Comparison of repeated low-level red-light therapy with single-vision spectacles, DIMS lenses, and orthokeratology for myopia control in children: a one-year retrospective cohort study

Comparison of repeated low-level red-light therapy with single-vision spectacles, DIMS lenses, and orthokeratology for myopia control in children: a one-year retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of repeated low-level red-light therapy with single-vision spectacles, DIMS lenses, and orthokeratology for myopia control in children: a one-year retrospective cohort study Limin Gu, Wenjie Li, Xiaojun Hu, Mei Tian, Yan Yan, Yujiao Zhang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9261382/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background To evaluate the 1-year efficacy of repeated low-level red-light (RLRL) therapy for myopia control in children and compare it with single-vision spectacles (SVS), defocus incorporated multiple segments (DIMS) spectacles, and orthokeratology (OK) in a real-world setting. Methods This retrospective study included 527 children (6–12 years) with mild to moderate myopia who received SVS (n = 139), DIMS (n = 121), RLRL (n = 122), or OK (n = 145) for at least one year. Changes in axial length (ΔAL) and spherical equivalent refraction (ΔSER) were assessed. Analysis of covariance (ANCOVA) adjusted for baseline values, with Bonferroni-corrected pairwise comparisons. Results Baseline AL differed significantly among groups (p < 0.001) and was adjusted for in analyses. RLRL resulted in the smallest adjusted ΔAL (0.10 mm, 95% CI 0.046–0.144) versus SVS (0.38 mm), DIMS (0.32 mm), and OK (0.25 mm) (all p < 0.001). For ΔSER (OK excluded), RLRL also showed least progression (–0.17 D, 95% CI − 0.263 to − 0.072) compared with SVS (–0.85 D) and DIMS (–0.57 D) (both p < 0.001). Subgroup analyses revealed consistent benefits across age, gender, and baseline myopia, with RLRL efficacy comparable to DIMS and OK in males and those with moderate myopia. No severe adverse events were reported. Conclusions RLRL therapy demonstrated superior 1-year efficacy in controlling myopia progression compared to SVS, DIMS, and OK, particularly in females and younger children. While short-term safety was reassuring, long-term retinal health monitoring remains warranted. myopia control repeated low-level red-light defocus incorporated multiple segments spectacles orthokeratology Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Myopia is a leading cause of visual impairment worldwide, with prevalence rising rapidly, particularly in urbanised East and Southeast Asia [ 1 , 2 ]. By 2050, an estimated 4.76 billion people (49.8% of the global population) will be myopic, nearly 1 billion of whom will have high myopia (≤–5.00 D or ≤–6.00 D) [ 2 , 3 ]. High myopia increases the risk of sight-threatening complications—including cataracts, myopic maculopathy, retinal detachment, and glaucoma—leading to irreversible vision loss and substantial socioeconomic burden [ 4 – 6 ]. Effective early intervention is therefore critical for preserving long-term ocular health [ 7 , 8 ]. Conventional single-vision spectacles (SVS) correct refractive error but do not slow axial elongation [ 9 ]. Established treatments such as low-dose atropine and orthokeratology (OK) are effective [ 10 – 13 ] but have limitations: atropine can cause photophobia, allergic conjunctivitis, and rebound effects [ 14 ]; OK carries risks of microbial keratitis and requires stringent lens care [ 15 , 16 ]. These challenges highlight the need for alternative, non-invasive, and safe options. Repeated low-level red-light (RLRL) therapy has emerged as a novel home-based intervention. Recent randomised controlled trials (RCTs) show that 650 nm RLRL significantly reduces axial elongation and spherical equivalent refraction (SER) progression compared with SVS, with some studies reporting axial shortening [ 17 – 19 ]. Proposed mechanisms include increased choroidal thickness and perfusion [ 20 – 22 ], upregulation of antioxidant enzymes (e.g., ALDH3A1 ) in retinal pigment epithelium [ 23 ], and modulation of inflammatory and oxidative stress pathways [ 24 , 25 ], which may alleviate scleral hypoxia—a key driver of axial elongation [ 26 , 27 ]. Despite promising efficacy, the evidence base for RLRL is evolving. Recent reports have raised safety concerns: one case documented retinal damage [ 28 ], and a cohort study using adaptive optics scanning laser ophthalmoscopy (AOSLO) found reduced cone density and subtle retinal abnormalities in treated children [ 29 ]. Optimal dosing, sustainability, and potential rebound effects also require further study [ 30 , 31 ]. Systematic reviews confirm efficacy but call for longer-term safety data [ 32 , 33 ]. This real-world study therefore evaluated the 1-year efficacy of RLRL for mild to moderate myopia in Chinese children, benchmarking it against SVS, DIMS spectacles, and OK, while exploring predictors of treatment response. Methods Subjects This retrospective study reviewed the medical records of children who visited Shanghai Aier Hospital between January 2023 and February 2025. Patients were divided into four treatment groups: SVS (control group), defocus incorporated multiple segments (DIMS) spectacles, RLRL combined with SVS, and OK. Treatment allocation was based on patient/parental choice following clinical consultation and assessment of suitability. Inclusion criteria were: (1) age 6–12 years; (2) cycloplegic SER between − 1.00 and − 5.00 D; (3) astigmatism ≤ 2.50 D; (4) anisometropia ≤ 1.50 D; (5) best-corrected visual acuity (BCVA) of 0.0 logMAR or better in each eye; (6) completion of at least one consecutive year of the assigned treatment. Exclusion criteria included strabismus, significant binocular vision dysfunction (e.g., convergence insufficiency), other ocular pathologies, or systemic diseases affecting ocular health. If both eyes met the criteria, only data from the right eye were included in the analysis. This study was approved by the Ethics Committee of Shanghai Aier Eye Hospital and adhered to the tenets of the Declaration of Helsinki. Treatments and ocular biometry measurements RLRL group : Participants wore SVS for refractive correction and underwent RLRL therapy using a desktop light therapy device (Eyerising, Suzhou Xuanjia Optoelectronics Technology, Jiangsu, China). The device delivers low-level red light with a wavelength of 650 ± 10 nm at an illuminance of approximately 1600 lux through the pupil to the fundus. The calculated power through a 4 mm pupil was 0.29 mW, classified as Class 1 per IEC 60825-1:2014, deemed safe for direct ocular exposure. Treatment was administered twice daily (at least 4 hours apart) on weekdays (5 days/week), with each session lasting 3 minutes, under parental supervision [ 17 ]. SVS group Participants wore conventional single-vision spectacles full-time. DIMS group Participants wore MiYOSMART DIMS spectacle lenses (HOYA Vision Care, Japan) [ 34 ]. These lenses feature a central 9 mm zone for distance correction surrounded by an annular multi-segmental zone (33 mm diameter) with a relative positive power of + 3.50 D. Daily wear time was recommended to be at least 12 hours. OK group Participants wore overnight orthokeratology lenses made of rigid gas-permeable material (CRT, Paragon Vision Sciences, USA). Standard fitting procedures, follow-up visits (1 day, 1 week, 1 month and then every 3 months), and safety monitoring (slit-lamp examination for corneal integrity, AL measurement and corneal endothelial cell count) were performed. AL was measured using the IOL Master 500 (Carl Zeiss, Germany). Cycloplegic SER was obtained via an autorefractor (Topcon, Japan) after instillation of 0.5% tropicamide eye drops (one drop every 5 minutes for a total of four drops). Measurements were taken at baseline and at the 12-month follow-up visit. Statistical analysis Statistical analyses were performed using IBM SPSS Statistics 23.0. Baseline characteristics were compared using one-way ANOVA for continuous variables and χ² tests for categorical variables. The primary outcome was change in axial length (ΔAL) from baseline