Faricimab in neovascular age-related macular degeneration: aqueous humor cytokine profiling and biomarker correlations.

PURPOSE: To investigate aqueous humor cytokine profile changes in neovascular age-related macular degeneration (nAMD) patients before and after intravitreal faricimab injection, and their correlation with biomarkers. METHODS: Twenty-three nAMD patients and 10 cataract controls were enrolled. Aqueous humor was collected from nAMD patients at baseline and 12 weeks post-faricimab injection, and from controls during phacoemulsification. Twelve cytokines were quantified via multiplex bead-based immunoassay. OCTA measured central macular thickness (CMT) and retinal vessel density in nAMD eyes. RESULTS: Baseline vascular endothelial growth factor (VEGF), Angiopoietin-2 (Ang-2) and HGF levels were higher in nAMD patients than controls. Post-treatment, VEGF and Ang-2 decreased below control levels, while hepatocyte growth factor (HGF) and interferon gamma protein 10 (IP-10) increased significantly. Reductions in Ang-2/VEGF correlated positively with decreased CMT and whole retinal thickness, with concurrent improvements in best-corrected visual acuity. Elevated IP-10 showed a correlative association with reduced superficial foveal vessel density. CONCLUSION: Faricimab dual-blockades VEGF/Ang-2, reducing their aqueous levels, improving CMT/whole retinal thickness and visual acuity. However, post-treatment HGF/IP-10 upregulation indicates compensatory inflammatory-angiogenic remodeling. IP-10 may serve as a potential correlative biomarker linked to subclinical capillary rarefaction. Future studies should explore combined anti-IP-10 therapy or extended dosing intervals to preserve foveal vasculature while maintaining anti-leakage efficacy.