Myopia is a widespread eye disease in the world. Every year, myopia-related complications causes a huge socioeconomic burden and especially progressive high myopia even may lead to potentially blinding complications. Currently, the best treatment strategy is to control the progression of myopia.
In this meta-analysis, less myopia progression was shown in the atropine treatment group than that of the control group during the whole observation period, with MD = -0.80, 95% CI (-0.94, -0.66). Moreover, there was a statistical difference among 0.05%, 0.5%, and 1.0% atropine groups (P = 0.004). Less axial elongation was also shown in the atropine treatment group, with MD = -0.26, 95% CI (-0.33, -0.18). This confirmed the role of atropine in myopia and suggested that its effectiveness was related to its dose , and 0.05% atropine could effectively control the progression of myopia .
Song et al. identified that the effectiveness of atropine was related to its dose. A low dose of atropine worsened the progression of myopia. 0.5% and 1.0% of atropine could safely and effectively control the progression of low to moderate myopia . However, the meta-analysis done by Song et al. only included 6 studies in 2011. In addition, the low-dose atropine only included 0.1% and 0.25% and no placebo control was used. Therefore, it is impossible to determine whether the low-dose atropine is ineffective or if it has a worse effectiveness than the higher dose of atropine.
Gong et al. reported that the effectiveness of atropine was independent of its dose, but its side effects were dose-dependent . However, it included the Cohort study which had insufficient evidence.
A recent 2-year follow-up observation  in children in the United States found that 0.01% atropine could effectively control the progression of myopia. A meta-analysis  published last year verified the effectiveness of 0.01% atropine on myopia, but it did not show the effectiveness of other doses.
When atropine was discontinued after one year usage in the atropine group, myopia progressed faster than that of the placebo group , especially for a high-dose atropine (low-dose atropine cases rebounded less after discontinuation) . Therefore, the effectiveness of rebound was closely related to its dose.
This meta-analysis provides evidence-based medical evidence for the use of atropine in controlling the progression of myopia by including only high-quality RCTs. This meta-analysis verified that the effectiveness of atropine in controlling myopia progression was closely related to the dose. 0.05% atropine might be the optimal dose which could slow the myopia progression and had the least adverse effects and rebound after discontinuation. Although only one study in our meta-analysis confirmed the effectiveness of 0.05% atropine, the study was of good quality after the Methodological Evaluation and was currently the largest placebo-controlled RCT to comprehensively evaluate its safety and effectiveness. In our study, the same conclusion is also got. Therefore, the study is sufficient to indicate that 0.05% may be the best dose of atropine according to all the doses of atropine in this meta-analysis. If atropine can be widely used in clinical prevention and controlling myopia, it will help prevent high myopia and related complications.
Kinoshita reported that the combined application of 0.01% atropine eye drops and orthokeratology can significantly slow the axis elongation compared to the use of orthokeratology alone . A retrospective study also reported similar results . But the elongation of the eye axis could not predict the progression of myopia accurately. Therefore, the effectiveness of the combined application of atropine and orthokeratology needed to be further studied.
There were several limitations. First, although this meta-analysis had established strict inclusion and exclusion criteria, the heterogeneity was still high after using the subgroup analysis. However, through the sensitivity analysis, the results of this meta-analysis were stable and consistent. Secondly, there were no studies involving 0.01% atropine in this study. And some of the included studies did not report adverse reactions, and few studies reported the progression of myopia after atropine was discontinued. The further determination and validation of the optimal dose required additional research.