular (CVD) mortality (HR 1.75; 95% CI, 1.24-2.49) than participants without. Diabetic retinopathy (DR) was associated with increased all-cause (HR 1.70; 95% CI, 1.25-2.36) and CVD mortality (HR 1.57; 95% CI, 1.05-2.43). Retinal vein occlusion (RVO) was associated with increased CVD mortality (HR 3.14; 95% CI, 1.26-7.73). No significant associations were observed between cataract, glaucoma and age-related macular degeneration with mortality. We conclude that persons with VI were more likely to die than persons without. DR and RVO are markers of CVD mortality.

Purpose: To compare and analyze differences and similarities between Japanese and French patients in subtype diagnosis of exudative age-related macular degeneration (AMD) as determined by fundus photography (FP) and fluorescein angiography (FA), and a multimodal imaging involving FP, FA, indocyanine green angiography (ICGA), and optical coherence tomography (OCT)., Design: Retrospective chart review., Methods: We determined the subtype diagnosis for 99 consecutive Japanese eyes and 94 consecutive French eyes with exudative AMD. The first-step diagnosis was made using FP and FA, while the second-step diagnosis was made using FP, FA/ICGA, and OCT. The diagnoses made by Japanese and French physicians were compared, and when the diagnoses differed, a third institute was consulted to arrive at a final consensus and diagnosis., Results: The first-step diagnosis showed 20%-30% disagreement against the final diagnosis, but the second-step diagnosis showed only 10% disagreement. Polypoidal choroidal vasculopathy (PCV) was observed more in Japanese patients (48%) than in French (9%), and the rate of PCV with type 1 or 2 choroidal neovascularization (CNV) was extremely low: 3% in Japanese and 0% in French. Type 1 CNV was found significantly more in French cases (53.3% vs 35.1%, P=.018), while the rate of eyes with type 2 CNV only or chorioretinal anastomosis was similar between populations., Conclusions: Multimodality imaging significantly improved the sub-classification of AMD. There were significant differences between the 2 series in the proportions of type 1 CNV and PCV, while the proportions of type 2 CNV only and chorioretinal anastomosis were similar between groups., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To compare the prevalence and risk factors for age-related macular degeneration (AMD) in 2 Indian populations, 1 living in urban Singapore and 1 in rural central India., Design: Population-based, cross-sectional studies of Indians aged 40+ years., Methods: Our analysis included 3337 Singapore-residing participants and 3422 India-residing participants. All participants underwent comprehensive systemic and ocular examinations and retinal photography. AMD was graded from retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Systemic and ocular risk factors were assessed for association with AMD., Results: Singapore-residing participants were older (mean age 57.8 years vs 53.8 years) and, after adjusting for age and sex, were more likely to have previous cataract surgery, higher body mass index, hypertension, diabetes, previous myocardial infarction, higher cholesterol, and lower creatinine levels, but less likely to be current smokers, than India-residing participants. The age-standardized prevalence of early and late AMD was 4.45% and 0.34%, respectively, in Singapore and 5.80% and 0.16%, respectively, in India. Shorter axial length was associated with early AMD in both Singapore and India, whereas previous cataract surgery, higher body mass index, hypertension, and lower cholesterol were associated with early AMD in Singapore but not in India., Conclusion: The prevalence of AMD was similar among Indian adults living in urban Singapore and rural India, despite differences in cardiovascular risk factor profile and demographics., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical characteristics and outcome of eyes with extrafoveal polypoidal choroidal vasculopathy (PCV) treated with argon laser., Design: Prospective cohort, noninterventional study., Methods: A prospective study of Asian patients with extrafoveal PCV, confirmed on indocyanine green angiography and treated with argon laser with and without anti-vascular endothelial growth factor (VEGF) therapy. Patients were followed-up over 12 months with visual, angiographic, and structural outcomes recorded., Results: Of the 93 eyes with PCV at baseline, 33 eyes (35.5%) in 31 patients had extrafoveal involvement and were treated with argon laser. Foveal involvement with fluid or blood at baseline was apparent in 23 eyes (69.7%), despite the extrafoveal location of 1 or more polyps. Of these 33 eyes, 12 (36.4%) also received anti-VEGF injections (median, 2.5 injections) over the 12-month period. Two eyes received photodynamic therapy rescue during subsequent follow-up and were excluded for visual outcome analysis. In the remaining 31 eyes, mean visual acuity improved from 0.57 logarithm of the minimal angle of resolution (logMAR) units (range, 0.00 to 2.0 logMAR; standard deviation, 0.51 logMAR) at baseline to 0.39 logMAR (range, 0.00 to 2.0 logMAR; standard deviation, 0.43 logMAR) at month 12 (P = .01), with a mean gain in visual acuity of 9.0 letters at month 12. Stable or improved vision (defined as losing 5 letters or fewer) was achieved in 28 eyes (90.3%). Use of anti-VEGF was associated with significantly thicker central subfield at baseline (347.6 vs 258.1 μm; P = .02) and resulted in similar vision and OCT results at month 3 and 12 compared with eyes that did not receive anti-VEGF., Conclusions: Argon laser treatment with selected use of anti-VEGF therapy achieves stable or improved visual outcome in most eyes with extrafoveal PCV, including eyes with fluid or blood affecting the fovea at presentation., (Copyright © 2013 Elsevier Inc. All rights reserved.)