Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial.

PURPOSE: To investigate the efficacy and safety of repeated low-level red-light(RLRL) therapy combined with orthokeratology(Ortho-k) among the children who, despite undergoing Ortho-k treatment, exhibited an axial elongation of at least 0.50mm over 1 year. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (ClinicaTrials.gov,NCT04722874). PARTICIPANTS: Eligible children were aged 8-13 years with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters in the initial Ortho-k fitting examination and had annual axial length (AL) elongation ≥ 0.50 mm despite undergoing Ortho-k for 1 year. A total of 48 children were enrolled from March 2021 to January 2022, and the final follow-up was completed in March 2023. METHODS: Children were randomly assigned to the RLRL combined with Ortho-k(RCO) or the Ortho-k group in a 2:1 ratio. The Ortho-k group wore Ortho-k at least 8 hours per night, while the RCO group received daily RLRL therapy twice a day for 3 minutes in addition to Ortho-k wearing. MAIN OUTCOME MEASURES: The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 post-randomization follow-up using the modified intention-to-treat principle. RESULTS: A total of 47(97.9%) children were included in the analysis (30 in the RCO group and 17 in the Ortho-k group). The mean axial elongation rate before the trial was 0.60mm/year in the RCO group and 0.61mm/year in the Ortho-k group. After 12 months following the intended intervention, the adjusted mean AL changes were -0.02mm(95% CI, -0.08 to +0.03 mm) in the RCO group and 0.27mm(0.19-0.34 mm) in the Ortho-k group. The adjusted mean difference in AL change was -0.29mm(-0.44 to -0.14mm) between the RCO and Ortho-k groups. The percentage of children achieving an uncorrected visual acuity greater than 20/25 was similar in the RCO (64.3%) and Ortho-k (65.5%) groups (Chi2 test, P=0.937). CONCLUSIONS: Combining RLRL therapy with Ortho-k may offer a promising approach to optimize axial elongation control among myopic children. This approach also potentially allows children to achieve satisfactory visual acuity, reducing the daytime dependence on corrective eyewear.

Role of lens in early refractive development: evidence from a large cohort of Chinese children.

AIMS: To document longitudinal changes in spherical equivalent refraction (SER) and related biometric factors during early refractive development. METHODS: This was a prospective cohort study of Chinese children, starting in 2018 with annual follow-ups. At each visit, children received cycloplegic autorefraction and ocular biometry measurements. Lens power (LP) was calculated using Bennett's formula. Children were divided into eight groups based on baseline age: the 3-year-old (n=426, 49.77% girls), 4-year-old (n=834, 47.36% girls), 6-year-old (n=292, 46.58% girls), 7-year-old (n=964, 43.46% girls), 9-year-old (n=981, 46.18% girls), 10-year-old (n=1181, 46.32% girls), 12-year-old (n=504, 49.01%) and 13-year-old (n=644, 42.70%) age groups. RESULTS: This study included right-eye data from 5826 children. The 3-year-old and 4-year-old age groups demonstrated an inflection point in longitudinal SER changes at a mild hyperopic baseline SER (+1 to +2 D), with children with more myopic SER showing hyperopic refractive shifts while those with more hyperopic SER showing myopic shifts. The hyperopic shift in SER was mainly attributed to rapid LP loss and was rarely seen in the older age groups. Axial elongation accelerated in the premyopia stage, accompanied by a partially counter-balancing acceleration of LP loss. For children aged 3-7 years, those with annual SER changes <0.25 D were all mildly hyperopic at baseline (mean: 1.23 D, 95% CI 1.20 to 1.27 D). CONCLUSION: Our findings suggest that during early refractive development, refractions cluster around or above +1.00 D. There is a pushback process in which increases in the rate of LP occur in parallel with increases in axial elongation.

Long-Term Risk and Prediction of Progression in Primary Angle Closure Suspect.

