Impact of ophthalmic clinical service use in mitigating myopia onset and progression in preschool children: a retrospective cohort study.

BACKGROUND: Although school screenings identify children with vision problems and issue referrals for medical treatment at an ophthalmic hospital, the effectiveness of this approach remains unverified. OBJECTIVE: To investigate the impact of ophthalmic clinical services on the onset and progression of myopia in preschool children identified with vision impairment. METHODS: Using data from the Shanghai Child and Adolescent Large-scale Eye Study (SCALE), this retrospective cohort study evaluated the visual development of children from three districts-Jing'an, Minhang, and Pudong-which are representative of geographic diversity and economic disparity in Shanghai's 17 districts. Initially, in 2015, the study encompassed 14,572 children aged 4-6 years, of whom 5,917 needed a referral. Our cohort consisted of 5,511 children who had two or more vision screenings and complete personal information over the follow-up period from January 2015 to December 2020. We divided these children into two groups based on their initial spherical equivalent (SE): a High-risk group (SE > -0.5 D) and a Myopia group (SE ≤ -0.5 D). Within each of these groups, we further categorized children into Never, Tardily, and Timely groups based on their referral compliance to compare the differences in the occurrence and progression of myopia. Cox proportional models were applied to estimate hazard ratios (HRs) for myopia incidence per person-years of follow-up in High-risk group. Generalized additive models(GAM) was used to calculating the progression for annual spherical equivalent changes in all children. RESULTS: Of the 5,511 preschool children (mean age, 5.25 years; 52.24% male) who received a referral recommendation, 1,327 (24.08%) sought clinical services at an ophthalmic hospital. After six years of follow-up, 65.53% of children developed myopia. The six-year cumulative incidence of myopia in the Never, Tardily, and Timely groups was 64.76%, 69.31%, and 57.14%, respectively. These percentages corresponded to hazard ratios (HRs) of 1.31 (95% CI, 1.10-1.55) for the Tardily group and 0.55 (95% CI, 0.33-0.93) for the Timely group, compared with the Never group. The HRs were adjusted for age, sex, and SE at study entry. Interestingly, the Timely group showed significantly less SE progression than the other groups (P < 0.001), and SE progression was higher in the High-risk group (-0.33 ± 0.37D/year) than in children with myopia (-0.08 ± 0.55D/year). CONCLUSION: Timely utilization of ophthalmic clinical services among children aged 4 to 6 years who fail school vision screenings can significantly reduce the incidence of myopia and slow SE progression.

Barriers and facilitators to using ophthalmic clinical health services following school vision screening: a mixed-methods study.

OBJECTIVE: To identify determinants of the utilisation of ophthalmic clinical health services among students who failed school vision screening. METHODS: This study employed a sequential explanatory mixed methods design, underpinned by Andersen's Behavioural Model of Health Service Utilisation. Data were initially gathered through interviews with 27 stakeholders-comprising 5 ophthalmologists, 7 community doctors, 7 public health professionals and 8 teachers. The qualitative insights informed the construction of a questionnaire, which subsequently garnered responses from 6215 participants. Qualitative data underwent thematic analysis with NVivo V.12, while quantitative data were analysed using multivariable multinomial logistic regression in SAS V.9.4. Data integration was performed using the Pillar Integration Process for a deductive, evidence-based synthesis of findings. RESULTS: The research revealed that students attending vision demonstration schools and receiving encouragement from schools or communities to access clinical ophthalmic services demonstrated higher adherence to referral (OR=1.66, 95% CI 1.30 to 2.12; OR=1.54, 95% CI 1.33 to 1.80). Conversely, older students and those from higher-income families exhibited lower adherence rates (OR=0.31, 95% CI 0.23 to 0.44; OR=0.34, 95% CI 0.25 to 0.46). Moreover, students with less urgent medical needs were more likely to adhere to referrals compared with those needing immediate referrals (OR=1.24, 95% CI 1.06 to 1.45).Four pillars emerged: (a) adherence decreased with age, (b) financial constraints did not pose an obstacle, (c) public health services played a critical role, (d) referral urgency did not linearly correlate with adherence. CONCLUSION: The utilisation of ophthalmic clinical health services following vision screening failure in students is significantly influenced by public health services provided by schools or communities, such as prompting those with abnormal screening results to access ophthalmic clinical health services.

