Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study

Abstract

Purpose: To evaluate the efficacy and safety of 0.05%, 0.025%, and 0.01% atropine eye drops over 2 years to determine which is the optimal concentration for longer-term myopia control.Design: Randomized, double-masked trial extended from the Low-Concentration Atropine for Myopia Progression (LAMP) Study.Participants: Three hundred eighty-three of 438 children (87%) aged 4 to 12 years with myopia of at least e1.0 diopter (D) originally randomized to receive atropine 0.05%, 0.025%, 0.01%, or placebo once daily in both eyes in the LAMP phase 1 study were continued in this extended trial (phase 2).Methods: Children in the placebo group (phase 1) were switched to receive 0.05% atropine from the beginning of the second-year follow-up, whereas those in the 0.05%, 0.025%, and 0.01% atropine groups continued with the same regimen. Cycloplegic refraction, axial length (AL), accommodation amplitude, photopic and mesopic pupil diameter, and best-corrected visual acuity were measured at 4-month intervals.Main Outcome Measures: Changes in spherical equivalent (SE) and AL and their differences between groups.Results: Over the 2-year period, the mean SE progression was 0.55AE0.86 D, 0.85AE0.73 D, and 1.12AE0.85 D in the 0.05%, 0.025%, and 0.01% atropine groups, respectively (P ¼ 0.015, P < 0.001, and P ¼ 0.02, respectively, for pairwise comparisons), with mean AL changes over 2 years of 0.39AE0.35 mm, 0.50AE0.33 mm, and 0.59AE0.38 mm (P ¼ 0.04, P < 0.001, and P ¼ 0.10, respectively). Compared with the first year, the second-year efficacy of 0.05% and 0.025% atropine remained similar (P >0.1), but improved mildly in the 0.01% atropine group (P ¼ 0.04). For the phase 1 placebo group, the myopia progression was reduced significantly after switching to 0.05% atropine (SE change, 0.18 D in second year vs. 0.82 D in first year [P < 0.001]; AL elongated 0.15 mm in second year vs. 0.43 mm in first year [P < 0.001]). Accommodation loss and change in pupil size in all concentrations remained similar to the first-year results and were well tolerated. Visual acuity and vision-related quality of life remained unaffected.Conclusions: Over 2 years, the efficacy of 0.05% atropine observed was double that observed with 0.01% atropine, and it remained the optimal concentration among the studied atropine concentrations in slowing myopia progression. Ophthalmology 2020;127:910-919 ª 2019 by the American Academy of Ophthalmology Supplemental material available at www.aaojournal.org.Myopia is a public health threat worldwide, with increasing prevalence in most regions over the past decades and especially in East Asia. 1e4 Low-concentration atropine eye drops are an emerging therapy for myopia control, 5,6 but their optimal concentration and long-term efficacy remain undefined. In the first-year (phase 1) results of the Low-Concentration Atropine for Myopia Progression (LAMP) study, 0.05% atropine conferred the best treatment-to-side effect ratio among 0.05%, 0.025%, and 0.01% atropine over 1 year. 7 Of note, in the Atropine for the Treatment of Myopi...

Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia

“…The findings of the present study, which are supported by observations made in a previous investigation, may suggest that EGF and members of the EGFR family, such as amphiregulin, are some of the substances that were positively or negatively associated with the development of experimental myopia in previous studies. These substances include dopamine, acetylcholine, and other molecules from the cholinergic system and GABAergic system, insulin, glucagon, glucagon‐like peptide‐1, basic fibroblast growth factor, transforming growth factor beta, vasoactive intestinal polypeptide, retinoic acid, nitric oxide, and sonic hedgehog as well as molecules derived from genes like the FBJ osteosarcoma oncogene and immediate early genes 14‐35 . Experimental investigations and clinical randomized trials have shown that atropine eye drops applied in low concentrations reduce the rate of myopization 35 .…”

“…These substances include dopamine, acetylcholine, and other molecules from the cholinergic system and GABAergic system, insulin, glucagon, glucagon‐like peptide‐1, basic fibroblast growth factor, transforming growth factor beta, vasoactive intestinal polypeptide, retinoic acid, nitric oxide, and sonic hedgehog as well as molecules derived from genes like the FBJ osteosarcoma oncogene and immediate early genes 14‐35 . Experimental investigations and clinical randomized trials have shown that atropine eye drops applied in low concentrations reduce the rate of myopization 35 . In guinea pigs, tree shrews and in monkeys, the anticholinergic agent pirenzepine, which has a high affinity for the muscarinic M1 receptor, selectivity decreases axial elongation when intraocularly applied 26,29,30 .…”

One‐year results of 0.01% atropine with orthokeratology (AOK) study: a randomised clinical trial

“…[14][15][16][17][18][19][20] Various concentrations of atropine eye drops have been investigated, and a concentration-dependent effect was observed for both their clinical efficacy as well as adverse side effects. [21][22][23][24][25][26] In spite of reports of their effectiveness in slowing axial elongation, the use of 0.1%, 0.5%, and 1% atropine was not well-accepted due to concentration-dependent side effects, including light sensitivity, reduced near vision and a significant rebound effect after discontinuation. [21][22][23][24][25] Although it was reported that 0.01% atropine could effectively slow myopia progression in terms of refractive error, with negligible side effects, neither a 1year nor 2-year application of 0.01% atropine significantly retarded axial elongation.…”

“…[25][26][27] However, a recent study showed the effective, safe performance of other low concentrations (0.05%, 0.025%) of atropine eye drops over two years, but the longer-term outcomes have not been published. 26 Based on these studies, the optimal concentration of atropine, which balances long-term safety and effectiveness, remains to be determined. Currently, 0.01% atropine is the most commonly agent used in East Asia, especially in Taiwan and Singapore.…”

The Effect of 0.01% Atropine Eye Drops Combined with Auricular Acupoint Stimulation on Myopia Progression and Choroidal Thickness: The Preliminary Results from a Randomized Controlled Trial

“…Therefore, a higher concentration atropine has been intended for children who showed poor response to 0.01% atropine. In LAMP2 study [19], the e cacy of 0.05% atropine on myopia control was twice that of 0.01% atropine. However, 0.05% atropine induced 2 D accommodative amplitude loss and 1.25 mm pupil dilation, not favorable in terms of long-term safety.…”