{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:43:42Z","timestamp":1787773422308,"version":"build-2784847793"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To explore the efficacy and safety of combined low-concentration atropine and orthokeratology lenses (AOK) for slowing the progression of myopia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this randomized, placebo-controlled, double-blinded, multicenter clinical trial. Children (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200996) aged 8\u201312 years with myopia between \u22121.00D and \u22124.00D and astigmatism of no more than 1.5D in either eye were randomly assigned to the AOK or orthokeratology (OK) group. The primary outcome, axial elongation, was examined at baseline and visited at 6, 12, 18 and 24 months, along with secondary outcomes, including tear meniscus height (TMH), non-invasive break-up time (NIBUT), visual acuity and dynamic changes of pupillary light reflex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over the 24 months, the axial elongation was significantly slower in the AOK group than in the OK group (0.33\u2009\u00b1\u20090.17\u2005mm vs. 0.43\u2009\u00b1\u20090.16\u2005mm, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004). In the subgroup analysis, there were significant differences in the change of axial length in the subgroup of subjects with an initial spherical equivalent refraction (SER) of \u22121.00 to \u22123.00D or aged 8\u201310 years (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017, 0.021, respectively). At the 24-month visit, the changes in TMH, NIBUT, visual acuity and pupil size in the AOK group were insignificantly different from those in the OK group (p&amp;gt;0.05, respectively). The latency of the pupillary light reflex was significantly longer in the AOK group than in the OK group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.029).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination of 0.01% atropine and orthokeratology produced a combined effect in slowing axial elongation over 2 years, with good tolerability and minimal ocular surface impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.chictr.org.cn\/showprojEN.html?proj=29216<\/jats:ext-link>\n                      , identifier ChiCTR1800018419.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1809296","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:38:53Z","timestamp":1777527533000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The efficacy and safety of combined 0.01% atropine and orthokeratology for childhood myopia control: a 2-year randomized clinical trial"],"prefix":"10.3389","volume":"14","author":[{"given":"Ying","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"National Clinical Research Center for Eye Diseases","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Qilu Hospital of Shandong University Dezhou Hospital","place":["Dezhou, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinting","family":"Liu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biomedical Informatics & Statistics Center, School of Public Health, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingru","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Mao","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center Sun Yat-Sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilian","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/519276a","article-title":"The myopia boom","volume":"519","author":"Dolgin","year":"2015","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1167\/iovs.18-25221","article-title":"Prevention and management of myopia and myopic pathology","volume":"60","author":"Saw","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.ophtha.2015.11.010","article-title":"Efficacy comparison of 16 interventions for myopia control in children: a network meta-analysis","volume":"123","author":"Huang","year":"2016","journal-title":"Ophthalmology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.ophtha.2011.07.031","article-title":"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)","volume":"119","author":"Chia","year":"2012","journal-title":"Ophthalmology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2285","DOI":"10.1016\/j.ophtha.2006.05.062","article-title":"Atropine for the treatment of childhood myopia","volume":"113","author":"Chua","year":"2006","journal-title":"Ophthalmology"},{"key":"B6","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":"B7","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1097\/OPX.0b013e31820f16fb","article-title":"Peripheral refraction in myopic children wearing orthokeratology and gas-permeable lenses","volume":"88","author":"Kang","year":"2011","journal-title":"Optom Vis Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1097\/OPX.0b013e3181d951f7","article-title":"Peripheral refraction in myopic patients after orthokeratology","volume":"87","author":"Queir\u00f3s","year":"2010","journal-title":"Optom Vis Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1080\/02713680590907256","article-title":"The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control","volume":"30","author":"Cho","year":"2005","journal-title":"Curr Eye Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1097\/OPX.0b013e318293657d","article-title":"High myopia-partial reduction ortho-k: a 2-year randomized study","volume":"90","author":"Charm","year":"2013","journal-title":"Optom