Atropine 0.01% eye drops slow myopia progression: a systematic review and Meta-analysis

Methodological quality of the review: High confidence

Author: Ying Zhao, Kai Feng, Rui-Bao Liu, Jin-Hua Pan, Lai-Lin Zhang, Zhu-Ping Xu, Xue-Jing Lu

Region: Not mentioned

Sector: Myopia

Subsector: Myopia treatment with Atropine 0.01%

Equity focus: No

Study population: Patient (aged from 6 to 23 years)

Type of programme: Hospital based

Review type: Other review

Quantitative synthesis method: Systematic review and meta-analysis

Qualitative synthesis method: Not applicable

Background: In the past two decades, a series of epidemiological studies have demonstrated that the persistently high prevalence of myopia has become a major public health problem. The factors associated with myopia induction include environment, ethnicity and inheritance. The progression of myopia in children and adolescents is gradual. Furthermore, early onset myopia can be associated with the development of high myopia, which could lead to several pathological complications, such as choroidal thinning, posterior scleral staphyloma, cataracts, peripheral retinal tears, myopic choroidal neovascularisation, glaucoma, macular degeneration, and even blindness. Atropine was first used to prevent myopia in the 1920s. Since then, numerous related studies have been conducted. In recent years, several studies were performed to compare the effectiveness of different concentrations of atropine in the control of myopia. They demonstrated that atropine 0.01% eye drops can achieve a balance between a higher efficacy and lower incidence of side effects than other concentrations.

Objectives: To evaluate the effects of atropine 0.01% on slowing myopia progression.

Main findings: Seven studies were eventually included. A total of 1,079 subjects were included (505 in the atropine eye drop group and 574 in the control group). The results of the axial length showed (Figure 3) that the atropine 0.01% group exhibited significantly better control of axial growth than the control group [MD=-0.12, 95% CI (-0.19, -0.06)]. There was no significant heterogeneity detected between the studies (P=0.21, I²=33%). The combined results demonstrated that atropine 0.01% yielded significantly greater improvement in axial length. There was a statistically significant difference between the atropine 0.01% group and control group in the overall effect [MD=-0.14, 95% CI (-0.25, -0.03)], and it was characterised by high heterogeneity (I²=88%, I²=0.01). There was no significant difference between atropine 0.01% eye drops and the control in the overall effect [MD=0.08, 95% CI (-0.27, 0.42)]. There was no significant difference between the atropine 0.01% and control groups in the overall effect [MD=0.09, 95% CI (-0.17, 0.36)]. Three studies showed that the changes in diopter due to atropine 0.01% eye drops were greater than those due to the control [MD=0.51, 95% CI (0.38, 0.64); MD=0.22, 95% CI (0.06, 0.38); MD=0.43, 95% CI (0.21, 0.65)]. There was no significant difference between the atropine 0.01% and control groups in the overall effect with respect to distance vision [MD=-0.01, 95% CI (-0.02, 0.00)]. A total of three studies reported adverse events. There were significant differences between the atropine 0.01% eye drops and the control with respect to adverse events [OR=0.26, 95% CI (0.11, 0.61)]. There was no significant heterogeneity detected between the studies. Funnel plot analysis suggested the possible presence of publication bias.

Based on the available evidence, authors conclude that atropine 0.01% eye drops offer benefits in controlling axial growth and safety without causing significant differences in diopter values, distance vision and intraocular pressure.

Methodology:

Inclusion criteria consisted of 1) the studies were clinical randomised controlled trials (RCTs) for the treatment of myopia with atropine 0.01% eye drops; 2) participants in the trials were people with a confirmed diagnosis of myopia; 3) we included atropine 0.01% eye drops for the treatment of myopia, and the control group was treated with atropine 0.1% or 0.5%, placebo or a blank control; 4) baseline data of the experimental and control groups was well-balanced between groups.

Relevant studies were searched in the Cochrane Library, PubMed, Embase, Ovid, CBM (http://www.sinomed.ac.cn/), CNKI (http://www.cnki.net/), VIP (http://www.cqvip.com/) and Wang Fang Data (http://www. wanfangdata.com.cn/) in Chinese. A supplementary search was conducted in OpenGrey (System for Information on Grey Literature in Europe; www.opengrey.eu/); the ISRCTN registry (www.isrctn.com/editAdvancedSearch); ClinicalTrials.gov (www.clinicaltrials.gov); and the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en), ranging from the dates of inception to 30 June 2018. Two review authors independently assessed the quality of all included studies. The quality of the selected studies was determined by the Cochrane Handbook 5.3, including six items: random sequence generation, allocation concealment, blinding of subjects and intervention providers (blinding of participants and caregivers), blinding of outcome assessments, incomplete outcome data, selective reporting, and other biases. Two reviewers judged whether the risk of bias was low, high or unclear Analysis: We used Review Manager 5.3 software (Copenhagen: the Nordic Cochrane Centre, the Cochrane Collaboration, 2014) for the statistical analysis. The odds ratio (OR) was used for count data, and the standard mean difference (SMD) was used for measurement data. Both of them used the 95% CI as the effect amount. First, the statistical heterogeneity of the included clinical RCTs was analysed using the Cochrane I² test. If I²<30%, the heterogeneity was small, and 30% <I²<50% indicated moderate heterogeneity. A fixed effects model was used if significant evidence of statistical heterogeneity or clinical diversity was not found (P≥0.10, I²≤50%).

Applicability/external validity: As mentioned, high-quality evidence suggested that atropine 0.01% eye drops provide superior benefit compared with high-concentration atropine in clinical trial populations. Atropine 0.01% eye drops are currently sold in Taiwan.

Geographic focus: Not discussed.

Summary of quality assessment: In conclusion, this study was attributed high confidence, as authors used rigorous methods to screen studies for inclusion and to analyse findings of included studies.