The Notch Phenomenon in Retinopathy of Prematurity: A Potential Marker of Delayed Retinal Vascularisation

To evaluate the association between the Notch phenomenon and retinal vascular maturation, the time to complete retinal vascularisation, and progression to severe retinopathy of prematurity (ROP) in treatment-naïve infants with early-stage disease.

In this retrospective observational study, 350 preterm infants with Stage 1-2 ROP managed conservatively were included. The Notch phenomenon was identified based on ICROP-3 criteria. Time to complete retinal vascularisation was assessed using both weeks from birth and postmenstrual age (PMA). Multivariable regression analyses were performed to assess the independent association between the Notch phenomenon and study outcomes after adjustment for gestational age (GA), birth weight (BW), oxygen therapy, and ROP Zone.

The Notch phenomenon was identified in 45 infants (12.9%). Among 324 infants with spontaneous regression, Notch(+) infants required significantly longer time to achieve complete retinal vascularisation than Notch(-) infants (14.85 ± 2.62 vs. 11.11 ± 2.45 weeks from birth; p < 0.001). PMA at the time of complete retinal vascularisation was also significantly higher in the Notch (+) group (45.15 ± 2.21 vs. 42.65 ± 1.87 weeks; p < 0.001), a difference confirmed by Kaplan-Meier analysis (median PMA, 45.50 vs. 42.60 weeks; log-rank p < 0.001). Progression to severe ROP occurred more frequently in infants with a Notch (17.8% vs. 5.9%; p = 0.01). After adjustment for GA, BW, oxygen therapy and ROP Zone, the Notch phenomenon remained an independent predictor of progression to severe, treatment-requiring ROP (OR = 5.10, 95% CI 1.95-13.35; p = 0.001).

In treatment-naïve infants with early-stage ROP, the Notch phenomenon is associated with delayed retinal vascular maturation and an increased risk of progression to severe disease, supporting its role as a clinically relevant morphologic risk marker in ROP follow-up.