Importance: Identifying primary angle closure suspect (PACS) eyes at risk of angle closure is crucial for its management. However, the risk of progression and its prediction are still understudied in long-term longitudinal studies about PACS. Objective: To explore baseline predictors and develop prediction models for the 14-year risk of progression from PACS to primary angle closure (PAC). Design, Setting, and Participants: This cohort study involved participants from the Zhongshan Angle Closure Prevention trial who had untreated eyes with PACS. Baseline examinations included tonometry, ultrasound A-scan biometry, and anterior segment optical coherence tomography (AS-OCT) under both light and dark conditions. Primary angle closure was defined as peripheral anterior synechiae in 1 or more clock hours, intraocular pressure (IOP) greater than 24 mm Hg, or acute angle closure. Based on baseline covariates, logistic regression models were built to predict the risk of progression from PACS to PAC during 14 years of follow-up. Results: The analysis included 377 eyes from 377 patients (mean [SD] patient age at baseline, 58.28 [4.71] years; 317 females [84%]). By the 14-year follow-up visit, 93 eyes (25%) had progressed from PACS to PAC. In multivariable models, higher IOP (odds ratio [OR], 1.14 [95% CI, 1.04-1.25] per 1-mm Hg increase), shallower central anterior chamber depth (ACD; OR, 0.81 [95% CI, 0.67-0.97] per 0.1-mm increase), and shallower limbal ACD (OR, 0.96 [95% CI, 0.93-0.99] per 0.01 increase in peripheral corneal thickness) at baseline were associated with an increased 14-year risk of progression from PACS to PAC. As for AS-OCT measurements, smaller light-room trabecular-iris space area (TISA) at 500 µm from the scleral spur (OR, 0.86 [95% CI, 0.77-0.96] per 0.01-mm2 increase), smaller light-room angle recess area (ARA) at 750 µm from the scleral spur (OR, 0.93 [95% CI, 0.88-0.98] per 0.01-mm2 increase), and smaller dark-room TISA at 500 µm (OR, 0.89 [95% CI, 0.80-0.98] per 0.01-mm2 increase) at baseline were identified as predictors for the 14-year risk of progression. The prediction models based on IOP and central and limbal ACDs showed moderate performance (area under the receiver operating characteristic curve, 0.69; 95% CI, 0.63-0.75) in predicting progression from PACS to PAC, and inclusion of AS-OCT metrics did not improve the model's performance. Conclusions and Relevance: This cohort study suggests that higher IOP, shallower central and limbal ACDs, and smaller TISA at 500 µm and light-room ARA at 750 µm may serve as baseline predictors for progression to PAC in PACS eyes. Evaluating these factors can aid in customizing PACS management.

Efficient Production of Flavonoid Glucuronides in Escherichia coli Using Flavonoid O-Glucuronosyltransferases Characterized from Marchantia polymorpha.

As a model liverwort, Marchantia polymorpha contains various flavone glucuronides with cardiovascular-promoting effects and anti-inflammatory properties. However, the related glucuronosyltransferases have not yet been reported. In this study, two bifunctional UDP-glucuronic acid/UDP-glucose:flavonoid glucuronosyltransferases/glucosyltransferases, MpUGT742A1 and MpUGT736B1, were identified from M. polymorpha. Extensive enzymatic assays found that MpUGT742A1 and MpUGT736B1 exhibited efficient glucuronidation activity for flavones, flavonols, and flavanones and showed promiscuous regioselectivity at positions 3, 6, 7, 3', and 4'. These enzymes catalyzed the production of a variety of flavonoid glucuronides with medicinal value, including apigenin-7-O-glucuronide and scutellarein-7-O-glucuronide. With the use of MpUGT736B1, apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide were prepared by scaled-up enzymatic catalysis and structurally identified by NMR spectroscopy. MpUGT742A1 also displayed glucosyltransferase activity on the 7-OH position of the flavanones using UDP-glucose as the sugar donor. Furthermore, we constructed four recombinant strains by combining the pathway for increasing the UDP-glucuronic acid supply with the two novel UGTs MpUGT742A1 and MpUGT736B1. When apigenin was used as a substrate, the extracellular apigenin-4'-O-glucuronide and apigenin-7,4'-di-O-glucuronide production obtained from the Escherichia coli strain BB2 reached 598 and 81 mg/L, respectively. Our study provides new candidate genes and strategies for the biosynthesis of flavonoid glucuronides.

