Anti-VEGF versus laser therapy for retinopathy of prematurity: a systematic review and meta-analysis focusing on recurrence patterns and retreatment needs

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Anti-vascular endothelial growth factor (anti-VEGF) therapy offers an alternative to laser photocoagulation, recurrence, and retreatment, particularly in Zone II disease. We conducted a systematic review and meta-analysis of studies published from 2010 to 2025 comparing anti-VEGF agents (bevacizumab, ranibizumab, aflibercept) with laser therapy in preterm infants with treatment-requiring ROP. Primary outcomes were recurrence and retreatment; secondary outcomes included time to recurrence, structural, and refractive outcomes. The risk of bias was assessed using RoB 2 and ROBINS-I tools, and the certainty of evidence was evaluated using GRADE. Fifteen studies with 1,784 eyes were included. Pooled recurrence (RR 1.78, 95% CI: 0.56–5.65) and retreatment rates (RR 1.80, 95% CI: 0.54–5.94) showed no statistically significant differences, with substantial heterogeneity (I²>80%). Subgroup analysis showed lower recurrence in Zone I (RR 0.52) but higher recurrence in Zone II (RR 3.42) following anti-VEGF therapy. Ranibizumab was associated with higher recurrence compared to other agents. After anti-VEGF therapy, recurrence occurred variably between 7 and 50 + weeks of post-treatment. GRADE assessment indicated low certainty for recurrence and retreatment, moderate for structural and refractive outcomes, and very low for neurodevelopmental safety. Anti-VEGF therapy is effective for Zone I ROP, but Zone II treatment requires careful monitoring due to higher recurrence and retreatment risk. Standardized protocols and extended follow-up are essential, and further high-quality studies are needed to optimize ROP management.