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.

The authors have declared no competing interest.

This study was funded by KX's funding support from the Wellcome Trust (216593/Z/19/Z) and National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and CH's funding support from the Wellcome Trust (213486/Z/18/Z).

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Ethics approval and consent to use patient data for analyses was approved by the Oxford University Hospitals Integrated Governance System (Oxford University Hospitals clinical audit approval no. 9080) and were conducted as an internal retrospective clinical audit. Due to the retrospective and anonymous nature of this audit, informed consent was waived by the ethics committee.

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