Efficacy and Safety of Consecutive Use of 1% and 0.01% Atropine for Myopia Control in Chinese Children: The Atropine for Children and Adolescent Myopia Progression Study

Luyao Ye, Hannan Xu, Ya Shi, Yao Yin, Tao Yu, Yajun Peng, Shanshan Li, Jiangnan He, Jianfeng Zhu, Xun Xu, Luyao Ye, Hannan Xu, Ya Shi, Yao Yin, Tao Yu, Yajun Peng, Shanshan Li, Jiangnan He, Jianfeng Zhu, Xun Xu

Abstract

Introduction: The purpose of this study was to investigate the efficacy and safety of consecutive use of 1% and 0.01% atropine compared with 0.01% atropine alone over 1 year.

Methods: A total of 207 participants aged 6-12 years with myopia of - 0.50 to - 6.00 D in both eyes were enrolled in this randomized, controlled, non-masked trial and randomly assigned (1:1) to groups A and B. Group A received 1% atropine weekly and were tapered to 0.01% atropine daily at the 6-month visit, and group B received 0.01% atropine daily for 1 year.

Results: Of the 207 participants, 109 were female (52.7%) and the mean (± standard deviation) age was 8.92 ± 1.61 years. Ninety-one participants (87.5%) in group A and 80 participants (77.7%) in group B completed the 1-year treatment. Group A exhibited less refraction progression (- 0.53 ± 0.49 D vs. - 0.74 ± 0.52 D; P = 0.01) and axial elongation (0.26 ± 0.17 mm vs. 0.36 ± 0.21 mm; P < 0.001) over 1 year compared with group B. The changes in refraction (- 0.82 ± 0.45 D vs. - 0.46 ± 0.35 D; P < 0.001) and axial length (0.29 ± 0.12 mm vs. 0.17 ± 0.11 mm; P < 0.001) during the second 6 months in group A were greater than those in group B, with 72.5% of participants presenting refraction rebound. No serious adverse events were reported.

Conclusions: The 1-year results preliminarily suggest that consecutive use of 1% and 0.01% atropine confers an overall better effect in slowing myopia progression than 0.01% atropine alone, despite myopia rebound after the concentration switch. Both regimens were well tolerated. The long-term efficacy and rebound after the concentration switch and regimen optimization warrant future studies to determine.

Trial registration number: Clinical Trials.gov PRS (Registration No. NCT03949101).

Keywords: Atropine; Consecutive use; Myopia control; Myopia rebound.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flowchart of the Atropine for Children and Adolescent Myopia Progression study
Fig. 2
Fig. 2
Changes in ocular parameters in two treatment groups over time: a spherical equivalent; b axial length; c lens power. Error bars represent standard error. D = diopter
Fig. 3
Fig. 3
Distribution of mild, moderate, and severe myopia progression over time in two treatment groups. Myopia progression if less than 0.00 D (no progression), between 0.00 D and less than 0.50 D (mild progression), between 0.50 D and less than 1.00 D (moderate progression), and greater than 1.00 D (severe progression)

