Development of refractive error in children treated for retinopathy of prematurity with anti-vascular endothelial growth factor (anti-VEGF) agents: A meta-analysis and systematic review

Abstract

Objective: To investigate refractive error development in preterm children with severe retinopathy of prematurity (ROP) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and laser photocoagulation.

Methods: Selection criteria were comparative studies that compared the refractive errors in children, birthweights ≤1500 grams and gestational ages ≤30 weeks, and treatments for Type I ROP with intravitreal bevacizumab (IVB) versus laser photocoagulation. Studies were identified using PubMed, Google Scholar, and published reviews. Meta-analyses were performed on the post-treatment outcomes of spherical equivalent (SEQ), cylindrical power, and prevalence of high myopia. Longitudinal development of refractive error in IVB, or in laser-treated children, or in normal full-term children was visually summarized.

Results: Two randomized controlled trials and 5 non-randomized studies, including a total of 272 eyes treated by IVB and 247 eyes treated by laser, were included in this study. Compared with laser-treated children, IVB-treated children have less myopic refractive error (P<0.001), lower prevalence of high myopia (P<0.05), and less astigmatism (P = 0.02).

Conclusions: Treatment with IVB is associated with less myopia and astigmatism than laser treatment for infants with severe ROP. Given the complexity of ROP and the variability of dosing, our review supports close monitoring of refractive error outcomes in children treated with IVB.

Fig 1. PRISMA flow diagram of study selection.

Fig 2. Risk of bias summary for included RCTs.

Fig 3. Forest plot of the comparison of SEQ between IVB and LASER treatments.

Pooled estimates for mean differences and 95% CI in diopters between two treatments. The black diamond symbol shows the estimated true effect size.

Fig 4. Forest plots of the prevalence of high myopia following IVB and laser treatments.

A) Pooled estimates for risk ratios and 95% CI in events of high myopia occurred following two treatments in RCTs. B) Pooled estimates for odds ratios and 95% CI in events of high myopia occurred following two treatments in NRSs. The black diamond symbol on the bottom row shows the estimated true effect size.

Fig 5. Forest plot of the comparison of astigmatism in cylinder power between IVB and laser treatments.

Pooled estimates for mean differences and 95% CI in diopters between two treatments. The black diamond symbol on the bottom row shows the estimated true effect size.

Fig 6. SEQ as a function of age summarized in literature.

A) Data from post IVB children. B) Data from the post-laser children. The blue fill color is IVB treatment related, while the red fill color is laser treatment related. The black round circles showed the normal full term population [48]. When information related to Zone I and Zone II, the triangle symbol is for Zone I; the square symbol is for Zone II. The blue symbols with dashed line showed the only longitudinal IVB study from Mexico colleagues [16]. Note: Standard deviations and ranges are not plotted on the figure because standard deviation ranges are generally significantly larger for IVB treated children than the normal population.