Clinical exit strategy in anti-VEGF therapy for neovascular AMD: incidence of recurrence and risk factors for relapse

Abstract Purpose To evaluate the recurrence rate of neovascular activity after discontinuation of intravitreal anti–vascular endothelial growth factor (VEGF) therapy in patients with neovascular age-related macular degeneration (AMD) and to identify baseline clinical and imaging factors associated with relapse following a clinical exit strategy. Methods In this retrospective cohort study, patients with neovascular AMD who discontinued anti-VEGF therapy due to a clinical decision were identified. Treatment discontinuation was based on the absence of foveal exudation on optical coherence tomography (OCT). Baseline demographic, clinical, and OCT characteristics were analyzed. The primary outcome was disease recurrence, defined as the need for a new intravitreal anti-VEGF injection during follow-up. Multivariate regression analysis was performed to identify baseline biomarkers associated with relapse. Results Seventy-eight patients (78 eyes) were included (mean age 82.3 ± 5.5 years; 78.2% women). Disease recurrence occurred in 38 patients (48.7%) after a mean of 389.0 ± 247.3 days, with 47.4% of relapses occurring within the first year. Visual acuity significantly worsened between treatment discontinuation and relapse ( p < 0.001). At the time of retreatment, intraretinal fluid, subretinal fluid, and subretinal hyperreflective material were observed in 57.9%, 63.2%, and 55.3% of eyes, respectively. Multivariate regression identified extrafoveal intraretinal fluid and retinal pigment epithelium tear at baseline as biomarkers associated with recurrence. Conclusions Recurrence after anti-VEGF discontinuation is common in neovascular AMD. The presence of extrafoveal intraretinal fluid and retinal pigment epithelium tear at treatment cessation may increase the risk of relapse, highlighting the need for cautious treatment exit strategies and close post-discontinuation monitoring.