Network Meta-analysis of Intraocular Lens Power Calculation Formula Accuracy in 1016 Eyes With Long Axial Length.

PURPOSE: To systematically review the literature and quantitatively synthesize the currently available evidence to compare the accuracy of different intraocular lens calculation formulas in eyes with long axial length (AL). DESIGN: Network meta-analysis. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for studies published between January 2000 and June 2022. Included were prospective or retrospective clinical studies reporting the following outcomes in cataract patients with long AL (ie, ≥26 mm): percentage of eyes with a prediction error (PE) within ±0.25, ±0.50, and ±1.00 diopters (D). Network meta-analysis was conducted using R software (version 4.2.1). RESULTS: Ten prospective or retrospective clinical studies, including 1016 eyes and 11 calculation formulas, were identified. A traditional meta-analysis showed that for the percentage of eyes with PE within ±0.25 and ±0.50 D, the Olsen, Kane, and Emmetropia Verifying Optical (EVO) all had insignificantly higher percentages compared with others. Considering the percentage of eyes with PE within ±1.00 D, the original and modified Wang-Koch adjustment formulas for Holladay 1 (H1-WK and H1-MWK) and EVO formulas showed superiority, but the difference was insignificant. This network meta-analysis revealed that compared with the widely used Barrett Universal II (BUII) formula, the Olsen, Kane, and EVO formulas had higher percentages of eyes with PE within ±0.25, ±0.50, and ±1.00 D (all odds ratios >1 but P >.05). Based on the surface under the cumulative ranking area (SUCRA) values for the percentage of eyes with PE within ±0.25 D, the Olsen (96.4%), Kane (77.5%), and EVO (75.9%) formulas had the highest probability of being in the top 3 of the 11 formulas. CONCLUSIONS: The Olsen, Kane, and EVO formulas may perform better than others in calculating IOL power in eyes with long AL. Nevertheless, there is still considerable uncertainty in this regard and the accuracy of these formulas in highly myopic eyes should be confirmed in studies based on large multicenter registries.

Effect of Extracurricular After-School Physical Activities on Academic Performance of Schoolchildren: A Cluster Randomized Clinical Trial.

Importance: The beneficial effects of increasing outdoor physical activity time on children's myopia onset and physical well-being are widely acknowledged. However, in countries with competitive educational systems, such as China, parents and school administrators may be relatively reluctant to increase the extracurricular physical activity time for children due to concerns that this action will compromise children's academic performance. Objective: To investigate whether additional extracurricular physical activity time after school compromises the academic performance of schoolchildren. Design, Setting, and Participants: This cluster randomized clinical trial was conducted from October 2020 to June 2021 in Yudu, Jiangxi, China. Eligible children in grades 3 and 4 from 24 elementary schools were randomized to the intervention or control group. Primary analysis was conducted in the full sample using the intention-to-treat principle. Interventions: The intervention group received 2 hours of after-school physical activity time outdoors on school days. The control group was free to arrange their after-school activity. Main Outcomes and Measures: The primary outcome was the between-group mean difference in mathematics test scores at the end of 1 academic year, with a noninferiority margin of -3.3 points. Standardized mathematics tests, physical fitness assessments (in reference to the 2018 National Physical Fitness Survey Monitoring Programme in China), and cycloplegic autorefraction were performed at baseline and the end of 1 academic year. Myopia was defined as a cycloplegic spherical equivalent refraction of -0.5 diopters or less in either eye. Results: A total of 2032 children (mean [SD] age, 9.22 [0.62] years; 1040 girls [51.2%]) from 24 schools were randomized to the intervention group (12 schools; 1012 children) or control group (12 schools; 1020 children). The mean (SD) mathematics score at the end of 1 academic year was 78.01 (17.56) points in the intervention group and 77.70 (17.29) points in the control group. The adjusted between-group mean difference was 0.65 points (95% CI, -2.85 to 4.15). The adjusted between-group mean difference in physical fitness score was 4.95 points (95% CI, 3.56-6.34; P < .001) and -1.90% (95% CI, -18.72% to 14.91%; P > .99) in myopia incidence. Conclusions and Relevance: Results of this trial indicate that, compared with the control practice of free play after school, adding 2 hours of extracurricular physical activity outdoors after school was noninferior in academic performance and had superior efficacy in improving physical fitness. Trial Registration: ClinicalTrials.gov Identifier: NCT04587765.

