Two-Year Results of 0.01% Atropine Eye Drops and 0.1% Loading Dose for Myopia Progression Reduction in Danish Children: A Placebo-Controlled, Randomized Clinical Trial

Abstract

We investigated the two-year safety and efficacy of 0.1% loading dose and 0.01% low-dose atropine eye drops in Danish children for reduction in myopia progression in an 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 and then 0.01% for eighteen months (loading dose group, N = 33), 0.01% for two years (0.01% group, N = 32) or placebo for two years (placebo, N = 32). Axial length (AL) and spherical equivalent refraction (SER) were primary outcomes. Secondary outcomes included adverse events and reactions, choroidal thickness, and other ocular biometrical measures. Outcomes were measured from baseline and at six-month intervals. Individual eyes nested by participant ID were analyzed with linear-mixed model analysis. Data were analyzed with intention-to-treat. Mean AL was 0.08 mm less (95% confidence interval (CI): -0.01; 0.17, p-value = 0.08) in the 0.1% loading dose and 0.10 mm less (95% CI: 0.01; 0.19, p-value = 0.02) in the 0.01% group after two years of treatment compared to placebo. Mean SER progression was 0.12 D (95% CI: -0.10; 0.33) less in the loading dose and 0.26 D (95% CI: 0.04; 0.48) less in the 0.01% groups after two years of treatment compared to placebo (p-value = 0.30 and 0.02, respectively). In total, 17 adverse events were reported in the second-year follow-up, and all were rated as mild. Adjusting for iris color did not affect treatment effect estimates. Intra-ocular pressure increased over two years comparably between all groups but remained within normal limits. Two-year treatment with 0.01% low-dose atropine eye drops is a safe and moderately efficacious intervention in Danish children for reducing myopia progression.

Keywords: axial length; low-dose atropine; myopia; myopia control; spherical equivalent.

Figure 1

Flow-chart diagram (Consolidated Standards of Reporting Trials, CONSORT) of the study. Abbreviations: 0.1% loading dose, group that received 0.1% for the first six months followed by 0.01% for the following 18 months; 0.01%, group that received 0.01% for two years; N, number.

Figure 2

Changes in axial length during treatment with low-dose atropine or placebo in Danish myopic children. Mean change in axial length is estimated using linear mixed modeling by follow-up visit for the intervention groups. Error bars show the means’ 95% CI. Abbreviations: 0.1% loading dose, group that received 0.1% for six months and then 0.01% for 18 months; 0.01%, group that received 0.01% for two years; mm, millimeters; mo, month; placebo, group that received placebo eye drops for two years.

Figure 3

Changes in spherical equivalent refraction during treatment with low-dose atropine or placebo in Danish myopic children. Mean change in spherical equivalent refraction is estimated using linear mixed modeling by follow-up visit for the intervention groups. Error bars show the means’ 95% CI. Abbreviations: 0.1% loading dose, group that applied 0.1% for six months and then 0.01% for 18 months; 0.01%, group that applied 0.01% for two years; D, diopters; mo, month; placebo, group that applied placebo eye drops for two years.