Neurodevelopmental disorders in infants treated with anti–VEGF agents vs. laser photocoagulation or cryotherapy for ROP

Objective To compare the incidence of early neurodevelopmental disorders in very preterm infants treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents versus laser photocoagulation and/or cryotherapy for retinopathy of prematurity (ROP). Design Nationwide population-based retrospective cohort study. Participants All very preterm newborns (gestational age <32 weeks) born in France between 2015 and 2022 who received treatment for ROP with anti-VEGF agents, laser photocoagulation, or cryotherapy within the first 24 weeks of life. Methods Using the French National Health Data System (SNDS), a medico-administrative database, we compared the incidence of early neurodevelopmental disorders between newborns treated with anti-VEGF agents and those treated with laser photocoagulation and/or cryotherapy, applying a propensity score-weighted logistic regression model with inverse probability of treatment weighting. Main Outcome Measures Incidence of early neurodevelopmental disorders within the first six years of life. Results The number of infants treated exclusively with anti-VEGF agents increased by 300% from 2015 to 2022. The primary comparative analysis was conducted on 102 newborns born between 2015 and 2019, for whom mother–infant linkage was available in the SNDS: 59 treated with anti-VEGF agents, and 43 with laser and/or cryotherapy. Early neurodevelopmental disorders within the first six years of life were not observed more frequently in infants treated with anti-VEGF agents than in those treated with laser and/or cryotherapy (71.4% vs. 58.1%; odds ratio [OR] 1.4; 95% confidence interval [CI] 0.8–2.4; P = 0.31). Conclusions Using intravitreal anti-VEGF agents in very preterm newborns did not increase the risk of early neurodevelopmental disorders within the first six years of life. While a small excess risk cannot be formally excluded, these results might be reassuring for clinical practice, particularly given the substantial increase in the use of anti-VEGF agents for the treatment of ROP in recent years.