Investigating Predictors of Retreatment following Initial Antivascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis

Purpose: To investigate factors contributing to retreatment after antivascular endothelial growth factor (anti-VEGF) therapy in patients with retinopathy of prematurity (ROP). Methods: All relevant publications released up to November 2022 from PubMed, Google Scholar, and Scopus were evaluated. An Excel checklist was developed for data extraction, including author names, publication year, sample size, mean gestational age (GA), birth weight (BW), zone of ROP, total and zone-specific retreatment incidence, and the percentage of aggressive posterior ROP eyes. The primary outcome was the incidence of retreatment (IR). The mixed methods appraisal tool was used to assess the quality of the papers. Results: The total IR was 19% (95% confidence interval (CI): 15%–23%). Among children treated with anti-VEGF agents, the highest IR occurred with intravitreal ranibizumab (IVR, 0.25 mg) (27%, 95% CI: 19%–35%) and intravitreal aflibercept (IVA, 0.4 mg) (27%, 95% CI: 6%–47%), followed by intravitreal conbercept (IVC, 0.25 mg) (16%, 95% CI: 13%–20%). The lowest IR was observed in children treated with intravitreal bevacizumab (IVB, 0.625 mg) (11%, 95% CI: 7%–14%). In the IVR group, the chance of retreatment increased by 7% for every 1-week increase in GA and 5% for every 100 g of BW. In general, the IR was significantly higher in Zone I ROP in comparison with Zone II. For patients with Zone I ROP who received IVR, the IR was 0.36 (95% CI: 0.09–0.62), while for those who underwent IVB, it was 0.06 (95% CI: 0.01–0.11). The difference between the two groups was statistically significant ( P = 0.03). The IR for retreatment in patients with Zone II ROP was 0.13 (95% CI: 0.01–0.26) for IVR and 0.00 (95% CI: 0.00–0.01) for the IVB subgroup ( P = 0.03). Conclusions: While anti-VEGF therapy is effective for ROP treatment, there are significant differences in IR among different agents. IVB treatment appears to yield the most consistent results compared to other agents.