Characteristics of retinal vascularization in reactivated retinopathy of prematurity and clinical outcome after reinjection of ranibizumab

Abstract This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of recurrence of retinopathy of prematurity (ROP) and whether repeated injection treatment will be effective in case of recurrence. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-reactivated ROP or reactivated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of retinal vascularization was measured with serial RETCAM™ fundus images using disc-fovea distance (DF) unit. ROP reactivation occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean reactivation interval after the initial injection was 9.0 ± 3.3 weeks (range 4–16). In the reactivated ROP group, the time required for the resolution of plus disease after injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the reactivated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with reactivated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of ROP recurrence. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating ROP recurrence.