Review of Fibrosis in Neovascular Age-Related Macular Degeneration

PURPOSE: To report the diagnosis and definitions, epidemiology, risk factors, and visual outcomes of fibrosis in neovascular age-related macular degeneration (nAMD). DESIGN: Systematic review and meta-analysis. METHODS: The review was performed using the Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies and randomized controlled trials were included. RESULTS: Identification of fibrosis is challenging. Optical coherence tomography angiography and polarizationsensitive optical coherence tomography represent novel options in multimodal imaging. The prevalence of fibrosis at baseline, 12, 24, and 60 months was 13%, 32%, 36%, and 56%, respectively. Approximately 60% of the fibrosis burden in nAMD at 5 years was present in the first year of treatment. Fibrosis development was highest in the first 12 months and slowed down over time. The risk factors of fibrosis included classic choroidal neovascularization (CNV), intra-retinal fluid, hemorrhage, hyperreflective material, CNV lesion size, and retinal thickness. Sub-retinal fluid and pigment epithelial detachment may be protective. Treatment-associated factors included disease activity and time to diagnosis. At baseline, the best corrected visual acuity in eyes with fibrosis was poorer than in eyes without fibrosis (-18.50 letters); this difference became larger at 12 months despite treatment (26.86 letters). CONCLUSIONS: There is a need to identify effective treatment strategies for fibrosis and to closely monitor atrisk patients. More studies involving multimodal imaging are required to clarify the definitions and grading criteria for fibrosis. (Am J Ophthalmol 2023;246: 192-222. (c) 2022 Elsevier Inc. All rights reserved.)