Development and validation of a smartwatch algorithm for differentiating physical activity intensity in health monitoring.

To develop and validate a machine learning based algorithm to estimate physical activity (PA) intensity using the smartwatch with the capacity to record PA and determine outdoor state. Two groups of participants, including 24 adults (13 males) and 18 children (9 boys), completed a sequential activity trial. During each trial, participants wore a smartwatch, and energy expenditure was measured using indirect calorimetry as gold standard. The support vector machine algorithm and the least squares regression model were applied for the metabolic equivalent (MET) estimation using raw data derived from the smartwatch. Exercise intensity was categorized based on MET values into sedentary activity (SED), light activity (LPA), moderate activity (MPA), and vigorous activity (VPA). The classification accuracy was evaluated using area under the ROC curve (AUC). The METs estimation accuracy were assessed via the mean absolute error (MAE), the correlation coefficient, Bland-Altman plots, and intraclass correlation (ICC). A total of 24 adults aged 21-34 years and 18 children aged 9-13 years participated in the study, yielding 1790 and 1246 data points for adults and children respectively for model building and validation. For adults, the AUC for classifying SED, MVPA, and VPA were 0.96, 0.88, and 0.86, respectively. The MAE between true METs and estimated METs was 0.75 METs. The correlation coefficient and ICC were 0.87 (p < 0.001) and 0.89, respectively. For children, comparable levels of accuracy were demonstrated, with the AUC for SED, MVPA, and VPA being 0.98, 0.89, and 0.85, respectively. The MAE between true METs and estimated METs was 0.80 METs. The correlation coefficient and ICC were 0.79 (p < 0.001) and 0.84, respectively. The developed model successfully estimated PA intensity with high accuracy in both adults and children. The application of this model enables independent investigation of PA intensity, facilitating research in health monitoring and potentially in areas such as myopia prevention and control.

Effect modification of time spent outdoors on the association between early childhood overweight and myopia: a one-year follow-up study.

BACKGROUND: This study examined the moderating role of outdoor time on the relationship between overweight and myopia. METHODS: The data for this study was obtained from a prospective study in Shanghai, where non-myopic children wore wristwear and were followed up for 1 year. Eye examinations were performed at each visit. The modification effect was assessed on the additive scale using multivariable logistic regression, and relative excess risk due to interaction was used to calculate the modification effect. RESULTS: A total of 4683 non-myopic children were included with 32.20% being overweight at baseline. Following a 1-year period, 17.42% of children had myopia. When compared to those who spent <90 minutes outdoors, children who spent >120 had a relative risk of myopia onset that was reduced to 0.61. As time spent outdoors decreased, more risks of myopia onset were identified among overweight children than among normal children, the modification effect on the additive scale was -0.007, with ~70% of this effect attributed to the modifying influence of outdoor time. CONCLUSIONS: Increasing outdoor time can reduce myopia more among overweight children than normal. Future interventions should focus on outdoor activities among overweight children to reduce myopia risks.

Sympathetic nervous system activity is associated with choroidal thickness and axial length in school-aged children.

BACKGROUND/AIMS: We aim to explore the effect of sympathetic nervous system (SNS) on choroid thickness (ChT) and axial length (AL). METHODS: Students of grade 2 and 3 from a primary school were included and followed for 1 year. Visual acuity, refraction, AL and ChT were measured. Morning urine samples were collected for determining SNS activity by analysing concentrations of epinephrine, norepinephrine and dopamine using the liquid chromatography-tandem mass spectrometry. The most important factor (factor 1) was calculated using factor analysis to comprehensively indicate the SNS activity. RESULTS: A total of 273 students were included, with an average age of 7.77±0.69 years, and 150 (54.95%) were boys. Every 1 µg/L increase in epinephrine is associated with 1.60 µm (95% CI 0.30 to 2.90, p=0.02) decrease in average ChT. Every 1 µg/L increase in norepinephrine is associated with 0.53 µm (95% CI 0.08 to 0.98, p=0.02) decrease in the ChT in inner-superior region. The factor 1 was negatively correlated with the ChT in the superior regions. Every 1 µg/L increase in norepinephrine was associated with 0.002 mm (95% CI 0.0004 to 0.004, p=0.016) quicker AL elongation. The factor 1 was positively correlated with AL elongation (coefficient=0.037, 95% CI 0.005 to 0.070, p=0.023). CONCLUSIONS: We hypothesised that chronic stress characterised by elevated level of the SNS, was associated with significant increase in AL elongation, probably through thinning of the choroid.

