Methodological quality of the review: Low confidence

Author: Helen A Mintz-Hittner, Megan M Geloneck

Region: Taiwan, Mexico, Germany, USA, Egypt, Canada, Brazil

Sector: Refractive error

Subsector: Anti-VEGF treatment on refractive error

Equity focus: No

Study population: General population

Type of programme: Hospital based

Review type: Other review

Quantitative synthesis method: Systematic review

Qualitative synthesis method: Not applicable

Background: Advances in treatment for retinopathy of prematurity (ROP) are allowing better anatomical and functional outcomes, with further prevention of blindness from retinal detachment. Perhaps the most recent addition to the ROP-treatment armamentarium are anti-VEGF agents. Anti-VEGF agents have considerable clinical benefits, including reduction in the rate of high and very high myopia following treatment, compared with peripheral ablation.

Authors concluded that anti-VEGF monotherapy for ROP leads to low levels of myopia, and there may be a differential effect of specific anti-VEGF agents utilised on refractive outcomes.

Objectives: The objective of this study was to investigate the contributions of these causative factors to the resulting refractive error seen in children treated by anti-VEGF agents for ROP.

Main findings: Eleven articles were identified relevant to the topic. In total, this amounted to 466 eyes (the number of infants was not consistently reported) treated with anti-VEGF agents for ROP: 378 eyes with intravitreal bevacizumab monotherapy (dosage ranging from 0.375 to 1.25 mg, with the majority administered 0.625 mg), 31 eyes with intravitreal ranibizumab monotherapy (0.25 mg), and 26 eyes with intravitreal aflibercept monotherapy (1 mg). The average SE refractive error reported after anti-VEGF monotherapy ranged from +0.75 D to -3.57 D. The average age at time of refraction in these studies ranged from 11.4 months to 5 years.

Methodology: A PubMed search was performed of several combinations of the following search terms: retinopathy of prematurity, ROP, refraction, refractive error, myopia, bevacizumab, ranibizumab, aflibercept, pegaptanib, anti-vascular endothelial growth factor and anti-VEGF. The last search update was performed on 13 January 2016. The reference list of each identified article was also reviewed to ensure completeness. Extracted information from each relevant article included the first author’s name, year of publication, country in which the study was conducted, average gestational age of each cohort, average birth weight of each cohort, percentage of eyes treated for zone I ROP, specific treatment modalities utilised, average adjusted age (gestational age + number of weeks of life) at time of treatment, average age at time of refraction, average spherical equivalent (SE) refractive error in diopters, prevalence of myopia (SE .-0.25 D), and prevalence of high myopia (SE .-5 D).

Applicability/external validity: Not discussed.

Geographic focus: This review was conducted in seven countries: Taiwan, Mexico, Germany, USA, Egypt, Canada and Brazil, As this is a drug showing benefits in myopia treatment, the results of this review may be applied to other countries.

Summary of quality assessment:

Overall, there is low confidence in the conclusions about the effects of this review, as important limitations were identified. Authors did not conduct a thorough search of the literature to ensure that all relevant studies were included in the review (potential publication bias). In addition, authors did not use rigorous methods to scree studies for inclusion, data extraction and assessing the methodological quality of included studies.