Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control
Authors: Repka Michael X. , Weise Katherine K. , Chandler Danielle L. , Wu Rui , Melia B. Michele , Manny Ruth E. , Kehler Lori Ann F. , Jordan Catherine O. , Raghuram Aparna , Summers Allison I. , Lee Katherine A. , Petersen David B. , Erzurum S. A. , Pang Yi , Lenhart Phoebe D. , Ticho Benjamin H. , Beck Roy W. , Kraker Raymond T. , Holmes Jonathan M. , Cotter Susan A. ,   Pediatric Eye Disease Investigator Group, Alexopoulous Denise D. , Allen Megan , Anderson Heather A. , Austin Darrell S. , Black Shane C. , Boyle Nicole M. , Casey Grant Andrew , Chandler Moriah Adine , Chinn Ryan , Clausius Deborah A. , Colon Beth J, , Conner Courtney L. , Curtis Linda T. , Dinani Zainab , Donahue Quayleen , Dubois Michelle , Evans Patricia L. , Fimbel Brooke P. , Fowler Melanie Kay , Golden Richard P. , Harper Beth G. , Henderson Robert J. , Ho Dieu-Hong , Hoepner James E. , Hopkins Kristine B. , Jenks Ashli S. , Kaplon Joseph D. , Khan Shabana , Koutnik Cassandra A. , Kuo Annie F. , Lee Jessy , Martinez Muriel M. , Marusic Sophia M. , McGregor Mary Lou , McMurtrey J. Ryan , Miller Kathryn B. , Mokka Preeti L. , Montejo Jenifer , Morrell Beth A. , Nylin Elyse , Odom Kimberly C. , Ortiz Gillaine , Parra Samantha A. , Perkins Kyle J. , Plum Larry W. , Redenbo Ellen Fiona , Robinson Julianne L. , Stutz Kathleen M. , Sutherland Desirae R. , Teodorescu Mircea X. , Torgensen Lori L. , Toro David O. , Turner Phillip B. , Weil Natalie C. , Wiecek Emily K. , Wilkins Carsyn S. , Woodard Victoria C. , Woodruff Kevin M. , Yin Huizi , Yumang Marika L. , Yamada Tomohiko , Ekdawi Noha S. , Leske David A. , Wallace David K. , Christian Melanie L. , Glaser Stephen R. , Birch Eileen E. , Chen Angela M. , Christiansen Stephen P. , Enyedi Laura B. , Everett Donald F. , Freedman Sharon F. , Good William V. , Jenewein Erin C. , London Richard , Manh Vivian M. , Morrison David G. , Pineles Stacy L. , Ralay Ranaivo Hantamalala , Roberts Tawna L. , Ruark Scott T. , Schweinler Bonita R. , Silver Jayne L. , Suh Donny W. , Verderber Lisa C. , Diener-West Marie , Baker John D. , Davis Barry , Higgins Rosemary D. , Poff Stephen W. , Saunders Richard A. , Tychsen Lawrence 
Published: July 2023

Importance

Controlling myopia progression is of interest worldwide. Low-dose atropine eye drops have slowed progression in children in East Asia.

Objective

To compare atropine, 0.01%, eye drops with placebo for slowing myopia progression in US children.

Design, Setting, and Participants

This 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]).

Intervention

Eligible 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 and Measures

Automated 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.

Results

A 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 Relevance

In 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 Registration

ClinicalTrials.gov Identifier: NCT03334253