December 15, 2023
By Dwight Akerman, OD, MBA, FAAO, FBCLA, FIACLE
Photo Credit: Geza Farkas, Dreamstime
Clinical trial results of topical atropine eye drops for childhood myopia control have been inconsistent across different short-term trials, making it crucial to establish its long-term safety and efficacy. To address this, researchers from the Singapore Eye Research Institute conducted the Atropine Treatment Long-term Assessment Study (ATLAS) to assess the 20-year follow-up outcomes and safety for the patients who participated in the ATOM1 study and the 10-year follow-up outcomes for the patients who took part in the ATOM2 study.
The ATLAS results, published recently in JAMA Ophthalmology, highlight the importance of randomized short-term treatment trials complemented with long-term follow-up of participants whenever the medical condition being studied may continue to progress after stopping the intervention. Myopia progression may continue for up to two decades after completing the randomized portion as well as the initial post-treatment observation portion of those trials.
The ATLAS study was a prospective, double-masked observational study of the ATOM1 and ATOM2 randomized clinical trials that took place at two single centers and included adults reviewed in 2021 through 2022 from the ATOM1 study (atropine 1% vs. placebo; 1999 through 2003) and the ATOM2 study (atropine 0.01% vs. 0.1% vs 0.5%; 2006 through 2012). In these cohorts, the use of short-term topical atropine eye drops ranging from 0.01% to 1.0% for two to four years starting at approximately 9 years of age with moderate myopia was not associated with differences in final refractive errors 10 to 20 years after treatment. There was no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group vs. the placebo group.
The researchers wrote in their paper that this study may support existing literature that atropine may be ineffective at reducing myopia progression, with this study specifically examining progress into adulthood through observation of outcomes over a 10- to 20-year period. These observations raise several research questions that warrant further study, including the duration of atropine treatment required to provide a sustained outcome, when treatment can be stopped, and whether tapering dosage or continuing treatment into the mid-teenage years is necessary.
The researchers concluded that among approximately one-quarter of the original participants, use of short-term topical atropine eye drops ranging from 0.01% to 1.0% for a duration of two to four years during childhood was not associated with differences in final refractive errors 10 to 20 years after treatment. There was no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group vs the placebo group. These findings may affect the design of future clinical trials, as further studies are required to investigate the duration and concentration of atropine for childhood myopia control.
An invited commentary by pediatric ophthalmologist Professor Michael Repka, MD, also published in JAMA Ophthalmology, pointed out that the ATLAS results did provide some assurance of safety as there were no differences in the rate of adverse events in all but one of their analyses. However, the long-term outcome data of atropine eye drops for myopia control needs to be interpreted with caution and largely should serve as a guide for future research planning. Dr. Repka noted that the long-term effectiveness of atropine for myopia control was called into question, and the findings were disappointing. After long-term follow-up of ATOM1 (about 20 years) and ATOM2 (about 10 years), 1.0% atropine eye drops for myopia control were not better than placebo or untreated eyes in ATOM1 and between concentrations in ATOM2 (0.01%, 0.1% and 0.5%) in terms of long-term refractive error outcomes. Myopic progression after the randomized clinical trial in ATOM2 was greater after stopping an atropine concentration of 0.5% than with lower concentrations (0.01% and 0.1%), thereby eliminating the initial benefit seen with the stronger dosage as was seen in earlier follow-up. Greater post-treatment progression was associated with younger age at treatment, identifying this as the group to target in future studies.
The commentary concluded that the ATLAS results remind us that there is uncertainty regarding the long-term value of atropine eye drops for myopia progression control. These findings highlight the need for randomized clinical studies to define effective and safe myopia control strategies early in myopia development but also include methods to obtain critical long-term studies of refractive error outcomes.
