ASSOCIATION OF RETINAL VEIN OCCLUSION WITH CARDIOVASCULAR EVENTS AND MORTALITY: A Systematic Review and Meta-analysis Purpose: Previous studies examining the association of retinal vein occlusion (RVO) and cardiovascular events have been inconsistent and have mostly focused on stroke and myocardial infarction. The goal of this study is to use meta-analysis to examine the available evidence examining the association of RVO with incident cardiovascular events and mortality. Methods: Systematic review and meta-analysis of all longitudinal cohort studies published in PubMed, Embase, and the Cochrane Library from inception to April 7, 2018, that evaluated the association of baseline RVO and incident cardiovascular events and/or mortality, that provided multivariate-adjusted risk estimates with 95% confidence intervals (95% CIs), and that had average follow-up ≥1 year. The Newcastle–Ottawa scale was used to assess study quality. Multivariate-adjusted risk estimates with 95% CI along with study characteristics were extracted from each study, and pooled risk ratios (RRs) with 95% CI were generated using a random-effects model with inverse-variance weighting to account for heterogeneity. Main outcomes were incident stroke (fatal or nonfatal), myocardial infarction, heart failure, peripheral arterial disease, all-cause mortality, and cardiovascular mortality. Results: Fifteen cohort studies with a total of 474,466 patients (60,069 with RVO and 414,397 without RVO) were included. Each study had Newcastle–Ottawa scale score ≥6, indicating moderate-to-high quality. Retinal vein occlusion was associated with increased risk of stroke (RR = 1.45; 95% CI, 1.31–1.60), myocardial infarction (RR = 1.26; 95% CI, 1.17–1.37), heart failure (RR = 1.53; 95% CI, 1.22–1.92), peripheral arterial disease (RR = 1.26; 95% CI, 1.09–1.46), and all-cause mortality (RR = 1.36; 95% CI, 1.02–1.81), but was not associated with increased risk of cardiovascular mortality (RR = 1.78; 95% CI, 0.70–4.48). Conclusion: This review suggests patients with RVO have an increased risk of cardiovascular events and all-cause mortality. More studies are needed to determine the highest risk periods for cardiovascular events and mortality after RVO and whether immediate cardiovascular evaluation and intervention will improve outcomes.

PHOTOCOAGULATION VERSUS RANIBIZUMAB FOR PROLIFERATIVE DIABETIC RETINOPATHY: Should Baseline Characteristics Affect Choice of Treatment? Purpose: Among eyes with proliferative diabetic retinopathy, identify whether baseline characteristics impact the benefit of ranibizumab over panretinal photocoagulation (PRP) in DRCR.net Protocol S. Methods: Participants had proliferative diabetic retinopathy, visual acuity of 20/320 or better, and no previous PRP. Eyes were randomized to PRP or intravitreous 0.5-mg ranibizumab. Results: Ranibizumab was superior to PRP for change in visual acuity and development of vision-impairing central-involved diabetic macular edema over 2 years (P < 0.001). Among 25 characteristics, there were none in which participants assigned to PRP had superior outcomes relative to ranibizumab-assigned participants. The relative benefit of ranibizumab over PRP for change in visual acuity seemed greater in participants with higher mean arterial pressure (P = 0.03), without previous focal/grid laser (P = 0.03), with neovascularization of the disk and elsewhere on clinical examination (P = 0.04), and with more advanced proliferative diabetic retinopathy on photographs (P = 0.02). For development of vision-impairing central-involved diabetic macular edema, the relative benefit of ranibizumab over PRP seemed greater among nonwhite participants (P = 0.01) and those with higher mean arterial pressure (P = 0.01). Conclusion: There were no characteristics identified in which outcomes were superior with PRP compared with ranibizumab. These exploratory analyses provide additional support that ranibizumab may be a reasonable alternative to PRP for proliferative diabetic retinopathy over a 2-year period.

