Anti-VEGF Agents and the Inner Retina in nAMD: A Narrative Review of RNFL and Ganglion Cell Changes

Anti-vascular endothelial growth factor (anti-VEGF) therapy is the cornerstone of care for neovascular age-related macular degeneration (nAMD), yet its effects on the inner retina are not widely studied. We conducted a narrative review, guided by the SANRA checklist, to map evidence on peripapillary retinal nerve fibre layer (pRNFL), macular RNFL, and ganglion cell-derived metrics (GCL/GCIPL/GCC) during anti-VEGF treatment. Major databases were searched from inception to 10 November 2025 for human studies reporting optical coherence tomography (OCT) measurements of inner-retinal structure during anti-VEGF treatment. Data were charted for study design, OCT device/segmentation, scan protocol, timing relative to injections, treatment regimen, fluid phenotype (intraretinal fluid [IRF], subretinal fluid [SRF], pigment epithelial detachment [PED]), follow-up interval, and magnitude of change (µm). Across cohorts and agents, global pRNFL thickness was largely stable over weeks to years, with short-term peri-injection fluctuations typically within device test-retest limits. In contrast, macular ganglion cell layers more often showed modest thinning over time, most consistently in eyes with baseline IRF; SRF-predominant disease showed less consistent inner-retinal change. Apparent between-agent differences were small and inconsistent; evidence specific to faricimab remains limited but generally reassuring for structural stability. Overall, most observed changes were often within OCT test-retest variability. In practice, clinicians should prioritise GCL/GCIPL monitoring where IRF is present, interpret small absolute changes against device repeatability, and avoid attributing trivial sectoral shifts to drug toxicity without corroboration.