Low-dose Atropine for Pediatric Myopia Progression Found Effective in Phase 3 Trial

Low-dose atropine at 0.01% concentration, was found to be effective in 3 main end points for the treatment of childhood myopia progression, which may indicate its validity as a treatment option. The study, published in JAMA Ophthalmology, also evaluated the efficacy of low-dose atropine at the 0.02% concentration compared with placebo.

The global prevalence of myopia was estimated to be 30% to 34% in 2020 and could increase to 50% by 2050. Atropine has been used as a treatment, as it may block receptors through the eye in order to limit choroidal and scleral thinning and slow eye elongation. Low-dose atropine is used off label in the United States.

This study aimed to report the 3-year results of the Childhood Atropine for Myopia Progression (CHAMP) phase 3 trial “that evaluated the efficacy and safety of low-dose atropine at concentrations of 0.01% and 0.02% vs placebo to treat myopia progression in children.”

The phase 3 trial was 3-armed, parallel, randomized, multicenter, double-masked, and placebo-controlled. The study was conducted in 27 clinical sites across North America and Europe. The safety and efficacy phase of the trial spanned 36 months, with participants randomly assigned to receive placebo, atropine 0.01%, or atropine 0.02% in a 2:2:3 ratio. Randomization was done by age and by refractive error. Participants in the placebo group were given medication of identical formulation but without the atropine.

Participants were included if they were aged 3 to 17 years or younger at the time of enrollment, had a myopic SER of –0.50 to –6.00 D in each eye, had astigmatism of no more than –1.50 D in each eye, and had anisometropic SER of less than 1.50 D. Participants were excluded if they had a history of ocular disease or surgery. The primary objective of the trial was to assess the progression of myopia in participants who were aged 6 to 10 years at the time of randomization. The primary end point was the number of participants who had less than 0.50 D progression of myopia from baseline at month 36.

There were 573 participants included in the study with a mean (SD) age of 8.9 (2.0) years; female participants made up 54.5% of the participants. A total of 53.8% of participants identified as White, 14.1% as Black or African American, 27.1% as Hispanic or Latino, 19% as Asian, and 11.2% as Other.

The difference in efficacy vs placebo was found to be significant for atropine 0.01% (odds ratio [OR], 4.54; 95% CI, 1.15-17.97) but not significant in atropine 0.02% (OR, 1.77; 95% CI, 0.50-6.26). Significantly higher responder rates were found in people who took atropine 0.01% compared with placebo whereas atropine 0.02% was only significant vs place at month 12 (OR, 4.78; 95% CI, 1.75-13.04).

Change in SER from baseline (LSM) after 36 months was –1.28 D (95% CI, –1.37 D to –1.19 D) in the placebo, –1.04 D (95% CI, –1.14 D to –0.94 D) in the atropine 0.01% group, and –1.18 D (95% CI, –1.26 D to –1.10 D) in the group that took atropine 0.02%. Atropine 0.01% was also able to reduce mean SER progression at month 24 (LSM change, 0.22 D; 95% CI, 0.08 D-0.35 D) whereas atopine 0.02% was able to reduce the mean SER progression at month 12 by 0.12 D (95% CI, 0-0.24 D).

LSM change from baseline to month 36 was 0.81 mm (95% CI, 0.76 mm-0.85 mm) in axial length in the placebo group, 0.68 mm (95% CI, 0.63 mm-0.72 mm) in the atropine 0.01 group, and 0.73 mm (95% CI, 0.69 mm-0.76 mm).

No increase in treatment-emergent adverse events associated with nonocular anti-muscarinic function with low-dose atropine treatments was found and there were no serious ocular treatment-emergent adverse events.

Potential bias that was introduced by participants who discontinued the trial medication and switched to confounding treatments was a limitation of this study. The relatively lower representation of participants who were aged 3 to 5 years and 11 to 17 years also acted as a limitation to this study.

The researchers concluded that atropine 0.01% was able to slow the progression of myopia in children aged 6 to 10 years. Atropine 0.01% was also able to increase the proportion of eyes with less than 0.5 D myopia progression after being treated for 3 years.

Reference

Zadnik K, Schulman E, Flitcroft I, et al. Efficacy and safety of 0.01% and 0.02% atropine for the treatment of pediatric myopia progression over 3 years: a randomized clinical trial. JAMA Ophthalmol. Published online June 1, 2023. doi:10.1001/jamaophthalmol.2023.2097