to 12 months. An analysis of covariance (ANCOVA) was conducted with treatment group as the fixed factor and baseline AL as a covariate to adjust for significant baseline differences. Adjusted marginal means for ΔAL were estimated for each group. The secondary outcome was change in spherical equivalent refraction (ΔSER). As orthokeratology temporarily alters corneal curvature, rendering refractive measurements invalid, the OK group was excluded from the SER analysis. ANCOVA with baseline SER as the covariate compared ΔSER among the SVS, DIMS, and RLRL groups. For all ANCOVA models, pairwise comparisons were performed on estimated marginal means with Bonferroni-correction for multiple comparisons. The primary focus was comparing RLRL against each of the other three groups (SVS, DIMS, OK). Statistical significance was set at p < 0.05 . Results Baseline characteristics of subjects A total of 527 children (527 right eyes) were included in the final analysis, comprising four treatment groups: SVS, n = 139; DIMS, n = 121; RLRL, n = 122; OK, n = 145. Baseline demographic and clinical characteristics are summarised in Table 1 . Table 1 Demographic and baseline characteristics of patients Sex (M/F) RLRL (n = 122) SVS (n = 139) DIMS (n = 121) OK (n = 145) p value 68/54 60/79 75/46 78/67 0.127 Intervention duration (days) 356 ± 64 351 ± 59 341 ± 58 359 ± 32 0.053 Age (years) 8.89 ± 1.56 9.07 ± 1.72 9.37 ± 1.45 9.14 ± 1.22 0.091 SER (D) –2.02 ± 1.24 –2.03 ± 1.10 –2.28 ± 0.99 –2.23 ± 0.89 0.098 AL (mm) 24.30 ± 0.85 24.04 ± 0.79 24.60 ± 1.00 24.60 ± 0.80 < 0.001 Data are presented as n/n or mean ± SD. There were no statistically significant differences among the groups in age, sex distribution, intervention duration, or baseline spherical equivalent refraction (SER) (all p > 0.05). However, a significant difference was observed in baseline axial length (AL) ( p < 0.001 ), with the RLRL and OK groups having slightly longer mean AL compared with the SVS and DIMS groups (Table 1 ). This baseline imbalance was adjusted for in the primary outcome analyses using analysis of covariance (ANCOVA). Primary outcomes: overall efficacy Axial length elongation (ΔAL) After adjusting for baseline AL (covariate value: 24.38 mm), the estimated marginal means for axial elongation over 12 months were: RLRL 0.10 mm (95% CI 0.046 to 0.144 mm), SVS 0.38 mm (95% CI 0.333 to 0.427 mm), DIMS 0.32 mm (95% CI 0.270 to 0.369 mm), and OK 0.25 mm (95% CI 0.200 to 0.290 mm) (Supplementary table 1 ). ANCOVA revealed a significant main effect of treatment group on ΔAL ( F ₍₃,₅₂₂₎ =25.692, p < 0.001 , partial η² =0.129). Bonferroni-adjusted pairwise comparisons confirmed that the RLRL group had significantly less axial elongation than each of the other three groups (all p < 0.001 ; Fig. 1 A). Spherical equivalent refraction progression (ΔSER) For the three groups with valid refractive measurements (SVS, DIMS, and RLRL; OK excluded), ANCOVA with baseline SER as covariate (covariate value: − 2.10 D) showed a significant overall group effect ( F ₍₂,₃₇₈₎ =51.871, p < 0.001 , partial η² =0.215). The adjusted marginal means for SER change were: RLRL − 0.17 D (95% CI − 0.263 to − 0.072 D), SVS − 0.85 D (95% CI − 0.935 to − 0.756 D), and DIMS − 0.57 D (95% CI − 0.661 to − 0.468 D) (Supplementary table 2). Pairwise comparisons demonstrated that RLRL resulted in significantly less myopic progression compared with both SVS and DIMS (both p < 0.001 ; Fig. 1 B). Subgroup analyses To evaluate the consistency of treatment effects across different patient populations, stratified analyses were performed by age, baseline myopia severity, and gender. All subgroup analyses employed ANCOVA with the corresponding baseline value (AL or SER) as a covariate. Subgroup analysis by age Participants were stratified into two age groups: ≤9 years (n = 243) and > 9 years (n = 284). Results are presented in Supplementary table 3–4 and Fig. 2 . Axial length elongation (ΔAL) In children aged ≤ 9 years, RLRL showed the smallest adjusted mean elongation (0.11 mm, 95% CI 0.049 to 0.176 mm), which was significantly less than SVS (0.44 mm, p < 0.001 ), DIMS (0.32 mm, p 9 years subgroup, RLRL again demonstrated superior efficacy (0.08 mm, 95% CI 0.002 to 0.154 mm) compared with SVS (0.34 mm, p < 0.001 ), DIMS (0.31 mm, p < 0.001 ), and OK (0.22 mm, p = 0.024) (Fig. 2 B; Supplementary table 3). Spherical equivalent refraction progression (ΔSER) For SER, the OK group was excluded. In the ≤ 9 years subgroup, RLRL (–0.16 D, 95% CI − 0.293 to − 0.025 D) was significantly superior to SVS (–0.86 D, p < 0.001) and DIMS (–0.61 D, p 9 years subgroup, RLRL (–0.19 D, 95% CI − 0.332 to − 0.047 D) significantly outperformed SVS (–0.83 D, p < 0.001 ) and DIMS (–0.53 D, p = 0.001) (Fig. 2 D; Supplementary table 4). Subgroup analysis by baseline myopia severity Participants were divided into mild myopia (SER≤–3.0 D, n = 434) and moderate myopia (SER>–3.0 D, n = 93) subgroups. Results are shown in Supplementary table 5–6 and Fig. 3 . Axial length elongation (ΔAL) In the mild myopia subgroup, RLRL had the smallest adjusted mean elongation (0.08 mm, 95% CI 0.020 to 0.131 mm), significantly less than SVS (0.38 mm, p < 0.001 ), DIMS (0.37 mm, p < 0.001 ), and OK (0.27 mm, p < 0.001 ) (Fig. 3 A; Supplementary table 5). In the moderate myopia subgroup, RLRL (0.18 mm, 95% CI 0.089 to 0.270 mm) was significantly more effective than SVS (0.40 mm, p = 0.012), but comparable to DIMS (0.06 mm, p = 0.579) and OK (0.11 mm, p = 1.000) (Fig. 3 B; Supplementary table 5). Spherical equivalent refraction progression (ΔSER) In the mild myopia subgroup, RLRL (–0.11 D, 95% CI − 0.228 to 0.002 D) was significantly superior to SVS (–0.84 D, p < 0.001 ) and DIMS (–0.63 D, p < 0.001 ) (Fig. 3 C; Supplementary table 6). In the moderate myopia subgroup, RLRL (–0.30 D, 95% CI − 0.458 to − 0.149 D) significantly outperformed SVS (–0.88 D, p < 0.001 ), but was comparable to DIMS (–0.35 D, p = 1.000) (Fig. 3 D; Supplementary table 6). Subgroup analysis by gender Participants were stratified by gender (male: n = 281; female: n = 246). Results are presented in Supplementary table 7–8 and Fig. 4 . Axial length elongation (ΔAL) In males, RLRL (0.14 mm, 95% CI 0.079 to 0.201 mm) was significantly more effective than SVS (0.35 mm, p < 0.001 ) and DIMS (0.32 mm, p < 0.001 ), but showed comparable efficacy to OK (0.21 mm, p = 0.276) (Fig. 4 A; Supplementary table 7). In females, RLRL demonstrated superior efficacy (0.06 mm, 95% CI − 0.013 to 0.134 mm) compared with all other interventions: SVS (0.44 mm, p < 0.001 ), DIMS (0.27 mm, p < 0.001 ), and OK (0.25 mm, p = 0.003) (Fig. 4 B; Supplementary table 7). Spherical equivalent refraction progression (ΔSER) In males, RLRL (–0.22 D, 95% CI − 0.341 to − 0.098 D) was significantly more effective than SVS (–0.88 D, p < 0.001 ) and DIMS (–0.57 D, p < 0.001 ) (Fig. 4 C; Supplementary table 8). In females, RLRL also showed superior efficacy (–0.11 D, 95% CI − 0.254 to 0.030 D) compared with both SVS (–0.82 D, p < 0.001 ) and DIMS (–0.55 D, p < 0.001 ) (Fig. 4 D; Supplementary table 8). In summary, subgroup analyses confirmed that RLRL therapy consistently provided effective myopia control across all demographic and clinical subgroups, with particularly pronounced benefits in females and younger children. However, in males and in children with moderate myopia, the efficacy of RLRL was comparable to that of DIMS spectacles and OK lens, suggesting that patient characteristics may influence treatment response. Discussion In this 1-year retrospective study, RLRL therapy was significantly more effective than SVS, DIMS spectacles, and OK in controlling axial elongation and myopic progression in children aged 6–12 years. The mean difference in axial elongation versus SVS (0.26 mm) is clinically significant, given that each millimetre of axial growth increases future myopic pathology risk [ 8 ]. These findings align with previous RCTs reporting 60–80% efficacy for RLRL [ 17 – 19 , 35 ]. RLRL yielded an adjusted mean axial elongation of only 0.10 mm—substantially less than DIMS (0.30 mm) and OK (0.23 mm)—making it a highly competitive option, especially for