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Purpose To assess the influence of baseline choroidal neovascularization (CNV) features on visual change and fluid resolution after anti–vascular endothelial growth factor (VEGF) treatment of eyes with neovascular age-related macular degeneration (nAMD). Design Post hoc analysis of 52-week data from the phase 3 Vascular Endothelial Growth Factor VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) Studies (VIEW) 1 and 2 clinical trials. Participants One thousand eight hundred four patients with nAMD. Methods Integrated data from VIEW 1 and 2 of 1804 eyes receiving intravitreal aflibercept injections (IAIs) 2 mg every 4 weeks, IAIs 2 mg every 8 weeks after 3 initial monthly doses, and ranibizumab every 4 weeks with documented baseline CNV type, total area, and leakage area were analyzed. Time to an event and cumulative incidence were evaluated by Kaplan-Meier analysis, and relative risks were estimated using proportional hazards analysis. Main Outcomes Measures Cumulative incidence of time to first sustained vision gain of 15 or more Early Treatment Diabetic Retinopathy Study letters, vision loss of more than 5 Early Treatment Diabetic Retinopathy Study letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by OCT with respect to CNV type, total CNV, and leakage area. Results Eyes with predominantly classic CNV (mean best-corrected visual acuity [BCVA], 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of 15 letters or more than eyes with occult CNV (mean BCVA, 57.9 letters at baseline; P Conclusions This post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area, and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD after anti-VEGF treatment.

International audience; PURPOSE: To evaluate the impact of baseline retinal capillary nonperfusion (RNP) and macular retinal capillary nonperfusion (MNP) status on outcomes at week 24 (W24). DESIGN: Post hoc analyses of 2 phase 3, randomized, double-masked, multicenter, sham-controlled studies. PARTICIPANTS: Three hundred sixty-six patients with macular edema secondary to central retinal vein occlusion randomized in COPERNICUS and GALILEO.METHODS: We randomized patients 3:2 to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until W24. RNP and MNP were assessed by a masked independent reading center.MAIN OUTCOME MEASURES: Proportion of patients with 10 disc areas (DA) or more of RNP and any degree of MNP at W24, relative risks of 10 DA or more of RNP or any degree of MNP at W24 developing, change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by baseline RNP and MNP status, and relationship between baseline RNP and MNP status. RESULTS: At baseline, 24.6% of patients showed 10 DA or more of RNP and 72.6% showed MNP, regardless of baseline RNP status. At W24, the pooled proportions of patients in the intravitreal aflibercept and sham groups with 10 DA or more of RNP were 11.6% and 29.0%, respectively (P = 0.0001); the respective proportions with any degree of MNP were 61.2% and 79.5% (P = 0.0008). Relative risks and 95% confidence intervals for intravitreal aflibercept versus sham were 0.4 (0.25-0.62) for 10 DA or more of RNP and 0.8 (0.68-0.90) for MNP, indicating a lower risk for these outcomes with intravitreal aflibercept than with sham. Mean BCVA change was greater in intravitreal aflibercept- versus sham-treated eyes, with less than 10 DA and 10 DA or more of RNP at baseline (+17.5 vs. +0.8 letters and +18.3 vs. -4.1 letters, respectively) and with and without baseline MNP (+15.7 vs. +0.3 letters and +17.1 vs. +0.4 letters, respectively). Agreement between baseline RNP and MNP status was low (kappa = 0.12). The proportions of patients with 1 or more ocular serious adverse event in the intravitreal aflibercept- and sham-treated groups, respectively, were 3.2% and 11.3%.CONCLUSIONS: At W24, visual and anatomic improvements, including perfusion status, were greater in eyes treated with intravitreal aflibercept than in eyes treated with sham, regardless of baseline RNP or MNP status.