IMPROVED DETECTION AND DIAGNOSIS OF POLYPOIDAL CHOROIDAL VASCULOPATHY USING A COMBINATION OF OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY Purpose: To assess the ability of optical coherence tomography (OCT) alone and in combination with OCT angiography (OCTA) to differentiate polypoidal choroidal vasculopathy (PCV) from neovascular age-related macular degeneration, as compared to fluorescein angiography and indocyanine green angiography. Methods: This is a cross-sectional study. All participants had a standardized history, clinical examination including measurement of best-corrected visual acuity, slit-lamp biomicroscopy, and indirect fundus examination, and underwent standardized imaging (color photography, fluorescein and indocyanine green angiography, OCT, and OCTA) after predefined protocols. We used a 2-step approach (Step 1: spectral domain OCT; Step 2: addition of OCTA) combining structural OCT and OCTA to differentiate 50 treatment-naive eyes with PCV, choroidal neovascularization, and retinal angiomatous proliferation and compared with the diagnosis based on fluorescein angiography and indocyanine green angiography. Spectral domain OCT signs used to diagnose PCV included presence of two out of three of any retinal pigment epithelium detachment (pigment epithelial detachment/double-layer sign), notched or narrow-peaked pigment epithelial detachment, or round subretinal pigment epithelium structure. Optical coherence tomography angiography signs used to diagnose PCV included presence of a localized subretinal pigment epithelium hyperflow signal in the cross-sectional OCTA and/or presence of a focal hyperflow sign in en face OCTA based on outer retina slab. Results: Based on fluorescein angiography and indocyanine green angiography, the diagnosis was choroidal neovascularization in 24 eyes, PCV in 23 eyes, and retinal angiomatous proliferation in 3 eyes. Based on spectral domain OCT signs, PCV was diagnosed in 19/23 (82.6%) eyes; however, specificity of OCT was only 51.9%. Cross-sectional OCTA showed a diffuse hyperflow signal in all 24 (100.0%) eyes with choroidal neovascularization, whereas a localized subretinal pigment epithelium hyperflow signal was detected in 19/23 (82.6%) eyes with PCV. En face OCTA only detected a nodular hyperflow signal in 10/23 eyes (43.5%) with PCV. Combination of OCT and OCTA achieved 82.6% sensitivity and 100.0% specificity for differentiating PCV from choroidal neovascularization/retinal angiomatous proliferation. Conclusion: Cross-sectional OCTA is more sensitive than en face OCTA in detecting flow signal in polyps. Combination of structural OCT and OCTA can be used to screen for PCV with a high level of sensitivity and specificity.

OPTICAL COHERENCE TOMOGRAPHY, FLUORESCEIN ANGIOGRAPHY, AND DIAGNOSIS OF CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION Purpose: To determine the sensitivity and specificity of different retinal imaging combinations for the diagnosis of choroidal neovascularization (CNV) in age-related macular degeneration. Methods: Patients aged 50 years or older referred for suspicious recent-onset CNV related to age-related macular degeneration were prospectively included for 6 months. Data recorded included color fundus photographs (CFPs), spectral domain optical coherence tomography (SD-OCT), and fluorescein angiography (FA) images. Five retina specialists randomly interpreted SD-OCT combined with CFP, and then FA combined with CFP. The reference diagnosis of CNV was based on the agreement of two readers in the interpretation of the SD-OCT + FA + CFP combination. Results: One hundred and forty-eight patients (148 eyes) were included. For the diagnosis of CNV, the sensitivity of both SD-OCT + CFP and FA + CFP was of 90.9%. Type 2 CNV was diagnosed in 98% to 100% of cases with SD-OCT + CFP or FA + CFP, whereas Type 1 CNV was diagnosed in 82.9% of cases with SD-OCT + CFP and 81.6% with FA + CFP. Conclusion: When used as a first diagnostic test, SD-OCT combined with CFP had sensitivity and specificity similar to those of FA combined with CFP, for the diagnosis of CNV in age-related macular degeneration. This shows the increasingly important role of SD-OCT as a first-line test in the diagnosis of CNV.