children averse to spectacles or contact lenses. Meta-analyses confirm RLRL's superior efficacy in reducing axial elongation compared with optical interventions [ 24 , 33 ]. Although we did not directly compare RLRL with low-dose atropine, a recent RCT found RLRL more effective in controlling axial elongation (0.08 mm vs. 0.33 mm) [ 36 ], suggesting that photobiomodulation and enhanced choroidal perfusion may more potently address structural drivers of myopia than muscarinic receptor modulation alone. Efficacy varied across subgroups. Older children (11–13 years) showed greater response, consistent with prior trials [ 17 , 35 ], possibly reflecting higher natural progression rates in younger children. DIMS spectacles performed comparably to RLRL in males and children with moderate myopia, suggesting that for these populations, a simpler spectacle-based intervention may suffice. This may partly relate to lower adherence to OK lens care in males, reducing real-world OK effectiveness [ 37 ]. These findings underscore the importance of personalised myopia management. RLRL's biological effects are under active investigation. Observed choroidal thickening supports the hypothesis that RLRL enhances choroidal blood flow, alleviating scleral hypoxia [ 21 , 22 , 27 ]. Choroidal thickening often signals halted ocular growth and predicts treatment response [ 21 , 38 , 39 ]. At the molecular level, RLRL upregulates ALDH3A1 , an antioxidant enzyme in retinal pigment epithelium, linking light exposure to protection against oxidative stress—a contributor to myopia pathogenesis [ 23 , 25 , 40 ]. Animal studies also suggest red light influences refractive development via dopamine release [ 41 ]. Axial shortening, observed in over 20% of RLRL-treated children [ 17 , 35 , 42 ], cannot be explained solely by choroidal thickening [ 22 ]. It likely involves scleral remodelling: improved choroidal and retinal oxygenation may alter signalling cascades (e.g., TGF-β, HIF-1α ) that drive extracellular matrix changes, yielding a less extensible sclera [ 26 , 27 , 43 ]. Greater compliance is associated with this phenomenon [ 42 , 44 ]. No severe adverse events, functional vision loss, or structural damage were observed on standard funduscopy or OCT, consistent with previous studies [ 17 – 19 , 35 ]. However, AOSLO has revealed reduced parafoveal cone density and hyperreflective signals in children using RLRL > 1 year [ 29 ], corroborated by a case of retinal damage [ 28 ]. These findings emphasise that safety evaluation must extend beyond conventional imaging. Although RLRL is Class 1 per IEC 60825-1:2014 [ 45 ], theoretical limits may be approached under certain conditions [ 46 ]. Long-term safety data remain limited [ 24 , 32 , 33 ]; rigorous surveillance with advanced imaging (e.g., AOSLO) is essential. Strengths include a large sample, multiple active comparators (SVS, DIMS, OK), and comprehensive subgroup analyses. Limitations include the retrospective, non-randomised design (selection bias), 1-year follow-up (insufficient for long-term or rebound assessment), lack of data on environmental factors or objective compliance monitoring, and restriction to Chinese children (limiting generalisability). Patient-reported outcomes were not collected. Large-scale, long-term randomised sham-controlled trials with high-resolution retinal imaging (e.g., AOSLO, OCT angiography) are needed to establish RLRL's long-term safety. Elucidating mechanisms of axial shortening—particularly scleral hypoxia and extracellular matrix remodelling—will guide treatment optimisation. Studies evaluating optimal dosing, combination therapies (e.g., with atropine or DIMS), and baseline predictors of response will enable more personalised strategies [ 40 ]. In conclusion, this study provides robust evidence that RLRL therapy is highly effective in controlling myopia progression in children, with efficacy superior to SVS, DIMS, and OK. While short-term safety appears favourable, potential subtle retinal changes warrant continued long-term monitoring. RLRL represents a valuable addition to evidence-based myopia control. Conclusion RLRL therapy demonstrated superior 1-year efficacy in controlling myopia progression compared with SVS, DIMS spectacles, and OK, with pronounced effects in females and younger children. Short-term safety was reassuring, supporting RLRL as a highly effective intervention, though long-term retinal health monitoring remains essential. Abbreviations AL Axial Length BCVA Best-Corrected Visual Acuity D Diopter DIMS Defocus Incorporated Multiple Segments OK Orthokeratology RLRL Repeated Low-Level Red-Light SER Spherical Equivalent Refraction SVS Single-Vision Spectacles ΔAL Change in Axial Length ΔSER Change in Spherical Equivalent Refraction Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Shanghai Aier Eye Hospital (SHAIER2022YN02) and followed the tenets of the Declaration of Helsinki. Because this was a retrospective analysis of de-identified medical records, the Ethics Committee waived the requirement for informed consent for the use of the data (in accordance with national regulations Guo Wei Ke Jiao Fa [2023] No. 4). All participants were under the age of 16. Of note, prior to receiving the clinical interventions whose outcomes were analyzed in this study (orthokeratology and 650 nm RLRL therapy), the parents or legal guardians of all participants had signed written informed consent forms for the clinical procedures themselves. No additional consent was required for this retrospective analysis. Consent for publication Not applicable Competing interests The authors declare that they have no competing interests. No financial or personal relationships with other people or organisations that could inappropriately influence (bias) this work have existed. Funding None Author Contribution Limin Gu designed the study. Limin Gu, Xiaojun Hu and Mei Tian collected and curated the data. Wenjie Li, Xiaojun Hu, and Yan Yan analyzed and interpreted the data. Yujiao Zhang and Xiuwen Liang prepared the figures. Limin Gu drafted the manuscript. Wenjie Li, Xiaojun Hu, Mei Tian, Yan Yan, Yujiao Zhang, Xiuwen Liang, and Shan Lin contributed to the critical revision of the manuscript for important intellectual content. Shan Lin supervised the study. Limin Gu and Shan Lin provided final approval of the version to be published. All authors read and approved the final manuscript. Acknowledgement The authors thank all the children and their families who involved in this study. We also acknowledge the clinical staff at Shanghai Bright Eye Hospital, Shanghai Aier Eye Hospital, China Central South University Xiangya Third Hospital, Eye & ENT Hospital of Fudan University, Jianshanhu Hospital, and Wuhan Bright Eye Hospital for their assistance. Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. References Baird PN, Saw SM, Lanca C, et al. Myopia Nat Rev Dis Primers. 2020;6:99. Holden BA, Fricke TR, Wilson DA, et al. 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Investigation of the Efficacy and Safety of 650 nm Low-Level Red Light for Myopia Control in Children: A Randomized Controlled Trial. Ophthalmol therapy. 2022;11:2259–70. IEC 60825-. 1:2014 Safety of laser products - Part 1: Equipment classification and requirements. IEC 60825-1:2014. Geneva: IEC; 2014. Ostrin LA, Schill AW. Red light instruments for myopia exceed safety limits. Ophthalmic physiological optics: J Br Coll Ophthalmic Opticians (Optometrists). 2024;44:241–8. Wildsoet CF, Chia A, Cho P, et al. IMI - Interventions Myopia Institute: Interventions for Controlling Myopia Onset and Progression Report. Invest Ophthalmol Vis Sci. 2019;60:M106–31. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable18.