Efficacy and safety of interventions to control myopia progression in children: an overview of systematic reviews and meta-analyses

Methodological quality of the review: High confidence

Author: Efthymia Prousali, Anna-Bettina Haidich, Andreas Fontalis, Nikolaos Ziakas, Periklis Brazitikos and Asimina Matafts

Region: Israel, Malaysia, China, Finland, Hong-Kong, Japan, Taiwan, Denmark, Singapore, Australia, Jordan, United States of America, Turkey, Canada, New-Zealand, Spain, Russia

Sector: Myopia

Subsector: Controling myopia progression in children

Equity focus: No

Study population: Children and adolescents

Type of programme: Hospital based

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analysis

Qualitative synthesis method: Not applicable

Background: Myopia is included in the 10 priority eye diseases in VISION 2020 campaign for the prevention of blindness and visual impairment, as declared by the World Health Organization (WHO). Myopia introduces significant social and psychological impact, as it appears to affect children’s perception of their physical appearance, athletic competence and social acceptance. A treatment that would halt or at least decelerate myopia’s progression rate is highly desirable, as severe myopia constitutes a substantial risk factor for several ocular conditions which can lead to blindness. Several interventions have been attempted to control myopic progression, some of which showed no effect and others were effective but with limitations. Long-term safety and efficacy of interventions to restrict myopia remains unresolved, resulting in the lack of universal consensus in myopia treatment.

Objectives: The present study is to synthesise evidence provided by systematic reviews (SRs) and meta-analyses (MAs) on myopia control.

Main findings: Forty-four unique primary studies contained in 18 eligible reviews and involving 6,400 children were included in the analysis. CCA was estimated as 6.2% and thus considered moderate. The overall risk of bias was ‘low’ in 14 reviews, unclear’ in three, and ‘high’ in one review. More than 50% of the RCTs were at low risk of bias for random sequence generation and allocation concealment and more than 80% of RCTs were at low risk of bias for selective outcome reporting. In RCTs, the results of the overall pooled analysis revealed that the under-corrected group showed greater change in refractive error (RE) in 1 year (MD 0.15, 95% CI 0.00 to 0.29), and in 2 years from baseline (MD 0.20, 95% CI 0.01 to 0.39). Results demonstrated the superior efficacy of atropine eyedrops; 1% atropine vs placebo (change in refraction: -0.78D, [-1.30 to -0.25] in 1 year), 0.025 to 0.05% atropine vs control (change in refraction: -0.51D, [-0.60 to -0.41] in 1 year), 0.01% atropine vs control (change in refraction: -0.50D, [-0.76 to -0.24] in 1 year). Findings showed that pirenzepine has a favorable effect on AL change, reducing it by -0.10mm in 1 year (95% CI, -0.18 to -0.01; GRADE evidence. Atropine was followed by orthokeratology (axial elongation: -0.19 mm, [-0.21 to -0.16] in 1 year) and novel multifocal soft contact lenses (change in refraction: -0.15D, [-0.27 to -0.03] in 1 year). As regards adverse events, 1% atropine induced blurred near vision (odds ratio [OR] 9.47, [1.17 to 76.78]) and hypersensitivity reactions (OR 8.91, [1.04 to 76.03]).

Authors conclude that existing evidence has failed to convince doctors to uniformly embrace treatments for myopic progression control, possibly due to the existence of some heterogeneity, reporting of side effects and lack of long-term follow-up. Research geared towards efficient interventions is still necessary.

Methodology: Inclusion criteria included children and adolescents, ≤18 years of age at baseline, diagnosed with myopia defined as spherical equivalent refraction ≤−0.25 dioptres, with or without astigmatism, without any ocular comorbidities, including strabismus and amblyopia. Interventions and comparators included studies in which any optical or pharmacological intervention for myopia control was compared to single vision spectacles, contact lenses or placebo. Primary outcomes regarded myopia progression and axial elongation as efficacy criteria. Unit of analysis of this overview were SRs or meta-analyses of randomised controlled trials (RCTs), pseudo-RCTs, cohort and case-control studies. Network meta-analyses were also reviewed. Only human studies with full text available were analysed.

Purposive literature search was conducted in the Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and Centre for Reviews and Dissemination (CRD) Health Technology Assessment (HTA) Database, using the keyword: myopia. A more comprehensive search strategy was applied in Medline and Embase, using medical subject headings (MeSH) and text words related to spectacles, contact lenses, anti-muscarinic agents, myopia and children to find any recent primary studies not included in the published systematic reviews. The last search date was 9 March 2018. For all included studies, reference lists were also searched. No language, study type or date restrictions were used. Two independent authors (EP, AF) performed all screening

steps. The same two independent authors (EP, AF) managed data in duplicate from each eligible study, using a data collection form in Microsoft Excel designed to include all the data required. A third author was involved to resolve any discrepancies, using the primary research paper (ABH). Two overview authors (EP, AF) independently assessed the methodological quality of each included SR and MA using the Risk Of Bias In Systematic Reviews (ROBIS) tool. The quality of evidence was evaluated by two independent authors (EP, AF) using four domains of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Index publications included in eligible systematic reviews and meta-analyses were employed as a unit of analysis to perform a meta-analysis using Review Manager software version 5.3. Continuous outcomes were expressed using mean differences with 95% confidence intervals (CIs), and dichotomous outcomes were expressed using odd ratios (ORs) with 95% CIs.

Applicability/external validity: Regarding external validity, the authors acknowledge some limitations which need to be considered when using the results in other settings. A number of treatments, such as atropine and OK, were represented by a larger number of reviews compared to other therapies, including bifocal or multifocal lenses, leading to a presence of publication bias. Finally, due to small sample sizes analysed, treatment effects are likely to be overestimated.

Geographic focus: the authors reported that this is the first overview of systematic reviews and meta-analyses on interventions for myopia control. Through this study, many studies were identified and synthesised all available high-level evidence.

Summary of quality assessment: High confidence was attributed to the conclusions about the effects of this study, as authors used rigorous methodology to conduct the review.