Long-term atropine use to treat myopia associated with increased risk of ocular complication in schoolchildren in Taiwan

The drug’s long-term safety is uncertain without studies with relatively long durations of follow-up, and a gap remains between clinical trials and practice. Image credit: AdobeStock/LenaMay

Recently reported results showed that longer term use of atropine to treat myopia in schoolchildren was associated with a higher risk of development of ocular complications. The study, led by first author Yao-Lin Liu, MD, noted that this risk may be confounded by myopia severity and warrants further investigation. Liu is associated with the Department of Ophthalmology, National Taiwan University Hospital, College of Medicine, National Taiwan University, and the Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, both in Taipei, Taiwan.

The investigators published their findings in JAMA Ophthalmology.

Because of the increasing prevalence of myopia, investigators worldwide are searching for ways to control the vision-threatening epidemic.

Liu and colleagues commented, “Slowing myopia progression by just 1 diopter might reduce the likelihood of developing myopic maculopathy by 40%,^2,6 underscoring the potential importance of preventive strategies.^3,5 Atropine has been shown to reduce the risk of myopic progression in some studies but not others."^{4-11, 7-14}

In addition, the drug’s long-term safety is uncertain without studies with relatively long durations of follow-up, and a gap remains between clinical trials and practice.

Atropine study methodology

The researchers conducted a retrospective, population-based cohort study using longitudinal data from Taiwan’s National Health Insurance Research Database (2000-2021). They collected data on the prescription of atropine.

The study included childrenwho were 8 to 15 years of age and newly diagnosed myopia; the study also included matched children without myopia in the period between 2001 and 2015.

The goal was to determine the ocular risks associated with atropine prescription in clinical practice for myopia control in Taiwanese children. The children were categorized by the cumulative duration and dose of the drug.

The main outcomes were the diagnoses of cataracts, primary open-angle glaucoma, and maculopathy during the observation period. The incidence rates of ocular complications after a minimum 5-year follow-up period were reported.

What did the analysis of atropine find?

This large study included 1,213,846 Taiwanese children (mean ± standard deviation) age at myopia diagnosis, 10.4 ± 1.9 years; 633, 440 [52.2%] female). Of them, 606, 923 children had myopia, and 406 ,383 (67.0%) were prescribed atropine.

“The incidence of ocular complications (cataracts, glaucoma, and maculopathy) was higher in the myopia group (1.54/10 ,000 person-years) compared with the nonmyopia group (0.96/10 ,000 person-years; adjusted hazard ratio HR [aHR], 1.49; 95% confidence interval [CI], 1.36-1.64),” they reported.

A comparison of the incidence of ocular complications between children with myopia who were treated with atropine and those who were not showed no difference between the users and nonusers (both 1.54/10 ,000 person-year; aHR, 1.05; 95% CI, 0.93-1.18).

The investigators did see an increased risk of development of ocular complications in children who used atropine for longer than 3 years (aHR, 1.51; 95% CI, 1.17-1.94). However, they pointed out, this trend was not present in children with high myopia (aHR, 1.10; 95% CI, 0.56-2.19). No increased risk was found among children with the highest quartile of cumulative atropine dose (aHR, 1.05; 95% CI, 0.89-1.25).

Liu and colleagues concluded, “This study found that longer term atropine prescription for myopia control was associated with an increased risk of ocular complications among schoolaged children; however, this risk may be confounded primarily by myopia severity and warrants further investigation. Notably, this study did not find an association of cumulative doses of atropine with an increased incidence of ocular complications. The risk of ocular complications from myopia may exceed that associated with long-term atropine use. These findings support monitoring of children receiving atropine for myopia treatment if these results are confirmed by future studies that address the limitations of this investigation.”

References:

1. Liu Y-L, Tsai J-T, Chiu K-Y, et al. Ocular risks of topical atropine prescriptions among Taiwanese children. JAMA Ophthalmol. 2025; published online September 11. doi: 10.1001/jamaophthalmol.2025.3090

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8. Repka MX, Weise KK, Chandler DL, et al; Pediatric Eye Disease Investigator Group. Low-dose 0.01% atropine eye drops vs placebo for myopia control: a randomized clinical trial. JAMA Ophthalmol. 2023;141:756-765. doi: 10.1001/jamaophthalmol.2023.2855

9. Zadnik K, Schulman E, Flitcroft I, et al; CHAMP Trial Group Investigators. Efficacy and safety of 0.01% and 0.02% atropine for the treatment of pediatric myopia progression over 3 years: a randomized clinical trial. JAMA Ophthalmol. 2023;141:990-999. doi:10.1001/jamaophthalmol.2023.2097

10. Zhang XJ, Zhang Y, Yip BHK, et al. Five-year clinical trial of the Low-Concentration Atropine for Myopia Progression (LAMP) study: phase 4 report. Ophthalmology. 2024;131(9):1011-1020. doi:10.1016/j.ophtha.2024.03.013

11. Loughman J, Lingham G, Nkansah EK, Kobia-Acquah E, Flitcroft DI. Efficacy and safety of different atropine regimens for the treatment of myopia in children: three-year results of the MOSAIC randomized clinical trial. JAMA Ophthalmol. 2025;143:134-144. doi:10.1001/jamaophthalmol.2024.5703