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 30 Apr, 2026 Reviewers agreed at journal 08 Apr, 2026 Reviewers invited by journal 06 Apr, 2026 Editor assigned by journal 06 Apr, 2026 Editor invited by journal 03 Apr, 2026 Submission checks completed at journal 03 Apr, 2026 First submitted to journal 03 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9261382","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":619910345,"identity":"e007a65a-61f1-4d7a-9e1e-152aeec0cb83","order_by":0,"name":"Limin Gu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYHACxgMJDBIM/MzMhx8QrQesRbKdLc2AeC0gwuA8j4IEUcrlIxIYDjzMscgzPszDYMBQYxNNUIvhDaCWxG0SxWaHeQ88YDiWlttAUMsMiJbEbYf5EgwYGw6ToGVzM4+BBFFa5CWgWjYwE6vFgOcBRMuMw8BATiDGL/LtCYwPf26rS+zvP3z4wYcaGyJsOcD/AcFLIKQcbAtBQ0fBKBgFo2AUAACg0EAvi59eJgAAAABJRU5ErkJggg==","orcid":"","institution":"Shanghai Bright Eye Hospital","correspondingAuthor":true,"prefix":"","firstName":"Limin","middleName":"","lastName":"Gu","suffix":""},{"id":619910346,"identity":"19736d7b-7e33-4807-b827-4dd73f71af29","order_by":1,"name":"Wenjie Li","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Wenjie","middleName":"","lastName":"Li","suffix":""},{"id":619910349,"identity":"05008d8a-f837-49db-8ebe-97ad1a654aa4","order_by":2,"name":"Xiaojun Hu","email":"","orcid":"","institution":"Eye \u0026 ENT Hospital of Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Xiaojun","middleName":"","lastName":"Hu","suffix":""},{"id":619910350,"identity":"8029ad64-484d-4381-86af-b7f36276834b","order_by":3,"name":"Mei Tian","email":"","orcid":"","institution":"Jianshanhu Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mei","middleName":"","lastName":"Tian","suffix":""},{"id":619910351,"identity":"26973165-39bf-4fd7-9858-5ccca1eff1b3","order_by":4,"name":"Yan Yan","email":"","orcid":"","institution":"Shanghai Bright Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Yan","suffix":""},{"id":619910354,"identity":"d20f1ac0-5af3-44f1-a454-c9e795614306","order_by":5,"name":"Yujiao Zhang","email":"","orcid":"","institution":"Shanghai Bright Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yujiao","middleName":"","lastName":"Zhang","suffix":""},{"id":619910356,"identity":"aec4ccad-2d5f-4c04-877b-71cca1e66fc6","order_by":6,"name":"Xiuwen Liang","email":"","orcid":"","institution":"Shanghai Bright Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiuwen","middleName":"","lastName":"Liang","suffix":""},{"id":619910358,"identity":"36024235-3e8a-40ad-ae05-1750543cacb3","order_by":7,"name":"Shan Lin","email":"","orcid":"","institution":"WuHan Bright Eye Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shan","middleName":"","lastName":"Lin","suffix":""}],"badges":[],"createdAt":"2026-03-30 00:53:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9261382/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9261382/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106960435,"identity":"68d64f7a-6710-4d30-ba71-e341955d9374","added_by":"auto","created_at":"2026-04-15 09:21:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":293779,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Mean change in axial length (ΔAL, mm) and (B) mean change in SER (ΔSER, D) after 12 months of treatment in the different groups. Data are presented as adjusted mean±SE from ANCOVA models controlling for baseline AL and SER. All statistical comparisons are versus the RLRL group. RLRL, repeated low‑level red‑light therapy + SVS; SVS, single‑vision spectacles; DIMS, defocus incorporated multiple segments spectacles; OK, orthokeratology. * \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001 (Bonferroni‑corrected). \u003cem\u003eThe detailed numerical data are provided in Supplementary Table 1 and Table 2.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9261382/v1/9d8ba8e685791405b48541e6.jpg"},{"id":106836333,"identity":"c8f408e8-b6af-471e-8828-6bed84437a4a","added_by":"auto","created_at":"2026-04-14 02:07:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":597858,"visible":true,"origin":"","legend":"\u003cp\u003eMean change in axial length (ΔAL, mm) and SER (ΔSER, D) after 12 months of treatment. (A) ΔAL in children aged ≤9 years; (B) ΔAL in children aged \u0026gt;9 years; (C) ΔSER in children aged ≤9 years; (D) ΔSER in children aged \u0026gt;9 years. Data are presented as adjusted mean±SE from ANCOVA models controlling for baseline AL and SER. All statistical comparisons are versus the RLRL group within each age stratum. RLRL, repeated low‑level red‑light therapy + SVS; SVS, single‑vision spectacles; DIMS, defocus incorporated multiple segments spectacles; OK, orthokeratology. # \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, * \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001 (Bonferroni‑corrected). \u003cem\u003eThe detailed numerical data are provided in Supplementary Table 3 and Table 4.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9261382/v1/3deefed13196303910f04d23.jpg"},{"id":106960545,"identity":"6748947f-c251-4fea-8490-b7252e2997f8","added_by":"auto","created_at":"2026-04-15 09:21:43","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":789452,"visible":true,"origin":"","legend":"\u003cp\u003eMean change in axial length (ΔAL, mm) and SER (ΔSER, D) after 12 months of treatment. (A) ΔAL in mild myopia (SER ≤ –3.00 D); (B) ΔAL in moderate myopia (SER \u0026gt; –3.00 D); (C) ΔSER in mild myopia (SER ≤ –3.00 D); (D) ΔSER in moderate myopia (SER \u0026gt; –3.00 D). Data are presented as adjusted mean±SE from ANCOVA models controlling for baseline AL and SER. All statistical comparisons are versus the RLRL group within each myopia severity stratum. RLRL, repeated low‑level red‑light therapy + SVS; SVS, single‑vision spectacles; DIMS, defocus incorporated multiple segments spectacles; OK, orthokeratology. # \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, * \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001 (Bonferroni‑corrected). \u003cem\u003eThe detailed numerical data are provided in Supplementary Table 5 and Table 6.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9261382/v1/0ff93b79ee42734fd45fbf81.jpg"},{"id":106836334,"identity":"bc327601-fda2-4a92-b881-b23ccc1053dc","added_by":"auto","created_at":"2026-04-14 02:07:44","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":668231,"visible":true,"origin":"","legend":"\u003cp\u003eMean change in axial length (ΔAL, mm) and SER (ΔSER, D) after 12 months of treatment. (A) ΔAL in males; (B) ΔAL in females; (C) ΔSER in males; (D) ΔSER in females. Data are presented as adjusted mean±SE from ANCOVA models controlling for baseline AL and SER. All statistical comparisons are versus the RLRL group within each gender stratum. RLRL, repeated low‑level red‑light therapy + SVS; SVS, single‑vision spectacles; DIMS, defocus incorporated multiple segments spectacles; OK, orthokeratology. # \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05, * \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001 (Bonferroni‑corrected). \u003cem\u003eThe detailed numerical data are provided in Supplementary Table 7 and Table 8.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9261382/v1/b4d4786695ed85e002472b6d.jpg"},{"id":106963117,"identity":"bbfe83ac-53d0-44ed-a21d-adf2132ac0aa","added_by":"auto","created_at":"2026-04-15 09:42:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3128084,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9261382/v1/c107d4f3-30d3-49da-9726-2863f5db476c.pdf"},{"id":106836331,"identity":"47c9a13d-0dff-4597-b34d-46aa0514c184","added_by":"auto","created_at":"2026-04-14 02:07:44","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":32510,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable18.docx","url":"https://assets-eu.researchsquare.com/files/rs-9261382/v1/2e94ee4b2697be64f591c4e1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of repeated low-level red-light therapy with single-vision spectacles, DIMS lenses, and orthokeratology for myopia control in children: a one-year retrospective cohort study","fulltext":[{"header":"Background","content":"\u003cp\u003eMyopia is a leading cause of visual impairment worldwide, with prevalence rising rapidly, particularly in urbanised East and Southeast Asia [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. By 2050, an estimated 4.76\u0026nbsp;billion people (49.8% of the global population) will be myopic, nearly 1\u0026nbsp;billion of whom will have high myopia (\u0026le;\u0026ndash;5.00 D or \u0026le;\u0026ndash;6.00 D) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. High myopia increases the risk of sight-threatening complications\u0026mdash;including cataracts, myopic maculopathy, retinal detachment, and glaucoma\u0026mdash;leading to irreversible vision loss and substantial socioeconomic burden [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Effective early intervention is therefore critical for preserving long-term ocular health [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eConventional single-vision spectacles (SVS) correct refractive error but do not slow axial elongation [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Established treatments such as low-dose atropine and orthokeratology (OK) are effective [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] but have limitations: atropine can cause photophobia, allergic conjunctivitis, and rebound effects [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]; OK carries risks of microbial keratitis and requires stringent lens care [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These challenges highlight the need for alternative, non-invasive, and safe options.