Ocular and developmental outcomes of a dosing study of bevacizumab for retinopathy of prematurity

Abstract

Purpose: To report 2-year ocular and developmental outcomes for infants receiving low doses of intravitreal bevacizumab for type 1 retinopathy of prematurity (ROP).

Methods: A total of 120 premature infants (mean birthweight, 687 g; mean gestational age, 24.8 weeks) with type 1 ROP were enrolled in a multicenter, phase 1 dose de-escalation study. One eye per infant received 0.25 mg, 0.125 mg, 0.063 mg, 0.031 mg, 0.016 mg, 0.008 mg, 0.004 mg, or 0.002 mg of intravitreal bevacizumab; fellow eyes when treated received one dosage level higher. At 2 years, 70 of 120 children (58%) underwent ocular examinations; 51 (43%) were assessed using the Bayley Scale of Infant and Toddler Development.

Results: Correlation coefficients for the association of total dosage of bevacizumab with Bayley subscales were -0.20 for cognitive (95% CI, -0.45 to 0.08), -0.15 for motor (95% CI, -0.41 to 0.14), and -0.19 for language (95% CI, -0.44 to 0.10). Fourteen children (21%) had myopia greater than -5.00 D in one or both eyes, 7 (10%) had optic nerve atrophy and/or cupping, 20 (29%) had strabismus, 8 (11%) had manifest nystagmus, and 9 (13%) had amblyopia.

Conclusions: In this study cohort, there was no statistically significant correlation between dosage of bevacizumab and Bayley scores at 2 years. However, the sample size was small and the retention rate relatively low, limiting our conclusions. Rates of high myopia and ocular abnormalities do not differ from those reported after larger bevacizumab doses.

FIG 1.

Bayley score versus logarithm base 2 of total bevacizumab dosage in mg. Each of the three Bayley composite scores is plotted against the log₂ of the total dosage (in the patient): cognitive (A), Spearman’s ρ (95% CI) = −0.20 (−0.45, 0.08); motor (B), Spearman’s ρ (95% CI) = −0.15 (−0.41, 0.14); language, Spearman’s ρ (95% CI) = −0.19 (−0.44, 0.10) Higher composite scores indicate better development in that domain. Total dosage in the patient ranged from 0.002 mg (log₂ 0.002 = −9.0) to 1.5 mg (log₂ 1.5 = 0.6).

FIG 2.

Refractive error vs postmenstrual age (PMA) at laser. Refractive error at the 24-month examination plotted against PMA at the time of laser if the eye received laser. Circles represent eyes that were in zone I at baseline; triangles, eyes that were in zone II.