Impact of Aflibercept Dosing Frequency on Retinal Nonperfusion Progression Assessed by Ultra-Widefield Angiography After Endolaserless Vitrectomy for Proliferative Diabetic Retinopathy–Related Vitreous Hemorrhage

Purpose: To investigate the effect of intravitreal (IVT) aflibercept injection monotherapy on retinal ischemia in eyes with severe proliferative diabetic retinopathy (PDR) that underwent pars plana vitrectomy (PPV) without panretinal photocoagulation (PRP) for vitreous hemorrhage. Methods: Thirty-one eyes with PDR-related vitreous hemorrhage underwent PPV without endolaser PRP and received 1 preoperative and 1 intraoperative IVT aflibercept injection before being randomized postoperatively to receive an IVT aflibercept injection once every 8 weeks (q8-week) or once every 16 weeks (q16-week). Ultra-widefield fluorescein angiography (FA) was performed 4 weeks post-PPV (baseline) and quarterly for 3 years. Images were independently graded at the Wisconsin Reading Center for the nonperfusion index, which is the proportion of assessable retinal area demonstrating capillary nonperfusion on ultra-widefield FA. Results: The IVT aflibercept q16-week group showed a significant increase in nonperfusion index of 0.096 by week 152 ( P < .0001), whereas the q8-week group showed no significant progression. The q8-week group received more total injections and reached therapeutic saturation earlier, whereas the q16-week group showed a significant increase in unscheduled rescue injections across successive intervals (weeks 52-104, P = .017; weeks 104-152, P = .045) and still demonstrated worsening ischemia. In the q16-week group, higher cumulative injection counts correlated positively with nonperfusion index burden ( P = .016), a relationship not observed in the q8-week group ( P = .82). Conclusions: In eyes with PDR that underwent PPV without PRP, more frequent aflibercept dosing (q8-week) mitigated progression of retinal nonperfusion compared with extended-interval (q16-week) aflibercept therapy, suggesting that tighter antivascular endothelial growth factor treatment intervals may slow retinal ischemic progression.