{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:49:47Z","timestamp":1791848987361,"version":"4.3.4"},"reference-count":130,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T00:00:00Z","timestamp":1767139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myopia is a major global public health concern, with a particularly high and increasing prevalence in East Asia. Although significant progress has been made in regard to developing strategies to slow the progression of myopia, the precise biological mechanisms underlying the onset and progression of myopia remain unclear. Repeated low-level red light (RLRL) therapy, a novel non-invasive photobiomodulation (PBM) technique, has demonstrated promising efficacy for controlling axial elongation and refractive error progression. This review first outlines the clinical definition, epidemiology, and global health impact of myopia, followed by the etiology-based pathogenesis and corresponding intervention strategies. Special attention has been given to emerging mechanistic evidence supporting RLRL, particularly its role in activating mitochondrial cytochrome c oxidase (CCO), enhancing retinal metabolism, influencing choroidal changes in blood perfusion and thickness, and in scleral remodeling. Finally, the feasibility and potential mechanism of the RLRL therapy for slowing myopia progression have been discussed from the perspective of safety.<\/jats:p>","DOI":"10.3390\/ijms27010428","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:08:00Z","timestamp":1767197280000},"page":"428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RLRL Therapeutic Feasibility and Potential Mechanism on Myopia"],"prefix":"10.3390","volume":"27","author":[{"given":"Yu-Jiao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Optometry, Dongshin University, Naju 58245, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Chul","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Optometry, Dongshin University, Naju 58245, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1497-0529","authenticated-orcid":false,"given":"Seung-Sik","family":"Cho","sequence":"additional","affiliation":[{"name":"Biomedicine, Health and Life Convergence Sciences, BK21 Four, College of Pharmacy, Mokpo National University, Muan 58554, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3972-3690","authenticated-orcid":false,"given":"Dae-Hun","family":"Park","sequence":"additional","affiliation":[{"name":"College of Korean Medicine, Dongshin University, Naju 58245, Jeonnam, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s40123-022-00490-2","article-title":"Light Signaling and Myopia Development: A Review","volume":"11","author":"Zhang","year":"2022","journal-title":"Ophthalmol. Ther."},{"key":"ref_2","unstructured":"Benjamin, W.J., and Borish, I.M. (2012). Refractive Status of the Eye. Borish\u2019s Clinical Refraction, Elsevier."},{"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","unstructured":"Benjamin, W.J., and Borish, I.M. (2012). Visual Acuity. Borish\u2019s Clinical Refraction, Elsevier."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Smith, G., and Atchison, D.A. (1997). Defocus, Depth-of-Field and Focussing Techniques. The Eye and Visual Optical Instruments, Cambridge University Press.","DOI":"10.1017\/CBO9780511609541.011"},{"key":"ref_6","unstructured":"Yanoff, M., and Duker, J.S. (2019). Ophthalmology, Elsevier. [5th ed.]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111092","DOI":"10.1016\/j.biopha.2020.111092","article-title":"Pharmacotherapeutic Candidates for Myopia: A Review","volume":"133","author":"Wang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_8","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. Primer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.12677\/HJO.2023.122012","article-title":"Progress in the Mechanism and Treatment of Myopia Control","volume":"12","author":"Yan","year":"2023","journal-title":"Hans J. Ophthalmol."},{"key":"ref_10","first-page":"12","article-title":"Repeated Low-level Red-light Intervention to Improve the Research Status of Adolescent Myopia","volume":"33","author":"Liu","year":"2024","journal-title":"Acta Laser Biol. Sin."},{"key":"ref_11","first-page":"471","article-title":"Research progress of red-light therapy in the treatment of ocular diseases","volume":"39","author":"Zhang","year":"2024","journal-title":"J. Ophthalmol. Guangzhou"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hamblin, M.R., de Sousa, M.V.P., and Agrawal, T. (2017). Preface. Handbook of Low-Level Laser Therapy, Pan Stanford Publishing.","DOI":"10.1201\/9781315364827"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, G., Li, B., Rong, H., Du, B., Wang, B., Hu, J., Zhang, B., and Wei, R. (2022). Axial Length Shortening and Choroid Thickening in Myopic Adults Treated with Repeated Low-Level Red Light. J. Clin. Med., 11.","DOI":"10.3390\/jcm11247498"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1136\/bjo-2024-325427","article-title":"Global Prevalence, Trend and Projection of Myopia in Children and Adolescents from 1990 to 2050: A Comprehensive Systematic Review and Meta-Analysis","volume":"109","author":"Liang","year":"2025","journal-title":"Br. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/OPX.0000000000000516","article-title":"The Age-Specific Prevalence of Myopia in Asia: A Meta-Analysis","volume":"92","author":"Pan","year":"2015","journal-title":"Optom. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ajo.2013.08.010","article-title":"Epidemiology and Disease Burden of Pathologic Myopia and Myopic Choroidal Neovascularization: An Evidence-Based Systematic Review","volume":"157","author":"Wong","year":"2014","journal-title":"Am. J. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1001\/archophthalmol.2011.230","article-title":"Prevalence and Characteristics of Myopic Retinopathy in a Rural Chinese Adult Population: The Handan Eye Study","volume":"129","author":"Gao","year":"2011","journal-title":"Arch. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1016\/j.ophtha.2010.01.020","article-title":"Prevalence and Progression of Myopic Retinopathy in Chinese Adults: The Beijing Eye Study","volume":"117","author":"Liu","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.ophtha.2018.10.029","article-title":"Potential Lost Productivity Resulting from the Global Burden of Myopia","volume":"126","author":"Naidoo","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1136\/bjophthalmol-2017-311625","article-title":"Myopia: Its Historical Contexts","volume":"102","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Consortium for Refractive Error and Myopia (CREAM), The Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications (DCCT\/EDIC) Research Group, Wellcome Trust Case Control Consortium 2 (WTCCC2), The Fuchs\u2019 Genetics Multi-Center Study Group, Verhoeven, V.J.M., Hysi, P.G., Wojciechowski, R., Fan, Q., Guggenheim, J.A., and H\u00f6hn, R. (2013). Genome-Wide Meta-Analyses of Multiancestry Cohorts Identify Multiple New Susceptibility Loci for Refractive Error and Myopia. Nat. Genet., 45, 314\u2013318. Correction in Nat. Genet.\u00a02013, 45, 712.","DOI":"10.1038\/ng.2554"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1007\/s00417-023-06045-w","article-title":"The Evolution of Mechanism of Accommodation and a Novel Hypothesis","volume":"261","author":"Zhang","year":"2023","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/s41433-023-02884-3","article-title":"Models of Myopia: The Effect of Accommodation, Lenses and Atropine","volume":"38","author":"Medina","year":"2024","journal-title":"Eye"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5896","DOI":"10.1038\/s41598-024-56563-8","article-title":"Model of Zonular Forces on the Lens Capsule during Accommodation","volume":"14","author":"Schachar","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.visres.2007.01.018","article-title":"Accommodation and Induced Myopia in Marmosets","volume":"47","author":"Troilo","year":"2007","journal-title":"Vis. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6765","DOI":"10.1167\/iovs.14-14524","article-title":"Axial Eye Growth and Refractive Error Development Can Be Modified by Exposing the Peripheral Retina to Relative Myopic or Hyperopic Defocus","volume":"55","author":"Nour","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"285","DOI":"10.4103\/tjo.TJO-D-22-00100","article-title":"Peripheral Defocus as It Relates to Myopia Progression: A Mini-Review","volume":"13","author":"Erdinest","year":"2023","journal-title":"Taiwan J. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1167\/iovs.06-0562","article-title":"Refractive Error, Axial Length, and Relative Peripheral Refractive Error before and after the Onset of Myopia","volume":"48","author":"Mutti","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1001\/archopht.122.6.897","article-title":"X-Linked High Myopia Associated with Cone Dysfunction","volume":"122","author":"Young","year":"2004","journal-title":"Arch. Ophthalmol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/tvst.6.3.2","article-title":"Role of a Dual Splicing and Amino Acid Code in Myopia, Cone Dysfunction and Cone Dystrophy Associated with L\/M Opsin Interchange Mutations","volume":"6","author":"Greenwald","year":"2017","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.preteyeres.2009.12.002","article-title":"The Multifunctional Choroid","volume":"29","author":"Nickla","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"18121","DOI":"10.1074\/jbc.M400381200","article-title":"Isoform-Specific Changes in Scleral Transforming Growth Factor-\u03b2 Expression and the Regulation of Collagen Synthesis during