The Mediterranean Diet and Age-Related Eye Diseases: A Systematic Review.

The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR) and dry eye syndrome (DES). In this study, we systematically reviewed studies in the literature that had reported associations between adherence to the MD and the five above-mentioned AREDs. Randomized controlled trials as well as prospective and retrospective observational studies were included; 1164 studies were identified, of which 1, 2, 9, 2 and 4 studies met our eligibility criteria for cataract, glaucoma, AMD, DR, and DES, respectively. According to these studies, higher MD adherence was associated with reduced risks of incident DR, incident AMD and progression to late AMD, but whether early and neovascular AMD could be alleviated remained to be debated. The results regarding the effects of the MD on DES were mixed, with three studies reporting an associations between MD and decreased severity or incidence of DES, whereas one study reported the opposite. No significant associations were observed between the MD and cataract or glaucoma. Generally, convincing evidence suggested a protective effect of the MD against AMD and DR. However, the evidence for cataract, glaucoma, and DES was less conclusive, and high-quality studies are needed for comprehensive evaluations of the potential benefits of MD on these eye diseases.

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.

Fourteen-Year Outcome of Angle-Closure Prevention with Laser Iridotomy in the Zhongshan Angle-Closure Prevention Study: Extended Follow-up of a Randomized Controlled Trial.

PURPOSE: This study aimed to evaluate the efficacy of laser peripheral iridotomy (LPI) prophylaxis for patients with primary angle-closure suspect (PACS) after 14 years and to identify risk factors for the conversion from PACS to primary angle closure (PAC). DESIGN: Extended follow-up of the Zhongshan Angle-Closure Prevention Study. PARTICIPANTS: Eight hundred eighty-nine Chinese patients 50 to 70 years of age with bilateral PACS. METHODS: Each patient received LPI in 1 randomly selected eye, with the fellow untreated eye serving as a control. Because the risk of glaucoma was low and acute angle closure (AAC) occurred only rarely, the follow-up was extended to 14 years despite substantial benefits of LPI reported after the 6-year visit. MAIN OUTCOME MEASURES: Incidence of PAC, a composite end point including peripheral anterior synechiae, intraocular pressure (IOP) of > 24 mmHg, or AAC. RESULTS: During the 14 years, 390 LPI-treated eyes and 388 control eyes were lost to follow-up. A total of 33 LPI-treated eyes and 105 control eyes reached primary end points (P < 0.01). Within them, 1 LPI-treated eye and 5 control eyes progressed to AAC. Primary angle-closure glaucoma was found in 2 LPI-treated eyes and 4 control eyes. The hazard ratio for progression to PAC was 0.31 (95% confidence interval, 0.21-0.46) in LPI-treated eyes compared with control eyes. At the 14-year visit, LPI-treated eyes showed more severe nuclear cataract, higher IOP, and larger angle width and limbal anterior chamber depth (LACD) than control eyes. Higher IOP, shallower LACD, and greater central anterior chamber depth (CACD) were associated with an increased risk of end points developing in control eyes. In the treated group, eyes with higher IOP, shallower LACD, or less IOP elevation after the darkroom prone provocative test (DRPPT) were more likely to demonstrate PAC after LPI. CONCLUIONS: Despite a two-third decrease in PAC occurrence after LPI, the cumulative risk of progression was relatively low in the community-based PACS population over 14 years. Apart from IOP, IOP elevation after DRPPT, CACD, and LACD, more risk factors are needed to achieve precise prediction of PAC occurrence and to guide clinical practice. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A medication-wide association study to identify medications associated with incident clinically significant diabetic retinopathy.

