Longitudinal Changes in Choroidal Structure Following Repeated Low-Level Red-Light Therapy for Myopia Control: Secondary Analysis of a Randomized Controlled Trial.

PURPOSE: Repeated low-level red-light (RLRL) therapy has been confirmed as a novel intervention for myopia control in children. This study aims to investigate longitudinal changes in choroidal structure in myopic children following 12-month RLRL treatment. MATERIALS AND METHODS: The current study is a secondary analysis from a multicenter, randomized controlled trial (NCT04073238). Choroidal parameters were derived from baseline and follow-up swept-source optical coherence tomography scans taken at 1, 3, 6, and 12 months. These parameters included the luminal area (LA), stromal area (SA), total choroidal area (TCA; a combination of LA and SA), and choroidal vascularity index (CVI; ratio of LA to TCA), which were automatically measured by a validated custom choroidal structure assessment tool. RESULTS: A total of 143 children (88.3% of all participants) with sufficient image quality were included in the analysis (n=67 in the RLRL and n=76 in the control groups). At the 12-month visit, all choroidal parameters increased in the RLRL group, with changes from baseline of 11.70×10 3  µm 2 (95% CI: 4.14-19.26×10 3  µm 2 ), 3.92×10 3  µm 2 (95% CI: 0.56-7.27×10 3  µm 2 ), 15.61×10 3  µm 2 (95% CI: 5.02-26.20×10 3  µm 2 ), and 0.21% (95% CI: -0.09% to 0.51%) for LA, SA, TCA, and CVI, respectively, whereas these parameters reduced in the control group. CONCLUSIONS: Following RLRL therapy, the choroidal thickening was found to be accompanied by increases in both the vessel LA and SA, with the increase in LA being greater than that of SA. In the control group, with myopia progression, both the LA and SA decreased over time.

Axial Shortening in Myopic Children after Repeated Low-Level Red-Light Therapy: Post Hoc Analysis of a Randomized Trial.

INTRODUCTION: Axial length (AL) elongation in myopia is considered irreversible. We aimed to systemically report unexpected AL shortening observed in a randomized clinical trial (RCT) after repeated low-level red-light (RLRL) therapy. METHODS: This is a post hoc analysis of a multicenter, single-masked RCT. Two hundred sixty-four myopic children aged 8-13 years allocated to RLRL treatment (intervention group) or a single vision spectacle (SVS, control group) were included. AL was measured using an IOL-master 500 at baseline, 1-, 3-, 6-, and 12-month follow-up visits. AL shortening was defined as AL reduction from baseline to follow-up visits at three cutoffs: > 0.05 mm, > 0.10 mm, and > 0.20 mm. Frequency of AL shortening at different cutoffs was calculated. Analysis was done with intent to treat (ITT). RESULTS: At 12-months follow up, frequency of AL shortening > 0.05 mm was 26/119 (21.85%) and 2/145 (1.38%) for the RLRL group versus the control group, respectively. The frequency was 18/119 (15.13%) versus 0/145 (0%) for AL shortening > 0.10 mm, and 7/119 (5.88%) versus 0/145 (0%), for AL shortening > 0.20 mm, respectively (p < 0.001). Mean AL shortening after 12 months (SD) was -0.156 (0.086) mm in the RLRL group and -0.06 mm in the control group. Age was significantly associated with AL shortening in the multivariable analysis. For the RLRL group that exhibited AL shortening (n = 56), choroidal thickness (ChT) thickening (0.056 mm) could only explain 28.3% of AL shortening (-0.20 mm). CONCLUSION: Nearly a quarter of children had > 0.05 mm AL shortening following 12 months of RLRL therapy, whereas AL shortening rarely occurred among controls. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04073238).

Clinically Significant Axial Shortening in Myopic Children After Repeated Low-Level Red Light Therapy: A Retrospective Multicenter Analysis.