LONG-TERM VISUAL CHANGES IN INITIALLY STRONGER FELLOW EYES IN PATIENTS WITH UNILATERAL TYPE 3 NEOVASCULARIZATION Purpose: To evaluate long-term visual changes in initially stronger fellow eyes in patients with unilateral Type 3 neovascularization. Methods: This retrospective study included 102 patients who were newly diagnosed with unilateral Type 3 neovascularization and in whom the best-corrected visual acuity (BCVA) of the fellow eye was initially better than that of the involved eye. All patients were treated with intravitreal anti–vascular endothelial growth factor injections. The BCVAs were compared at diagnosis, 12 months, 24 months, and the final visit. In patients who experienced ≥3 lines of visual deterioration in the BCVA of the fellow eye, the reason for visual deterioration was also verified. Results: The patients were followed for 45.9 ± 18.5 months after diagnosis. At diagnosis, the fellow-eye BCVA was better than that of the initially involved eye in all 102 patients. However, the fellow-eye visual acuity was the same or worse than that of the initially involved eye in 13 patients (12.7%) at 12 months, in 20 patients (19.6%) at 24 months, and in 24 patients (23.5%) at the final visit. At the final visit, 53 patients (51.9%) had experienced ≥3 lines of deterioration in the BCVA of the fellow eye. Fellow-eye neovascularization occurred in 42 patients, and geographic atrophy involving the fovea was noted in the remaining 11 patients. Conclusion: Deterioration of the visual acuity of the fellow eye is frequently noted in unilateral Type 3 neovascularization. As a result of this deterioration, the initially stronger fellow eye did not remain stronger in 23.5% of the patients, suggesting the need for long-term strict treatment of the initially involved eye even when the visual acuity of the fellow eye is good.

VISUALIZATION OF CHOROIDAL NEOVASCULARIZATION USING TWO COMMERCIALLY AVAILABLE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DEVICES Purpose: To compare the sensitivity of detection and the measured size of choroidal neovascularization (CNV) on two commercially available spectral domain optical coherence tomography angiography (OCTA) devices, the Optovue RTVue XR Avanti with AngioVue and the Zeiss Cirrus HD-OCT with AngioPlex. Methods: Patients with CNV lesions were imaged consecutively on both OCTA devices on the same day of their visit. 3 × 3 mm and 6 × 6 mm scans centered at the fovea were obtained. Two independent masked readers evaluated the OCTA images for CNV identification and its area measurements. Results: No significant differences were observed between the 2 OCTA devices in CNV area measurements on their 3 × 3 mm and 6 × 6 mm scans. However, there was suboptimal performance of their automated segmentation algorithms as compared to manually adjusted segmentation for visualizing CNV lesions. Conclusion: There was no significant difference in the size of the CNV lesion as measured on either commercially available spectral domain OCTA device. Both devices were comparable in their detection of CNV lesions on manual adjustment of segmentation lines. However, their automated segmentation algorithms need improvement to allow for accurate measurement of CNV lesions for routine clinical application.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHARACTERISTICS OF POLYPOIDAL CHOROIDAL VASCULOPATHY SECONDARY TO CHRONIC CENTRAL SEROUS CHORIORETINOPATHY Purpose: To report diagnostic capability of optical coherence tomography angiography (OCTA) in detecting polypoidal choroidal vasculopathy and its morphologic characteristics in white patients with chronic central serous chorioretinopathy. Methods: Retrospective consecutive series of 20 eyes (17 consecutive patients) with a diagnosis of polypoidal choroidal vasculopathy secondary to chronic central serous chorioretinopathy based on clinical and multimodal imaging were included. All patients underwent a complete ophthalmologic examination, including best-correct visual acuity, fundus autofluorescence, fluorescein and indocyanine green angiography, spectral-domain optical coherence tomography, and OCTA. Results: In all eyes (100%), OCTA revealed the branching vascular network as a hyperflow lesion in both choriocapillaris and outer retina layers. Segmentation of the choriocapillaris in OCTA, in correspondence of the polypoidal dilation detected at indocyanine green angiography, showed a hyperflow round structure in 75% of cases and hypoflow round structure in 15%. Two of 20 eyes (10%) had no detectable polyps on OCTA. Conclusion: Optical coherence tomography angiography is a noninvasive imaging modality allowing a good visualization of both branching vascular network and polyp dilations. Our findings suggest that OCTA is a useful tool in the investigation of chronic central serous chorioretinopathy complicated by polypoidal choroidal vasculopathy.

