Retinopathy of prematurity risk predictors in peripheral avascular retina after intravitreal ranibizumab treatment: Vasculogenesis analysis Running Title: Predictors for Retinopathy Recurrence Post-Ranibizumab

Abstract The predictors of risk for peripheral avascular areas (PAR) in retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) monotherapy is still unknown. This retrospective study included 64 infants (118 eyes) who developed type 1 ROP and received IVR between July 2019 and March 2021. Retinal vascular outgrowth speed (RVOS) was assessed by measuring the disc diameter (DD) 2 months post-IVR. Potential risk factors were identified to develop a predictive nomogram model for PAR. Decision curve analysis (DCA) was performed to determine the clinical utility of the nomogram model. Mean RVOS was 0.9±0.6 DD/month in all eyes 2 months post-IVR; RVOS in the treated eyes was higher than that in the non-treated eyes. Completed retinal vascularization was detected in 69 eyes (58.5%) and persistent PAR in 49 eyes (41.5%). Multiple logistic regression analysis showed that postnatal age (PNA) at IVR, ROP lesion’s cumulative clock hours (ROP_CCH), RVOS after IVR, and lesion severity were independent risk factors for PAR. DCA showed the nomogram model provides a fine net benefit. These data showed that IVR treatment accelerates RVOS. Further, RVOS is inversely related to PAR. The proposed nomogram model can potentially be effective in the individualized prediction of PAR after IVR.