Efficacy, Safety and Acceptability of Orthokeratology on Slowing Axial Elongation in Myopic Children by Meta-Analysis

Methodological quality of the review: Medium confidence

Author: Shi-Ming Li, Meng-Tian Kang, Shan-Shan Wu, Luo-Ru Liu, He Li, Zhuo Chen and Ningli Wang

Region: Hong-Kong, Japan, Spain, China

Sector: Myopia

Subsector: Myopia treatment

Equity focus: Focus on Caucasian children

Study population: Children (6 to 17 years)

Type of programme: Community based (home treatment and follow-up)

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: Myopia has been a public health issue worldwide, especially in Asian areas. There is an increasing prevalence of myopia in children, with early onset and high myopia becoming more prevalent over recent decades. Orthokeratology was first introduced in the early 1960s but was shown to be ineffective. Some recent randomised controlled trials (RCTs) have reported that orthokeratology is effective in slowing axial elongation in myopic children with an estimated difference of 0.27-0.33mm during two years compared with spectacles correction, and the effect is also comparable with atropine application. There were more well-conducted prospective observational studies that reported the effect of orthokeratology on slowing axial elongation in children. However, it remains unclear as to whether the study design had an effect on the slowing of axial elongation. It is also unclear whether orthokeratology has different effects on slowing axial elongation correspondent to ethnicity.

Objectives: to evaluate the efficacy, safety and acceptability of orthokeratology compared with control (single vision spectacle), based on RCTs and prospective observational studies, on slowing axial elongation in Asian and Caucasian children and to determine whether there was a difference in the outcomes of RCT and observational cohort studies, or differences in children with different levels of myopia and ethnicity.

Main findings: Nine studies were finally included in this meta-analysis, of which three were RCTs and six were cohort studies; both designs included 667 children aged 6 to 16 years. The quality of the included RCT and cohort studies was high. Two years’ mean differences in axial elongation were -0.27mm (95% confidence intervals [CI], -0.32 to -0.23) in all studies, -0.28mm (95% CI, -0.35 to -0.20) in RCTs and -0.27mm (95% CI, -0.32 to -0.22) in cohort studies (P<0.01). At 6 months, 1 year, 1.5 years and 2 years, mean differences in axial elongation were -0.13 mm, -0.19mm, -0.23mm, and -0.27mm (P<0.01), respectively. The effect was greater in Asian children than Caucasian (-0.28mm versus -0.22mm) and in children with moderate to high myopia when compared to children with low myopia (-0.35mm versus -0.25 mm). Orthokeratology had more non-significant adverse events (odd ratio [OR], 8.87; 95% CI, 3.79-20.74; P<0.01) but comparable dropout rates (OR=0.84, 95% CI, 0.40-1.74, P=0.64) than control.

Methodology: Inclusion criteria consisted of: 1) participants who were school-aged children (6 to 17 years) with myopia (-0.25 to -10D); 2) orthokeratology was used in at least one treatment arm and single vision spectacles in another as control; 3) mean axial length elongation was studied as primary outcome, and secondary outcomes were the number of adverse events and the dropout rate from baseline to the end of the intervention period; 4) follow-up period >6 months.

A systematic literature search with language restriction in English was conducted in Medline, Embase and the Cochrane Library for randomised controlled trials and observational studies on humans, up to 10 January 2015. The following Medical Subject Heading terms and keywords were used: myopia, refractive errors, clinical trial, randomised controlled trial, cohort study, orthokeratology, contact lens, reshape, corneal, controls, eyeglasses, placebo and children, as well as some relevant free terms. Boolean operator ‘‘AND’’, ‘‘OR’’, ‘‘NOT’’ were used to combine all search sets. References within those retrieved trials were used to search for additional studies. Authors also searched in Chinese Clinical Trial Registry, World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov to retrieve those ongoing trials. We used a protocol for the present review which was used in our previous meta-analysis. Two reviewers independently and jointly determined the eligibility of studies (SML and SSW) and extracted information from them (SML and MTK). Quality of selected trials was determined according to Jadad scoring for RCTs. Newcastle-Ottawa Quality Assessment Scale (NOS) items were used to assess the quality of selected cohort studies.

Differences in axial elongation between two groups were expressed as weighted mean differences (WMDs). Acceptability was evaluated by the dropout rate of subjects who were lost to follow-up during the treatment. Odds ratio (OR) with 95% CI of proportions of adverse events was also calculated. Heterogeneity among studies was evaluated using X² test and I² statistics. A P value less than 0.1 was considered significant for the test of heterogeneity.

Applicability/external validity: The focus was on Caucasian children. For external consideration, the authors acknowledge some limitations which need to be taken into consideration: only axial elongation was evaluated in our study due to scarcity of reports on myopia progression in refractive error. Only studies in English were included in this meta-analysis, which may cause potential publication bias and limit the number of studies to be included. Finally, only one trial was conducted in Caucasian children in Spain.

Geographic focus: Focus just on Caucasian population.

Summary of quality assessment:

Overall, this study was attributed medium confidence, as authors did not conduct a through search of the literature to ensure that all relevant studies were identified, increasing the chance of publication bias within the review.