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The pathogenesis of subretinal fibrosis in nAMD is largely driven by epithelial\u2013mesenchymal and endothelial\u2013mesenchymal transition within the retinal pigment epithelium and endothelium of the choroidal circulation. Upregulation of vascular endothelial growth factor (VEGF) expression further contributes to the observed fibrovascular content and increased vascular permeability. There is a substantial need for direct therapeutic strategies for fibrosis in nAMD, including anti-fibrotic agents. Until direct treatment strategies are developed, the management of nAMD using anti-VEGF agents must be optimized. However, fibrosis can occur in some patients otherwise successfully treated with anti-VEGF therapy, resulting in the loss of previous visual acuity (VA) gains experienced after treatment initiation. This review summarizes the current understanding of the mechanisms driving fibrosis in nAMD, risk factors for fibrosis development, and limitations of current detection methods. Available evidence on how different factors relating to anti-VEGF therapy (e.g., specific agent, delays in administration, extended administration intervals, dosing or treatment regimen) and the early detection of nAMD impact the risk of fibrosis is also discussed. Lastly, insights into potential future directions for the management of fibrosis in nAMD, particularly the development of anti-fibrotic agents, are deliberated.<\/jats:p>","DOI":"10.1007\/s00417-025-06890-x","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T08:43:11Z","timestamp":1761122591000},"page":"19-34","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Management of fibrosis in neovascular age-related macular degeneration"],"prefix":"10.1007","volume":"264","author":[{"given":"Usha","family":"Chakravarthy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J. 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None relevant to submitted work.AF declares no competing interests.GDP declares no competing interests.TP has received speaker fees and Advisory Board member fees from Novartis, Bayer, Roche, Apellis, Alimera, AbbVie, Optos, and Heidelberg. Investigator-initiated grants are in progress with Boehringer Ingelheim.TR declares no competing interests.SRS has received honoraria as a consultant\/advisor for 4D Molecular Therapeutics, Alexion, Allergan, Alnylam Pharmaceuticals, Amgen, Apellis Pharmaceuticals, Astellas Pharma, Bayer, Boehringer Ingelheim, ONL Therapeutics, Biogen, iCare Inc., Genentech\/Roche, Neurotech International, Iveric Bio, Janssen Pharmaceuticals, Nanoscope Therapeutics, Samsung Bioepis, Optos, Oxurion\/ThromboGenics, Regeneron Pharmaceuticals, Vertex Pharmaceuticals, Novartis Pharma AG, Heidelberg Engineering, Inc., Carl Zeiss Meditec, Character Bio. He also reports lecture fees from Carl Zeiss Meditec, Heidelberg Engineering, Inc., Nidek Co. 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