\u003c/p\u003e \u003cp\u003eRepeated low-level red-light (RLRL) therapy has emerged as a novel home-based intervention. Recent randomised controlled trials (RCTs) show that 650 nm RLRL significantly reduces axial elongation and spherical equivalent refraction (SER) progression compared with SVS, with some studies reporting axial shortening [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Proposed mechanisms include increased choroidal thickness and perfusion [\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], upregulation of antioxidant enzymes (e.g., \u003cem\u003eALDH3A1\u003c/em\u003e) in retinal pigment epithelium [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], and modulation of inflammatory and oxidative stress pathways [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], which may alleviate scleral hypoxia\u0026mdash;a key driver of axial elongation [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Despite promising efficacy, the evidence base for RLRL is evolving. Recent reports have raised safety concerns: one case documented retinal damage [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], and a cohort study using adaptive optics scanning laser ophthalmoscopy (AOSLO) found reduced cone density and subtle retinal abnormalities in treated children [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Optimal dosing, sustainability, and potential rebound effects also require further study [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Systematic reviews confirm efficacy but call for longer-term safety data [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis real-world study therefore evaluated the 1-year efficacy of RLRL for mild to moderate myopia in Chinese children, benchmarking it against SVS, DIMS spectacles, and OK, while exploring predictors of treatment response.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSubjects\u003c/h2\u003e \u003cp\u003e This retrospective study reviewed the medical records of children who visited Shanghai Aier Hospital between January 2023 and February 2025. Patients were divided into four treatment groups: SVS (control group), defocus incorporated multiple segments (DIMS) spectacles, RLRL combined with SVS, and OK. Treatment allocation was based on patient/parental choice following clinical consultation and assessment of suitability.\u003c/p\u003e \u003cp\u003eInclusion criteria were: (1) age 6\u0026ndash;12 years; (2) cycloplegic SER between \u0026minus;\u0026thinsp;1.00 and \u0026minus;\u0026thinsp;5.00 D; (3) astigmatism\u0026thinsp;\u0026le;\u0026thinsp;2.50 D; (4) anisometropia\u0026thinsp;\u0026le;\u0026thinsp;1.50 D; (5) best-corrected visual acuity (BCVA) of 0.0 logMAR or better in each eye; (6) completion of at least one consecutive year of the assigned treatment. Exclusion criteria included strabismus, significant binocular vision dysfunction (e.g., convergence insufficiency), other ocular pathologies, or systemic diseases affecting ocular health.\u003c/p\u003e \u003cp\u003eIf both eyes met the criteria, only data from the right eye were included in the analysis. This study was approved by the Ethics Committee of Shanghai Aier Eye Hospital and adhered to the tenets of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTreatments and ocular biometry measurements\u003c/h3\u003e\n\u003cp\u003e \u003cem\u003eRLRL group\u003c/em\u003e: Participants wore SVS for refractive correction and underwent RLRL therapy using a desktop light therapy device (Eyerising, Suzhou Xuanjia Optoelectronics Technology, Jiangsu, China). The device delivers low-level red light with a wavelength of 650\u0026thinsp;\u0026plusmn;\u0026thinsp;10 nm at an illuminance of approximately 1600 lux through the pupil to the fundus. The calculated power through a 4 mm pupil was 0.29 mW, classified as Class 1 per IEC 60825-1:2014, deemed safe for direct ocular exposure. Treatment was administered twice daily (at least 4 hours apart) on weekdays (5 days/week), with each session lasting 3 minutes, under parental supervision [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSVS group\u003c/strong\u003e \u003cp\u003eParticipants wore conventional single-vision spectacles full-time.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDIMS group\u003c/strong\u003e \u003cp\u003eParticipants wore MiYOSMART DIMS spectacle lenses (HOYA Vision Care, Japan) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. These lenses feature a central 9 mm zone for distance correction surrounded by an annular multi-segmental zone (33 mm diameter) with a relative positive power of +\u0026thinsp;3.50 D. Daily wear time was recommended to be at least 12 hours.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eOK group\u003c/strong\u003e \u003cp\u003eParticipants wore overnight orthokeratology lenses made of rigid gas-permeable material (CRT, Paragon Vision Sciences, USA). Standard fitting procedures, follow-up visits (1 day, 1 week, 1 month and then every 3 months), and safety monitoring (slit-lamp examination for corneal integrity, AL measurement and corneal endothelial cell count) were performed.\u003c/p\u003e \u003c/p\u003e \u003cp\u003eAL was measured using the IOL Master 500 (Carl Zeiss, Germany). Cycloplegic SER was obtained via an autorefractor (Topcon, Japan) after instillation of 0.5% tropicamide eye drops (one drop every 5 minutes for a total of four drops). Measurements were taken at baseline and at the 12-month follow-up visit.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics 23.0. Baseline characteristics were compared using one-way ANOVA for continuous variables and χ\u0026sup2; tests for categorical variables.\u003c/p\u003e \u003cp\u003eThe primary outcome was change in axial length (ΔAL) from baseline to 12 months. An analysis of covariance (ANCOVA) was conducted with treatment group as the fixed factor and baseline AL as a covariate to adjust for significant baseline differences. Adjusted marginal means for ΔAL were estimated for each group.\u003c/p\u003e \u003cp\u003eThe secondary outcome was change in spherical equivalent refraction (ΔSER). As orthokeratology temporarily alters corneal curvature, rendering refractive measurements invalid, the OK group was excluded from the SER analysis. ANCOVA with baseline SER as the covariate compared ΔSER among the SVS, DIMS, and RLRL groups.\u003c/p\u003e \u003cp\u003eFor all ANCOVA models, pairwise comparisons were performed on estimated marginal means with Bonferroni-correction for multiple comparisons. The primary focus was comparing RLRL against each of the other three groups (SVS, DIMS, OK). Statistical significance was set at \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/em\u003e.