Myopia Progression","volume":"279","author":"Jobling","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E7091","DOI":"10.1073\/pnas.1721443115","article-title":"Scleral Hypoxia Is a Target for Myopia Control","volume":"115","author":"Wu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ophtha.2021.11.023","article-title":"Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children","volume":"129","author":"Jiang","year":"2022","journal-title":"Ophthalmology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1111\/ceo.14149","article-title":"Sustained and Rebound Effect of Repeated Low-level Red-light Therapy on Myopia Control: A 2-year Post-trial Follow-up Study","volume":"50","author":"Xiong","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Valter, K., Tedford, S.E., Eells, J.T., and Tedford, C.E. (2024). Photobiomodulation Use in Ophthalmology\u2014An Overview of Translational Research from Bench to Bedside. Front. Ophthalmol., 4.","DOI":"10.3389\/fopht.2024.1388602"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"M20","DOI":"10.1167\/iovs.18-25957","article-title":"IMI\u2014Defining and Classifying Myopia: A Proposed Set of Standards for Clinical and Epidemiologic Studies","volume":"60","author":"Flitcroft","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","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_39","unstructured":"Stedman, T.L. (1972). Myopia. Stedman\u2019s Medical Dictionary: A Vocabulary of Medicine and Its Allied Sciences, with Pronunciations and Derivations, Williams & Wilkins."},{"key":"ref_40","unstructured":"Duke-Elder, S. (1970). Ophthalmic Optics and Refraction, Kimpton."},{"key":"ref_41","unstructured":"World Health Organization (2015). The Impact of Myopia and High Myopia: Report of the Joint World Health Organization\u2013Brien Holden Vision Institute Global Scientific Meeting on Myopia, World Health Organization."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"The CREAM Consortium, 23andMe Research Team, UK Biobank Eye and Vision Consortium, Tedja, M.S., Wojciechowski, R., Hysi, P.G., Eriksson, N., Furlotte, N.A., Verhoeven, V.J.M., and Iglesias, A.I. (2018). Genome-Wide Association Meta-Analysis Highlights Light-Induced Signaling as a Driver for Refractive Error. Nat. Genet., 50, 834\u2013848.","DOI":"10.1038\/s41588-018-0127-7"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1016\/j.ophtha.2012.04.020","article-title":"The Association between Time Spent Outdoors and Myopia in Children and Adolescents","volume":"119","author":"Sherwin","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1001\/jama.2015.10803","article-title":"Effect of Time Spent Outdoors at School on the Development of Myopia Among Children in China: A Randomized Clinical Trial","volume":"314","author":"He","year":"2015","journal-title":"JAMA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.1167\/iovs.18-24415","article-title":"Dim Light Exposure and Myopia in Children","volume":"59","author":"Landis","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"k2022","DOI":"10.1136\/bmj.k2022","article-title":"Education and Myopia: Assessing the Direction of Causality by Mendelian Randomisation","volume":"361","author":"Mountjoy","year":"2018","journal-title":"BMJ"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/00004397-200604630-00006","article-title":"The Mechanism of Accommodation and Presbyopia","volume":"46","author":"Schachar","year":"2006","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02720789","article-title":"Ueber die Accommodation des Auges","volume":"1","author":"Helmholtz","year":"1855","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1046\/j.1475-1313.1999.00414.x","article-title":"Near Vision, Lags of Accommodation and Myopia","volume":"19","author":"Charman","year":"1999","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.visres.2011.02.016","article-title":"Accommodative Lag and Juvenile-Onset Myopia Progression in Children Wearing Refractive Correction","volume":"51","author":"Berntsen","year":"2011","journal-title":"Vis. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1016\/S0042-6989(98)00087-X","article-title":"A Model of the Contribution of Oculomotor and Optical Factors to Emmetropization and Myopia","volume":"38","author":"Flitcroft","year":"1998","journal-title":"Vis. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1046\/j.1475-1313.1995.9598238i.x","article-title":"Shifts in Tonic Accommodation after near Work Are Related to Refractive Errors in Children","volume":"15","author":"Gwiazda","year":"1995","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_53","first-page":"1024","article-title":"The Relationship between Tonic Accommodation and Ciliary Muscle Innervation","volume":"26","author":"Gilmartin","year":"1985","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.visres.2008.10.010","article-title":"The Effect of Modulating Ocular Depth of Focus upon Accommodation Microfluctuations in Myopic and Emmetropic Subjects","volume":"49","author":"Day","year":"2009","journal-title":"Vis. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1167\/iovs.06-1264","article-title":"Effects of Foveal Ablation on Emmetropization and Form-Deprivation Myopia","volume":"48","author":"Smith","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1523\/JNEUROSCI.23-07-02645.2003","article-title":"Different Circuits for ON and OFF Retinal Ganglion Cells Cause Different Contrast Sensitivities","volume":"23","author":"Zaghloul","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1167\/iovs.11-8959","article-title":"Near Work\u2013Induced Contrast Adaptation in Emmetropic and Myopic Children","volume":"53","author":"Yeo","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1167\/iovs.62.13.5","article-title":"Retinal OFF-Pathway Overstimulation Leads to Greater Accommodation-Induced Choroidal Thinning","volume":"62","author":"Read","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1167\/iovs.08-3325","article-title":"Retinal and Choroidal Biometry in Highly Myopic Eyes with Spectral-Domain Optical Coherence Tomography","volume":"50","author":"Ikuno","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ajo.2015.04.018","article-title":"Choroidal Thickness Profiles in Myopic Eyes of Young Adults in the Correction of Myopia Evaluation Trial Cohort","volume":"160","author":"Harb","year":"2015","journal-title":"Am. J. Ophthalmol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"45059","DOI":"10.1038\/srep45059","article-title":"Choroidal Thickness in 3001 Chinese Children Aged 6 to 19 Years Using Swept-Source OCT","volume":"7","author":"Xiong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1167\/iovs.64.6.4","article-title":"IMI\u2014The Dynamic Choroid: New Insights, Challenges, and Potential Significance for Human Myopia","volume":"64","author":"Ostrin","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ye, Y., Liu, F., Xian, Y., Li, M., Niu, L., Zhou, X., and Zhao, J. (2025). Correlation of Contrast Sensitivity at Low Spatial Frequencies with Myopic Shift in Chinese Children. BMC Ophthalmol., 25.","DOI":"10.1186\/s12886-025-03858-7"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jphotobiol.2013.06.004","article-title":"Low Level Laser Therapy Increases Angiogenesis in a Model of Ischemic Skin Flap in Rats Mediated by VEGF, HIF-1\u03b1 and MMP-2","volume":"125","author":"Cury","year":"2013","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/00006324-199906000-00013","article-title":"Progression of Myopia in Hong Kong Chinese Schoolchildren Is Slowed by Wearing Progressive Lenses","volume":"76","author":"Leung","year":"1999","journal-title":"Optom. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1167\/iovs.02-0816","article-title":"A Randomized Clinical Trial of Progressive Addition Lenses versus Single Vision Lenses on the Progression of Myopia in Children","volume":"44","author":"Gwiazda","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1097\/OPX.0b013e3181f6f776","article-title":"Study of Theories about Myopia Progression (STAMP) Design and Baseline Data","volume":"87","author":"Berntsen","year":"2010","journal-title":"Optom. Vis. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1167\/iovs.11-7769","article-title":"A Randomized Trial Using Progressive Addition Lenses to Evaluate Theories of Myopia Progression in Children with a High Lag of Accommodation","volume":"53","author":"Berntsen","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5761","DOI":"10.1167\/iovs.13-11904","article-title":"Peripheral Defocus and Myopia Progression in Myopic Children Randomly Assigned to Wear Single Vision and Progressive Addition Lenses","volume":"54","author":"Berntsen","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1136\/bjophthalmol-2018-313739","article-title":"Defocus Incorporated Multiple Segments (DIMS) Spectacle Lenses Slow Myopia Progression: A 2-Year Randomised Clinical Trial","volume":"104","author":"Lam","year":"2020","journal-title":"Br. J. Ophthalmol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1001\/jamaophthalmol.2022.0401","article-title":"Spectacle Lenses with Aspherical Lenslets for Myopia Control vs Single-Vision Spectacle Lenses: A Randomized Clinical Trial","volume":"140","author":"Bao","year":"2022","journal-title":"JAMA Ophthalmol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/OPX.0000000000001410","article-title":"A 3-Year Randomized Clinical Trial of MiSight Lenses for Myopia Control","volume":"96","author":"Chamberlain","year":"2019","journal-title":"Optom. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1136\/bjo-2021-321005","article-title":"Control of Myopia Using Diffusion Optics Spectacle Lenses: 12-Month Results of a Randomised Controlled, Efficacy and Safety Study (CYPRESS)","volume":"107","author":"Rappon","year":"2023","journal-title":"Br. J. Ophthalmol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1167\/iovs.10-5485","article-title":"Influence of Overnight Orthokeratology on Axial Elongation in Childhood Myopia","volume":"52","author":"Kakita","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.ophtha.2014.09.028","article-title":"Myopia Control during Orthokeratology Lens Wear in Children Using a Novel Study Design","volume":"122","author":"Swarbrick","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ophtha.2018.11.026","article-title":"Use of Orthokeratology for the Prevention of Myopic Progression in Children","volume":"126","author":"VanderVeen","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1167\/iovs.11-8453","article-title":"Long-Term Effect of Overnight Orthokeratology on Axial Length Elongation in Childhood Myopia: A 5-Year Follow-Up Study","volume":"53","author":"Hiraoka","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.jaapos.2015.04.006","article-title":"Therapeutic Effect of Atropine 1% in Children with Low Myopia","volume":"19","author":"Yi","year":"2015","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_79","doi-asserted-by":"crossref","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","volume":"123","author":"Chia","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_80","first-page":"CD004916","article-title":"Interventions to Slow Progression of Myopia in Children","volume":"2020","author":"Walline","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"8004","DOI":"10.1167\/iovs.13-12476","article-title":"Progressive Myopia or Hyperopia Can Be Induced in Chicks and Reversed by Manipulation of the Chromaticity of Ambient Light","volume":"54","author":"Foulds","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.visres.2013.10.020","article-title":"Interactions of Chromatic and Lens-Induced Defocus during Visual Control of Eye Growth in Guinea Pigs (Cavia porcellus)","volume":"94","author":"Jiang","year":"2014","journal-title":"Vis. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.exer.2016.12.004","article-title":"The Wavelength Composition and Temporal Modulation of Ambient Lighting Strongly Affect Refractive Development in Young Tree Shrews","volume":"155","author":"Gawne","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6490","DOI":"10.1167\/iovs.15-17025","article-title":"Effects of Long-Wavelength Lighting on Refractive Development in Infant Rhesus Monkeys","volume":"56","author":"Smith","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.exer.2018.07.004","article-title":"Narrow-Band, Long-Wavelength Lighting Promotes Hyperopia and Retards Vision-Induced Myopia in Infant Rhesus Monkeys","volume":"176","author":"Hung","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_86","first-page":"6823965","article-title":"Axial Length and Ocular Development of Premature Infants without ROP","volume":"2017","author":"Zha","year":"2017","journal-title":"J. Ophthalmol."},{"key":"ref_87","first-page":"761823","article-title":"Increased Expression of CCN2 in the Red Flashing Light-Induced Myopia in Guinea Pigs","volume":"2013","author":"Wang","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/php.12864","article-title":"Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation","volume":"94","author":"Hamblin","year":"2018","journal-title":"Photochem. Photobiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.7150\/ijms.85746","article-title":"Repeated Low-Level Red-Light Therapy for Controlling Onset and Progression of Myopia-a Review","volume":"20","author":"Zhu","year":"2023","journal-title":"Int. J. Med. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7209","DOI":"10.1093\/emboj\/20.24.7209","article-title":"RTG-Dependent Mitochondria to Nucleus Signaling Is Negatively Regulated by the Seven WD-Repeat Protein Lst8p","volume":"20","author":"Liu","year":"2001","journal-title":"EMBO J."},{"key":"ref_91","first-page":"99","article-title":"Energy Metabolism of the Visual System","volume":"2","year":"2010","journal-title":"Eye Brain"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bse0470001","article-title":"The Mitochondrial Respiratory Chain","volume":"47","author":"Rich","year":"2010","journal-title":"Essays Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/191144a0","article-title":"Coupling of Phosphorylation to Electron and Hydrogen Transfer by a Chemi-Osmotic Type of Mechanism","volume":"191","author":"Mitchell","year":"1961","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1146\/annurev.bi.54.070185.005055","article-title":"The Mitochondrial Electron Transport and Oxidative Phosphorylation Systems","volume":"54","author":"Hatefi","year":"1985","journal-title":"Annu. Rev. Biochem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1109\/JSTQE.2016.2561201","article-title":"Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy","volume":"22","author":"Hamblin","year":"2016","journal-title":"IEEE J. Sel. Top. Quantum Electron."