A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments

Ophthalmology. 2018 Dec;125(12):1961-1966. doi: 10.1016/j.ophtha.2018.05.001. Epub 2018 Jun 7.

Abstract

Purpose: Intravitreal bevacizumab is increasingly used to treat severe retinopathy of prematurity (ROP), but it enters the bloodstream, and there is concern that it may alter development of other organs. Previously we reported short-term outcomes of 61 infants enrolled in a dose de-escalation study, and we report the late recurrences and additional treatments.

Design: Masked, multicenter, dose de-escalation study.

Participants: A total of 61 premature infants with type 1 ROP.

Methods: If type 1 ROP was bilateral at enrollment, then the study eye was randomly selected. In the study eye, bevacizumab intravitreal injections were given at de-escalating doses of 0.25 mg, 0.125 mg, 0.063 mg, or 0.031 mg; if needed, fellow eyes received 1 dose level higher: 0.625 mg, 0.25 mg, 0.125 mg, or 0.063 mg, respectively. After 4 weeks, additional treatment was at the discretion of the investigator.

Main outcome measures: Early and late ROP recurrences, additional treatments, and structural outcomes after 6 months.

Results: Of 61 study eyes, 25 (41%; 95% confidence interval [CI], 29%-54%) received additional treatment: 3 (5%; 95% CI, 1%-14%) for early failure (within 4 weeks), 11 (18%; 95% CI, 9%-30%) for late recurrence of ROP (after 4 weeks), and 11 (18%; 95% CI, 9%-30%) for persistent avascular retina. Re-treatment for early failure or late recurrence occurred in 2 of 11 eyes (18%; 95% CI, 2%-52%) treated with 0.25 mg, 4 of 16 eyes (25%; 95% CI, 7%-52%) treated with 0.125 mg, 8 of 24 eyes (33%; 95% CI, 16%-55%) treated with 0.063 mg, and 0 (0%; 95% CI, 0%-31%) of 10 eyes treated with 0.031 mg. By 6 months corrected age, 56 of 61 study eyes had regression of ROP with normal posterior poles, 1 study eye had developed a Stage 5 retinal detachment, and 4 infants had died of preexisting medical conditions.

Conclusions: Retinal structural outcomes are very good after low-dose bevacizumab treatment for ROP, although many eyes received additional treatment.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Bevacizumab / administration & dosage*
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Infant, Low Birth Weight
  • Infant, Newborn
  • Infant, Premature
  • Intravitreal Injections
  • Laser Coagulation
  • Male
  • Recurrence
  • Retina / physiopathology
  • Retinopathy of Prematurity / diagnosis
  • Retinopathy of Prematurity / drug therapy*
  • Retinopathy of Prematurity / physiopathology
  • Retreatment
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

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