Cylinder power progression associated with axial length in young children: a two-year follow-up study.

PURPOSE: To describe the association of refraction development and axial length (AL) in young children and provide new insights into the progression of cylinder power. METHODS: Children (2-3 grades) were enrolled from primary schools in Shanghai and followed up for two years. Cycloplegic refraction, AL, and corneal curvature radius were measured. Refraction parameters were compared among groups with different AL, AL1 (AL < 23.5 mm), AL2 (23.5 mm ≤ AL < 24.5 mm), and AL3 (AL ≥ 24.5 mm). Multiple regression analysis was used to explore risk factors of diopter of cylinder (DC) progression. RESULTS: In total, out of 6891 enrolled children, 5961 participants (7-11 yrs) were included in the final analysis. Over the two-year period, the cylinder power significantly changed, and those with longer AL had more rapid DC progression over the two years (AL1, -0.09 ± 0.35 D; AL2, -0.15 ± 0.39 D; AL3, -0.29 ± 0.44 D) (P < 0.001). The change in DC was independently associated with AL at baseline (P < 0.001). The proportion of with-the-rule astigmatism increased from 91.3% to 92.1% in AL1 group, from 89.1% to 91.8% in AL2 group and from 87.1% to 92.0% in AL3 group. CONCLUSIONS: Young children with long AL experienced rapid progression of cylinder power. Both the control of myopia progression and attention to the correction of astigmatism are necessary in the health management of children with long AL. The significantly increased AL in participants might contribute to both the extent and direction of astigmatism.

Anisometropia and its association with refraction development in highly myopic children.

CLINICAL RELEVANCE: Anisometropia can affect visual development in children. Investigations of anisometropia in high myopes would explore potential causes related to anisometropia, highlighting the management of anisometropia in high myopia. BACKGROUND: The prevalence of anisometropia ranged from 0.6% to 4.3% in general paediatric population and from 7% to 14% in myopes. Anisometropia is regarded as an associated factor for myopia development, while myopia progression is a stimulus driving anisometropic development. The purpose of this study was to investigate the prevalence of anisometropia and its association with refraction development in Chinese children with high myopia. METHODS: In the cohort study, a total of 1,577 highly myopic (spherical equivalent ≤-5.0D) children aged 4-18 years were included. Refractive parameters (dioptre of sphere, dioptre of cylinder, corneal curvature radius, and axial length) of both eyes were measured after cycloplegia. The prevalence and degree of anisometropia were compared among refractive groups (non-parametric tests or chi-square tests), and regression analyses were used to determine associated factors of anisometropia. The statistical significance was set to P < 0.05 (two-tailed). RESULTS: In highly myopic children with a mean (standard deviation) age of 13.06 (2.80) years, the proportions of spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia ≥1.00 D were 34.5%, 21.9% and 39.9%, respectively. There was more spherical equivalent anisometropia associated with more severe astigmatism (P for trend <0.001). In the multivariate regression analysis, more spherical equivalent anisometropia, cylindrical anisometropia and spherical anisometropia were associated with higher degrees of astigmatism (standard beta = -0.175, -0.148 and -0.191, respectively). More spherical anisometropia was associated with better spherical power (standard beta = 0.116). CONCLUSION: The proportion of anisometropia in highly myopic children was high, compared with previously reported general population, and more severe anisometropia was associated with higher degree of cylindrical power, but not spherical power.

Cutoff values of axial length/corneal radius ratio for determining myopia vary with age among 3-18 years old children and adolescents.

