Secondary 12-Month Ocular Outcomes of a Phase 1 Dosing Study of Bevacizumab for Retinopathy of Prematurity.

Importance: Lower bevacizumab dosages are being used for type 1 retinopathy of prematurity, but there are limited data on long-term ocular outcomes with lower doses. Objective: To evaluate ocular outcomes at 12 months' corrected age for eyes that received a dose of 0.625 mg, 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg of bevacizumab for type 1 retinopathy of prematurity. Design, Setting, and Participants: This prospective cohort study used a masked, multicenter, phase 1 dose de-escalation study design and was conducted from April 2016 to October 2017. Study eyes were treated with a dose of 0.25, 0.125, 0.063, or 0.031 mg of bevacizumab; fellow eyes were treated with a dosage 1 level higher than the study eye. Additional treatment after 4 weeks was at investigator discretion. Data analysis occurred from November 2018 to March 2019. Interventions: Intravitreous bevacizumab injections of 0.625 mg to 0.031 mg. Main Outcomes and Measures: Visual fixation, amblyopia, alignment, nystagmus, cycloplegic refraction, and ocular examinations were assessed at 12 months' corrected age as preplanned secondary outcomes. The primary outcome 4 weeks after treatment and secondary outcomes after 6 months' corrected age have been previously reported. Results: Forty-six of 61 infants (75%) had a 12-month follow-up examination (46 study eyes and 43 fellow eyes; median [interquartile range] birth weight, 650 [590-760] g). Of 87 eyes with a cycloplegic refraction, 12 (14% [95% CI, 7%-27%]) had myopia of more than -5.00 D spherical equivalent; 2 (2%; [95% CI, 0%-8%]) had hyperopia greater than 5.00 D spherical equivalent; and 5 infants (11% [95% CI, 4%-24%]) had anisometropia greater than 1.50 D spherical equivalent. Abnormalities of the cornea, lens, or anterior segment were reported in 1 eye (1% [95% CI, 0%-6%]), 3 eyes (3% [95% CI, 1%-10%]), and 3 eyes (3% [95% CI, 1%-10%]), respectively. Optic nerve atrophy was identified in 11 eyes (13% [95% CI, 6%-26%]), and 1 eye (1% [95% CI, 0%-6%]) had total retinal detachment. Strabismus was reported in 13 infants (30% [95% CI, 17%-45%]), manifest nystagmus in 7 infants (15% [95% CI, 6%-29%]), and amblyopia in 3 infants (7% [95% CI, 1%-18%]). Overall, 98% of infants had central fixation in each eye (44 of 45 eyes). Conclusions and Relevance: In this study of low-dose bevacizumab, the secondary outcomes of high myopia, strabismus, retinal detachment, nystagmus, and other ocular abnormalities at 1 year were consistent with rates reported in other studies with higher dosages. Trial Registration: ClinicalTrials.gov identifier: NCT02390531.