Clinical Risk Factors for Retinopathy of Prematurity Reactivation after Intravitreal Anti-Vascular Endothelial Growth Factor Injection

OBJECTIVE:To assess the rate and risk factors for reactivation of retinopathy of prematurity (ROP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents. STUDY DESIGN:Infants who received IVI therapy between 2017 and 2022 were enrolled and divided into two groups: those with and without ROP reactivation. Information on ROP variables and patient variables were analyzed using multivariable logistic regression. RESULTS:A total of 114 infants with 223 eyes were enrolled in the study. The ROP reactivation rate was 11.4% of infants (9.9% of eyes). The mean duration of reactivation was 84 ± 45 days. Among the 223 eyes treated with IVI, reactivation rates were 6% for bevacizumab, 13.9% for aflibercept, and 22.2% for ranibizumab. A multivariable regression model showed that ranibizumab was an independent risk factor (OR: 11.4, p=0.008) for reactivation. Other risk factors included infants with periventricular leukomalacia (OR: 13.8, p=0.003), patent ductus arteriosus ligation (OR: 10.7, p=0.032), and infants who still required invasive mechanical ventilation on the day of IVI therapy (OR: 7.0, p=0.018). CONCLUSIONS:All anti-VEGF agents carry a risk of ROP reactivation, with the risk being higher with ranibizumab 0.25 mg than with bevacizumab 0.625 mg. Reactivation of ROP should be assessed vigilantly, especially in those infants with increased risks. Future research to determine the optimal anti-VEGF selection and dosage in high-risk infants is warranted.