PURPOSE: To investigate the effectiveness and cutoffs of axial length/corneal radius (AL/CR) ratio for myopia detection in children by age. METHODS: Totally, 21 kindergartens and schools were enrolled. Non-cycloplegic autorefraction (NCAR), axial length (AL), horizontal and vertical meridian of corneal radius (CR1, CR2), and cycloplegic autorefraction were measured. Receiver operating characteristic (ROC) curve was used to obtain the effectiveness and cutoff for myopia detection. RESULTS: Finally, 7803 participants aged 3-18 years with mean AL/CR ratio of 2.99 ± 0.16 were included. Area under the ROC curve (AUC) of AL/CR ratio for myopia detection (0.958 for AL/CR1, 0.956 for AL/CR2, 0.961 for AL/CR) was significantly larger than that of AL (0.919, all P < 0.001), while AUCs of the three were similar with different cutoffs (> 2.98, > 3.05, and > 3.02). When divided by age, the ROC curves of AL/CR ratio in 3- to 5-year-olds showed no significance or low accuracy (AUCs ≤ 0.823) in both genders. In ≥ 6-year-olds, the accuracies were promising (AUCs ≥ 0.883, all P < 0.001), the cutoffs basically increased with age (from > 2.93 in 6-year-olds to > 3.07 in 18-year-olds among girls, and from > 2.96 in 6-year-olds to > 3.07 in 18-year-olds among boys). In addition, boys presented slightly larger cutoffs than girls in all ages except for 16 and 18 years old. For children aged 3-5 years, AL/CR ratio or AL combined with NCAR increased AUC to > 0.900. CONCLUSION: AL/CR ratio provided the best prediction of myopia with age-dependent cutoff values for all but preschool children, and the cutoffs of boys were slightly larger than those of girls. For preschool children, AL/CR ratio or AL combined with NCAR is recommended to achieve satisfactory accuracy. AL/CR ratio calculated by two meridians showed similar predictive power but with different cutoffs.

Macular and peripapillary Choroidal Vascularity Index in children with different refractive status.

OBJECTIVES: To characterize choroidal vascular changes in children with different refractive status. METHODS: A study including 5864 children aged 6-9 years was performed to investigate the choroidal vascular index (CVI) in myopic, emmetropic and hyperopic eyes. Each participant had a comprehensive ocular examination with cycloplegic autorefraction performed, axial length (AL) measured and Swept Source-Optical Coherence Tomography (SS-OCT) scans acquired. Choroidal thickness (ChT) was measured by built-in software, and CVI was calculated using a previously validated self-developed algorithm. RESULTS: The mean ChT and CVI were 275.88 ± 53.34 µm and 34.91 ± 3.83 in the macula region, and 191.96 ± 46.28 µm and 32.35 ± 4.21 in the peripapillary region. CVI was significantly lowest for myopes, followed by emmetropes and hyperopes (P < 0.001). CVI varied between different sectors separated by the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid (P < 0.001). Macular CVI decreased horizontally from nasal to temporal quadrant with lowest in center fovea, and vertically from superior to inferior quadrants. Peripapillary CVI was highest in the nasal and lowest in the inferior sector. Multiple regression showed that spherical equivalent (SE), AL, intraocular pressure (IOP), ChT, age, and gender were significantly related to CVI (P < 0.05). CONCLUSIONS: In children, the distribution of CVI in the posterior pole is not uniform. A decreased CVI was observed from hyperopia to myopia and was associated with decreased SE, elongated AL, and choroidal thinning. Further study of changes in CVI during myopia onset and progression is required to better understand the role of the choroidal vasculature in myopia development.

Normative value of hyperopia reserve and myopic shift in Chinese children and adolescents aged 3-16 years.

