3-year results of 0.01% and 0.1% loading dose atropine treatment including washout in Danish children with myopia: a placebo-controlled, randomised clinical trial

Aim: To examine the safety and efficacy of low-dose atropine (0.01% and 0.1% loading dose) after 2-year treatment and 1-year washout in 6-year-old to 12-year-old Danish children with myopia. Methods: Investigator-initiated, placebo-controlled, double-blind, randomised clinical trial. Of 124 screened children, 97 were randomised to receive 0.01% low-dose atropine for 24 months (0.01%) or 0.1% low-dose atropine for 6 months, then 0.01% for 18 months (0.1% loading dose) or placebo, followed by a 1-year washout. Altogether, 91 participants completed the study. The primary outcome was myopia progression (axial length (AL) and spherical equivalent refraction (SER)). Secondary outcomes were adverse events, ocular biometrical measurements and treatment responder eyes (myopia progression less than -0.50 diopters (D)). Constrained linear mixed models were constructed with individual eyes nested by participant ID, according to intention-to-treat. The responder analysis used Fisher's exact test. Significance levels were adjusted for multiple comparisons. Adjusted p values <0.05 were considered significant. Results: At 3 years, the mean AL was -0.06 mm (95% CI -0.18; 0.07) and -0.09 mm (95% CI -0.21; 0.04) less compared with placebo in the 0.1% loading dose group and 0.01% group. Mean SER was -0.02 D (95% CI -0.30; 0.26) less and 0.17 D (95% CI -0.11; 0.45) more compared with placebo in the 0.1% loading dose group and 0.01% group. There was no significant group difference in the responder eyes. Conclusion: There was no difference in myopia progression between groups following washout. A 6-month 0.1% loading dose did not improve efficacy compared with 0.01%. The 0.1% loading dose showed a rebound effect after dose switching.