Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children

Abstract

ImportanceEarly onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed.ObjectiveTo evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia.Design, Setting, and ParticipantsThis randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than −1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022.InterventionsParticipants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years.Main Outcomes and MeasuresThe primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least −0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D).ResultsOf the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year.Conclusions and RelevanceAmong children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety.Trial RegistrationChinese Clinical Trial Registry: ChiCTR-IPR-15006883

Can We Prevent or Delay the Onset of Myopia?

“…Methods evaluated include multifocal contact lenses, orthokeratology, and low-dose atropine eyedrops, which have had the most attention in randomized clinical trials (RCTs). The authors of the LAMP2 clinical trial reported in JAMA provide (in eTable 1 in their Supplement) an overview of 27 completed RCTs and 18 ongoing trials of low-dose atropine treatment. What is unique about the LAMP2 trial is its prophylactic rather than therapeutic focus.…”

“…Adherence to treatment in this trial was assessed by diaries kept by each participant's family. Good adherence was defined as participants receiving their assigned treatment for a weekly average of 5.25 days over the trial's 2-year period and was found to exceed 90% in all 3 groups, with only slight differences by atropine dose (eTable 3 in the Supplement for Yam et al 2 ) not judged to be relevant by the authors. As with any treatment that involves daily administration, and often in this case by a parent, adherence to atropine treatment that is reported in a trial context may well exceed that to be predicted in daily life.…”

Delaying the Onset of Nearsightedness

“…Three studies have indicated that nightly administration of low-concentration atropine eyedrops can delay the onset of myopia and/or reduce the shift of refractive error in the myopic direction. [14][15][16] The Low-Concentration Atropine for Myopia Prevention (LAMP2) study 17 reported in this issue of JAMA is the first large-scale, 2-year randomized clinical trial to investigate the effects of nightly administration of 0.05% or 0.01% atropine eyedrops vs placebo eyedrops in children without myopia. The objective of the study was to determine whether low-concentration atropine eyedrops could delay the onset of myopia and reduce the percentage of children who experience a 1.00 D myopic shift in refractive error.…”

Error in Figure

“…The Original Investigation titled “Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial,” published in the February 14, 2023, issue of JAMA , included an error in Figure 1 that indicated an incorrect number of participants included in the primary outcome analyses in the placebo group, a duplicate reference, and an incorrect funding number. These errors have been corrected online; Figure 1 now indicates the correct number of participants analyzed, the duplicate reference was removed, and the correct funding number is now included in the Funding section.…”