Retinal vascularization rate predicts retinopathy of prematurity and remains unaffected by low-dose bevacizumab treatment

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Abstract
Purpose: To assess the rate of retinal vascularisation derived from ultra-widefield (UWF) imaging-based retinopathy of prematurity (ROP) screening as predictor of type 1 ROP and characterise the effect of anti-VEGF therapy on vascularisation rate. Design: Retrospective, consecutive cohort study. Subjects: 132 eyes of 76 premature infants with mean gestational age (GA) of 26.0(±2.0SD) weeks and birth weight (BW) of 815(±264) g, who underwent longitudinal UWF imaging for ROP screening. Setting/Venue: Level 3 neonatal unit in Oxford, United Kingdom Methods: The extent of retinal vascularisation 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 timepoints plotted against post-menstrual age (PMA) enabled calculation of temporal vascularisation 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: Rate of retinal vascularisation. Results: Slower retinal vascularisation 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=0.04). 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 post-treatment imaging follow-up of 7.7(±7.9) weeks (p=0.60 right eyes, p=0.71 left eyes). Conclusions: UWF imaging-based ROP screening enables quantification of retinal vascularisation rate, which can provide early prediction of type 1 ROP independent of BW and GA. Rate of physiological retinal vascularisation 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.
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