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. 2023 Oct 1;141(10):990-999.
doi: 10.1001/jamaophthalmol.2023.2097.

Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial

Karla Zadnik  1 , Erica Schulman  2 , Ian Flitcroft  3 , Jennifer S Fogt  1 , Louis C Blumenfeld  4 , Tung M Fong  5 , Eric Lang  5 , Houman D Hemmati  5 , Simon P Chandler  5 ; CHAMP Trial Group Investigators
Collaborators, Affiliations

Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial

Karla Zadnik et al. JAMA Ophthalmol. .

Erratum in

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Zadnik reported receiving consultant fees from Vyluma Inc during the conduct of the study. Dr Schulman reported receiving logistical and financial support from SUNY College of Optometry during the conduct of the study. Dr Flitcroft reported receiving consulting fees from Vyluma Inc; personal fees from CooperVision, EsilorLuxottica, Johnson & Johnson Vision, and Thea; contractual fees for analyses from Ocumetra; and having the following patents pending outside the submitted work: 63/414,779; 63/348,256; 63/402,374; 17/767530; and 20788700.1. Dr Fogt reported receiving grants from Vyluma Inc (an affiliate of Nevakar), Bausch+Lomb, Eyenovia, Innovega, CooperVision, and Interojo; personal fees from Alcon; and financial support from Tearoptix outside the submitted work. Dr Blumenfeld reported receiving personal fees from Vyluma Inc during the conduct of the study. Dr Fong reported receiving consultant fees and being an employee of Vyluma Inc during the conduct of the study. Dr Lang reported receiving grants from Vyluma Inc during the conduct of the study. Dr Hemmati reported receiving personal fees and being an employee of Vyluma Inc outside the submitted work. Dr Chandler reported being an employee of Vyluma Inc outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Disposition
AE indicates adverse event; ITT, intention to treat; mITT, modified intention to treat.
Figure 2.
Figure 2.. Change in Ophthalmic Parameters Over Time
A, Proportion with less than 0.50-diopter (D) myopia progression (responder) (modified intention-to-treat [mITT] set). P value for odds ratio (OR) (low-dose atropine/placebo). B, Least squares mean change from baseline in spherical equivalent refractive error (SER; mITT set). P value for least squares mean difference (low-dose atropine − placebo). C, Least squares mean change from baseline in axial length (mITT set). P value for least squares mean difference (low-dose atropine − placebo).
See this image and copyright information in PMC

Comment in

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