INTRODUCTION: Myopia is recognized as a progressive eye disease. The aim of this study was to evaluate the frequency and associated factors of clinically significant axial length (AL) shortening among myopic children following repeated low-level red light (RLRL) therapy. METHODS: The clinical data that were collected for the myopic children aged 3-17 years who received an RLRL therapy delivered by home-use desktop light device that emitted light at 650 nm for at least 1 year, were reviewed. The clinical data included AL, spherical equivalent refraction (SER), and visual acuity measured at baseline and follow-up. The primary outcomes were frequency of AL shortening of > 0.05 mm, > 0.10 mm, and > 0.20 mm per year, and associated factors of AL shortening per year. RESULTS: A total of 434 myopic children with at least 12 months of follow-up data were included. The mean age of participants was 9.7 (2.6) years with SER of -3.74 (2.60) diopters. There were 115 (26.50%), 76 (17.51%), and 20 (4.61%) children with AL shortening based on cutoffs of 0.05 mm/year, 0.10 mm/year, and 0.20 mm/year, respectively. In the multivariable model, AL shortening was significantly associated with older baseline age, female gender, and longer baseline AL or greater spherical equivalent refraction (all P < 0.05). Among AL shortened eyes, the mean AL difference (standard deviation, SD) was -0.142 (0.094) mm/year. Greater AL shortening was observed among children who were younger and had longer baseline AL (all P < 0.05). CONCLUSIONS: More than a quarter of children had AL shortening > 0.05 mm following RLRL therapy, and the overall mean AL change was -0.142 mm/year. Further studies should explore the mechanisms underlying AL shortening.

Longitudinal Changes and Predictive Value of Choroidal Thickness for Myopia Control after Repeated Low-Level Red-Light Therapy.

PURPOSE: To evaluate longitudinal changes in macular choroidal thickness (mCT) in myopic children treated for 1 year with repeated low-level red-light (RLRL) therapy and their predictive value for treatment efficacy on myopia control. DESIGN: A secondary analysis of data from a multicenter, randomized controlled trial (RCT; NCT04073238). PARTICIPANTS: Myopic children aged 8-13 years who participated in the RCT at 2 of 5 sites where mCT measurements were available. METHODS: Repeated low-level red-light therapy was delivered using a home-use desktop light device that emitted red-light at 650 nm. Choroidal thickness was measured by SS-OCT at baseline and 1-, 3-, 6-, and 12-month follow-ups. Visual acuity, axial length (AL), cycloplegic spherical equivalent refraction (SER), and treatment compliance were measured. MAIN OUTCOME MEASURES: Changes in mCT at 1, 3, 6, and 12 months relative to baseline, and their associations with myopia control. RESULTS: A total of 120 children were included in the analysis (RLRL group: n = 60; single-vision spectacle [SVS] group: n = 60). Baseline characteristics were well balanced between the 2 groups. In the RLRL group, changes in mCT from baseline remained positive over 1 year, with a maximal increase of 14.755 µm at 1 month and gradually decreasing from 5.286 µm at 3 months to 1.543 µm at 6 months, finally reaching 9.089 µm at 12 months. In the SVS group, mCT thinning was observed, with changes from baseline of -1.111, -8.212, -10.190, and -10.407 µm at 1, 3, 6, and 12 months, respectively. Satisfactory myopia control was defined as annual progression rates of less than 0, 0.05, or 0.10 mm for AL and less than 0, 0.25, or 0.50 diopters for SER. Models that included mCT changes at 3 months alone had acceptable predictive discrimination of satisfactory myopia control over 12 months, with areas under the curve of 0.710-0.786. The predictive performance of the models did not significantly improve after adding age, gender, and baseline AL or SER. CONCLUSIONS: This analysis from a multicenter RCT found RLRL induced sustained choroidal thickening over the full course of treatment. Macular choroidal thickness changes at 3 months alone can predict 12-month myopia control efficacy with reasonable accuracy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Efficacy Comparison of Repeated Low-Level Red Light and Low-Dose Atropine for Myopia Control: A Randomized Controlled Trial.

