A Meta-Analysis of Neurodevelopmental Outcomes following Intravitreal Bevacizumab for the Treatment of Retinopathy of Prematurity

Neonatology. 2023;120(5):577-588. doi: 10.1159/000531541. Epub 2023 Jul 24.

Abstract

Background: Retinopathy of prematurity (ROP) is the most common cause of preventable blindness in preterm infants. First-line treatments include intravitreal bevacizumab (IVB) or laser photocoagulation (LPC).

Objectives: The aim of the study was to evaluate neurodevelopmental safety of IVB compared to LPC for ROP.

Methods: MEDLINE, Embase, and Cochrane library were searched up to September 2022. Studies were included with at least 12-month follow-up of primary outcomes such as severe neurodevelopmental impairment (sNDI), cerebral palsy (CP), and hearing impairment (HI). Secondary outcomes were moderate-to-severe neurodevelopmental impairment (msNDI), Bayley Scores of Infant Development (BSID-III), and visual impairment.

Results: 1,231 patients from 11 comparative studies were included. Quality of evidence was rated low for all outcomes. IVB was associated with a higher risk for sNDI (risk ratio [RR] = 1.25, 95% confidence interval [CI]: [1.01, 1.53], p = 0.04); and CP (RR = 1.40, CI: [1.08, 1.81], p = 0.01) compared to LPC. There was no significant difference between IVB and LPC for msNDI (RR = 1.15, CI: [0.98, 1.35], p = 0.08) and HI (RR = 1.43, CI: [0.86, 2.39], p = 0.17). BSID-III percentile scores were similar between IVB and LPC, with weighted mean differences of 1.51 [CI = -1.25, 4.27], 2.43 [CI = -1.36, 6.22], and 1.97 [CI = -1.06, 5.01] for cognitive, language, and motor domains, respectively (p > 0.05).

Conclusion: To our knowledge, this is the largest meta-analysis on neurodevelopmental outcomes and the first to rigorously examine IVB monotherapy in ROP treatment. Compared to LPC, there was a marginally increased risk for sNDI and CP with IVB but little or no difference in the risk of msNDI and HI. Further randomized studies are needed to strengthen these findings.

Keywords: Development; Neurodevelopment; Preterm infant; Retinopathy of prematurity; Vascular endothelial growth factor.

Publication types

  • Meta-Analysis

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Bevacizumab / adverse effects
  • Child
  • Child Development
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Retinopathy of Prematurity* / drug therapy
  • Retrospective Studies

Substances

  • Bevacizumab
  • Angiogenesis Inhibitors

Grants and funding

No funding or sponsorship was granted or needed in support of this study.