Retinal Vascularization Rate Predicts Retinopathy of Prematurity and Remains Unaffected by Low-Dose Bevacizumab Treatment.

Purpose: To assess the rate of retinal vascularization derived from ultra-widefield (UWF) imaging-based retinopathy of prematurity (ROP) screening as predictor of type 1 ROP and characterize the effect of anti-vascular endothelial growth factor (anti-VEGF) therapy on vascularization rate.

Design: Retrospective, consecutive cohort study.

Subjects: The study included 132 eyes of 76 premature infants with a mean gestational age (GA) of 26.0 (±2.0 SD) weeks and birthweight (BW) of 815 (±264) g, who underwent longitudinal UWF imaging for ROP screening, at a level 3 neonatal unit in Oxford, United Kingdom.

Methods: The extent of retinal vascularization on each UWF image was measured as the ratio between "disc-to-temporal vascular front" and "disc-to-fovea" distance along a straight line bisecting the vascular arcades. Measurements from ≥3 time points plotted against post-menstrual age (PMA) enabled calculation of temporal vascularization rate (TVR) for each eye. Using TVR, GA, and BW as predictors, a machine learning model was created to classify eyes as either group AB (no ROP and type 2 ROP) or group C (type 1 ROP). The model was validated in a withheld cohort of 32 eyes (19 infants), of which 8 eyes (5 infants) required treatment. TVR in 37 eyes (20 infants) was compared before and after ultra-low-dose (0.16 mg) intravitreal bevacizumab treatment.

Main Outcome Measures: The rate of retinal vascularization was determined.

Results: Slower retinal vascularization correlated with increasing ROP severity, with TVR being 29% slower in group C eyes (n=50) than group AB eyes (n=33 no ROP and n=49 type 2 ROP) (P = .04). Our model correctly predicted ROP outcomes of 30/32 eyes, achieving a balanced accuracy of 95.8%. No significant change in TVR was found before and after bevacizumab treatment with mean posttreatment imaging follow-up of 7.7 (±7.9) weeks (P = .60 right eyes, P = .71 left eyes).

Conclusions: UWF imaging-based ROP screening enables quantification of retinal vascularization rate, which can provide early prediction of type 1 ROP independent of BW and GA. Rate of physiological retinal vascularization does not appear to be significantly affected by ultra-low-dose anti-VEGF treatment, which has significant implications for the development of peripheral avascular retina and timing of anti-VEGF intervention to prevent disease progression in high-risk infants.