Background: Diabetic retinopathy, a common microvascular complication of diabetes mellitus, is one of the leading causes of vision loss worldwide. Although some oral drugs have been suggested to affect the risk of diabetic retinopathy, systematic evaluation about the associations between medications and diabetic retinopathy is still absent. Objective: To comprehensively investigate associations of systemic medications with incident clinically significant diabetic retinopathy (CSDR). Design: Population-based cohort study. Methods: From 2006 to 2009, more than 26 000 participants residing in New South Wales were enrolled in the 45 and Up study. Diabetic participants with self-reported physician diagnosis or records of anti-diabetic medication prescriptions were finally included in the current analysis. CSDR was defined as diabetic retinopathy cases requiring retinal photocoagulation recorded in the Medicare Benefits Schedule database from 2006 to 2016. Prescriptions of systemic medication from 5 years to 30 days prior to CSDR were retrieved from the Pharmaceutical Benefits Scheme. The study participants were equally split into training and testing datasets. Logistic regression analyses were performed for the association between each of systemic medication and CSDR in the training dataset. After controlling the false discovery rate (FDR), significant associations were further validated in the testing dataset. Results: The 10-year incidence of CSDR was 3.9% (n = 404). A total of 26 systemic medications were found to be positively associated with CSDR, among which 15 were validated by the testing dataset. Additional adjustments for pertinent comorbidities suggested that isosorbide mononitrate (ISMN) (OR: 1.87, 95%CI: 1.00-3.48), calcitriol (OR: 4.08, 95% CI: 2.02-8.24), three insulins and analogues (e.g., intermediate-acting human insulin, OR: 4.28, 95% CI: 1.69-10.8), five anti-hypertensive medications (e.g., furosemide, OR: 2.53, 95% CI: 1.77-3.61), fenofibrate (OR: 1.96, 95% CI: 1.36-2.82) and clopidogrel (OR: 1.72, 95% CI: 1.15-2.58) were independently associated with CSDR. Conclusion: This study investigated the association of a full spectrum of systemic medications with incident CSDR. ISMN, calcitriol, clopidogrel, a few subtypes of insulin, anti-hypertensive and cholesterol-lowering medications were found to be associated with incident CSDR.

A Deep Learning-Based Fully Automated Program for Choroidal Structure Analysis Within the Region of Interest in Myopic Children.

Purpose: To develop and validate a fully automated program for choroidal structure analysis within a 1500-µm-wide region of interest centered on the fovea (deep learning-based choroidal structure assessment program [DCAP]). Methods: A total of 2162 fovea-centered radial swept-source optical coherence tomography (SS-OCT) B-scans from 162 myopic children with cycloplegic spherical equivalent refraction ranging from -1.00 to -5.00 diopters were collected to develop the DCAP. Medical Transformer network and Small Attention U-Net were used to automatically segment the choroid boundaries and the nulla (the deepest point within the fovea). Automatic denoising based on choroidal vessel luminance and binarization were applied to isolate choroidal luminal/stromal areas. To further compare the DCAP with the traditional handcrafted method, the luminal/stromal areas and choroidal vascularity index (CVI) values for 20 OCT images were measured by three graders and the DCAP separately. Intraclass correlation coefficients (ICCs) and limits of agreement were used for agreement analysis. Results: The mean ± SD pixel-wise distances from the predicted choroidal inner, outer boundary, and nulla to the ground truth were 1.40 ± 1.23, 5.40 ± 2.24, and 1.92 ± 1.13 pixels, respectively. The mean times required for choroidal structure analysis were 1.00, 438.00 ± 75.88, 393.25 ± 78.77, and 410.10 ± 56.03 seconds per image for the DCAP and three graders, respectively. Agreement between the automatic and manual area measurements was excellent (ICCs > 0.900) but poor for the CVI (0.627; 95% confidence interval, 0.279-0.832). Additionally, the DCAP demonstrated better intersession repeatability. Conclusions: The DCAP is faster than manual methods. Also, it was able to reduce the intra-/intergrader and intersession variations to a small extent. Translational Relevance: The DCAP could aid in choroidal structure assessment.