EVALUATION OF MULTISPECTRAL IMAGING IN DIAGNOSING DIABETIC RETINOPATHY Purpose: To investigate multispectral imaging (MSI) as a novel diagnostic approach for diabetic retinopathy (DR) in clinic. Methods: A total of 50 Type-2 diabetic patients (99 eyes) were enrolled in this cross-sectional study. All subjects underwent digital fundus photography (DFP), MSI, and fundus fluorescein angiography. A total exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value of no DR/mild nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative diabetic retinopathy (PDR) grading were calculated based on DFP and MSI and were compared with fundus fluorescein angiography. Results: Compared with fundus fluorescein angiography, the exact agreement for MSI was 0.835; for DFP, it was 0.614; the sensitivity for no DR/mild NPDR in both MSI and DFP was 100%, and for severe NPDR/PDR, it was 97.4% and 88.3%. The specificity for no DR/mild NPDR in MSI and DFP was 96.3% and 95%, and for severe NPDR/PDR, it was 100% in both. The positive predictive value for no DR/mild NPDR in MSI and DFP was 86.4% and 82.6%, and for severe NPDR/PDR, it was 100% in both; the negative predictive value for no DR/mild NPDR in MSI and DFP was 100%, and for severe NPDR/PDR, it was 91.7% and 71.0% in both. Conclusion: Multispectral imaging displayed an excellent agreement with fundus fluorescein angiography in DR grading, which suggested that it might serve as a new diagnostic technique and an informative tool for evaluating DR.

DECREASED RETINAL CAPILLARY DENSITY IS ASSOCIATED WITH A HIGHER RISK OF DIABETIC RETINOPATHY IN PATIENTS WITH DIABETES Purpose: To quantify retinal microvascular alterations using optical coherence tomography angiography in diabetic patients, and to evaluate the accuracy of decreased vessel density (VD) in predicting early diabetic retinopathy (DR). Methods: One hundred and two eyes of 51 diabetic patients and 92 eyes of 46 individuals without diabetes were examined. Duration of diabetes, insulin therapy, blood pressure, HbA1C, dyslipidemia, axial length, and the presence of DR were recorded. Retinal VD was measured using optical coherence tomography angiography. The effect of risk factors on VD and on DR was assessed using multivariable regression analyzes. Results: Compared with controls, VD was lower in diabetic patients (P < 0.05) and correlated with diabetes duration (P = 0.02). Decreased VD was associated with a higher risk of DR (odds ratio: 1.24, P = 0.009) after controlling for systemic and ocular confounding variables. Eyes with a VD of <50% had an odds ratio of 4.55 (P = 0.003) for DR and an odds ratio of 3.22 (P = 0.03) for decreased visual acuity (<20/25) after controlling for systemic and ocular confounding factors. Conclusion: The risk of DR and vision loss is substantially higher in eyes with lower VD, suggesting that optical coherence tomography angiography metrics may serve as prognostic biomarkers for the prediction of early onset DR.

PHACOEMULSIFICATION CATARACT SURGERY WITH PROPHYLACTIC INTRAVITREAL BEVACIZUMAB FOR PATIENTS WITH COEXISTING DIABETIC RETINOPATHY: A Meta-Analysis Purpose: To evaluate the clinical effectiveness of intravitreal bevacizumab (IVB) injection combined with cataract surgery in the treatment of patients with cataract and coexisting diabetic retinopathy (DR). Methods: Pertinent comparative studies were identified through systemic searches of PubMed, EMBASE, and the Cochrane Controlled Trials Register up to March 1, 2016. Outcome measures included corrected distance vision acuity, central macular thickness, and progression of DR and maculopathy. A meta-analysis was performed using RevMan (Cochrane Collaboration, Oxford, United Kingdom). Results: Six studies describing a total of 283 eyes were identified. The meta-analysis results showed that corrected distance vision acuity measured at 1 month and 3 months after cataract surgery was significantly better in the IVB groups than in the control groups (P < 0.00001 and P = 0.01), whereas the corrected distance vision acuity at 6 months did not vary significantly between the 2 groups (P = 0.24). Similarly, the central macular thickness at 1, 3, and 6 months after surgery was significantly thinner in the IVB groups than in the control groups (P = 0.01, P = 0.0004, and P = 0.01, respectively). At 6 months, the progression of postoperative DR and maculopathy occurred more frequently in the control group than in the IVB group (P = 0.0001 and P < 0.0001, respectively). Conclusion: Our meta-analysis indicates that cataract surgery combined with IVB seems to be an effective treatment in patients with coexisting DR in the short term (up to 6 months). More randomized, prospective, and large-sample–sized trials are needed to evaluate the long-term effects of IVB at the time of cataract surgery in patients with DR.