Real-world functional and anatomical outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration: a phenotype-based analysis by pachychoroid and polypoidal lesion status

Abstract Background To evaluate the short-term functional and anatomical outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration (nAMD), and to explore whether the early treatment response varied according to pachychoroid and polypoidal lesion status. Methods This retrospective, multicenter observational study evaluated 45 treatment-naïve eyes of 45 patients with nAMD who received three monthly loading injections of aflibercept 8 mg. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative findings (subretinal fluid SRF, intraretinal fluid IRF, and subretinal hyperreflective material SHRM) were assessed at baseline and at 1, 2, and 4 months. Pachychoroid and polypoidal lesion status was determined using multimodal imaging. Longitudinal changes were analyzed using linear mixed-effects models, with subgroup analyses by pachychoroid and polypoidal lesion status. Results At 4 months, mean BCVA improved from 0.27 ± 0.33 to 0.20 ± 0.31 logMAR ( P = 0.005), CRT decreased from 382.1 ± 189.7 to 231.3 ± 109.1 μm, and CCT from 263.0 ± 146.5 to 231.0 ± 127.2 μm (both P < 0.001). The dry macula rate (absence of both SRF and IRF) increased from 17.8% to 75.6% ( P < 0.001). Functional and retinal anatomical responses were broadly consistent across phenotypes, with no significant time-by-phenotype interactions for BCVA or CRT. Pachychoroid eyes showed a greater CCT reduction (interaction P < 0.001), but this was no longer significant after adjusting for baseline CCT. As exploratory observations, the time-by-polypoidal-lesion interaction for BCVA was not significant ( P = 0.052), and residual SHRM at 4 months was present in 0% of polypoidal-lesion eyes versus 22.2% of those without ( P = 0.067). Conclusions Intravitreal aflibercept 8 mg led to significant short-term improvements in BCVA, CRT, CCT, and exudative findings in treatment-naïve nAMD, with benefit observed irrespective of pachychoroid or polypoidal lesion status.