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.

Interventions recommended for myopia prevention and control among children and adolescents in China: a systematic review.

In 2018, a consortium of government bodies in China led by the Ministry of Education released the Comprehensive Plan to Prevent Nearsightedness among Children and Teenagers (CPPNCT), aiming to reduce the incidence of myopia and control myopic progression in China. Recommendations span from home-based to school-based interventions, including time outdoors, physical activity, light exposure, near-work activity, screen time, Chinese eye exercises, diet and sleep. To date, the levels of evidence for this suite of interventions have not been thoroughly investigated. This review has summarised the evidence of the interventions recommended by the CPPNCT in myopia prevention and control. Thus, the following statements are supposed by the evidence: (1) Increasing time outdoors and reducing near-work time are effective in lowering incident myopia in school-aged children. (2) All interventions have a limited effect on myopia progression. Ongoing research may lead to a better understanding of the underlying mechanisms of myopia development, the interaction of different interventions and recommendations, confounding variables and their true effect on myopia prevention, and the identification of those most likely to respond to specific interventions. This field may also benefit from longer-term studies of the various interventions or strategies covered within this review article, to better understand the persistence of treatment effects over time and explore more novel approaches to myopia control.

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.

Association between statin use and the risks of glaucoma in Australia: a 10-year cohort study.

SYNOPSIS: In a cohort of middle-aged and elderly Australians, we found that long-term statin use was associated with a higher risk of glaucoma onset. As to subtypes of statins, the increased risk was only found in rosuvastatin users. PURPOSE: To investigate the relationship between statin use and glaucoma onset in a 10-year longitudinal study. METHODS: This nested case-control study was based on data from a large-scale cohort of Australians aged over 45 years old. Medication exposure was identified by claims records from the Pharmaceutical Benefits Scheme during the follow-up period (2009-2016). The onset of glaucoma was defined as the people with at least three claims of antiglaucoma medications. Controls matched by age, gender and cardiovascular diseases were selected from participants without prescription of antiglaucoma medications. A conditional logistic regression model was used to assess the association between statin use and glaucoma onset. RESULTS: The proportion of statin users was higher in the case group (40.5%) than that in the control group (38.4%). After adjusting for baseline characteristics and longitudinal claims records, statin use was not associated with glaucoma onset (OR 1.04, 95% CI 0.97 to 1.11). However, an increased risk of glaucoma onset was observed in participants with a longer duration of statin use (>3 years vs <1 year: OR 1.12, 95% CI 1.04 to 1.21). With respect to specific types of statins, participants taking rosuvastatin were more likely to suffer from glaucoma (OR 1.11, 95%CI 1.01 to 1.22). The use of other statins was not significantly associated with glaucoma onset. CONCLUSIONS: Long-term statin use was found to be associated with a higher risk of glaucoma onset in this study. Regarding specific types of statins, the increased risk of glaucoma onset was only observed in users of rosuvastatin.

Retinal age gap as a predictive biomarker of stroke risk.

BACKGROUND: The aim of this study is to investigate the association of retinal age gap with the risk of incident stroke and its predictive value for incident stroke. METHODS: A total of 80,169 fundus images from 46,969 participants in the UK Biobank cohort met the image quality standard. A deep learning model was constructed based on 19,200 fundus images of 11,052 disease-free participants at baseline for age prediction. Retinal age gap (retinal age predicted based on the fundus image minus chronological age) was generated for the remaining 35,917 participants. Stroke events were determined by data linkage to hospital records on admissions and diagnoses, and national death registers, whichever occurred earliest. Cox proportional hazards regression models were used to estimate the effect of retinal age gap on risk of stroke. Logistic regression models were used to estimate the predictive value of retinal age and well-established risk factors in 10-year stroke risk. RESULTS: A total of 35,304 participants without history of stroke at baseline were included. During a median follow-up of 5.83 years, 282 (0.80%) participants had stroke events. In the fully adjusted model, each one-year increase in the retinal age gap was associated with a 4% increase in the risk of stroke (hazard ratio [HR] = 1.04, 95% confidence interval [CI]: 1.00-1.08, P = 0.029). Compared to participants with retinal age gap in the first quintile, participants with retinal age gap in the fifth quintile had significantly higher risks of stroke events (HR = 2.37, 95% CI: 1.37-4.10, P = 0.002). The predictive capability of retinal age alone was comparable to the well-established risk factor-based model (AUC=0.676 vs AUC=0.661, p=0.511). CONCLUSIONS: We found that retinal age gap was significantly associated with incident stroke, implying the potential of retinal age gap as a predictive biomarker of stroke risk.