References

    1. Holden BA, Fricke TR, Wilson DA, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016;123:1036–1042. doi: 10.1016/j.ophtha.2016.01.006.
    1. Fricke TR, Jong M, Naidoo KS, et al. Global prevalence of visual impairment associated with myopic macular degeneration and temporal trends from 2000 through 2050: systematic review, meta-analysis and modelling. Br J Ophthalmol. 2018;102:855–862. doi: 10.1136/bjophthalmol-2017-311266.
    1. Gong Q, Janowski M, Luo M, et al. Efficacy and adverse effects of atropine in childhood myopia: a meta-analysis. JAMA Ophthalmol. 2017;135:624–630. doi: 10.1001/jamaophthalmol.2017.1091.
    1. Chia A, Chua WH, Cheung YB, et al. Atropine for the treatment of childhood myopia: safety and efficacy of 0.5%, 0.1%, and 0.01% doses (Atropine for the Treatment of Myopia 2) Ophthalmology. 2012;119:347–354. doi: 10.1016/j.ophtha.2011.07.031.
    1. Yam JC, Jiang Y, Tang SM, et al. 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. 2019;126:113–124. doi: 10.1016/j.ophtha.2018.05.029.
    1. Yam JC, Li FF, Zhang X, et al. Two-year clinical trial of the low-concentration atropine for myopia progression (LAMP) study: phase 2 report. Ophthalmology. 2020;127:910–919. doi: 10.1016/j.ophtha.2019.12.011.
    1. Foo LL, Htoon H, Farooqui SZ, Chia A. Part-time use of 1% atropine eye drops for prevention of myopia progression in children. Int Ophthalmol. 2020;40:1857–1862. doi: 10.1007/s10792-020-01356-x.
    1. Ye L, Shi Y, Yin Y, et al. Effects of atropine treatment on choroidal thickness in myopic children. Invest Ophthalmol Vis Sci. 2020;61:15.
    1. Tong L, Huang XL, Koh AL, Zhang X, Tan DT, Chua WH. Atropine for the treatment of childhood myopia: effect on myopia progression after cessation of atropine. Ophthalmology. 2009;116:572–579. doi: 10.1016/j.ophtha.2008.10.020.
    1. Chia A, Chua WH, Wen L, Fong A, Goon YY, Tan D. Atropine for the treatment of childhood myopia: changes after stopping atropine 0.01%, 0.1% and 0.5% Am J Ophthalmol. 2014;157:451–457. doi: 10.1016/j.ajo.2013.09.020.
    1. Polling JR, Tan E, Driessen S, et al. A 3-year follow-up study of atropine treatment for progressive myopia in Europeans. Eye (Lond) 2020;34:2020–2028. doi: 10.1038/s41433-020-1122-7.
    1. Zhu Q, Tang Y, Guo L, et al. Efficacy and safety of 1% atropine on retardation of moderate myopia progression in Chinese school children. Int J Med Sci. 2020;17:176–181. doi: 10.7150/ijms.39365.
    1. Ye L, Li S, Shi Y, et al. Comparisons of atropine versus cyclopentolate cycloplegia in myopic children. Clin Exp Optom. 2021;104:143–150. doi: 10.1111/cxo.13128.
    1. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–497. doi: 10.1056/NEJMra050100.
    1. Rozema JJ, Atchison DA, Tassignon MJ. Comparing methods to estimate the human lens power. Invest Ophthalmol Vis Sci. 2011;52:7937–7942. doi: 10.1167/iovs.11-7899.
    1. Duenas M, Salazar A, Ojeda B, Arana R, Failde I. Generalized estimating equations (GEE) to handle missing data and time-dependent variables in longitudinal studies: an application to assess the evolution of health related quality of life in coronary patients. Epidemiol Prev. 2016;40:116–123.
    1. Wei S, Li SM, An W, et al. Safety and efficacy of low-dose atropine eyedrops for the treatment of myopia progression in Chinese children: a randomized clinical trial. JAMA Ophthalmol. 2020;138(11):1178. doi: 10.1001/jamaophthalmol.2020.3820.
    1. Fu A, Stapleton F, Wei L, et al. Effect of low-dose atropine on myopia progression, pupil diameter and accommodative amplitude: low-dose atropine and myopia progression. Br J Ophthalmol. 2020;104:1535–1541.
    1. Jiang Y, Zhu Z, Tan X, et al. Effect of repeated low-level red-light therapy for myopia control in children: a multicenter randomized controlled trial. Ophthalmology. 2022;129:509–519. doi: 10.1016/j.ophtha.2021.11.023.
