Introduction: Treatment of exudative age-related macular degeneration (ARMD) has shifted to pro re nata and treat-extend-stop strategies. However, a rational discontinuation strategy is lacking. To develop such a strategy, it is important to determine choroidal neovascularization (CNV) recurrence rates after anti-VEGF treatment is discontinued. Here we report prospective data on persistent and recurrent CNV activity after discontinuation of bevacizumab treatment. Methods: This prospective, single-center clinical trial enrolled 191 patients with exudative ARMD. Patients were randomly assigned to receiving intravitreal bevacizumab injections every 4, 6, or 8 weeks for 1 year. CNV activity was determined in the 157 patients who completed the 1-year treatment regimen. Patients with inactive CNV were then followed for signs of CNV reactivation. Results: After 1 year of treatment, 66 (42%) of the 157 patients still had signs of persistent active CNV. Of the remaining 91 (58%) patients, 61 (67%) needed retreatment for active CNV within the first year after discontinuation of treatment (mean 4.28 ± 0.29 months). CNV was reactivated in 50 (80%) of the 61 patients within 6 months after their final treatment for CNV. Conclusion: Based on quiescent disease, anti-VEGF therapy was discontinued in 58% of the patients after they received bevacizu-mab injections every 4, 6, or 8 weeks for 1 year; 67% showed reactivated CNV within a year after discontinuation. The high reactivation rate of CNV shown in this study should help clinicians to develop rational discontinuation protocols. Trial Registration: This study is registered as NTR1174 at http://www.trialregister.nl.

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