Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity: Reactivations, Additional Treatments, and 12-Month Outcomes

• Published in: Ophthalmology (Rochester, Minn.) Vol. 129; no. 10; pp. 1120 - 1128
• Main Authors: Freedman, Sharon F., Hercinovic, Amra, Wallace, David K., Kraker, Raymond T., Li, Zhuokai, Bhatt, Amit R., Boente, Charline S., Crouch, Eric R., Hubbard, G. Baker, Rogers, David L., VanderVeen, Deborah, Yang, Michael B., Cheung, Nathan L., Cotter, Susan A., Holmes, Jonathan M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2022
• Subjects: Angiogenesis Inhibitors - therapeutic use; Bevacizumab - therapeutic use; Gestational Age; Humans; Infant; Infant, Newborn; Intravitreal Injections; Laser Coagulation; Retinopathy of Prematurity - diagnosis; Retinopathy of Prematurity - drug therapy; Retinopathy of Prematurity - surgery; Retrospective Studies; Pediatric ophthalmology; Retinopathy of prematurity; Bevacizumab
• ISSN: 0161-6420; 1549-4713
• DOI: 10.1016/j.ophtha.2022.05.019

Low-dose and very low-dose intravitreal bevacizumab (IVB) have been reported successful in short-term treatment of type 1 retinopathy of prematurity (ROP), down to an initial dose of 0.004 mg. We now report 12-month outcomes for these infants. Masked, multicenter, dose de-escalation study 120 prematurely-born infants with type 1 ROP A cohort of 120 infants with type 1 ROP in at least one eye from two sequential dose de-escalation studies of low-dose (0.25, 0.125, 0.063, and 0.031 mg) or very low-dose (0.016, 0.008, 0.004, and 0.002 mg) IVB to the study eye; the fellow eye (if also type 1) received one dose level higher. After primary success or failure at 4 weeks, clinical management was at investigator discretion, including all additional treatment. Reactivation of severe ROP by 6 months corrected age, additional treatments, retinal and other ocular structural outcomes, and refractive error at 12 months corrected age. Sixty-two (55%) of 113 study eyes and 55 of 98 (56%) fellow eyes received additional treatment. Of the study eyes, 31 (27%) received additional ROP treatment (6 for initial treatment failure, 4 for reactivation ≤4 weeks, 21 (19%) for later reactivation) and 31 (27%) had prophylactic laser for persistent avascular retina. There was no trend toward a higher risk of additional ROP treatment related to initial IBV doses. However, time to reactivation among study eyes was shorter in eyes that received very low-dose bevacizumab (mean 76.4 days) compared with low dose (mean 85.7 days). At 12 months, poor retinal outcomes and anterior segment abnormalities were both uncommon (3% and 5%, respectively), optic atrophy was noted in 10%, the median refraction was mildly myopic (-0.31D), and strabismus was present in 29% of infants. Retinal structural outcomes were very good after low- and very low-dose IVB as initial treatment for type 1 ROP, although many eyes received additional treatment. The rate of reactivation of severe ROP was not associated with dose; however, a post-hoc data driven analysis suggested that reactivation was sooner with very low doses.