This meta-analysis of prospective randomized controlled trials (RCTs) was performed according to the PRISMA statement. The PRISMA Checklist were shown in the Supplementary Dataset. No protocol existed for this meta-analysis.
Information source and search strategy
A purposive literature search was conducted in PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to yield relevant studies, using Medical Subject Headings (MeSH) and free words combined with myopia and atropine. ((((((((((((Atropine)) OR (Atropinol)) OR (Atropine Sulfate)) OR (Sulfate, Atropine)) OR (Atropine Sulfate Anhydrous)) OR (Anhydrous, Atropine Sulfate)) OR (Sulfate Anhydrous, Atropine)) OR (AtroPen)) OR (Atropin Augenöl)) OR (Augenöl, Atropin))) AND (((((Nearsightednesses)) OR (Nearsightedness)) OR (Myopias)) OR (Myopia)) was used in searching the Pubmed. We also searched clinicaltrials.gov and the reference lists of published reviews to find additional relevant studies. The last search date was January 20, 2020. It is noted that only studies published in English were used.
Eligibility criteria
The included studies must meet the following criteria:
(1) A randomized placebo-controlled clinical trials.
(2) Spherical equivalent refraction more than -0.25D measured by cycloplegic autorefraction was diagnosed with myopia.
(3) All patients were under 18 years old.
(4) Atropine was used for at least one year.
(5) The study reported at least the annual rate of myopia progression.
Congling Zhao and Chunyan Cai independently reviewed titles, abstracts, and full-length articles to identify potentially eligible articles using the criteria listed above. Disagreements regarding eligibility were resolved through a discussion with Qiang Ding. When a study was reported more than once, only the latest study was included to avoid double inclusion of data. When a study contained different doses of atropine, only the dose recommended by the study was included. The exclusion studies list and exclusion reason were shown in the Supplementary Dataset.
Data Extraction
Two reviewers (Congling Zhao and Qiang Ding) independently extracted information using the pre-established data extraction tables, including the following: (1) Basic characteristics of the study, including the name of the first author, year of publication, and follow-up time (2) Basic characteristics of the patients, including the age of the patients, equivalent spherical power before treatment, changes in cycloplegic spherical equivalent, changes in axial elongation, adverse reactions, etc.
Qualitative Assessment
The quality of the included studies was assessed by the Cochrane Handbook, including 6 items: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessments, incomplete outcome data, selective reporting, and other biases. Two reviewers determined the risk of bias which had three options (low, high, and unclear). When necessary, we contacted the authors of the study to obtain the full text or related information for an accurate assessment.
Statistical Analysis
Review Manager (version 5.3; Cochrane Collaboration) was used for data analysis. The statistical heterogeneity of included studies was tested by the Cochrane I2 test. If I2 was 50% or less, indicating a low-to-moderate heterogeneity, a fixed-effect model was used. If I2 was higher than 50%, indicating a high degree of heterogeneity, a random effects model was applied. MD with a 95% confidence interval (CI) was used to estimate the effect. A sensitivity analysis was performed by excluding the included studies one by one.