Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial

JAMA Ophthalmol. 2014 Nov;132(11):1327-33. doi: 10.1001/jamaophthalmol.2014.2772.

Abstract

Importance: Children born prematurely who develop retinopathy of prematurity (ROP) often develop myopia, and those who require laser treatment may develop very high myopia, which has considerable clinical consequences.

Objective: To report refractive outcomes in preterm infants who developed ROP in zone I or zone II posterior as stage 3+ ROP or aggressive posterior ROP (APROP).

Design, setting, and participants: All infants received intravitreal bevacizumab or laser therapy in a prospective, stratified, randomized, controlled, masked, multicenter clinical trial, Bevacizumab Eliminates the Angiogenic Threat for ROP (BEAT-ROP). Children who received intravitreal bevacizumab or laser in the BEAT-ROP clinical trial, with treatment randomized by infant, underwent cycloplegic retinoscopic refraction at a mean age of 2½ years. Fifteen centers with both pediatric and vitreoretinal ophthalmologists participating in level 3 neonatal intensive care units in academic centers with institutional review board approval were included in the trial. Of the originally enrolled 150 infants (300 eyes) in the BEAT-ROP clinical trial, 13 infants (26 eyes) died (6 received intravitreal bevacizumab; 7 received laser) and 19 eyes had intraocular surgery (6 infants bilaterally). Thus, 45 eyes (19 infants bilaterally) were excluded, leaving 131 infants (255 eyes, including 21 eyes that received a successful second treatment for recurrence).

Interventions: Follow-up of the BEAT-ROP cohort.

Main outcomes and measures: Spherical equivalent refractive outcomes and their distribution by ROP zone and treatment.

Results: Refractions were available for 109 of 131 eligible infants (83.2%) and 211 of 255 eyes (82.7%). Mean (SD) spherical equivalent refractions were as follows: zone I, -1.51 (3.42) diopters (D) in 52 eyes that received intravitreal bevacizumab and -8.44 (7.57) D in 35 eyes that received laser treatment (P < .001); and zone II posterior, -0.58 (2.53) D in 58 eyes that received intravitreal bevacizumab and -5.83 (5.87) D in 66 eyes that received laser treatment (P < .001). Very high myopia (≥-8.00 D) occurred in zone I in 2 of 52 (3.8%) eyes that received intravitreal bevacizumab and in 18 of 35 (51.4%) eyes that received laser treatment (P < .001). Very high myopia occurred in zone II posterior in 1 of 58 (1.7%) eyes that received intravitreal bevacizumab and in 24 of 66 (36.4%) eyes that received laser treatment (P < .001).

Conclusions and relevance: More very high myopia was found in eyes that received laser treatment than in eyes that received intravitreal bevacizumab. This difference is possibly related to anterior segment development that is present with intravitreal bevacizumab but minimal or absent following laser treatment.

Trial registration: clinicaltrials.gov Identifier: NCT00622726.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Child, Preschool
  • Double-Blind Method
  • Follow-Up Studies
  • Gestational Age
  • Humans
  • Infant, Extremely Low Birth Weight
  • Infant, Premature
  • Intravitreal Injections
  • Laser Coagulation / adverse effects*
  • Laser Coagulation / methods
  • Myopia, Degenerative / diagnosis
  • Myopia, Degenerative / etiology*
  • Prospective Studies
  • Refraction, Ocular / physiology
  • Retinopathy of Prematurity / drug therapy
  • Retinopathy of Prematurity / surgery
  • Retinopathy of Prematurity / therapy*
  • Retinoscopy
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity / physiology

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Bevacizumab

Associated data

  • ClinicalTrials.gov/NCT00622726