Ten-Year Incidence of Fibrosis and risk factors for its development in Neovascular Age-related Macular Degeneration

Purpose: To report incidence and risk factors for fibrosis at 10 years in a large cohort of neovascular age-related macular degeneration (nAMD). Design: Retrospective, multicenter, cohort study. Methods: We included 225 naïve nAMD eyes who underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined clinically assessing photographs, fundus descriptions or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as sub-retinal pigment epithelium (RPE), mixed, sub-retinal. Results: Mean age at baseline was of 72.1±6.9 years. Incidence rate of fibrosis was estimated to be 8.9 per 100 person-years with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8% and subretinal in 22.7%. Independent factors associated with fibrosis included: larger central subfield thickness variation (p<0.001), submacular hemorrhages (p=0.008), higher number of injections (p=0.01) and worse baseline visual acuity (VA) (p=0.03). Type 2 macular neovascularization was significantly associated with mixed and sub-retinal fibrosis. VA significantly declined over 10 years (-16.4 ETDRS letters), particularly in eyes with mixed and sub-retinal fibrosis (p<0.001). Conclusions: We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset significantly impacted on final VA. This supports the hypothesis that nAMD patients should be promptly treated with pro-active regimens.