BACKGROUND: This research aims to generate normative values of hyperopia reserve and refractive progression as effective tools to estimate the risk of myopia. METHODS: A 1-year follow-up study was conducted among Chinese children and adolescents aged 3-16 years selected from schools and kinder gardens using cluster sampling. All participants underwent examinations including visual acuity, axial length and cycloplegic autorefraction (1% cyclopentolate). Percentiles of spherical equivalent (SE) were calculated using Lambda-Mu-Sigma (LMS) method. Age-specific refractive progression and hyperopia reserve were determined by backward calculation. RESULTS: Of 3118 participants, 1702 (54.6%) were boys with a mean baseline age of 7.30 years. The 50th percentile of SE estimated by LMS decreased from 1.04 D at 3 years to -2.04 D at 16 years in boys, while from 1.29 D to -2.81 D in girls. The 1-year refractive progression of myopes (0.81 D) was greater than that of non-myopes (0.51 D). The normative value of hyperopia reserve was 2.64 (range: 2.40 D-2.88 D) at 3 years and -0.35 (range: -0.50 to -0.17) D at 16 years, with the maximum progression of 0.35 D at the age of 6 years. CONCLUSION: Age-specific normative values of hyperopia reserve and yearly myopic shift in children and adolescents aged 3-16 years were provided, helping identify and monitor myopia and giving prevention in advance.

Add-On Effect of 0.01% Atropine in Orthokeratology Wearers for Myopia Control in Children: A 2-Year Retrospective Study.

INTRODUCTION: Orthokeratology (OK) and low-concentration atropine are recommended approaches for controlling myopia. However, children with younger age and lower myopia are more likely to experience rapid axial progression during OK or atropine monotreatment. This study aimed to assess the efficacy of OK combined with low-concentration atropine for myopia control in children over 24 months and to determine whether the effect was sustainable. METHODS: In this retrospective study, we reviewed medical records of baseline and follow-up visits from children (7-14 years) applying OK for myopia control. Sixty-eight children receiving monoorthokeratology treatment (OK group) and 68 children who received 0.01% atropine in combination with orthokeratology simultaneously (AOK group) were included. A series of ophthalmic tests at baseline were conducted, and axial length (AL) was measured every 6 months. The comparison of AL change at different visits between the two groups was performed by repeated measures multivariate analyses of variance (RM-MANOVA). RESULTS: There were no significant differences in baseline characters between the two groups (p > 0.05). The AL significantly increased over time in both groups (all p < 0.05), and the 2-year change in AOK was 0.16 mm (36%) lower than in OK (0.28 ± 0.22 mm versus 0.44 ± 0.34 mm, p = 0.001). Compared with OK group, the significant suppression of AL elongation in the AOK group was observed in 0-6, 6-12, and 12-18 month periods (suppression rate: 62.5%, 33.3%, 38.5%, respectively, p < 0.05), while there was no significant difference in the 18-24 month period (p = 0.105). The multiple regression analysis showed an interaction between age and treatment effect (interaction coefficient = 0.06, p = 0.040), indicating one year age decrease approximately associated with 0.06 mm increased retardation in AL elongation in the AOK group. CONCLUSION: The add-on effect of 0.01% atropine in OK wearers only occurred within 1.5 years, and younger children benefited more from the combination treatment.

Myopic maculopathy among Chinese children with high myopia and its association with choroidal and retinal changes: the SCALE-HM study.

AIMS: To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes. METHODS: This cross-sectional study included Chinese children aged 4-18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy. RESULTS: In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of -8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 µm (area under the curve (AUC)=0.801) and 83.85 µm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively. CONCLUSION: A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy. TRIAL REGISTRATION NUMBER: NCT03666052.

Normative data for axial elongation in Asian children.

