Comparison of agents using higher dose anti-VEGF therapy for treatment-resistant neovascular age-related macular degeneration

Purpose To explore the comparative efficacy and safety of higher dose intravitreal bevacizumab, ranibizumab, or aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). Methods Retrospective analysis of 37 eyes of 35 patients with treatment-resistant nAMD divided into 3 cohorts based on high-dose treatment received: 3 mg aflibercept, 0.75 mg or 1.0 mg ranibizumab, and 1.8 mg or 2.5 mg bevacizumab. The eyes were analyzed at standardized time points up to 48 months. Included eyes demonstrated active nAMD with persistent exudation on imaging for at least 6 months with at least 4 anti-VEGF injections during this time. Outcomes included change in visual acuity (VA), central retinal thickness (CRT), intraocular pressure (IOP), retinal morphology, adverse event occurrence, and yearly intravitreal injection (IVI) rate. Results There was no significant difference in VA or IOP change compared to the initiation of high-dose treatment for any agent or comparing between agents at any time point ( p > 0.05). CRT improved at month 1, 3, 6, and 12 with all 3 agents ( p < 0.05 for all) with a greater CRT reduction seen for ranibizumab than aflibercept at month 6 ( p < 0.05), although baseline CRT was greater in the ranibizumab group than the aflibercept group ( p < 0.05). Mean absolute CRT was similar at month 6 for all agents ( p > 0.05). IVI rates pre- and post-conversion to higher-dose therapy were similar (1 injection per 5.7–6.4 weeks). Mean follow-up was 22.8 months. Conclusions Higher dose therapy may achieve improved anatomic outcomes and maintain vision, but frequent injections are required to achieve this. There was no detected difference in efficacy or safety between agents.