Purpose To determine whether wet age-related macular degeneration (AMD) treatment outcomes within prespecified patient subgroups were consistent with overall study results. Additionally, this subanalysis investigated whether there were any relationships between baseline characteristics and evaluated treatment outcomes. Design Post hoc subanalysis of The VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, 2 similarly designed prospective, multicenter, double-masked, active-controlled, parallel-group, randomized clinical trials. Participants Two thousand four hundred twelve patients with an active subfoveal choroidal neovascularization (CNV) lesion of any subtype secondary to AMD. Methods Primary and key secondary visual end points at week 52 were examined to explore the consistency of effect among prespecified subgroups of 5 baseline characteristics: age, best-corrected visual acuity (BCVA), lesion type, lesion size, and central retinal thickness (CRT). Additionally, within-group analyses were conducted to determine whether the mean changes in BCVA and CRT at 52 weeks were associated positively or negatively with the baseline characteristics of interest. Main Outcome Measures Consistency of treatment outcomes among prespecified subgroups of baseline characteristics. Results For each baseline characteristic, tests for interaction within each prespecified subgroup and among the subgroups were not significant, suggesting that relative visual outcomes for each treatment arm were consistent with overall study outcomes. Within-group analysis revealed a significant association between baseline age, BCVA, and lesion size with BCVA outcomes at 52 weeks; namely, older age, greater BCVA, and larger lesion size were associated with lower mean BCVA gains at 52 weeks. Conclusions Patients in all subgroups of baseline age, BCVA, lesion type, lesion size, and CRT experienced visual outcomes consistent with those of the overall study population. Additionally, baseline older age, better BCVA, and larger CNV lesion size were found to be associated independently with lower mean BCVA gains after 52 weeks of anti–vascular endothelial growth factor therapy. The influence of baseline age, BCVA, and CNV lesion size on treatment outcomes is consistent with other reports from large, prospective trials in wet AMD.

Purpose To examine the relationship between glycemic control at baseline and response to anti–vascular endothelial growth factor treatment for diabetic macular edema (DME). Design Post hoc analysis of 2 similarly designed phase III trials, VISTA and VIVID. Participants Patients with central-involved DME. Methods Both VISTA and VIVID compared efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for DME. Current analysis focused on comparison within each treatment group in an integrated VISTA and VIVID dataset. Baseline hemoglobin A1c (HbA1c) was partitioned into 4 quartiles: 4.5% to Main Outcome Measures Change from baseline best-corrected visual acuity (BCVA), central subfield thickness (CST), and HbA1c. Results In the IAI group, mean BCVA improvement from baseline did not depend on baseline HbA1c at week 52 ( P = 0.1852), but seemed to be dependent at week 100 ( P = 0.0425). The mean CST reduction from baseline was independent of baseline HbA1c at both weeks 52 ( P = 0.1857) and 100 ( P = 0.7346). Mean HbA1c change from baseline in IAI group was small across all HbA1c quartiles. In the laser group, the mean BCVA gain decreased with increasing baseline HbA1c at both weeks 52 ( P = 0.0421) and 100 ( P = 0.0001). Similarly, the mean CST decrease was greater with decreasing baseline HbA1c, at both weeks 52 ( P = 0.0065) and 100 ( P = 0.0162). The mean HbA1c change from baseline in the laser group was minimal across HbA1c quartiles, although glycemic control tended to worsen in upper quartiles. Conclusions The benefit of IAI in patients with DME was less dependent on their presenting glycemic status as opposed to laser.

Purpose To assess the long-term safety and vision change in patients who received intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration in an extension study after completing VIEW 1 trial. Design Prospective, open-label, multicenter, extension study. Participants Three hundred twenty-three patients. Methods In VIEW 1, 1217 patients were randomized to receive fixed dosing of 0.5 mg IAI every 4 weeks (0.5q4), 2 mg IAI every 4 weeks (2q4), 2 mg IAI every 8 weeks after 3 initial monthly dosing (2q8), or 0.5 mg ranibizumab every 4 weeks (Rq4) from baseline through week 52, followed by modified quarterly injections of the same dose of anti-vascular endothelial growth factor agent from weeks 52 to 96. After completing VIEW 1 at week 96, patients (n = 323) enrolled in an extension study and received 2 mg IAI on a modified quarterly injection schedule followed by at least an every 8-week dosing through week 212. Main Outcome Measures Long-term safety and vision change in patients followed for a median duration of 116 weeks in the extension study (total follow-up time of 212 weeks from the VIEW 1 baseline). Results Patients enrolled in the extension study gained a mean of 10.2 letters from the VIEW 1 baseline at week 96. These patients largely maintained vision over the extension study with a mean gain of 7.1 letters from the VIEW 1 baseline to week 212. The proportion of patients who lost ≥15 letters from the VIEW 1 extension baseline was 8.2% at week 212. Mean number of injections was 12.9 (range, 1–41) in the extension study. The most common serious ocular adverse event was endophthalmitis (0.9%). The overall incidence of Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events was 6.2%. Conclusions Vision gains achieved with anti-vascular endothelial growth factor therapy in VIEW 1 were largely maintained by continued treatment with IAI 2 mg in the extension study. Anti-vascular endothelial growth factor injections (including 4 years of IAI 2 mg) were well-tolerated with no new safety signals compared with the known profile of IAI.