Double-dose intravitreal faricimab in resistant neovascular age-related macular degeneration: safety and efficacy

Background Anti-VEGF therapy remains the mainstay treatment for neovascular age-related macular degeneration (nAMD), yet a subset of eyes exhibit resistance to standard treatment regimens. This study evaluates the safety and efficacy of double-dose intravitreal faricimab (12 mg) in a series of eyes with nAMD refractory to bevacizumab, aflibercept, and standard-dose faricimab. Methods This retrospective case series included 26 eyes from 24 patients with treatment-resistant nAMD who received intravitreal faricimab 12 mg every 4 weeks for three loading injections, followed by a treat-and-extend regimen when anatomic stability was achieved. Primary anatomic outcomes included central subfield thickness (CST), central foveal thickness (CFT), maximum macular thickness (MMT), pigment epithelial detachment (PED) height and volume, and intraretinal (IRF), subretinal (SRF), and total retinal fluid (TRF) volumes. Best-corrected visual acuity (BCVA) served as the functional endpoint. Safety measures included intraocular pressure (IOP), intraocular inflammation, systemic adverse events, and new-onset geographic atrophy (GA). Results Over a mean follow-up of 10.6 months, significant anatomical improvements were observed, including reductions in CFT (p=0.0029), MMT (p=0.0007), CST (p=0.0067), PED maximum height (p=0.0241), and TRF (p=0.0341). PED volume significantly decreased at 4 weeks (p=0.0394) but was not sustained. IRF and SRF reductions were not individually significant. BCVA, which had declined significantly in the 24 weeks prior to switching (p≈0.04), remained stable throughout treatment with double-dose faricimab (p>0.6). At final visit, 57.7% of eyes achieved complete dryness, and IOP remained stable. Among eyes without baseline GA, one developed new-onset GA. Conclusions Double-dose faricimab demonstrated meaningful anatomic improvements and stable functional outcomes in highly treatment-resistant nAMD, with acceptable short-term safety. These preliminary findings support the potential utility of faricimab dose escalation in refractory cases, but larger prospective controlled studies are required to validate these observations.