{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:18:54Z","timestamp":1791555534330,"version":"4.3.4"},"reference-count":27,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T00:00:00Z","timestamp":1676592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bagenkop Nielsens \u00d8jen-Fond"},{"name":"Fight for Sight Denmark"},{"name":"Fonden for Faglig Udvikling i Speciall\u00e6gepraksis"},{"name":"The Danish Research Foundation"},{"name":"Synoptik-Fonden"},{"name":"Danish Regions"},{"name":"Gangstedfonden"},{"name":"Reimbursement from Regional COVID-19 funds"},{"name":"Aase og Ejnar Danielsens Fond"},{"name":"A.P. M\u00f8ller Fonden (L\u00e6gefonden)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>This study aimed to investigate changes in non-cycloplegic ocular biometrics during the initial six months of treatment with a 0.1% atropine loading dose and 0.01% atropine compared with a placebo and analyze their contribution to the treatment effect on cycloplegic spherical equivalent (SE) progression. The study was based on a randomized, double-masked, placebo-controlled, multicenter trial evaluating a 0.1% atropine six-month loading dose and 0.01% atropine in reducing myopic progression in Danish children. The treatment phase was 24 months, and the washout phase was 12 months. Parameters measured included changes in axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and choroidal thickness (ChT), while cycloplegic SE and lens power were calculated. Longitudinal changes and contributions to treatment effects were analyzed using constrained linear mixed models and mediation analyses, respectively. After six months, AL was 0.13 mm shorter (95% confidence interval [CI], \u22120.18 to \u22120.07 [adjusted p &lt; 0.001]) and 0.06 mm shorter (95% CI, \u22120.11 to \u22120.01 [adjusted p = 0.060]) with a 0.1% atropine loading dose and 0.01% atropine, respectively, compared to the placebo group. Similar concentration-dependent changes were found with ACD, LT, VCD, ChT, and cycloplegic SE. Although the treatment effects trended toward concentration-dependent responses, only the treatment effect mediated by AL at three months differed significantly between 0.01% atropine and a 0.1% atropine loading dose (adjusted p = 0.023). Several ocular biometrics, including AL, ACD, and LT, changed dose-dependently during low-dose atropine treatment. Moreover, the treatment effect of atropine on SE progression was mediated by a subset of ocular biometrics, mainly AL, with trends toward concentration dependency and distributional shifts over time.<\/jats:p>","DOI":"10.3390\/jcm12041605","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T02:27:24Z","timestamp":1676600844000},"page":"1605","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Low-Dose Atropine Induces Changes in Ocular Biometrics in Myopic Children: Exploring Temporal Changes by Linear Mixed Models and Contribution to Treatment Effect by Mediation Analyses"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7325-0217","authenticated-orcid":false,"given":"Anders","family":"Hvid-Hansen","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Copenhagen University Hospital\u2014Rigshospitalet-Glostrup, DK-2600 Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Copenhagen University Hospital\u2014Rigshospitalet-Glostrup, DK-2600 Glostrup, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, DK-2200 K\u00f8benhavn N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Hjortdal","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Aarhus University Hospital, DK-8200 Aarhus N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Southern Denmark\u2014Vejle Hospital, DK-7100 Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brice","family":"Ozenne","sequence":"additional","affiliation":[{"name":"Department of Public Health, Section of Biostatistics, University of Copenhagen, DK-1014 K\u00f8benhavn K, Denmark"},{"name":"Neurobiology Research Unit, Copenhagen University Hospital\u2014Rigshospitalet, DK-2200 K\u00f8benhavn N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Kessel","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Copenhagen University Hospital\u2014Rigshospitalet-Glostrup, DK-2600 Glostrup, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, DK-2200 K\u00f8benhavn N, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41572-020-00231-4","article-title":"Myopia","volume":"6","author":"Baird","year":"2020","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s10654-015-0010-0","article-title":"Prevalence of refractive error in Europe: The European Eye Epidemiology (E3) Consortium","volume":"30","author":"Williams","year":"2015","journal-title":"Eur. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1111\/j.1475-1313.2005.00298.x","article-title":"Myopia and associated pathological complications","volume":"25","author":"Saw","year":"2005","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/S0140-6736(12)60272-4","article-title":"Myopia","volume":"379","author":"Morgan","year":"2012","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1097\/IAE.0000000000001489","article-title":"Overview of the Complications of High Myopia","volume":"37","author":"Kuno","year":"2017","journal-title":"Retina"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.ophtha.2016.01.006","article-title":"Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050","volume":"123","author":"Holden","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100923","DOI":"10.1016\/j.preteyeres.2020.100923","article-title":"Efficacy in myopia control","volume":"83","author":"Brennan","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","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":"ref_9","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1097\/APO.0000000000000256","article-title":"Low-Concentration Atropine Eye Drops for Myopia Progression","volume":"8","author":"Li","year":"2019","journal-title":"Asia-Pac. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.ophtha.2020.06.004","article-title":"Differential Effects on Ocular Biometrics by 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study","volume":"127","author":"Li","year":"2020","journal-title":"Ophthalmology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0021-5155(02)00479-3","article-title":"The change in ocular refractive components after cycloplegia in children","volume":"46","author":"Gao","year":"2002","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1475-1313.1988.tb01082.x","article-title":"A method of determining the equivalent powers of the eye and its crystalline lens without resort to phakometry","volume":"8","author":"Bennett","year":"1988","journal-title":"Ophthalmic. Physiol. Opt."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7937","DOI":"10.1167\/iovs.11-7899","article-title":"Comparing methods to estimate the human lens power","volume":"52","author":"Rozema","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","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":"ref_15","first-page":"1","article-title":"Myopia progression in young school children. A prospective study of myopia progression and the effect of a trial with bifocal lenses and beta blocker eye drops","volume":"200","author":"Jensen","year":"1991","journal-title":"Acta Ophthalmol. Suppl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4310\/SII.2009.v2.n4.a7","article-title":"Conceptual issues concerning mediation, interventions and composition","volume":"2","author":"Vansteelandt","year":"2009","journal-title":"Stat. Its Interface"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_18","unstructured":"R Core Team (2021). R: A Language and Environment for Statistical Computing, R Core Team. R Foundation for Statistical Computing."},{"key":"ref_19","unstructured":"Ozenne, B., and Forman, J. (2023, January 02). LMMstar: Repeated Measurement Models for Discrete Times. Available online: https:\/\/cran.r-project.org\/web\/packages\/LMMstar\/index.html."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1007\/s00180-012-0344-y","article-title":"Linear latent variable models: The lava-package","volume":"28","author":"Holst","year":"2013","journal-title":"Comput Stat."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Atchison, D., and Smith, G. (2000). Optics of the Human Eye, Butterworth-Heinemann.","DOI":"10.1016\/B978-0-7506-3775-6.50024-9"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.1167\/iovs.14-14716","article-title":"Analysis of Changes in Refraction and Biometry of Atropine- and Placebo-Treated Eyes","volume":"56","author":"Kumaran","year":"2015","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_23","first-page":"137","article-title":"An ultrasound biomicroscopic study on changes of the structure of ocular anterior segment after topical application of cycloplegia","volume":"34","author":"Wang","year":"1998","journal-title":"Zhonghua Yan Ke Za Zhi"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.jfo.2020.04.023","article-title":"Effect of 0.01% atropine eye drops on choroidal thickness in myopic children","volume":"43","author":"Li","year":"2020","journal-title":"J. Fr. Ophtalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ajo.2021.12.014","article-title":"The Association of Choroidal Thickening by Atropine with Treatment Effects for Myopia: Two-Year Clinical Trial of the Low-concentration Atropine for Myopia Progression (LAMP) Study","volume":"237","author":"Yam","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","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":"ref_27","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.ophtha.2021.10.002","article-title":"Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression (LAMP) Study: Continued Versus Washout: Phase 3 Report","volume":"129","author":"Yam","year":"2022","journal-title":"Ophthalmology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1605\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:39:09Z","timestamp":1760121549000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/4\/1605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,17]]},"references-count":27,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["jcm12041605"],"URL":"https:\/\/doi.org\/10.3390\/jcm12041605","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,17]]}}}