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline characteristics of subjects\u003c/h2\u003e \u003cp\u003eA total of 527 children (527 right eyes) were included in the final analysis, comprising four treatment groups: SVS, n\u0026thinsp;=\u0026thinsp;139; DIMS, n\u0026thinsp;=\u0026thinsp;121; RLRL, n\u0026thinsp;=\u0026thinsp;122; OK, n\u0026thinsp;=\u0026thinsp;145. Baseline demographic and clinical characteristics are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and baseline characteristics of patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex (M/F)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRLRL (n\u0026thinsp;=\u0026thinsp;122)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSVS (n\u0026thinsp;=\u0026thinsp;139)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDIMS (n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOK (n\u0026thinsp;=\u0026thinsp;145)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68/54\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60/79\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75/46\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78/67\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.127\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntervention duration (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e356\u0026thinsp;\u0026plusmn;\u0026thinsp;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e351\u0026thinsp;\u0026plusmn;\u0026thinsp;59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e341\u0026thinsp;\u0026plusmn;\u0026thinsp;58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e359\u0026thinsp;\u0026plusmn;\u0026thinsp;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e8.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e9.37\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e9.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSER (D)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e\u0026ndash;2.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u0026ndash;2.03\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;2.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;2.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAL (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e24.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e24.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e24.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e24.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eData are presented as n/n or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThere were no statistically significant differences among the groups in age, sex distribution, intervention duration, or baseline spherical equivalent refraction (SER) (all \u003cem\u003ep\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/em\u003e However, a significant difference was observed in baseline axial length (AL) (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), with the RLRL and OK groups having slightly longer mean AL compared with the SVS and DIMS groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This baseline imbalance was adjusted for in the primary outcome analyses using analysis of covariance (ANCOVA).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrimary outcomes: overall efficacy\u003c/h2\u003e \u003cp\u003eAxial length elongation (ΔAL)\u003c/p\u003e \u003cp\u003eAfter adjusting for baseline AL (covariate value: 24.38 mm), the estimated marginal means for axial elongation over 12 months were: RLRL 0.10 mm (95% CI 0.046 to 0.144 mm), SVS 0.38 mm (95% CI 0.333 to 0.427 mm), DIMS 0.32 mm (95% CI 0.270 to 0.369 mm), and OK 0.25 mm (95% CI 0.200 to 0.290 mm) (Supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). ANCOVA revealed a significant main effect of treatment group on ΔAL (\u003cem\u003eF\u003c/em\u003e₍₃,₅₂₂₎ =25.692, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e, partial \u003cem\u003eη\u0026sup2;\u003c/em\u003e=0.129). Bonferroni-adjusted pairwise comparisons confirmed that the RLRL group had significantly less axial elongation than each of the other three groups (all \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSpherical equivalent refraction progression (ΔSER)\u003c/p\u003e \u003cp\u003eFor the three groups with valid refractive measurements (SVS, DIMS, and RLRL; OK excluded), ANCOVA with baseline SER as covariate (covariate value: \u0026minus;\u0026thinsp;2.10 D) showed a significant overall group effect (\u003cem\u003eF\u003c/em\u003e₍₂,₃₇₈₎ =51.871, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e, partial \u003cem\u003eη\u0026sup2;\u003c/em\u003e=0.215). The adjusted marginal means for SER change were: RLRL \u0026minus;\u0026thinsp;0.17 D (95% CI \u0026minus;\u0026thinsp;0.263 to \u0026minus;\u0026thinsp;0.072 D), SVS \u0026minus;\u0026thinsp;0.85 D (95% CI \u0026minus;\u0026thinsp;0.935 to \u0026minus;\u0026thinsp;0.756 D), and DIMS \u0026minus;\u0026thinsp;0.57 D (95% CI \u0026minus;\u0026thinsp;0.661 to \u0026minus;\u0026thinsp;0.468 D) (Supplementary table 2). Pairwise comparisons demonstrated that RLRL resulted in significantly less myopic progression compared with both SVS and DIMS (both \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSubgroup analyses\u003c/h3\u003e\n\u003cp\u003eTo evaluate the consistency of treatment effects across different patient populations, stratified analyses were performed by age, baseline myopia severity, and gender. All subgroup analyses employed ANCOVA with the corresponding baseline value (AL or SER) as a covariate.\u003c/p\u003e\n\u003ch3\u003eSubgroup analysis by age\u003c/h3\u003e\n\u003cp\u003eParticipants were stratified into two age groups: \u0026le;9 years (n\u0026thinsp;=\u0026thinsp;243) and \u0026gt;\u0026thinsp;9 years (n\u0026thinsp;=\u0026thinsp;284). Results are presented in Supplementary table 3\u0026ndash;4 and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAxial length elongation (ΔAL)\u003c/p\u003e \u003cp\u003eIn children aged\u0026thinsp;\u0026le;\u0026thinsp;9 years, RLRL showed the smallest adjusted mean elongation (0.11 mm, 95% CI 0.049 to 0.176 mm), which was significantly less than SVS (0.44 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), DIMS (0.32 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), and OK (0.27 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA; Supplementary table 3). In the \u0026gt;\u0026thinsp;9 years subgroup, RLRL again demonstrated superior efficacy (0.08 mm, 95% CI 0.002 to 0.154 mm) compared with SVS (0.34 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), DIMS (0.31 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), and OK (0.22 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB; Supplementary table 3).\u003c/p\u003e \u003cp\u003eSpherical equivalent refraction progression (ΔSER)\u003c/p\u003e \u003cp\u003eFor SER, the OK group was excluded. In the \u0026le;\u0026thinsp;9 years subgroup, RLRL (\u0026ndash;0.16 D, 95% CI \u0026minus;\u0026thinsp;0.293 to \u0026minus;\u0026thinsp;0.025 D) was significantly superior to SVS (\u0026ndash;0.86 D, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DIMS (\u0026ndash;0.61 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC; Supplementary table 4). Similarly, in the \u0026gt;\u0026thinsp;9 years subgroup, RLRL (\u0026ndash;0.19 D, 95% CI \u0026minus;\u0026thinsp;0.332 to \u0026minus;\u0026thinsp;0.047 D) significantly outperformed SVS (\u0026ndash;0.83 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) and DIMS (\u0026ndash;0.53 D, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD; Supplementary table 4).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis by baseline myopia severity\u003c/h2\u003e \u003cp\u003eParticipants were divided into mild myopia (SER\u0026le;\u0026ndash;3.0 D, n\u0026thinsp;=\u0026thinsp;434) and moderate myopia (SER\u0026gt;\u0026ndash;3.0 D, n\u0026thinsp;=\u0026thinsp;93) subgroups. Results are shown in Supplementary table 5\u0026ndash;6 and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAxial length elongation (ΔAL)\u003c/p\u003e \u003cp\u003eIn the mild myopia subgroup, RLRL had the smallest adjusted mean elongation (0.08 mm, 95% CI 0.020 to 0.131 mm), significantly less than SVS (0.38 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), DIMS (0.37 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), and OK (0.27 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA; Supplementary table 5). In the moderate myopia subgroup, RLRL (0.18 mm, 95% CI 0.089 to 0.270 mm) was significantly more effective than SVS (0.40 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), but comparable to DIMS (0.06 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.579) and OK (0.11 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB; Supplementary table 5).