Abstract
Topical Atropine for Childhood Myopia Control: The Atropine Treatment Long-Term Assessment Study
Yong Li, Michelle Yip, Yilin Ning, Joey Chung, Angeline Toh, Cheryl Leow, Nan Liu, Daniel Ting, Leopold Schmetterer, Seang-Mei Saw, Jost B Jonas, Audrey Chia, Marcus Ang
Importance: Clinical trial results of topical atropine eye drops for childhood myopia control have shown inconsistent outcomes across short-term studies, with little long-term safety or other outcomes reported.
Objective: To report the long-term safety and outcomes of topical atropine for childhood myopia control.
Design, Setting, and Participants: This prospective, double-masked observational study of the Atropine for the Treatment of Myopia (ATOM)1 and ATOM2 randomized clinical trials took place at 2 single centers and included adults reviewed in 2021 through 2022 from the ATOM1 study (atropine 1% vs placebo; 1999 through 2003) and the ATOM2 study (atropine 0.01% vs 0.1% vs 0.5%; 2006 through 2012).
Main Outcome Measures: Change in cycloplegic spherical equivalent (SE) with axial length (AL); incidence of ocular complications.
Results: Among the original 400 participants in each original cohort, the study team evaluated 71 of 400 ATOM1 adult participants (17.8% of original cohort; study age, mean [SD] 30.5 [1.2] years; 40.6% female) and 158 of 400 ATOM2 adult participants (39.5% of original cohort; study age, mean [SD], 24.5 [1.5] years; 42.9% female) whose baseline characteristics (SE and AL) were representative of the original cohort. In this study, evaluating ATOM1 participants, the mean (SD) SE and AL were −5.20 (2.46) diopters (D), 25.87 (1.23) mm and –6.00 (1.63) D, 25.90 (1.21) mm in the 1% atropine-treated and placebo groups, respectively (difference of SE, 0.80 D; 95% CI, −0.25 to 1.85 D; P = .13; difference of AL, −0.03 mm; 95% CI, −0.65 to 0.58 mm; P = .92). In ATOM2 participants, the mean (SD) SE and AL was −6.40 (2.21) D; 26.25 (1.34) mm; −6.81 (1.92) D, 26.28 (0.99) mm; and −7.19 (2.87) D, 26.31 (1.31) mm in the 0.01%, 0.1%, and 0.5% atropine groups, respectively. There was no difference in the 20-year incidence of cataract/lens opacities, myopic macular degeneration, or parapapillary atrophy (β/γ zone) comparing the 1% atropine-treated group vs the placebo group.
Conclusions and Relevance: Among approximately one-quarter of the original participants, use of short-term topical atropine eye drops ranging from 0.01% to 1.0% for a duration of 2 to 4 years during childhood was not associated with differences in final refractive errors 10 to 20 years after treatment. There was no increased incidence of treatment or myopia-related ocular complications in the 1% atropine-treated group vs the placebo group. These findings may affect the design of future clinical trials, as further studies are required to investigate the duration and concentration of atropine for childhood myopia control.
Key Points
Question: What long-term outcomes were noted in adulthood among individuals receiving atropine during childhood for myopia?
Findings: Among approximately one-quarter of the original cohort who received childhood atropine treatment (0.01% to 1.0%) for myopia control (2 to 4 years duration), there were no identified differences in final refractive errors. There was no association with increased incidence of treatment or myopia-related ocular complications in 1% atropine-treated vs placebo groups.
Meaning: Long-term follow-up of a minority of participants who received atropine for a limited duration during childhood did not affect final refractive errors or incidence of ocular complications in adulthood.
Li Y, Yip M, Ning Y, et al. Topical atropine for childhood myopia control: the atropine treatment long-term assessment study. JAMA Ophthalmol. November 30, 2023. [Epub ahead of print].
DOI: https://doi.org/10.1001/jamaophthalmol.2023.5467
Repka MX. Atropine eye drops for myopia control in childhood—more long-term data, please. JAMA Ophthalmol. November 30, 2023. [Epub ahead of print].
DOI: https://doi.org/10.1001/jamaophthalmol.2023.5610
