Neovascular Remodeling and Subretinal Fibrosis as Biomarkers for Predicting Incomplete Response to Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration

Purpose: To compare the progression of neovascular remodeling and subretinal fibrosis in neovascular age-related macular degeneration (NVAMD) after anti-vascular endothelial growth factor (VEGF) therapy. Methods: Twenty eyes from 20 patients with subretinal fibrosis complicating NVAMD were retrospectively reviewed. All patients complied with at least three consecutive monthly intravitreal treatments and final follow-up visit at 12 months after the initial anti-VEGF treatment of aflibercept or ranibizumab. Using optical coherence tomography angiography (OCTA), the central macular thickness (CMT), microvascular density in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal neovascularization (CNV) lesions, as well as subretinal fibrotic lesions were compared between baseline and final visit. Results: The mean number for anti-VEGF injections was 4.40 ± 0.88 during the 12 months of follow-up. There was no significant difference in best-corrected visual acuity (BCVA) and vascular density in SCP and DCP (p > 0.05) between baseline and final follow-up. The CMT decreased from 434.95 ± 87.62 μm at baseline to 365.15 ± 78.92 μm at final visit (p = 0.02). Compared with the baseline, the fine vessels, such as capillary tufts, regressed and the relative density of CNV lesion decreased by 19.12% (p = 0.01), while the relative density of the subretinal fibrosis increased approximately 1.21-fold (p = 0.03) at the final follow-up. Conclusions: The progression of neovascular remodeling and subretinal fibrosis may serve as biomarkers to predict incomplete response to anti-VEGF therapy in patients with NVAMD. Subretinal fibrosis complicating NVAMD remains a major obstacle for the management of NVAMD, and anti-VEGF treatment is a potential therapeutic strategy to target neovascular remodeling and subretinal fibrosis as either an additive or alternative therapeutic approach for NVAMD.