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.mito.2015.07.002","article-title":"The Subunit Composition and Function of Mammalian Cytochrome c Oxidase","volume":"24","author":"Kadenbach","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3934\/biophy.2017.3.337","article-title":"Mechanisms and Applications of the Anti-Inflammatory Effects of Photobiomodulation","volume":"4","author":"Hamblin","year":"2017","journal-title":"AIMS Biophys."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1111\/j.1751-1097.2008.00394.x","article-title":"Mitochondrial Signaling in Mammalian Cells Activated by Red and Near-IR Radiation","volume":"84","author":"Karu","year":"2008","journal-title":"Photochem. Photobiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1107\/S1744309109055109","article-title":"X-Ray Structure of the NO-Bound CuB in Bovine Cytochrome c Oxidase","volume":"66","author":"Ohta","year":"2010","journal-title":"Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.exger.2010.01.003","article-title":"The Sites and Topology of Mitochondrial Superoxide Production","volume":"45","author":"Brand","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.bbabio.2009.06.004","article-title":"SR\/ER\u2013Mitochondrial Local Communication: Calcium and ROS","volume":"1787","year":"2009","journal-title":"Biochim. Biophys. Acta BBA-Bioenerg."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.bbrc.2019.01.083","article-title":"Connecting CuA with Metal Centers of Heme a, Heme a, CuB and Zn by Pathways with Hydrogen Bond as the Bridging Element in Cytochrome c Oxidase","volume":"510","author":"Ramasarma","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.bbabio.2010.12.016","article-title":"A Combined Quantum Chemical and Crystallographic Study on the Oxidized Binuclear Center of Cytochrome c Oxidase","volume":"1807","author":"Kaila","year":"2011","journal-title":"Biochim. Biophys. Acta BBA-Bioenerg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.bbabio.2011.09.004","article-title":"Proton-Pumping Mechanism of Cytochrome c Oxidase: A Kinetic Master-Equation Approach","volume":"1817","author":"Kim","year":"2012","journal-title":"Biochim. Biophys. Acta BBA-Bioenerg."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1073\/pnas.081088398","article-title":"On the Role of the K-Proton Transfer Pathway in Cytochrome c Oxidase","volume":"98","author":"Sigurdson","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e57092","DOI":"10.15252\/embr.202357092","article-title":"The Functional Significance of Mitochondrial Respiratory Chain Supercomplexes","volume":"24","author":"Kohler","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"22872","DOI":"10.1038\/s41598-021-02311-1","article-title":"Weeklong Improved Colour Contrasts Sensitivity after Single 670 Nm Exposures Associated with Enhanced Mitochondrial Function","volume":"11","author":"Shinhmar","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/lsm.20924","article-title":"Mitochondrial Signaling for Histamine Releases in Laser-irradiated RBL-2H3 Mast Cells","volume":"42","author":"Wu","year":"2010","journal-title":"Lasers Surg. Med."},{"key":"ref_109","first-page":"535","article-title":"Mechanisms of Nitric Oxide Synthesis and Action in Cells","volume":"39","author":"Arzumanian","year":"2003","journal-title":"Medicina"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8915867","DOI":"10.1155\/2021\/8915867","article-title":"Orthokeratology and Low-Intensity Laser Therapy for Slowing the Progression of Myopia in Children","volume":"2021","author":"Xiong","year":"2021","journal-title":"BioMed Res. Int."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/opo.12939","article-title":"Low-intensity, Long-wavelength Red Light Slows the Progression of Myopia in Children: An Eastern China-based Cohort","volume":"42","author":"Zhou","year":"2022","journal-title":"Ophthalmic Physiol. Opt."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.25.3.036003","article-title":"High-Throughput Single-Cell Live Imaging of Photobiomodulation with Multispectral near-Infrared Lasers in Cultured T Cells","volume":"25","author":"Katagiri","year":"2020","journal-title":"J. Biomed. Opt."