Purpose: To compare the treatment efficacy between repeated low-level red light (RLRL) therapy and 0.01% atropine eye drops for myopia control. Methods: A single-masked, single-center, randomized controlled trial was conducted on children 7 to 15 years old with cycloplegic spherical equivalent refraction (SER) ≤ -1.00 diopter (D) and astigmatism ≤ 2.50 D. Participants were randomly assigned to the RLRL group or low-dose atropine (LDA, 0.01% atropine eye drops) group and were followed up at 1, 3, 6, and 12 months. RLRL treatment was provided by a desktop light therapy device that emits 650-nm red light. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in SER. Results: Among 62 eligible children equally randomized to each group (31 in the RLRL group, 31 in the LDA group), 60 children were qualified for analysis. The mean 1-year change in AL was 0.08 mm (95% confidence interval [CI], 0.03-0.14) in the RLRL group and 0.33 mm (95% CI, 0.27-0.38) in the LDA group, with a mean difference (MD) of -0.24 mm (95% CI, -0.32 to -0.17; P < 0.001). The 1-year change in SER was -0.03 D (95% CI, -0.01 to -0.08) in the RLRL group and -0.60 D (95% CI, -0.7 to -0.48) in the LDA group (MD = 0.57 D; 95% CI, 0.40-0.73; P < 0.001). The progression of AL < 0.1 mm was 53.2% and 9.7% (P < 0.001) in the RLRL and LDA groups, respectively. For AL ≥ 0.36 mm, progression was 9.7% and 50.0% (P < 0.001) in the RLRL and LDA groups, respectively. Conclusions: In this study, RLRL was more effective for controlling AL and myopia progression over 12 months of use compared with 0.01% atropine eye drops. Translational Relevance: RLRL therapy significantly slows axial elongation and myopia progression compared with 0.01% atropine; thus, it is an effective alternative treatment for myopia control in children.

Sustained and rebound effect of repeated low-level red-light therapy on myopia control: A 2-year post-trial follow-up study.

BACKGROUND: To evaluate the long-term efficacy and safety of continued repeated low-level red-light (RLRL) therapy on myopia control over 2 years, and the potential rebound effect after treatment cessation. METHODS: The Chinese myopic children who originally completed the one-year randomised controlled trial were enrolled. Children continued RLRL-therapy were defined as RLRL-RLRL group, while those who stopped and switched to single-vision spectacle (SVS) in the second year were RLRL-SVS group. Likewise, those who continued to merely wear SVS or received additional RLRL-therapy were SVS-SVS and SVS-RLRL groups, respectively. RLRL-therapy was provided by an at-home desktop light device emitting red-light of 650 nm and was administered for 3 min at a time, twice a day and 5 days per week. Changes in axial length (AL) and cycloplegic spherical equivalence refraction (SER) were measured. RESULTS: Among the 199 children who were eligible, 138 (69.3%) children attended the examination and 114 (57.3%) were analysed (SVS-SVS: n = 41; SVS-RLRL: n = 10; RLRL-SVS: n = 52; RLRL-RLRL: n = 11). The baseline characteristics were balanced among four groups. In the second year, the mean changes in AL were 0.28 ± 0.14 mm, 0.05 ± 0.24 mm, 0.42 ± 0.20 mm and 0.12 ± 0.16 mm in SVS-SVS, SVS-RLRL, RLRL-SVS and RLRL-RLRL group, respectively (p < 0.001). The respective mean SER changes were -0.54 ± 0.39D, -0.09 ± 0.55D, -0.91 ± 0.48D, and -0.20 ± 0.56D (p < 0.001). Over the 2-year period, axial elongation and SER progression were smallest in RLRL-RLRL group (AL: 0.16 ± 0.37 mm; SER: -0.31 ± 0.79D), followed by SVS-RLRL (AL: 0.44 ± 0.37 mm; SER: -0.96 ± 0.70D), RLRL-SVS (AL: 0.50 ± 0.28 mm; SER: -1.07 ± 0.69D) and SVS-SVS group (AL: 0.64 ± 0.29 mm; SER: -1.24 ± 0.63D). No self-reported adverse events, functional or structural damages were noted. CONCLUSIONS: Continued RLRL therapy sustained promising efficacy and safety in slowing myopia progression over 2 years. A modest rebound effect was noted after treatment cessation.

