Efficacy Comparison of 16 Interventions for Myopia Control in Children

Methodological quality of the review: High confidence

Author: Jinhai Huang, MD, Daizong Wen, Qinmei Wang, Colm McAlinden, Ian Flitcroft, Haisi Chen, Seang Mei Saw, Hao Chen, Fangjun Bao, Yune Zhao, Liang Hu, Xuexi Li, Rongrong Gao, Weicong Lu, Yaoqiang Du, Zhengxuan Jinag, Ayong Yu, Hengli Lian, Qiuruo Jiang, Ye Yu, Jia Qu

Region: Israel, China, Hong-Kong, Malesia, USA, Denmark, Finland, Japan, New England, Singapore, Taiwan

Sector: Myopia

Subsector: Myopia control and treatment

Equity focus: No

Study population: Children

Type of programme: Hospital based

Review type: Other review

Quantitative synthesis method: A Network meta-analysis

Qualitative synthesis method: Not applicable

Background: Myopia has emerged as a worldwide public health issue and is one of the five ocular conditions identified as immediate priorities by the World Health Organization’s Global Initiative for the Elimination of Avoidable Blindness. In addition to the optical impact of myopia on vision and the associated costs of correction, myopia is a major risk factor for ocular disease. Standard clinical care currently treats only the optical and medical consequences of myopia rather than limiting its progression. Despite the lack of consensus on the causes of myopia, a range of potential interventions to reduce its progression have been tested. There are inconsistencies among trials examining the same intervention.

Objectives: To determine the effectiveness of different interventions to slow down the progression of myopia in children.

Main findings: Thirty RCTs, with a total of 5,387 people, involving 5,422 eyes, were included in this study. Overall, the trials that we included in this analysis seem to have a low to moderate risk of bias, with most of the trials reporting adequate random sequence generation, allocation concealment and blinding of outcome assessment. Network meta-analysis showed that in comparison with placebo or single vision spectacle lenses, high-dose atropine (refraction change: 0.68 [0.52-0.84]; axial length change: -0.21 [-0.28 to -0.16]), moderate-dose atropine (refraction change: 0.53 [0.28-0.77]; axial length change: -0.21 [-0.32 to -0.12]), and low-dose atropine (refraction change: 0.53 [0.21-0.85]; axial length change: -0.15 [-0.25 to -0.05]) markedly slowed myopia progression. Pirenzepine (refraction change: 0.29 [0.05-0.52]; axial length change: -0.09 [-0.17 to -0.01]), orthokeratology (axial length change: -0.15 [-0.22 to -0.08]), and peripheral defocus modifying contact lenses (axial length change: -0.11 [-0.20 to -0.03]) showed moderate effects. Progressive addition spectacle lenses (refraction change: 0.14 [0.02e0.26]; axial length change: -0.04 [-0.09 to -0.01]) showed slight effects.

Authors conclude that their network analysis indicates that a range of interventions can significantly reduce myopia progression when compared with single vision spectacle lenses or placebo. In terms of refraction, atropine, pirenzepine and progressive addition spectacle lenses were effective. In terms of axial length, atropine, orthokeratology, peripheral defocus modifying contact lenses, pirenzepine and progressive addition spectacle lenses were effective. The most effective interventions were pharmacologic, that is, muscarinic antagonists, such as atropine and pirenzepine. Certain specially designed contact lenses, including orthokeratology and peripheral defocus modifying contact lenses, had moderate effects, whereas specially designed spectacle lenses showed minimal effect.

Methodology: Inclusion criteria: Trials were eligible for our network meta-analysis if they: 1) compared interventions for slowing the progression of myopia to control patients or other therapeutic interventions in children; and 2) had a treatment duration of at least one year. We excluded trials if they: 1) included patients aged more than 18 years when enrolled in trials; 2) included patients with less than 0.25 D of spherical equivalent myopia at baseline; 3) were a non-randomised or noncomparative study; 4) did not have the required outcome measures; or 5) failed to provide data suitable for meta-analysis. We used mean annual change in refraction (diopters/year) and mean annual change in axial length (millimeters/year) as our primary outcomes. We specified tropicamide as a placebo at the outset, because a previous study by Shih et al, found that 0.5% tropicamide had a similar effect to placebo on myopia progression. Likewise, single vision spectacle lenses were prespecified as a control along with placebo. Furthermore, the concentration of atropine was classed into three groups: high-dose atropine (1% and 0.5%), moderate-dose atropine (0.1%), and low-dose atropine (0.01%).

The research was performed with Medline, Embase, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases (from inception to August 2014) for RCTs in any language. Two investigators (D.Z.W., J.H.H.) independently reviewed the titles, abstracts, and full text articles for inclusion using standardised data extraction forms. The following information from each trial: 1) first author; 2) year of publication; 3) follow-up duration; 4) type of intervention; 5) sample size; 6) baseline characteristics (age, refraction, axial length, dropouts from total number); and 7) end points (mean change in refraction and axial length). Study quality was assessed by Cochrane Collaboration’s Risk of Bias method.

Authors conducted direct head-to-head comparisons using a random effects model to estimate weighted mean differences and 95% confidence intervals (CIs), and assessed heterogeneity with the I² statistic, with I² values greater than 50% indicating substantial heterogeneity. We performed direct comparisons using STATA version 10.0 (StataCorp LP, College Station, TX).

Applicability/external validity: Regarding external validity, the authors highlighted some limitations which need to be taken into consideration when using the results: articles include used a multifocal spectacle lenses which have different refractive powers for each patient, and the off axis effects of orthokeratology vary with refractive correction. There is also presence of information bias: the study provides information on the efficacy but not the safety of different treatment options because of lack of data within the included articles.

Geographic focus: Not discussed.

Summary of quality assessment:

High confidence was attributed to the conclusions about the effects of this study, as authors used rigorous and appropriate methods to conduct the review.