Prevention of myopia shift and myopia onset using 0.01% atropine in premyopic children — a prospective, randomized, double-masked, and crossover trial

Abstract

To evaluate the e cacy of 0.01% atropine eye drops in preventing myopia shift and myopia onset in premyopic children. A prospective, randomized, double-masked, placebo-controlled, crossover trial was conducted over 13 months. Sixty premyopic children aged 6-12 years with cycloplegic spherical equivalent refraction (SER) > -0.75 D and ≤ + 0.50 D in both eyes were assigned in a 1:1 ratio to receive one drop of 0.01% atropine or placebo once nightly for 6 months (period 1), followed by a 1-month recovery period. Then, the 0.01% atropine group was crossed over to the placebo group, and the latter was crossed over to the 0.01% atropine group for another 6 months (period 2). The primary outcomes were changes in SER and axial length (AL), and the secondary outcomes were the proportion of myopia onset (SER ≤ -0.75D) and fast myopic shift (change in SER ≤ -0.25D) in the two periods. Generalized estimating equation (GEE) model performed statistically signi cant treatment effect of 0.01% atropine compared with placebo (p SER = 0.02, p AL < 0.001), with a mean SER and AL difference of 0.20D (-0.15 ± 0.26D vs. -0.34 ± 0.34D) and 0.11mm (0.17 ± 0.11mm vs. 0.28 ± 0.14mm) in period 1, and 0.17D (-0.18 ± 0.24D vs. -0.34 ± 0.31D) and 0.10mm (0.15 ± 0.15mm vs. 0.24 ± 0.11mm) in period 2. GEE model showed that the proportion of myopia onset (p = 0.004) and fast myopic shift (p = 0.009) were signi cantly lower in the 0.01% atropine group than that in the placebo group. The period effect was not statistically signi cant (all p > 0.05). 0.01% atropine signi cantly prevented myopic shift, axial elongation, and myopia onset in premyopic schoolchildren in central Mainland China.Conclusions: Within the limits of only two consecutive 6-month observation period, 0.01% atropine eye drops effectively prevented myopic shift, axial elongation, and myopia onset in premyopic children.Trial registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2000034760). Registered 18 July 2020. What Is Known• Minimal studies on interventions for pre-myopia, despite the International Myopia Institute stating that preventing myopia is an "even more valuable target" for science and practice than reducing progression after onset.What Is New • 0.01% atropine eye drops may safely and effectively reduce the proportion of myopia onset and fast myopic shift in premyopic schoolchildren.

Myopia Control: Are We Ready for an Evidence Based Approach?

“…Similarly, in another recently published systematic review the estimated mean difference (MD) for myopia progression for atropine was found to be 0.29 D (95% CI 0.22–0.36; p = 0.03) [ 58 ]. In the present review, the most recent 16 out of initial 41 articles on RCTs were analyzed (Supplementary Table 3 ): a noticeable difference between these studies can be observed in terms of sample size [ 107 – 109 ], study length and design [ 110 – 114 ], the age of the children studied [ 106 , 109 ], location of trial [ 115 – 117 ], and the different atropine doses, which varied between 0.0025% and 1%, as well as the application frequency of drops [ 110 , 114 , 118 , 119 ], and lastly their aims [ 109 , 111 , 112 , 120 ]. Almost half of the selected studies were conducted in East Asia, in predominately Chinese ethnic children [ 109 , 110 , 114 , 115 , 118 – 120 ].…”

“…In the present review, the most recent 16 out of initial 41 articles on RCTs were analyzed (Supplementary Table 3 ): a noticeable difference between these studies can be observed in terms of sample size [ 107 – 109 ], study length and design [ 110 – 114 ], the age of the children studied [ 106 , 109 ], location of trial [ 115 – 117 ], and the different atropine doses, which varied between 0.0025% and 1%, as well as the application frequency of drops [ 110 , 114 , 118 , 119 ], and lastly their aims [ 109 , 111 , 112 , 120 ]. Almost half of the selected studies were conducted in East Asia, in predominately Chinese ethnic children [ 109 , 110 , 114 , 115 , 118 – 120 ]. Four studies were conducted in Europe [ 107 , 111 , 112 , 116 ], two in India [ 113 , 117 ], one in Iran [ 108 ], one in the USA [ 121 ], and one in Australia [ 106 ].…”

“…However, both the effect and safety of atropine remain controversial, which likely has led to differing opinions on its use [ 66 , 121 , 126 ]. In regions where atropine is relatively widely used to control myopia progression in children, studies are being conducted to investigate its use for preventing myopia onset in premyopic children and have shown positive results [ 109 , 120 ].…”

Daily Low-Level Red Light for Spherical Equivalent Error and Axial Length in Children With Myopia

“…Previously, few studies on myopia prevention were conducted because of ethical debates. Two recent studies explored the possibility of using atropine for myopia prevention and reported opposite findings. For 650-nm LLRL, a clinical trial reported a 54.1% reduction in incident myopia among children with premyopia within 12 months .…”

Efficacy and Safety of Low-Dose Atropine on Myopia Prevention in Premyopic Children: Systematic Review and Meta-Analysis

“…Despite its significance, a lack of consensus remains regarding the precise definition of premyopia. In addition, the lack of standardized tools for risk stratification and management in these children complicates this scenario [ 16 , 17 , 18 ].…”