Open Access

Ines D. Nagel, Melanie D. Tran, Haochen Zhang, Lingyun Cheng, Anna Heinke, Nehal N. Mehta, Dirk-Uwe Bartsch, Fritz G. P. Kalaw, Mohamed Morsy, Arthur J. Mueller, William R. Freeman

• Macular neovascularization (MNV) in age-related macular degeneration (AMD) remains a therapeutic challenge, especially in eyes resistant to conventional anti-VEGF therapy. This study evaluates the anatomical and functional response to Faricimab in patients with persistent fluid despite intensified Aflibercept treatment and explores potential benefits of dose escalation. This cross-sectional study included 25 eyes from 23 patients with active MNV resistant to standard anti-VEGF therapy. All had persistent fluid on OCT despite monthly injections and received off-label double-volume Aflibercept 4 mg (0.1 ml) for at least three doses. Eyes with persistent fluid were switched to Faricimab 6 mg. In non-responders, Faricimab was further escalated to 12 mg (0.1 ml). Retinal fluid volumes and pigment epithelium detachment (PED) were analyzed using AI-based OCT segmentation. MNV activity was assessed using AI-based OCTA analysis. Faricimab 6 mg significantly reduced PED volume (p < 0.05),Macular neovascularization (MNV) in age-related macular degeneration (AMD) remains a therapeutic challenge, especially in eyes resistant to conventional anti-VEGF therapy. This study evaluates the anatomical and functional response to Faricimab in patients with persistent fluid despite intensified Aflibercept treatment and explores potential benefits of dose escalation. This cross-sectional study included 25 eyes from 23 patients with active MNV resistant to standard anti-VEGF therapy. All had persistent fluid on OCT despite monthly injections and received off-label double-volume Aflibercept 4 mg (0.1 ml) for at least three doses. Eyes with persistent fluid were switched to Faricimab 6 mg. In non-responders, Faricimab was further escalated to 12 mg (0.1 ml). Retinal fluid volumes and pigment epithelium detachment (PED) were analyzed using AI-based OCT segmentation. MNV activity was assessed using AI-based OCTA analysis. Faricimab 6 mg significantly reduced PED volume (p < 0.05), especially after the first two injections. However, changes in intraretinal and subretinal fluid were not significant. In the Faricimab 12 mg subgroup, no additional anatomical benefit was observed. OCTA showed a trend toward reduced vascular activity after switching to Faricimab 6 mg, but no further change with dose escalation. In MNV eyes resistant to high-dose Aflibercept, Faricimab 6 mg provides meaningful anatomical improvement, particularly in PED volume. However, escalating Faricimab to 12 mg offers no additional benefit, suggesting therapeutic saturation at the standard dose.…