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.

Longitudinal Changes in Lens Thickness and Lens Power Among Persistent Non-Myopic and Myopic Children.

Purpose: To assess the longitudinal changes in crystalline lens in persistent non-myopic and myopic children. Methods: Four cohorts of children were recruited from Guangzhou, China, from first year of kindergarten (G0, n = 1129), first year of primary school (G1, n = 1324), fourth year of primary school (G4, n = 1854), and first year of junior high school (G7, n = 867) in 2018 and followed up annually for 2 years. All children received cycloplegic autorefraction and ocular biometry measurement. Children were classified into categories of persistent non-myopia (PNM; spherical equivalent refraction [SER] ≥-0.5 diopter [D] at baseline and during follow-up), persistent myopia (PM; SER <-0.5 D at baseline and during follow-up), or newly developed myopia (NDM: SER ≥-0.5 D at baseline and <-0.5 D during follow-up). Results: The mean (SD) age was 3.69 (0.34) years for children in G0, 6.79 (0.35) years in G1, 9.52 (0.42) years in G4, and 12.56 (0.38) years in G7. A LOWESS plot showed a three-stage pattern of change in lens thickness (LT) in PNM children including a rapid decrease from 3 to 7 years of age and a slower decrease from 7 to 11 years, followed by an increase thereafter. Similar trends were observed in the PM and NDM groups, although there was less change in LT. In contrast, lens power (LP) decreased consistently in all cohorts during the follow-up. No significant changes in LT or LP were observed around myopia onset. Conclusions: The lens showed a three-stage pattern of change in LT, whereas there was continuous loss of LP in children ages 3 to 15 years.

Diabetes mellitus and incident glaucoma in Australia: a 10-year cohort study from the 45 and Up Study.

Background: Understanding the relationship between diabetes mellitus (DM) and the severity of glaucoma is important for the primary prevention of incident glaucoma. This paper aims to examine the association between DM and incident glaucoma. Methods: The 45 and Up Study is a prospective cohort study where Australians aged ≥45 years old were enrolled. The incident of glaucoma at follow-up is the main outcome measured. Glaucoma incidence was identified as those with recorded glaucoma-related medication from the Pharmaceutical Benefits Scheme or surgery recorded in the Medicare Benefits Schedule. Patients with glaucoma were classified into the medical glaucoma group (with glaucoma-related medication but not surgery) and the surgical glaucoma group (with glaucoma-related surgery). A Cox regression model was used to calculate the hazard ratios (HRs) to examine the association between baseline DM and the risk of developing glaucoma during the follow-up period. The reference groups are as follows: (I) non-DM participant; (II) participant with DM, duration between 0 and 5 years; (III) participant uses insulin. Results: A total of 255,547 eligible participants, with no glaucoma diagnosis at baseline, were included. During the follow-up period, 7,667 patients (3.0%) were identified as medical glaucoma only and 2,326 patients (0.9%) underwent glaucoma surgery. After controlling for confounders, baseline DM was associated with an increased risk of glaucoma in the medical glaucoma group only [hazard ratio (HR) =1.36, 95% confidence interval (CI) =1.07-1.72, P=0.002]. However, baseline DM (HR =0.97, 95% CI =0.57-1.65, P=0.979) was not associated with an increased risk of surgical glaucoma. Conclusions: DM was associated with an increased risk of medical glaucoma only, there was no association identified with surgical glaucoma in the Australian population recruited in the 45 and Up Study.