Effects of vascular endothelial growth factor and angiopoietin-2 inhibitions on intraretinal hyperreflective foci in neovascular age-related macular degeneration

PURPOSE: To investigate the association of hyperreflective foci (HRFs) with disease activity in treatment-naïve neovascular age-related macular degeneration (nAMD) and to compare the effects of anti-vascular endothelial growth factor (VEGF) therapy versus dual VEGF-A/angiopoietin-2 (Ang-2) inhibition on HRFs. STUDY DESIGN: Retrospective, single-center, interventional study METHODS: This study included 72 eyes with treatment-naïve nAMD. Thirty-two consecutive eyes received aflibercept 2mg and 40 consecutive eyes received faricimab, each undergoing three monthly loading injections. HRF presence and area, central retinal thickness (CRT), best-corrected visual acuity (BCVA), and associated parameters were evaluated at baseline and after loading. HRFs were quantified using binarized spectral-domain optical coherence tomography (SD-OCT) images with automated assistance. RESULTS: At baseline, 45 eyes (62.5%) exhibited HRFs, all in the outer retina, with 10 eyes (13.9%) also showing inner retinal HRFs. Outer HRF area positively correlated with CRT and the maximum height of serous retinal detachment (SRD), while inner HRFs were associated with intraretinal fluid. Both treatments significantly improved BCVA and CRT. HRF presence and area decreased after treatment, primarily in the outer retina. After adjustment for baseline HRF area and clinical parameters, faricimab achieved a more substantial reduction in total, outer, and inner HRF areas than aflibercept. CONCLUSIONS: HRFs correlated with layer-specific exudative change. Faricimab resulted in a more pronounced reduction in HRFs than aflibercept despite comparable anatomical improvements, suggesting superior control of inflammation-related retinal changes.