    1. He M, Du Y, Liu Q, et al. Effects of orthokeratology on the progression of low to moderate myopia in Chinese children. BMC Ophthalmol. 2016;16:126. doi: 10.1186/s12886-016-0302-5.
    1. Lyu Y, Ji N, Fu AC, et al. Comparison of administration of 0.02% atropine and orthokeratology for myopia control. Eye Contact Lens. 2021;47:81–85. doi: 10.1097/ICL.0000000000000699.
    1. Lam CSY, Tang WC, Tse DY, et al. Defocus incorporated multiple segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical trial. Br J Ophthalmol. 2020;104:363–368. doi: 10.1136/bjophthalmol-2018-313739.
    1. Chamberlain P, Peixoto-de-Matos SC, Logan NS, Ngo C, Jones D, Young G. A 3-year randomized clinical trial of misight lenses for myopia control. Optom Vis Sci. 2019;96:556–567. doi: 10.1097/OPX.0000000000001410.
    1. Saw SM, Tong L, Chua WH, et al. Incidence and progression of myopia in Singaporean school children. Invest Ophthalmol Vis Sci. 2005;46:51–57. doi: 10.1167/iovs.04-0565.
    1. Hu Y, Ding XH, Guo XX, Chen YX, Zhang J, He MG. Association of age at myopia onset with risk of high myopia in adulthood in a 12-year follow-up of a Chinese cohort. JAMA Ophthalmol. 2020;138:1129–1134. doi: 10.1001/jamaophthalmol.2020.3451.
    1. Barathi VA, Weon SR, Beuerman RW. Expression of muscarinic receptors in human and mouse sclera and their role in the regulation of scleral fibroblasts proliferation. Mol Vis. 2009;15:1277–1293.
    1. Barathi VA, Beuerman RW. Molecular mechanisms of muscarinic receptors in mouse scleral fibroblasts: prior to and after induction of experimental myopia with atropine treatment. Mol Vis. 2011;17:680–692.
    1. Liu Q, Wu J, Wang X, Zeng J. Changes in muscarinic acetylcholine receptor expression in form deprivation myopia in guinea pigs. Mol Vis. 2007;13:1234–1244.
    1. Iribarren R. Crystalline lens and refractive development. Prog Retin Eye Res. 2015;47:86–106. doi: 10.1016/j.preteyeres.2015.02.002.
    1. Wu JF, Bi HS, Wang SM, et al. Refractive error, visual acuity and causes of vision loss in children in Shandong, China. The Shandong Children Eye Study. PLoS ONE. 2013;8:e82763. doi: 10.1371/journal.pone.0082763.
    1. He M, Zeng J, Liu Y, Xu J, Pokharel GP, Ellwein LB. Refractive error and visual impairment in urban children in southern China. Invest Ophthalmol Vis Sci. 2004;45:793–799. doi: 10.1167/iovs.03-1051.
    1. Tedja MS, Haarman AEG, Meester-Smoor MA, et al. IMI—myopia genetics report. Invest Ophthalmol Vis Sci. 2019;60:M89–M105. doi: 10.1167/iovs.18-25965.
    1. Yip VC, Pan CW, Lin XY, et al. The relationship between growth spurts and myopia in Singapore children. Invest Ophthalmol Vis Sci. 2012;53:7961–7966. doi: 10.1167/iovs.12-10402.
    1. Bez D, Megreli J, Bez M, Avramovich E, Barak A, Levine H. Association between type of educational system and prevalence and severity of myopia among male adolescents in Israel. JAMA Ophthalmol. 2019;137:887–893. doi: 10.1001/jamaophthalmol.2019.1415.
    1. He X, Sankaridurg P, Wang J, et al. Time outdoors in reducing myopia: a school-based cluster randomized trial with objective monitoring of outdoor time and light intensity. Ophthalmology. 2022 doi: 10.1016/j.ophtha.2022.06.024.
    1. Popova J, Robeva A, Zaharieva S. Muscarinic receptor activity change after prolonged treatment with growth hormone and somatostatin. Comp Biochem Physiol C Comp Pharmacol Toxicol. 1990;96:119–123. doi: 10.1016/0742-8413(90)90055-E.
    1. Cardoso CC, Ricardo VP, Frussa-Filho R, Porto CS, Abdalla FM. Effects of 17β-estradiol on expression of muscarinic acetylcholine receptor subtypes and estrogen receptor alpha in rat hippocampus. Eur J Pharmacol. 2010;634:192–200. doi: 10.1016/j.ejphar.2010.02.032.
    1. Norbury R, Travis MJ, Erlandsson K, Waddington W, Ell PJ, Murphy DG. Estrogen therapy and brain muscarinic receptor density in healthy females: a SPET study. Horm Behav. 2007;51:249–257. doi: 10.1016/j.yhbeh.2006.10.007.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe