{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:46:05Z","timestamp":1782794765716,"version":"3.54.5"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Low-concentration atropine (0.01%) has been widely investigated as a safe intervention for myopia control in children, yet its true efficacy remains uncertain due to inconsistent trial findings and high heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An artificial intelligence (AI)-assisted systematic review and Bayesian multivariate meta-analysis of randomised controlled trials (RCTs) was performed to evaluate 0.01% atropine in children. An AI pipeline was employed for literature screening, deduplication and structured data extraction. The primary outcomes were annualised changes in spherical equivalent refraction (SER, D\/year) and axial length (AL, mm\/year). Bayesian joint models synthesised SER and AL effects, explored heterogeneity with meta-regression and assessed the probability of clinically meaningful benefits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The 17 RCTs included demonstrated that 0.01% atropine significantly reduced AL (mean deviation [MD]\u202f=\u202f0.04\u202fmm\/year; 95% credible interval [CrI]: \u22120.02\u20130.06), whereas the effect on SER was modest and heterogeneous (MD\u202f=\u202f0.07 D\/year; 95% CrI: \u22120.04 to 0.18). Meta-regression indicated attenuated efficacy in older children, in cohorts with longer baseline AL and in more recent or Western trials. The probability of achieving clinically meaningful thresholds (\u22650.25 D\/year SER; \u22650.10\u202fmm\/year AL) was 68 and 72%, respectively. Sensitivity analyses confirmed robustness of results, though small-study bias was likely.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results revealed that 0.01% atropine confers modest suppression of AL in paediatric myopia, with refractive benefits less consistent and context dependent. Although safe and well tolerated, its clinical impact is limited compared with higher concentrations, and its optimal use may be as part of combination strategies or in younger, fast-progressing children.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1752902","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:24:03Z","timestamp":1782793443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of 0.01% atropine for myopia control in children: an artificial intelligence-assisted multivariate Bayesian meta-analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Like","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ophthalmological and Optometric Medicine, Hebei Eye Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmological and Optometric Medicine, Hebei Eye Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujing","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmological and Optometric Medicine, Hebei Eye Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmological and Optometric Medicine, Hebei Eye Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmological and Optometric Medicine, Hebei Eye Hospital","place":["Xingtai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s10384-021-00822-y","article-title":"Efficacy and safety of 0.01% atropine for prevention of childhood myopia in a 2-year randomized placebo-controlled study","volume":"65","author":"Hieda","year":"2021","journal-title":"Jpn J Ophthalmol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"CD014758","DOI":"10.1002\/14651858.CD014758.pub2","article-title":"Interventions for myopia control in children: a living systematic review and network meta-analysis","volume":"2023","author":"Lawrenson","year":"2023","journal-title":"Cochrane Database Syst Rev"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e2340986","DOI":"10.1001\/jamanetworkopen.2023.40986","article-title":"Cost-effectiveness analysis of myopia progression interventions in children","volume":"6","author":"Agyekum","year":"2023","journal-title":"JAMA Netw Open"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1177\/11206721211038817","article-title":"Analysis of treatment response about low-dose (0.01%) atropine eye-drops in myopic children","volume":"32","author":"Jeon","year":"2022","journal-title":"Eur J Ophthalmol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1001\/jamaophthalmol.2024.5703","article-title":"Efficacy and safety of different atropine regimens for the treatment of myopia in children: three-year results of the MOSAIC randomized clinical trial","volume":"143","author":"Loughman","year":"2025","journal-title":"JAMA Ophthalmol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.ophtha.2015.07.004","article-title":"Five-year clinical trial on atropine for the treatment of myopia 2: myopia control with atropine 0.01% eyedrops","volume":"123","author":"Chia","year":"2016","journal-title":"Ophthalmology"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1111\/opo.13485","article-title":"Effect of 0.025% atropine on ocular biometry changes during accommodation","volume":"45","author":"Hughes","year":"2025","journal-title":"Ophthalmic Physiol Opt"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s40123-019-00217-w","article-title":"Atropine 0.01% eye drops for myopia control in American children: a multiethnic sample across three US sites","volume":"8","author":"Larkin","year":"2019","journal-title":"Ophthalmol Ther"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"231","DOI":"10.4103\/tjo.tjo_31_22","article-title":"Myopia control utilizing low-dose atropine as an isolated therapy or in combination with other optical measures: a retrospective cohort study","volume":"13","author":"Erdinest","year":"2022","journal-title":"Taiwan J Ophthalmol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1447558","DOI":"10.3389\/fopht.2024.1447558","article-title":"Comparison of different concentrations atropine in controlling children and adolescent myopia: an umbrella review of systematic reviews and meta-analyses","volume":"4","author":"Chen","year":"2024","journal-title":"Front Ophthalmol (Lausanne)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1111\/opo.13417","article-title":"Myopia control strategies: a systematic review and meta-meta-analysis","volume":"45","author":"Zaabaar","year":"2025","journal-title":"Ophthalmic Physiol Opt"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e934475","DOI":"10.12659\/MSM.934475","article-title":"Editorial: review articles, systematic reviews, Meta-analysis, and the updated preferred reporting items for systematic reviews and Meta-analyses (PRISMA) 2020 guidelines","volume":"27","author":"Parums","year":"2021","journal-title":"Med Sci Monit"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1001\/jamasurg.2021.0522","article-title":"MOOSE reporting guidelines for meta-analyses of observational studies","volume":"156","author":"Brooke","year":"2021","journal-title":"JAMA Surg"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1001\/jamaophthalmol.2023.2097","article-title":"Efficacy and safety of 0.01 and 0.02% atropine for the treatment of pediatric myopia progression over 3 years: a randomized clinical trial","volume":"141","author":"Zadnik","year":"","journal-title":"JAMA Ophthalmol."},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2023.4206","article-title":"CHAMP Trial Group Investigators. Clarifications for primary and secondary outcomes and analyses","author":"Zadnik","year":"","journal-title":"JAMA Ophthalmol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ophtha.2018.05.029","article-title":"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","volume":"126","author":"Yam","year":"2019","journal-title":"Ophthalmology"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1001\/jamaophthalmol.2020.3820","article-title":"Safety and efficacy of low-dose atropine Eyedrops for the treatment of myopia progression in Chinese children: a randomized clinical trial","volume":"138","author":"Wei","year":"2020","journal-title":"JAMA Ophthalmol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1016\/j.ophtha.2019.12.011","article-title":"Two-year clinical trial of the low-concentration atropine for myopia progression (LAMP) study: phase 2 report","volume":"127","author":"Yam","year":"2020","journal-title":"Ophthalmology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.ophtha.2021.01.026","article-title":"Atropine for the treatment of childhood myopia in India: multicentric randomized trial","volume":"128","author":"Saxena","year":"2021","journal-title":"Ophthalmology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"11588","DOI":"10.1038\/s41598-022-15686-6","article-title":"Efficacy of 0.01% atropine for myopia control in a randomized, placebo-controlled trial depends on baseline electroretinal response","volume":"12","author":"Chan","year":"2022","journal-title":"Sci Rep"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1111\/ceo.14148","article-title":"Low-concentration atropine eyedrops for myopia control in a multi-racial cohort of Australian children: a randomised clinical trial","volume":"50","author":"Lee","year":"2022","journal-title":"Clin Experiment Ophthalmol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1080\/02713683.2022.2162925","article-title":"Low dose atropine in preventing the progression of childhood myopia: a randomised controlled trial","volume":"48","author":"Sharma","year":"2022","journal-title":"Curr Eye Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1186\/s12886-022-02635-0","article-title":"Combination of orthokeratology lens with 0.01% atropine in slowing axial elongation in children with myopia: a randomized double-blinded clinical trial","volume":"22","author":"Yu","year":"2022","journal-title":"BMC Ophthalmol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1001\/jamaophthalmol.2023.2855","article-title":"Low-dose 0.01% atropine eye drops vs placebo for myopia control: a randomized clinical trial","volume":"141","author":"Repka","year":"2023","journal-title":"JAMA Ophthalmol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1111\/opo.12722","article-title":"One-year results of 0.01% atropine with orthokeratology (AOK) study: a randomised clinical trial","volume":"40","author":"Tan","year":"2020","journal-title":"Ophthalmic Physiol Opt"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3390\/jpm13020325","article-title":"Myopia control with low-dose atropine in European children: six-month results from a randomized, double-masked, placebo-controlled, multicenter study","volume":"13","author":"Hvid-Hansen","year":"2023","journal-title":"J Pers Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1358046","DOI":"10.3389\/fmed.2024.1358046","article-title":"Effect of 0.01% atropine combined with orthokeratology lens on axial elongation: a 2-year randomized, double-masked, placebo-controlled, cross-over trial","volume":"11","author":"Li","year":"2024","journal-title":"Front Med (Lausanne)"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e245","DOI":"10.1111\/aos.15761","article-title":"Myopia outcome study of atropine in children: two-year result of daily 0.01% atropine in a European population","volume":"102","author":"Loughman","year":"2024","journal-title":"Acta Ophthalmol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1001\/jamaophthalmol.2024.2295","article-title":"0.01% atropine eye drops in children with myopia and intermittent exotropia: the AMIXT randomized clinical trial","volume":"142","author":"Wang","year":"2024","journal-title":"JAMA Ophthalmol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e84010","DOI":"10.7759\/cureus.84010","article-title":"Safety and efficacy of atropine 0.05% versus 0.01% for prevention of myopic progression in Indian children: a randomized clinical trial","volume":"17","author":"Janti","year":"2025","journal-title":"Cureus"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1001\/jamaophthalmol.2025.2321","article-title":"Orthokeratology, 0.04% atropine, and 0.01% atropine for myopia control: a randomized clinical trial","volume":"143","author":"Xu","year":"2025","journal-title":"JAMA Ophthalmol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"6668","DOI":"10.4103\/jfmpc.jfmpc_1339_22","article-title":"Efficacy of atropine for myopia control in children: a meta-analysis of randomized controlled trials","volume":"11","author":"Kumari","year":"2022","journal-title":"J Family Med Prim Care"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e001321","DOI":"10.3945\/cdn.117.001321","article-title":"Quinoa seed lowers serum triglycerides in overweight and obese subjects: a dose-response randomized controlled clinical trial","volume":"1","author":"Navarro-Perez","year":"2017","journal-title":"Curr Dev Nutr"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1177\/1120672121998960","article-title":"Update and guidance on management of myopia. European Society of Ophthalmology in cooperation with international myopia institute","volume":"31","author":"N\u00e9meth","year":"2021","journal-title":"Eur J Ophthalmol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3390\/jpm14020175","article-title":"Two-year results of 0.01% atropine eye drops and 0.1% loading dose for myopia progression reduction in Danish children: a placebo-controlled, randomized clinical trial","volume":"14","author":"Hansen","year":"2024","journal-title":"J Pers Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1343698","DOI":"10.3389\/fphar.2024.1343698","article-title":"Myopia progression after cessation of atropine in children: a systematic review and meta-analysis","volume":"15","author":"Lee","year":"2024","journal-title":"Front Pharmacol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1016\/j.jfo.2021.07.005","article-title":"Myopia progression and axial elongation in Spanish children: efficacy of atropine 0.01% eye-drops","volume":"44","author":"Moriche-Carretero","year":"2021","journal-title":"J Fr Ophtalmol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/978-3-030-74334-5_7","article-title":"The sclera and its role in regulation of the refractive state","volume-title":"Pathologic Myopia","author":"Summers","year":"2021"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s44271-024-00159-5","article-title":"Behavioural determinants of physiologically-relevant light exposure","volume":"2","author":"Biller","year":"2024","journal-title":"Commun Psychol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"115027","DOI":"10.1016\/j.jpba.2022.115027","article-title":"Quantification of uracil, dihydrouracil, thymine and dihydrothymine for reliable dihydropyrimidine dehydrogenase (DPD) phenotyping critically depend on blood and plasma storage conditions","volume":"221","author":"van den Wildenberg","year":"2022","journal-title":"J Pharm Biomed Anal"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1752902\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:24:05Z","timestamp":1782793445000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1752902\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":40,"alternative-id":["10.3389\/fmed.2026.1752902"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1752902","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"article-number":"1752902"}}