Use of antihypertensive medications and the risk of glaucoma onset: Findings from the 45 and Up Study.

BACKGROUND: Abnormal blood pressure is a potential risk factor for glaucoma. However, the role of antihypertensive medications on glaucoma pathogenesis is controversial. This study aims to investigate the association between the use of antihypertensive medications and glaucoma onset. METHODS: This nested case-control study, based on a large-scale longitudinal cohort in Australia, retrieved participants' claims records on drugs and Medicare services from national health databases. Participants with three or more claim records of anti-glaucoma medications from 2009 to 2016 were classified as glaucoma patients; those with none were classified as controls. Claim records of antihypertensive medications were identified within the 5 years before glaucoma onset and contemporary periods in matched controls without glaucoma. The association between the use of antihypertensive medications and glaucoma onset was assessed by multivariable logistic regression models. RESULTS: A total of 6748 cases and 13 496 controls were analysed. Compared with controls, the proportion of users of antihypertensive medications was slightly higher in glaucoma patients (46.9% vs. 46.0%, p > 0.05). After adjustments for demographics, health-related factors and medical history, the association between the use of antihypertensive medications and glaucoma onset was nonsignificant (OR 0.95, 95% CI = 0.89-1.02). As for specific subtypes, only beta-blocking agents (BBA) (OR 0.82, 95% CI = 0.75-0.90) and diuretics (OR 0.85, 95% CI = 0.77-0.95) were significantly associated with reduced risks of glaucoma onset. CONCLUSIONS: This study indicated that the use of antihypertensive medications was not associated with glaucoma onset. Decreased risks of glaucoma onset in users of BBA and diuretics require further validation.

Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children: A Multicenter Randomized Controlled Trial.

PURPOSE: To assess the efficacy and safety of repeated low-level red-light (RLRL) therapy in myopia control in children. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial. PARTICIPANTS: Two hundred sixty-four eligible children 8 to 13 years of age with myopia of cycloplegic spherical equivalent refraction (SER) of -1.00 to -5.00 diopters (D), astigmatism of 2.50 D or less, anisometropia of 1.50 D or less, and best-corrected visual acuity (BCVA) of 0.0 logarithm of the minimum angle of resolution or more were enrolled in July and August 2019. Follow-up was completed in September 2020. METHODS: Children were assigned randomly to the intervention group (RLRL treatment plus single-vision spectacle [SVS]) and the control group (SVS). The RLRL treatment was provided by a desktop light therapy device that emits red light of 650-nm wavelength at an illuminance level of approximately 1600 lux and a power of 0.29 mW for a 4-mm pupil (class I classification) and was administered at home under supervision of parents for 3 minutes per session, twice daily with a minimum interval of 4 hours, 5 days per week. MAIN OUTCOME MEASURES: The primary outcome and a key secondary outcome were changes in axial length and SER measured at baseline and the 1-, 3-, 6-, and 12-month follow-up visits. Participants who had at least 1 postrandomization follow-up visit were analyzed for treatment efficacy based on a longitudinal mixed model. RESULTS: Among 264 randomized participants, 246 children (93.2%) were included in the analysis (117 in the RLRL group and 129 in the SVS group). Adjusted 12-month axial elongation and SER progression were 0.13 mm (95% confidence interval [CI], 0.09-0.17mm) and -0.20 D (95% CI, -0.29 to -0.11D) for RLRL treatment and 0.38 mm (95% CI, 0.34-0.42 mm) and -0.79 D (95% CI, -0.88 to -0.69 D) for SVS treatment. The differences in axial elongation and SER progression were 0.26 mm (95% CI, 0.20-0.31 mm) and -0.59D (95% CI, -0.72 to -0.46 D) between the RLRL and SVS groups. No severe adverse events (sudden vision loss ≥2 lines or scotoma), functional visual loss indicated by BCVA, or structural damage seen on OCT scans were observed. CONCLUSIONS: Repeated low-level red-light therapy is a promising alternative treatment for myopia control in children with good user acceptability and no documented functional or structural damage.