Low- and Very Low-Dose Bevacizumab for Retinopathy of Prematurity

Abstract

Objective

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.

Design

Masked, multicenter, dose de-escalation study

Participants

120 prematurely-born infants with type 1 ROP

Methods

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.

Main Outcome Measures

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.

Results

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.

Conclusions

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.