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- Title
Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial.
- Authors
Zadnik, Karla; Schulman, Erica; Flitcroft, Ian; Fogt, Jennifer S.; Blumenfeld, Louis C.; Fong, Tung M.; Lang, Eric; Hemmati, Houman D.; Chandler, Simon P.
- Abstract
This randomized clinical trial investigates if low-dose atropine, 0.01% or 0.02%, slows the progression of myopia in children. Key Points: Question: Does low-dose atropine in concentrations of 0.01% and/or 0.02% slow the progression of myopia? Finding: In this randomized clinical trial including 573 participants in the safety set and 489 participants in the modified intention-to-treat set over 3 years of therapy, 0.02% atropine vs placebo did not significantly increase the proportion of participants' eyes responding to therapy; however, 0.01% atropine increased the responder portion and reduced both myopia progression and axial elongation vs placebo over 3 years of therapy. Meaning: Trial results show that the efficacy and safety observed may be supportive of low dose atropine as a pharmacological treatment option for myopia progression in children. Importance: The global prevalence of myopia is predicted to approach 50% by 2050, increasing the risk of visual impairment later in life. No pharmacologic therapy is approved for treating childhood myopia progression. Objective: To assess the safety and efficacy of NVK002 (Vyluma), a novel, preservative-free, 0.01% and 0.02% low-dose atropine formulation for treating myopia progression. Design, Setting, and Participants: This was a double-masked, placebo-controlled, parallel-group, randomized phase 3 clinical trial conducted from November 20, 2017, through August 22, 2022, of placebo vs low-dose atropine, 0.01% and 0.02% (2:2:3 ratio). Participants were recruited from 26 clinical sites in North America and 5 countries in Europe. Enrolled participants were 3 to 16 years of age with −0.50 diopter (D) to −6.00 D spherical equivalent refractive error (SER) and no worse than −1.50 D astigmatism. Interventions: Once-daily placebo, low-dose atropine, 0.01%, or low-dose atropine, 0.02%, eye drops for 36 months. Main Outcomes and Measures: The primary, prespecified end point was the proportion of participants' eyes responding to 0.02% atropine vs placebo therapy (<0.50 D myopia progression at 36 months [responder analysis]). Secondary efficacy end points included responder analysis for atropine, 0.01%, and mean change from baseline in SER and axial length at month 36 in a modified intention-to-treat population (mITT; participants 6-10 years of age at baseline). Safety measurements for treated participants (3-16 years of age) were reported. Results: A total of 576 participants were randomly assigned to treatment groups. Of these, 573 participants (99.5%; mean [SD] age, 8.9 [2.0] years; 315 female [54.7%]) received trial treatment (3 participants who were randomized did not receive trial drug) and were included in the safety set. The 489 participants (84.9%) who were 6 to 10 years of age at randomization composed the mITT set. At month 36, compared with placebo, low-dose atropine, 0.02%, did not significantly increase the responder proportion (odds ratio [OR], 1.77; 95% CI, 0.50-6.26; P =.37) or slow mean SER progression (least squares mean [LSM] difference, 0.10 D; 95% CI, −0.02 D to 0.22 D; P =.10) but did slow mean axial elongation (LSM difference, −0.08 mm; 95% CI, −0.13 mm to −0.02 mm; P =.005); however, at month 36, compared with placebo, low-dose atropine, 0.01%, significantly increased the responder proportion (OR, 4.54; 95% CI, 1.15-17.97; P =.03), slowed mean SER progression (LSM difference, 0.24 D; 95% CI, 0.11 D-0.37 D; P <.001), and slowed axial elongation (LSM difference, −0.13 mm; 95% CI, −0.19 mm to −0.07 mm; P <.001). There were no serious ocular adverse events and few serious nonocular events; none was judged as associated with atropine. Conclusions and Relevance: This randomized clinical trial found that 0.02% atropine did not significantly increase the proportion of participants' eyes responding to therapy but suggested efficacy for 0.01% atropine across all 3 main end points compared with placebo. The efficacy and safety observed suggest that low-dose atropine may provide a treatment option for childhood myopia progression. Trial Registration: ClinicalTrials.gov Identifier: NCT03350620
- Publication
JAMA Ophthalmology, 2023, Vol 141, Issue 10, p990
- ISSN
2168-6165
- Publication type
Article
- DOI
10.1001/jamaophthalmol.2023.2097