Study: 0.04% Atropine Outperforms Ortho-K and 0.01% Atropine for Myopia Control

A new randomized clinical trial from China compares 0.01% and 0.04% atropine with orthokeratology for pediatric myopia control. Published in JAMA Ophthalmology, the study found 0.04% atropine most effective in slowing axial elongation over two years. While results support mid-dose atropine use, expert commentary cautions against overinterpreting age-specific outcomes due to small subgroup sizes and potential behavioral confounders during COVID-19 lockdowns. Photo: Getty Images; Robert Ensley, OD. Click image to enlarge.  Atropine and orthokeratology (ortho-K) have emerged as effective and relatively safe therapies for myopia control in children and adolescents; however, clear guidance is lacking. The LAMP study demonstrated that 0.05% atropine successfully controls disease progression, but concerns remain about discomfort, leading most practitioners to opt for lower doses of the drug. Ortho-K, which also demonstrates the ability to slow myopia, carries risks such as corneal abrasion and infectious keratitis. The question of which method is more safe and effective—and for which ages—led a group of researchers from China to conduct a study comparing these therapies, the results of which were just published in JAMA Ophthalmology.1This was a three-arm, multicenter randomized clinical trial conducted in Shanghai. Participants included 209 children (49.8% female), aged eight to 15 years, with refractive errors between -1D and -4D. Children were placed in three groups: 0.01% atropine, 0.04% atropine and ortho-K. Roughly 70% of each group completed the two-year follow-up. The aggregate numbers of subjects in each group completing the trial were 48, 48 and 53, respectively—a point criticized by some as insufficiently powered. According to the results, the two-year axial length (AL) growth in the 0.01% atropine group was significantly greater than that in the 0.04% atropine group (difference, 0.18mm). However, no significant difference was found between the 0.01% atropine group and the ortho-K group (difference, 0.08mm). For secondary analyses, 0.04% atropine showed the best treatment effect at every visit, followed by ortho-K and 0.01% atropine. Age was negatively associated with eye elongation in all subjects, especially the 0.01% atropine group.Among adverse effects and events, photophobia occurred in 55.2% of participants in the 0.04% atropine group and in 25.3% of those in the 0.01% atropine group at the three-month visit. By the two-year visit, this declined in both groups, according to the study, to 22.9% and 2.1%, respectively.The researcher wrote in their paper, “In this study, AL growth in the 0.01% atropine or ortho-K groups was consistent with previous reports” but with some notable differences. The mean two-year axial elongation with 0.04% atropine was lower than expected, likely due to participants in this study being older than those in the LAMP study, but after adjusting for age, 0.04% appeared comparable to 0.05%.“In addition, although baseline myopia was milder in our study, the unclear association between baseline myopia and myopia progression under atropine treatment means this factor currently cannot explain the difference.”Overall, the researchers say, “our findings suggest that ortho-K should be used in younger children to maximize its advantage over 0.01% atropine; 0.04% atropine might benefit younger children with mild myopia, although further validation is needed.”Although the comparative design of this study is clinically valuable, an invited commentary, also published in JAMA Ophthalmology, raises some questions about the interpretation of the data.2 The commentary authors wrote that “some conclusions are surprising.” They cite the age range, eight to 15 years, as a period with marked differences in AL growth. “It is well established that AL elongation slows with age,” they wrote. “In the trial, nearly 75% of the 209 enrolled children were aged 11 years or younger, yet the authors attribute the superiority of 0.04% atropine over ortho-K to its use in ‘older children.’ What is the source of this insight, and what data support this conclusion?”In particular, the commentary authors referenced the study’s supplementary data on mean differences between treatment arms in two age strata at 24 months, “which indeed favors 0.04% over 0.01% atropine in younger children,” they wrote. “However, both of these figures support the possibility that 0.04% atropine outperforms ortho-K in younger children. Visual representations of the entire growth trajectories are lacking, and subgroups are so small (16-18 per group) that this conclusion lacks validity. A more solid interpretation is that 0.04% atropine is more effective than ortho-K and 0.01% atropine across the entire age range included in this study.”Additional drawbacks mentioned in the commentary are the small sample sizes in each treatment arm, as well as the absence of behavioral data. The authors wrote that spreading 209 participants across three treatment arms limited the statistical power to detect differences. “This is further complicated by the lack of information on behavioral confounders, such as outdoor time and near work,” they continued. “Given the study started in 2021, during periods of COVID-19–related school closures and lockdowns, these behavioral exposures were considerably more common with a potentially greater effect on results.”Ultimately, despite these debates, the commentary concluded that, “the key message is clear: 0.01% atropine for myopia control is insufficient, reinforcing the concept that particular higher dosages of atropine reach effective myopia control.” Click here for the journal source and here for the commentary. Xu H, Chen M, Ye L, et al. Orthokeratology, 0.04% atropine, and 0.01% atropine for myopia control: A randomized clinical trial. JAMA Ophthalmol. July 24, 2025. [Epub ahead of print.]Polling JR, Klaver CCW. Interpreting myopia control modalities in a 2-year trial. JAMA Ophthalmol. July 24, 2025. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.