Huy Tran, M.D.
PhD candidate, Brien Holden Vision Institute
Although concentration-dependent efficacy and side effects were reported with atropine and a case made for low concentration atropine, i.e., 0.01% as an effective dose with lowered side effects, the lack of an appropriate placebo group rendered the data uncertain. The LAMP study was a randomized, double-masked, placebo-controlled study that aimed to determine the efficacy of three different low-concentration atropine eye drops, 0.05%, 0.025%, and 0.01% compared to 0.9% sodium chloride over a 1-year period. The study plans to continue beyond the 1-year period to further evaluate the efficacy, long-term safety, and rebound effects.
In the study, 438 myopic children aged between 4 and 12 years old were randomly allocated into four groups in a 1:1:1:1 ratio to receive nightly either one in three concentrations of atropine or the placebo drops. The primary variables studied were changes in spherical equivalent and axial length over a 1-year period. There were no significant differences between groups at the baseline visit. All of the participants were followed using an identical protocol at 2 weeks, 4, 8, and 12 months.
After one year, the mean change in spherical equivalent was −0.81 ± 0.53D, −0.59 ± 0.61D, −0.46 ± 0.45D,−0.27 ± 0.61D and the change in axial length was 0.41 ± 0.22 mm, 0.36 ± 0.29 mm, 0.29 ± 0.20 mm, 0.20 ± 0.25 mm in the placebo, 0.01%, 0.025% and 0.05% atropine eye drops, respectively. Atropine at 0.05% concentration showed the best efficacy in slowing myopia, whereas the change in axial length with 0.01% was not significant. The myopia control effects of low-concentration atropine were significant and dose-dependent concerning spherical equivalent and axial length, except the group of 0.01% atropine. Changes in accommodative amplitude and pupil diameter followed a concentration-dependent response, whereas visual acuity was not significantly affected and subjective symptoms were not significant.
The study confirmed the efficacy of low-concentration atropine at dose of 0.05% and 0.025% for slowing myopia but did not find 0.01% to be effective. Although the study was double masked, reporting of symptoms by the participants and the presence of a dilated pupil would have complicated masking, but the authors indicated that investigators involved in measuring outcome measures were always masked.
Yam JC, Jiang Y, Tang SM, Law AKP, Chan JJ, Wong E, Ko ST, Young AL, Tham CC, Chen LJ, Pang CP.
PURPOSE: Low-concentration atropine is an emerging therapy for myopia progression, but its efficacy and optimal concentration remain uncertain. Our study aimed to evaluate the efficacy and safety of low-concentration atropine eye drops at 0.05%, 0.025%, and 0.01% compared with placebo over a 1-year period.
DESIGN: Randomized, placebo-controlled, double-masked trial.
PARTICIPANTS: A total of 438 children aged 4 to 12 years with myopia of at least -1.0 diopter (D) and astigmatism of -2.5 D or less.
METHODS: Participants were randomly assigned in a 1:1:1:1 ratio to receive 0.05%, 0.025%, and 0.01% atropine eye drops, or placebo eye drop, respectively, once nightly to both eyes for 1 year. Cycloplegic refraction, axial length (AL), accommodation amplitude, pupil diameter, and best-corrected visual acuity were measured at baseline, 2 weeks, 4 months, 8 months, and 12 months. Visual Function Questionnaire was administered at the 1-year visit.
MAIN OUTCOME MEASURES: Changes in spherical equivalent (SE) and AL were measured, and their differences among groups were compared using generalized estimating equation.
RESULTS: After 1 year, the mean SE change was -0.27±0.61 D, -0.46±0.45 D, -0.59±0.61 D, and -0.81±0.53 D in the 0.05%, 0.025%, and 0.01% atropine groups, and placebo groups, respectively (P < 0.001), with a respective mean increase in AL of 0.20±0.25 mm, 0.29±0.20 mm, 0.36±0.29 mm, and 0.41±0.22 mm (P < 0.001). The accommodation amplitude was reduced by 1.98±2.82 D, 1.61±2.61 D, 0.26±3.04 D, and 0.32±2.91 D, respectively (P < 0.001). The pupil sizes under photopic and mesopic conditions were increased respectively by 1.03±1.02 mm and 0.58±0.63 mm in the 0.05% atropine group, 0.76±0.90 mm and 0.43±0.61 mm in the 0.025% atropine group, 0.49±0.80 mm and 0.23±0.46 mm in the 0.01% atropine group, and 0.13±1.07 mm and 0.02±0.55 mm in the placebo group (P < 0.001). Visual acuity and vision-related quality of life were not affected in each group.
CONCLUSIONS: The 0.05%, 0.025%, and 0.01% atropine eye drops reduced myopia progression along a concentration-dependent response. All concentrations were well tolerated without an adverse effect on vision-related quality of life. Of the 3 concentrations used, 0.05% atropine was most effective in controlling SE progression and AL elongation over a period of 1 year.
Yam, J. C., Jiang, Y., Tang, S. M., Law, A. K., Chan, J. J., Wong, E., … & Pang, C. P. (2019). Low-concentration Atropine for Myopia Progression (LAMP) study: a randomized, double-blinded, placebo-controlled trial of 0.05%, 0.025%, and 0.01% atropine eye drops in myopia control. Ophthalmology, 126(1), 113-124.