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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\u00a0mg (0.1\u00a0ml) for at least three doses. Eyes with persistent fluid were switched to Faricimab 6\u00a0mg. In non-responders, Faricimab was further escalated to 12\u00a0mg (0.1\u00a0ml). 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\u00a0mg significantly reduced PED volume (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), especially after the first two injections. However, changes in intraretinal and subretinal fluid were not significant. In the Faricimab 12\u00a0mg subgroup, no additional anatomical benefit was observed. OCTA showed a trend toward reduced vascular activity after switching to Faricimab 6\u00a0mg, but no further change with dose escalation. In MNV eyes resistant to high-dose Aflibercept, Faricimab 6\u00a0mg provides meaningful anatomical improvement, particularly in PED volume. However, escalating Faricimab to 12\u00a0mg offers no additional benefit, suggesting therapeutic saturation at the standard dose.<\/jats:p>","DOI":"10.1038\/s41598-025-09910-2","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:19:37Z","timestamp":1759241977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Faricimab at 6 and 12\u00a0mg reduces pigment epithelium detachment in treatment-resistant macular neovascularization: an OCT and AI analysis"],"prefix":"10.1038","volume":"15","author":[{"given":"Ines D.","family":"Nagel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie D.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haochen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Heinke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehal N.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk-Uwe","family":"Bartsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz G. 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Aflibercept therapy for exudative age-related macular degeneration resistant to bevacizumab and ranibizumab. Am J Ophthalmol 156, 15\u201322.e11 (2013). https:\/\/doi.org\/10.1016\/j.ajo.2013.02.017","DOI":"10.1016\/j.ajo.2013.02.017"},{"key":"9910_CR3","doi-asserted-by":"publisher","first-page":"100906","DOI":"10.1016\/j.preteyeres.2020.100906","volume":"82","author":"PS Mettu","year":"2021","unstructured":"Mettu, P. S., Allingham, M. J. & Cousins, S. W. Incomplete response to Anti-VEGF therapy in neovascular AMD: exploring disease mechanisms and therapeutic opportunities. Prog Retin Eye Res. 82, 100906. https:\/\/doi.org\/10.1016\/j.preteyeres.2020.100906 (2021).","journal-title":"Prog Retin Eye Res."},{"key":"9910_CR4","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1007\/s00417-024-06421-0","volume":"262","author":"M Schneider","year":"2024","unstructured":"Schneider, M. et al. Short-term outcomes of treatment switch to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration. Graefes Arch. Clin. Exp. Ophthalmol. 262, 2153\u20132162. https:\/\/doi.org\/10.1007\/s00417-024-06421-0 (2024).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"9910_CR5","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ophtha.2013.08.035","volume":"121","author":"AA Chang","year":"2014","unstructured":"Chang, A. A. et al. Intravitreal Aflibercept for treatment-resistant neovascular age-related macular degeneration. Ophthalmology 121, 188\u2013192. https:\/\/doi.org\/10.1016\/j.ophtha.2013.08.035 (2014).","journal-title":"Ophthalmology"},{"key":"9910_CR6","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1007\/s00417-021-05547-9","volume":"260","author":"GK Broadhead","year":"2022","unstructured":"Broadhead, G. K., Keenan, T. D. L., Chew, E. Y., Wiley, H. E. & Cukras, C. A. 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