Vis Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"7077","DOI":"10.1167\/iovs.12-10565","article-title":"Retardation of myopia in orthokeratology (ROMIO) study: a 2-year randomized clinical trial","volume":"53","author":"Cho","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"12750","DOI":"10.1038\/s41598-020-69710-8","article-title":"Efficacy of combined orthokeratology and 0.01% atropine solution for slowing axial elongation in children with myopia: a 2-year randomised trial","volume":"10","author":"Kinoshita","year":"2020","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1007\/s10384-018-0608-3","article-title":"Additive effects of orthokeratology and atropine 0.01% ophthalmic solution in slowing axial elongation in children with myopia: first year results","volume":"62","author":"Kinoshita","year":"2018","journal-title":"Jpn J Ophthalmol"},{"key":"B14","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":"B15","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1136\/bjo-2022-321272","article-title":"Effect of atropine, orthokeratology and combined treatments for myopia control: a 2-year stratified randomised clinical trial","volume":"107","author":"Xu","year":"2023","journal-title":"Br J Ophthalmol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1159\/000055537","article-title":"Development of a simple dry eye model in the albino rabbit and evaluation of some tear substitutes","volume":"31","author":"Burgalassi","year":"1999","journal-title":"Ophthalmic Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1186\/s13063-021-05825-1","article-title":"Efficacy of combined orthokeratology and 0.01% atropine for myopia control: the study protocol for a randomized, controlled, double-blind, and multicenter trial","volume":"22","author":"Yuan","year":"2021","journal-title":"Trials"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1111\/opo.13023","article-title":"Association between axial length elongation and spherical equivalent progression in Chinese children and adolescents","volume":"42","author":"Liu","year":"2022","journal-title":"Ophthalmic Physiol Opt"},{"key":"B19","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/aos.13603","article-title":"Axial length growth and the risk of developing myopia in European children","volume":"96","author":"Tideman","year":"2018","journal-title":"Acta Ophthalmol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1007\/s10792-020-01658-0","article-title":"Clinical efficacy of 0.01% atropine in retarding the progression of myopia in children","volume":"41","author":"Zhao","year":"2021","journal-title":"Int Ophthalmol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.preteyeres.2017.06.003","article-title":"Dopamine signaling and myopia development: what are the key challenges","volume":"61","author":"Zhou","year":"2017","journal-title":"Prog Retin Eye Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1111\/opo.13276","article-title":"Impact of pupil and defocus ring intersection area on retinal defocus","volume":"44","author":"Guo","year":"2024","journal-title":"Ophthalmic Physiol Opt"},{"key":"B23","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1089\/jop.2011.0027","article-title":"The long-term results of using low-concentration atropine eye drops for controlling myopia progression in schoolchildren","volume":"27","author":"Wu","year":"2011","journal-title":"J Ocul Pharmacol Ther"},{"key":"B24","doi-asserted-by":"publisher","first-page":"7380","DOI":"10.1038\/s41598-022-10978-3","article-title":"Characteristics of responders to atropine 0.01% as treatment in Asian myopic children","volume":"12","author":"Lee","year":"2022","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1111\/opo.12990","article-title":"Factors determining the myopia control effect of an orthokeratology lens: a two-year multi-level model","volume":"42","author":"Chen","year":"2022","journal-title":"Ophthalmic Physiol Opt"},{"key":"B26","doi-asserted-by":"publisher","first-page":"600","DOI":"10.3109\/02713683.2015.1050743","article-title":"Efficacy, safety and acceptability of orthokeratology on slowing axial elongation in myopic children by meta-analysis","volume":"41","author":"Li","year":"2016","journal-title":"Curr Eye Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/1471-2415-14-141","article-title":"The control effect of orthokeratology on axial length elongation in Chinese children with myopia","volume":"14","author":"Zhu","year":"2014","journal-title":"BMC Ophthalmol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"280","DOI":"10.3389\/fphar.2015.00280","article-title":"Effects of topical fucosyl-lactose, a milk oligosaccharide, on dry eye model: an example of nutraceutical candidate","volume":"6","author":"Bucolo","year":"2015","journal-title":"Front Pharmacol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"109331","DOI":"10.1016\/j.mehy.2019.109331","article-title":"Will the long-term use of atropine eye drops in children increase the risk of dry eye?","volume":"132","author":"Zhao","year":"2019","journal-title":"Med Hypotheses"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1809296\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:38:54Z","timestamp":1777527534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1809296\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":29,"alternative-id":["10.3389\/fped.2026.1809296"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1809296","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,30]]},"article-number":"1809296"}}