The effect of 0.01% atropine and orthokeratology on ocular axial elongation for myopia children: A meta-analysis (a PRISMA-compliant article)

Authors: Yu Y, Jiasu L.

Geographical coverage: None specified – although the authors indicated that the majority of the studies included originated in Asia.

Sector: Biomedical

Sub-sector: Treatment

Equity focus: Focuses solely on children – see below.

Study population: Children with myopia aged 18 and under.

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background: Myopia is increasing among children. There is some evidence that the administration of atropine and orthokeratology can slow its progression, although the impact of these two treatments has rarely been assessed in conjunction.

Objectives: This meta-analysis aimed to identify the therapeutic effect of 0.01% atropine with orthokeratology on ocular axial elongation for children with myopia.

Main findings:

Overall, authors found that 0.01% atropine is effective in slowing axial elongation in myopia children with orthokeratology.

The searched keywords identified 36 articles. 12 articles were excluded after a review of titles and abstracts and 15 after full-texts and data integrity were reviewed. Nine studies that met all inclusion criteria were included in the meta-analysis. The pooled data comprised a total of 191 children in OKA group and 196 children in OK group (that is, without the combined treatment). The pooled summary weighted mean differences of AL change was -0.90.

Authors identified a number of limitations, including the relatively small sample sizes involved and the low level of quality of the included studies. The majority of included studies originated from Asia, which may adversely affect the reliability and validity of the results.

The authors indicate that, due to their study’s limitations, further detailed studies that focus on the effect of different concentrations and administration frequencies of atropine combined with orthokeratology on myopia are required to confirm their findings.  Due to the small sample size involved, they also indicated that well-designed multi-centre studies with large samples should be conducted.

Methodology:

Meta-analysis was conducted using Stata version 14.0 and Review Manager version 5.3 softwares. The weighted mean differences were calculated to analyse the change of ocular axial length (AL) between orthokeratology combined with 0.01% atropine (OKA) and) alone. The Cochran’s Q-statistic and I² test were used to evaluate potential heterogeneity between studies. To evaluate the influence of single studies on the overall estimate, a sensitivity analysis was performed. Subgroup and meta-regression analyses were also performed to investigate potential sources of heterogeneity. Begger funnel plots and Egger linear regression tests were conducted to investigate publication bias.

The study involved the following eligibility criteria. Type of study: this study included high quality randomised controlled trials, cohort studies and case-control studies. Type of patients: the patients should be children aged younger than 18 years, with myopia. There were no restrictions of race, age, education background and economic status. Intervention and comparison: this study compared orthokeratology combined with 0.01% atropine (OKA) with orthokeratology (OK) for myopia control. Type of outcomes: the primary outcome was ocular axial elongation.

Authors searched PubMed, Cochrane Library and CBM databases from inception to 1 July 2021.

Data was systematically extracted from all included studies by two researchers using a standardised form. The quality of the primary studies was assessed using the Cochrane risk-of-bias tool by two independent researchers and an additional investigator in the case of any conflicts. The risk of bias for each study was evaluated according to selection bias, performance bias, detection bias, attrition bias, reporting bias and other sources of bias. Each of these biases were classified as high risk (score 0), low risk (score 2) and unclear risk of bias (score 1). The total risk of bias was calculated by a summation of all categories.

Review Manager 5.3 and Stata version 14.0 software were used for the meta-analysis. Authors calculated the weighted mean differences with their 95% confidence intervals to analyse the change of axial length between OKA and OK. The Cochran’s Q-statistic and I² test were used to evaluate potential heterogeneity between studies. If significant heterogeneity was detected (Q test p 50%), a random-effects model or fixed-effects model was used. To evaluate the influence of single studies on the overall estimate, a sensitivity analysis was performed. Authors also performed subgroup and meta-regression analyses to investigate potential sources of heterogeneity. They conducted Begger funnel plots and Egger linear regression tests to investigate publication bias.

Applicability/external validity: Authors note that “the majority of included studies originated from Asia, which may adversely affect the reliability and validity of the results”. However, no geographic restriction on the data to be extracted was put in place at the outset – which might suggest much of the data in the area presently originates from this reason.

Geographic focus: Authors note that the majority of the included studies were conducted in Asia (although no further information is provided regarding specific countries). As a result, the extent to which findings might apply to LMIC countries specifically is unclear (although the fact many studies were published in Chinese, makes it almost certain that countries such as China were included).

Summary of quality assessment:

While the inclusion criteria and data extraction processes for this study are robust, the literature search was not sufficiently exhaustive – with restrictions based on language and publication, no consultation of reference lists of academic experts. The approaches to the analysis of the data were generally robust; however, there was no analysis of the results on the basis of the quality of the different studies involved. In addition, as noted by the authors themselves, the pooled sample size of the analysed sample is comparatively small, given the small number of studies involved. For these reasons, we would have “low confidence” in the results of this study.