Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control

Abstract

ImportanceControlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia.ObjectiveTo compare atropine, 0.01%, eye drops with placebo for slowing myopia progression in US children.Design, Setting, and ParticipantsThis was a randomized placebo-controlled, double-masked, clinical trial conducted from June 2018 to September 2022. Children aged 5 to 12 years were recruited from 12 community- and institution-based practices in the US. Participating children had low to moderate bilateral myopia (−1.00 diopters [D] to −6.00 D spherical equivalent refractive error [SER]).InterventionEligible children were randomly assigned 2:1 to 1 eye drop of atropine, 0.01%, nightly or 1 drop of placebo. Treatment was for 24 months followed by 6 months of observation.Main Outcome MeasuresAutomated cycloplegic refraction was performed by masked examiners. The primary outcome was change in SER (mean of both eyes) from baseline to 24 months (receiving treatment); other outcomes included change in SER from baseline to 30 months (not receiving treatment) and change in axial length at both time points. Differences were calculated as atropine minus placebo.ResultsA total of 187 children (mean [SD] age, 10.1 [1.8] years; age range, 5.1-12.9 years; 101 female [54%]; 34 Black [18%], 20 East Asian [11%], 30 Hispanic or Latino [16%], 11 multiracial [6%], 6 West/South Asian [3%], 86 White [46%]) were included in the study. A total of 125 children (67%) received atropine, 0.01%, and 62 children (33%) received placebo. Follow-up was completed at 24 months by 119 of 125 children (95%) in the atropine group and 58 of 62 children (94%) in the placebo group. At 30 months, follow-up was completed by 118 of 125 children (94%) in the atropine group and 57 of 62 children (92%) in the placebo group. At the 24-month primary outcome visit, the adjusted mean (95% CI) change in SER from baseline was −0.82 (−0.96 to −0.68) D and −0.80 (−0.98 to −0.62) D in the atropine and placebo groups, respectively (adjusted difference = −0.02 D; 95% CI, −0.19 to +0.15 D; P = .83). At 30 months (6 months not receiving treatment), the adjusted difference in mean SER change from baseline was −0.04 D (95% CI, −0.25 to +0.17 D). Adjusted mean (95% CI) changes in axial length from baseline to 24 months were 0.44 (0.39-0.50) mm and 0.45 (0.37-0.52) mm in the atropine and placebo groups, respectively (adjusted difference = −0.002 mm; 95% CI, −0.106 to 0.102 mm). Adjusted difference in mean axial elongation from baseline to 30 months was +0.009 mm (95% CI, −0.115 to 0.134 mm).Conclusions and RelevanceIn this randomized clinical trial of school-aged children in the US with low to moderate myopia, atropine, 0.01%, eye drops administered nightly when compared with placebo did not slow myopia progression or axial elongation. These results do not support use of atropine, 0.01%, eye drops to slow myopia progression or axial elongation in US children.Trial RegistrationClinicalTrials.gov Identifier: NCT03334253

Topical Atropine for Childhood Myopia Control

“…Zadnik et al also recently reported reduction in myopia progression in their secondary outcome of 0.01% atropine compared with placebo but not for the primary outcome of 0.02% atropine over 3 years of treatment. However, other similar randomized clinical trials by the National Eye Institute-sponsored Pediatric Eye Disease Investigator Group did not show a benefit of 0.01% atropine compared with placebo and suggested evaluation of the use of higher concentrations . While a Cochrane meta-analysis further supports that low dose atropine (less than 0.1%) had a mean treatment difference of 0.24 D with equivalence criteria being less than 0.25 D, these studies do not incorporate the recent lack of an effect for the primary 0.02% atropine trial by Zadnik et al nor the lack of an effect of the 0.01% atropine dose in the Pediatric Eye Disease Investigator Group.…”

“…Over the past decades, topical administration of atropine eye drops has been demonstrated to be a safe and effective intervention in slowing the onset of myopia and reducing myopia progression in children . However, a recent clinical trial of 0.01% low-dose atropine eye drops did not slow myopia progression or axial elongation in US children . Additionally, a recent meta-analysis reported that low-dose (less than 0.1%) atropine met the equivalence criterion (less than 0.25 diopters [D]) showing a mean treatment difference of 0.24 D .…”

Atropine Eye Drops for Myopia Control in Childhood—More Long-Term Data, Please

“…These initial study results led to the widespread administration and rapid adoption of nightly administration of low-dose atropine eye drops (0.01% to 0.05%) to young children with low myopia (−1 diopter [D] to −6 D) to slow progression of the myopia and axial elongation of the eye. More recently completed studies in Australia, North American, and Europe have found smaller or no effects of the low concentrations studied (0.01% and 0.02%) in terms of slowing myopia progression . Each of these randomized clinical trials was launched recognizing that the primary and secondary outcomes would necessarily be short term and thus would be unable to provide the long-term outcomes needed to completely assess efficacy and safety.…”

“…Nonetheless, the observation of increased risks for MMD with atropine concentrations of 0.1% and 0.5% deserves additional research. Of note, the 0.01% concentration used in many current studies did not show any increase in adverse events …”

JAMA Ophthalmology—The Year in Review, 2023

“…To assist with these challenges, beginning in 2024, the JAMA Ophthalmology editors are inviting experts to help synthesize such topics relevant to ophthalmology within succinct, relatively short summaries that follow the examples of JAMA Insights, JAMA Clinical Evidence Synopsis , and JAMA Clinical Guidelines Synopses . For example, 2 of the top 3 articles by views/downloads in 2023 (Table) were randomized clinical trials evaluating the potential risks and benefits of low-dose atropine eye drops vs placebo for myopia control. The goal of these educational initiatives will be to provide pithy evaluations across clinical trials like these for the busy reader and to synthesize new information rapidly that might change clinical practice in a way that is complementary to reviews, book chapters, or more extensive guidelines.…”