Safety and efficacy of 0.01% and 0.1% low-dose atropine eye drop regimens for reduction of myopia progression in Danish children: a randomized clinical trial examining one-year effect and safety

Abstract

Background: To investigate the efficacy and safety of 0.1% and 0.01% low-dose atropine eye drops in reducing myopia progression in Danish children.

Methods: Investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months followed by 0.01% for six months (loading dose group, Number (N) = 33), 0.01% for twelve months (0.01% group, N = 32) or vehicle for twelve months (placebo, N = 32). Primary outcomes were axial length and spherical equivalent refraction. Secondary outcomes included adverse events and reactions, choroidal thickness and ocular biometry. Outcomes were measured at baseline and three-month intervals. Data was analyzed with linear-mixed model analysis according to intention-to-treat.

Results: Mean axial elongation was 0.10 mm less (95% confidence interval (CI): 0.17; 0.02, adjusted-p = 0.06) in the 0.1% loading dose and 0.07 mm less (95% CI: 0.15; 0.00, adjusted-p = 0.16) in the 0.01% group at twelve months compared to placebo. Mean spherical equivalent refraction progression was 0.24 D (95% CI: 0.05; 0.42) less in the loading dose and 0.19 D (95% CI: 0.00; 0.38) less in the 0.01% groups at twelve months, compared to placebo (adjusted-p = 0.06 and 0.14, respectively). A total of 108 adverse events were reported during the initial six-month loading dose period, primarily in the loading dose group, and 14 were reported in the six months following dose switching, all deemed mild except two serious adverse events, unrelated to the intervention.

Conclusions: Low-dose atropine eye drops are safe over twelve months in otherwise healthy children. There may be a modest but clinically relevant reduction in myopia progression in Danish children after twelve months treatment, but the effect was statistically non-significant after multiple comparisons adjustment. After dose-switching at six months the loading dose group approached the 0.01% group, potentially indicating an early "rebound-effect".

Trial registration: this study was registered in the European Clinical Trials Database (EudraCT, number: 2018-001286-16) 05/11/2018 and first posted at www.

Clinicaltrials: gov (NCT03911271) 11/04/2019, prior to initiation.

Keywords: Atropine; Axial length; Eye drops; Myopia; Myopia control; Spherical equivalent refraction.

Fig. 1

Consolidated Standards of Reporting Trials (CONSORT) flow-chart diagram of the study. Abbreviations: 0.1% loading dose, group receiving 0.1% for the first six months followed by 0.01% for 18 months; 0.01%, group receiving 0.01% for 24 months; N, Number

Fig. 2

Estimated mean change in Axial Length pr. visit divided by intervention group. Error bars denote the 95% CI of the mean changes. Abbreviations: 0.1% loading dose, group receiving 0.1% for the first six months followed by 0.01% for 18 months; 0.01%, group receiving 0.01% for 24 months; mm, millimeters; mo, month; placebo, group receiving vehicle eye drops for 24 months

Fig. 3

Estimated mean change in Spherical Equivalent Refraction pr. visit divided by intervention group. Error bars denote the 95% CI of the mean changes. Abbreviations: 0.1% loading dose, group receiving 0.1% for the first six months followed by 0.01% for 18 months; 0.01%, group receiving 0.01% for 24 months; mm, millimeters; mo, month; placebo, group receiving vehicle eye drops for 24 months; D, diopters; mo, month; placebo, group receiving vehicle eye drops for 24 months