Choroidal Changes After Intravitreal Aflibercept, Faricimab, Brolucizumab, and High Dose Aflibercept in Treatment-Naïve Neovascular AMD

Purpose To compare choroidal structural changes after a loading phase of different anti–vascular endothelial growth factor (VEGF) agents in treatment-naïve neovascular age-related macular degeneration (nAMD). Design Retrospective, monocentric, observational cohort study. Subjects Fifty-six eyes of 56 treatment-naïve patients with nAMD. Methods, Intervention, or Testing Patients received three consecutive monthly intravitreal injections of aflibercept 2 mg, aflibercept 8 mg, brolucizumab, or faricimab. Multimodal imaging was performed at baseline and at 3 months using swept-source optical coherence tomography. Central choroidal thickness (CCT) and choroidal vascularity index (CVI) were quantified. Changes from baseline were analyzed within and between treatment groups, with adjustment for age. Main Outcome Measures Change in central choroidal thickness and choroidal vascularity index after the loading phase. Results All treatment groups demonstrated a significant reduction in CCT at 3 months (all p ≤ 0.006). The greatest mean CCT reduction was observed with brolucizumab, followed by aflibercept 8 mg, faricimab, and aflibercept 2 mg. Age-adjusted analysis showed a significant effect of treatment on CCT change, with a significant treatment-by-age interaction (F(3,48) = 6.24, p = 0.001, η2 = 0.197). CVI decreased significantly only in the aflibercept 8 mg group (mean change –4.9; p = 0.004), driven by a preferential reduction in the luminal component (p = 0.002). Brolucizumab predominantly affected the stromal component (p = 0.006) without significant change in CVI. Conclusions Anti-VEGF therapy induces significant choroidal thinning in treatment-naïve nAMD during the loading phase. However, different agents demonstrate distinct choroidal compartmental effects. These findings suggest drug-specific patterns of choroidal remodeling, potentially influenced by molecular and pharmacologic properties, warranting further prospective evaluation to determine their clinical implications.