Anti-VEGF therapy versus laser photocoagulation for Type 1 Zone II retinopathy of prematurity: a meta-analysis of randomized controlled trials

Laser photocoagulation is the standard treatment for Type 1 Zone II retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (anti-VEGF) agents are increasingly used, but their comparative efficacy and safety remain uncertain. This meta-analysis aimed to compare anti-VEGF therapy with laser photocoagulation for Type 1 Zone II ROP. We systematically searched PubMed, Embase, Cochrane Library, and Web of Science from inception to May 10, 2026, for randomized controlled trials (RCTs) comparing anti-VEGF (bevacizumab, ranibizumab, or aflibercept) with laser photocoagulation in preterm infants diagnosed with Type 1 Zone II ROP. Primary outcomes were ROP recurrence and treatment success; secondary outcome was adverse events. A random-effects model was used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I² statistics. Sensitivity and exploratory subgroup analyses were performed. The study was registered with PROSPERO (CRD420261287600). Six RCTs involving 466 infants were included. Anti-VEGF therapy did not significantly reduce ROP recurrence compared with laser (OR 1.79, 95% CI 0.89–3.61; I² = 55.5%; 5 studies). Treatment success was higher with anti-VEGF (OR 6.07, 95% CI 1.35–27.38; I² = 75.5%; 4 studies), but the prediction interval crossed 1.0 (0.18–207.5), and sensitivity analysis excluding one study rendered the effect non-significant. Adverse events were reported in only two studies and showed no significant difference (OR 0.62, 95% CI 0.08–4.87; I² = 79%). Exploratory subgroup analyses suggested potential effect modification by disease severity, ROP zone, drug type, and follow-up duration, but these were underpowered and hypothesis-generating. In Type 1 Zone II ROP, anti-VEGF therapy has comparable efficacy to laser photocoagulation regarding recurrence and may be associated with higher initial treatment success, but the evidence is limited by heterogeneity, small sample sizes, and variable outcome definitions. Safety could not be reliably assessed. Larger, long-term RCTs are needed. CRD420261287600. Not applicable.