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"C817","DOI":"10.1152\/ajpcell.00139.2004","article-title":"Calcium, ATP, and ROS: A Mitochondrial Love-Hate Triangle","volume":"287","author":"Brookes","year":"2004","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1158\/0008-5472.CAN-05-2519","article-title":"Role of Hypoxia-Inducible Factor (HIF)-1\u03b1 versus HIF-2\u03b1 in the Regulation of HIF Target Genes in Response to Hypoxia, Insulin-Like Growth Factor-I, or Loss of von Hippel-Lindau Function: Implications for Targeting the HIF Pathway","volume":"66","author":"Carroll","year":"2006","journal-title":"Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1007\/s10103-013-1264-y","article-title":"Liver Regeneration Following Partial Hepatectomy Is Improved by Enhancing the HGF\/Met Axis and Akt and Erk Pathways after Low-Power Laser Irradiation in Rats","volume":"28","author":"Tobar","year":"2013","journal-title":"Lasers Med. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Rola, P., W\u0142odarczak, S., Lesiak, M., Doroszko, A., and W\u0142odarczak, A. (2022). Changes in Cell Biology under the Influence of Low-Level Laser Therapy. Photonics, 9.","DOI":"10.3390\/photonics9070502"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1167\/iovs.64.2.2","article-title":"Calcipotriol Attenuates Form Deprivation Myopia Through a Signaling Pathway Parallel to TGF-\u03922\u2013Induced Increases in Collagen Expression","volume":"64","author":"Jiao","year":"2023","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"jcs223230","DOI":"10.1242\/jcs.223230","article-title":"Hypoxia Suppresses Myofibroblast Differentiation by Changing RhoA Activity","volume":"132","author":"Leinhos","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Magar, A.G., Morya, V.K., Kwak, M.K., Oh, J.U., and Noh, K.C. (2024). A Molecular Perspective on HIF-1\u03b1 and Angiogenic Stimulator Networks and Their Role in Solid Tumors: An Update. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063313"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/s41392-023-01460-1","article-title":"Angiogenic Signaling Pathways and Anti-Angiogenic Therapy for Cancer","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"38527","DOI":"10.1074\/jbc.M104536200","article-title":"Synergistic Cooperation between Hypoxia and Transforming Growth Factor-\u03b2 Pathways on Human Vascular Endothelial Growth Factor Gene Expression","volume":"276","author":"Botella","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_122","unstructured":"Therapeutic Goods Administration (2024). Eyerising Myopia Management Device\u2014Home-Use Myopia Control Red Light Device (ARTG 412752), Department of Health and Aged Care."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/ICU.0000000000001154","article-title":"Photobiomodulation: Evidence and Applications in Ophthalmology","volume":"36","author":"Tan","year":"2025","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"E005","DOI":"10.1017\/S0952523824000075","article-title":"The Interaction between Luminance Polarity Grouping and Symmetry Axes on the ERP Responses to Symmetry","volume":"41","author":"Dering","year":"2024","journal-title":"Vis. Neurosci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"E004","DOI":"10.1017\/S0952523824000038","article-title":"Electroretinographic Responses to Periodic Stimuli in Primates and the Relevance for Visual Perception and for Clinical Studies","volume":"41","author":"Kremers","year":"2024","journal-title":"Vis. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"E001","DOI":"10.1017\/S0952523822000086","article-title":"Impact of Glaucoma on the Spatial Frequency Processing of Scenes in Central Vision","volume":"40","author":"Trouilloud","year":"2023","journal-title":"Vis. Neurosci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.4103\/ijo.IJO_15_22","article-title":"Red Light Irradiation as an Intervention for Myopia","volume":"70","author":"Huang","year":"2022","journal-title":"Indian J. Ophthalmol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e239612","DOI":"10.1001\/jamanetworkopen.2023.9612","article-title":"Effect of Repeated Low-Level Red Light on Myopia Prevention Among Children in China with Premyopia: A Randomized Clinical Trial","volume":"6","author":"He","year":"2023","journal-title":"JAMA Netw. Open"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.ophtha.2024.05.015","article-title":"Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology","volume":"131","author":"Xiong","year":"2024","journal-title":"Ophthalmology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1001\/jamaophthalmol.2023.1548","article-title":"Retinal Damage After Repeated Low-Level Red-Light Laser Exposure","volume":"141","author":"Liu","year":"2023","journal-title":"JAMA Ophthalmol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/428\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:09:28Z","timestamp":1767197368000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/1\/428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,31]]},"references-count":130,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27010428"],"URL":"https:\/\/doi.org\/10.3390\/ijms27010428","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,31]]}}}