\u003c/p\u003e \u003cp\u003eSpherical equivalent refraction progression (ΔSER)\u003c/p\u003e \u003cp\u003eIn the mild myopia subgroup, RLRL (\u0026ndash;0.11 D, 95% CI \u0026minus;\u0026thinsp;0.228 to 0.002 D) was significantly superior to SVS (\u0026ndash;0.84 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) and DIMS (\u0026ndash;0.63 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC; Supplementary table 6). In the moderate myopia subgroup, RLRL (\u0026ndash;0.30 D, 95% CI \u0026minus;\u0026thinsp;0.458 to \u0026minus;\u0026thinsp;0.149 D) significantly outperformed SVS (\u0026ndash;0.88 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), but was comparable to DIMS (\u0026ndash;0.35 D, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD; Supplementary table 6).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis by gender\u003c/h2\u003e \u003cp\u003eParticipants were stratified by gender (male: n\u0026thinsp;=\u0026thinsp;281; female: n\u0026thinsp;=\u0026thinsp;246). Results are presented in Supplementary table 7\u0026ndash;8 and Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAxial length elongation (ΔAL)\u003c/p\u003e \u003cp\u003eIn males, RLRL (0.14 mm, 95% CI 0.079 to 0.201 mm) was significantly more effective than SVS (0.35 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) and DIMS (0.32 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), but showed comparable efficacy to OK (0.21 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.276) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA; Supplementary table 7). In females, RLRL demonstrated superior efficacy (0.06 mm, 95% CI \u0026minus;\u0026thinsp;0.013 to 0.134 mm) compared with all other interventions: SVS (0.44 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), DIMS (0.27 mm, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e), and OK (0.25 mm, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB; Supplementary table 7).\u003c/p\u003e \u003cp\u003eSpherical equivalent refraction progression (ΔSER)\u003c/p\u003e \u003cp\u003eIn males, RLRL (\u0026ndash;0.22 D, 95% CI \u0026minus;\u0026thinsp;0.341 to \u0026minus;\u0026thinsp;0.098 D) was significantly more effective than SVS (\u0026ndash;0.88 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) and DIMS (\u0026ndash;0.57 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC; Supplementary table 8). In females, RLRL also showed superior efficacy (\u0026ndash;0.11 D, 95% CI \u0026minus;\u0026thinsp;0.254 to 0.030 D) compared with both SVS (\u0026ndash;0.82 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) and DIMS (\u0026ndash;0.55 D, \u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD; Supplementary table 8).\u003c/p\u003e \u003cp\u003e In summary, subgroup analyses confirmed that RLRL therapy consistently provided effective myopia control across all demographic and clinical subgroups, with particularly pronounced benefits in females and younger children. However, in males and in children with moderate myopia, the efficacy of RLRL was comparable to that of DIMS spectacles and OK lens, suggesting that patient characteristics may influence treatment response.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this 1-year retrospective study, RLRL therapy was significantly more effective than SVS, DIMS spectacles, and OK in controlling axial elongation and myopic progression in children aged 6\u0026ndash;12 years. The mean difference in axial elongation versus SVS (0.26 mm) is clinically significant, given that each millimetre of axial growth increases future myopic pathology risk [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These findings align with previous RCTs reporting 60\u0026ndash;80% efficacy for RLRL [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRLRL yielded an adjusted mean axial elongation of only 0.10 mm\u0026mdash;substantially less than DIMS (0.30 mm) and OK (0.23 mm)\u0026mdash;making it a highly competitive option, especially for children averse to spectacles or contact lenses. Meta-analyses confirm RLRL's superior efficacy in reducing axial elongation compared with optical interventions [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Although we did not directly compare RLRL with low-dose atropine, a recent RCT found RLRL more effective in controlling axial elongation (0.08 mm vs. 0.33 mm) [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], suggesting that photobiomodulation and enhanced choroidal perfusion may more potently address structural drivers of myopia than muscarinic receptor modulation alone.\u003c/p\u003e \u003cp\u003eEfficacy varied across subgroups. Older children (11\u0026ndash;13 years) showed greater response, consistent with prior trials [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], possibly reflecting higher natural progression rates in younger children. DIMS spectacles performed comparably to RLRL in males and children with moderate myopia, suggesting that for these populations, a simpler spectacle-based intervention may suffice. This may partly relate to lower adherence to OK lens care in males, reducing real-world OK effectiveness [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. These findings underscore the importance of personalised myopia management.\u003c/p\u003e \u003cp\u003eRLRL's biological effects are under active investigation. Observed choroidal thickening supports the hypothesis that RLRL enhances choroidal blood flow, alleviating scleral hypoxia [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Choroidal thickening often signals halted ocular growth and predicts treatment response [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. At the molecular level, RLRL upregulates \u003cem\u003eALDH3A1\u003c/em\u003e, an antioxidant enzyme in retinal pigment epithelium, linking light exposure to protection against oxidative stress\u0026mdash;a contributor to myopia pathogenesis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Animal studies also suggest red light influences refractive development via dopamine release [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAxial shortening, observed in over 20% of RLRL-treated children [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], cannot be explained solely by choroidal thickening [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. It likely involves scleral remodelling: improved choroidal and retinal oxygenation may alter signalling cascades (e.g., TGF-β, \u003cem\u003eHIF-1α\u003c/em\u003e) that drive extracellular matrix changes, yielding a less extensible sclera [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Greater compliance is associated with this phenomenon [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNo severe adverse events, functional vision loss, or structural damage were observed on standard funduscopy or OCT, consistent with previous studies [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. However, AOSLO has revealed reduced parafoveal cone density and hyperreflective signals in children using RLRL\u0026thinsp;\u0026gt;\u0026thinsp;1 year [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], corroborated by a case of retinal damage [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. These findings emphasise that safety evaluation must extend beyond conventional imaging. Although RLRL is Class 1 per IEC 60825-1:2014 [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e], theoretical limits may be approached under certain conditions [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. Long-term safety data remain limited [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]; rigorous surveillance with advanced imaging (e.g., AOSLO) is essential.