Sequential switch from first-line anti-VEGF therapy to faricimab and subsequent aflibercept 8mg in treatment-resistant neovascular AMD

<title>Abstract</title> <p> <bold>Purpose:</bold> To evaluate anatomical and functional outcomes in treatment-resistant neovascular age-related macular degeneration (nAMD) following sequential switching from first-generation anti-vascular endothelial growthfactor (anti-VEGF) therapy to faricimab and subsequently to aflibercept 8mg. <bold>Methods:</bold> This retrospective, single-center, real-world cohort study included 60 eyes from 48 patients with treatment-resistant nAMD and persistent exudation despite ranibizumab or aflibercept 2mg administered at intervals shorter than 6 weeks. Eyes were sequentially switched from first-generation anti-VEGF therapy to faricimab and subsequently to aflibercept 8mg. Anatomical and functional outcomes were evaluated at predefined time points before and after each treatment switch, including exudation status, best-corrected visual acuity (BCVA), central macular thickness (CMT), fibrovascular pigment epithelial detachment (fvPED) height, recurrence-free interval, and safety. <bold>Results:</bold> Complete fluid resolution was observed in 41/60 eyes after the switch to faricimab and in 44/60 eyes after the subsequent switch to aflibercept 8mg. No significant difference was observed in the paired comparison of anatomical status between treatment phases (p=0.48). BCVA changes were comparable following both switches (ΔBCVA 0.01±0.15 vs 0.02±0.14 logMAR, p=0.53). Greater reductions in CMT and fvPED height were observed after the initial switch to faricimab (ΔCMT −33.67±84.43 µm vs −22.62±49.34 µm, p=0.027; ΔfvPED −40.73±64.05 µm vs −16.69±30.63 µm, p=0.0036), whereas aflibercept 8mg was associated with a slightly longer recurrence-free interval (5.45±1.73 vs 4.95±1.22 weeks; p=0.045). No new cases of macular atrophy, fibrosis, or intraocular inflammation were observed. <bold>Conclusions:</bold> In treatment-resistant nAMD, sequential use of faricimab followed by aflibercept 8mg resulted in progressive anatomical improvement, maintained visual outcomes, a modest prolongation of recurrence-free intervals, and a comparable safety profile. </p>