Recurrence of Retinopathy of Prematurity Following Anti-vascular Endothelial Growth Factor (Anti-VEGF) Therapy: A Systematic Review and Meta-Analysis.

Retinopathy of prematurity (ROP) is a neovascular disorder which affects premature infants and can lead to childhood blindness. Treatment includes laser photocoagulation and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, both effective options. However, laser photocoagulation can lead to refractive errors, while anti-VEGF therapy can result in disease recurrence. Our systematic review aimed to evaluate the recurrence rates of ROP following treatment with anti-VEGF agents compared to other anti-VEGF agents and laser photocoagulation. We also aimed to measure the retreatment intervals and assess successful retreatment rates to identify the most effective treatment modality. Our review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included both randomized controlled trials (RCTs) and non-randomized comparative studies (NCS). A thorough search of MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Studies were assessed using the Cochrane Risk of Bias (RoB2) tool and the Newcastle-Ottawa Scale (NOS). Random-effects and fixed-effects models were used to measure pooled estimates. The outcomes were reported as risk ratios (RR) and standardized mean differences (SMD). A total of 21 studies (six RCTs and 15 NCS) with 6,152 eyes were included. Overall, anti-VEGF agents showed a higher risk of recurrence compared to laser photocoagulation (RR=2.14, 95% CI: 1.06-4.33, p=0.03). Conbercept demonstrated a significantly lower risk of recurrence than laser photocoagulation and ranibizumab (RR=0.47, 95% CI: 0.39-0.58, p<0.00001), while aflibercept showed a higher recurrence risk compared to bevacizumab (RR=12.61, 95% CI: 6.43-24.73, p<0.00001). Bevacizumab was associated with a longer retreatment interval than laser photocoagulation (SMD=0.89, 95% CI: 0.61-1.17, p<0.00001). No significant differences in retreatment success rates between bevacizumab and laser photocoagulation were observed. Anti-VEGF therapy is effective in the treatment of ROP; however, it is associated with a higher risk of recurrence compared to laser photocoagulation. Conbercept shows greater efficacy in reducing recurrence risk and prolonging the retreatment interval compared to ranibizumab. Aflibercept demonstrated inconsistent outcomes. No significant difference in recurrence rates was observed between bevacizumab and ranibizumab. Recurrences occurred significantly later when anti-VEGF therapy was used compared to laser photocoagulation. Successful retreatment rates between bevacizumab and laser photocoagulation were similar.