\u003c/p\u003e \u003cp\u003eStrengths include a large sample, multiple active comparators (SVS, DIMS, OK), and comprehensive subgroup analyses. Limitations include the retrospective, non-randomised design (selection bias), 1-year follow-up (insufficient for long-term or rebound assessment), lack of data on environmental factors or objective compliance monitoring, and restriction to Chinese children (limiting generalisability). Patient-reported outcomes were not collected.\u003c/p\u003e \u003cp\u003eLarge-scale, long-term randomised sham-controlled trials with high-resolution retinal imaging (e.g., AOSLO, OCT angiography) are needed to establish RLRL's long-term safety. Elucidating mechanisms of axial shortening\u0026mdash;particularly scleral hypoxia and extracellular matrix remodelling\u0026mdash;will guide treatment optimisation. Studies evaluating optimal dosing, combination therapies (e.g., with atropine or DIMS), and baseline predictors of response will enable more personalised strategies [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn conclusion, this study provides robust evidence that RLRL therapy is highly effective in controlling myopia progression in children, with efficacy superior to SVS, DIMS, and OK. While short-term safety appears favourable, potential subtle retinal changes warrant continued long-term monitoring. RLRL represents a valuable addition to evidence-based myopia control.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eRLRL therapy demonstrated superior 1-year efficacy in controlling myopia progression compared with SVS, DIMS spectacles, and OK, with pronounced effects in females and younger children. Short-term safety was reassuring, supporting RLRL as a highly effective intervention, though long-term retinal health monitoring remains essential.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cp\u003eAL Axial Length\u003c/p\u003e \u003cp\u003eBCVA Best-Corrected Visual Acuity\u003c/p\u003e \u003cp\u003eD Diopter\u003c/p\u003e \u003cp\u003eDIMS Defocus Incorporated Multiple Segments\u003c/p\u003e \u003cp\u003eOK Orthokeratology\u003c/p\u003e \u003cp\u003eRLRL Repeated Low-Level Red-Light\u003c/p\u003e \u003cp\u003eSER Spherical Equivalent Refraction\u003c/p\u003e \u003cp\u003eSVS Single-Vision Spectacles\u003c/p\u003e \u003cp\u003eΔAL Change in Axial Length\u003c/p\u003e \u003cp\u003eΔSER Change in Spherical Equivalent Refraction\u003c/p\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003e The study was approved by the Ethics Committee of Shanghai Aier Eye Hospital (SHAIER2022YN02) and followed the tenets of the Declaration of Helsinki. Because this was a retrospective analysis of de-identified medical records, the Ethics Committee waived the requirement for informed consent for the use of the data (in accordance with national regulations Guo Wei Ke Jiao Fa [2023] No. 4). All participants were under the age of 16. Of note, prior to receiving the clinical interventions whose outcomes were analyzed in this study (orthokeratology and 650 nm RLRL therapy), the parents or legal guardians of all participants had signed written informed consent forms for the clinical procedures themselves. No additional consent was required for this retrospective analysis.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors declare that they have no competing interests. No financial or personal relationships with other people or organisations that could inappropriately influence (bias) this work have existed.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLimin Gu designed the study. Limin Gu, Xiaojun Hu and Mei Tian collected and curated the data. Wenjie Li, Xiaojun Hu, and Yan Yan analyzed and interpreted the data. Yujiao Zhang and Xiuwen Liang prepared the figures. Limin Gu drafted the manuscript. Wenjie Li, Xiaojun Hu, Mei Tian, Yan Yan, Yujiao Zhang, Xiuwen Liang, and Shan Lin contributed to the critical revision of the manuscript for important intellectual content. Shan Lin supervised the study. Limin Gu and Shan Lin provided final approval of the version to be published. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors thank all the children and their families who involved in this study. We also acknowledge the clinical staff at Shanghai Bright Eye Hospital, Shanghai Aier Eye Hospital, China Central South University Xiangya Third Hospital, Eye \u0026amp; ENT Hospital of Fudan University, Jianshanhu Hospital, and Wuhan Bright Eye Hospital for their assistance.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBaird PN, Saw SM, Lanca C, et al. Myopia Nat Rev Dis Primers. 2020;6:99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolden BA, Fricke TR, Wilson DA, et al. 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Invest Ophthalmol Vis Sci. 2019;60:M106\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"myopia control, repeated low-level red-light, defocus incorporated multiple segments spectacles, orthokeratology","lastPublishedDoi":"10.21203/rs.3.rs-9261382/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9261382/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo evaluate the 1-year efficacy of repeated low-level red-light (RLRL) therapy for myopia control in children and compare it with single-vision spectacles (SVS), defocus incorporated multiple segments (DIMS) spectacles, and orthokeratology (OK) in a real-world setting.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 527 children (6\u0026ndash;12 years) with mild to moderate myopia who received SVS (n\u0026thinsp;=\u0026thinsp;139), DIMS (n\u0026thinsp;=\u0026thinsp;121), RLRL (n\u0026thinsp;=\u0026thinsp;122), or OK (n\u0026thinsp;=\u0026thinsp;145) for at least one year. Changes in axial length (ΔAL) and spherical equivalent refraction (ΔSER) were assessed. Analysis of covariance (ANCOVA) adjusted for baseline values, with Bonferroni-corrected pairwise comparisons.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBaseline AL differed significantly among groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and was adjusted for in analyses. RLRL resulted in the smallest adjusted ΔAL (0.10 mm, 95% CI 0.046\u0026ndash;0.144) versus SVS (0.38 mm), DIMS (0.32 mm), and OK (0.25 mm) (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). For ΔSER (OK excluded), RLRL also showed least progression (\u0026ndash;0.17 D, 95% CI \u0026minus;\u0026thinsp;0.263 to \u0026minus;\u0026thinsp;0.072) compared with SVS (\u0026ndash;0.85 D) and DIMS (\u0026ndash;0.57 D) (both p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Subgroup analyses revealed consistent benefits across age, gender, and baseline myopia, with RLRL efficacy comparable to DIMS and OK in males and those with moderate myopia. No severe adverse events were reported.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eRLRL therapy demonstrated superior 1-year efficacy in controlling myopia progression compared to SVS, DIMS, and OK, particularly in females and younger children. While short-term safety was reassuring, long-term retinal health monitoring remains warranted.\u003c/p\u003e","manuscriptTitle":"Comparison of repeated low-level red-light therapy with single-vision spectacles, DIMS lenses, and orthokeratology for myopia control in children: a one-year retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-14 02:07:40","doi":"10.21203/rs.3.rs-9261382/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-30T19:00:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"265011380037049686476861387913597304375","date":"2026-04-08T21:12:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-06T21:11:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-06T21:06:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-03T15:48:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-03T14:49:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2026-04-03T14:43:21+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ad5c1783-d91c-4087-87e5-b3b81f9af43a","owner":[],"postedDate":"April 14th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-04-30T19:00:16+00:00","index":49,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-14T02:07:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-14 02:07:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9261382","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9261382","identity":"rs-9261382","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}