AIM: To determine the influence of refractive error (RE), age, gender and parental myopia on axial elongation in Chinese children and to develop normative data for this population. METHODS: This is a retrospective analysis of eight longitudinal studies conducted in China between 2007 and 2017. Data of 4701 participants aged 6-16 years with spherical equivalent from +6 to -6D contributed to one, two or three annualised progression data resulting in a dataset of 11,262 eyes of 26.6%, 14.8% and 58.6% myopes, emmetropes and hyperopes, respectively. Longitudinal data included axial length and cycloplegic spherical equivalent RE. Axial elongation was log-transformed to develop an exponential model with generalised estimating equations including main effects and interactions. Model-based estimates and their confidence intervals (CIs) are reported. RESULTS: Annual axial elongation decreased significantly with increasing age, with the rate of decrease specific to the RE group. Axial elongation in myopes was higher than in emmetropes and hyperopes but these differences reduced with age (0.58, 0.45 and 0.27 mm/year at 6 years and 0.13, 0.06 and 0.05 mm/year at 15 years for myopes, emmetropes and hyperopes, respectively). The rate of elongation in incident myopes was similar to that in myopes at baseline (0.33 vs. 0.34 mm/year at 10.5 years; p = 0.32), while it was significantly lower in non-myopes (0.20 mm/year at 10.5 years, p < 0.001). Axial elongation was greater in females than in males and in those with both parents myopic compared with one or no myopic parent, with larger differences in non-myopes than in myopes (p < 0.01). CONCLUSIONS: Axial elongation varied with age, RE, gender and parental myopia. Estimated normative data with CIs could serve as a virtual control group.

The rate of orthokeratology lens use and associated factors in 33,280 children and adolescents with myopia: a cross-sectional study from Shanghai.

OBJECTIVES: To investigate the rate of orthokeratology lens (ortho-k lens) use and its associated factors in children and adolescents with myopia. METHODS: Cross-sectional study. Children from 104 primary and middle schools in Shanghai were enrolled by cluster sampling. Ophthalmic examinations were conducted and information was obtained using questionnaires for associated factors analysis. RESULTS: A total of 72,920 children and adolescents were included, among which 32,259 were the potential population for ortho-k lens use. A total of 1021 participants used ortho-k lenses, equating to a use rate of 1.4% in the total population and 3.1% in the potential population. Age (OR 0.91, 95% CI: 0.88-0.95, p < 0.001), BMI (≥95th percentile: OR 0.48, 95% CI: 0.35-0.66, p < 0.001), age at initiation of refractive correction (≤12 years: OR 1.75, 95% CI: 1.31-2.33, p < 0.001), and parental myopia (either: OR 2.09, 95% CI: 1.58-2.75, p < 0.001; both: OR 3.94, 95% CI: 3.04-5.11, p < 0.001) were independently associated with ortho-k lens use. Of the ortho-k lenses users, 12.4% had a logMAR CVA of ≥0.3. A correction target (SE) of ≤-3.0 D (OR 2.05, 95% CI: 1.38-3.05, p < 0.001) and a sleeping duration of ≤6 h (OR 4.19, 95% CI: 2.03-8.64, p < 0.001) were factors independently associated with CVA ≥ 0.3. CONCLUSIONS: A certain proportion of children and adolescents in Shanghai chose to wear ortho-k lenses, related to the situation of parents and children themselves. Health education and follow-ups should be strengthened to ensure orthokeratology application quality.

Time outdoors positively associates with academic performance: a school-based study with objective monitoring of outdoor time.

BACKGROUND: To explore the relationship between outdoor time and academic performance among school-aged children. METHODS: This study was designed as a cross-sectional study. Data were derived from a school-based prospective children myopia intervention study (STORM). Outdoor time was recorded by self-developed algorithm-validated wristwatches in real-time and calculated as the cumulative average of 10 months. The academic performance was recorded and provided by the participating schools and further standardized. Other information was collected using an online standardized questionnaire. Mixed-effects model and B-Spline method were used to investigate the association between time spent on different types of daily activity, including outdoor activity and academic performance. RESULTS: A total of 3291 children with mean age 9.25 years were included in the final analysis. Overall, outdoor time was associated with academic performance in a non-linear manner; specifically, not exceeding 2.3 h per day, outdoor time was positively associated with academic performance; exceeding 2.3 h per day, this association became non-significant. Likewise, daily sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner, resulting in turning points of 11.3 and 1.4 h per day, respectively. Separate analysis showed that outdoor time and sleep duration but not out-of-school learning time were positively associated with academic performance in Chinese, mathematics and English. CONCLUSION: Outdoor time, sleep duration and out-of-school learning time were associated with academic performance in a non-linear manner. Promotion of outdoor time may not negatively impact on academic performance. TRIAL REGISTRATION: Our study was registered in ClinicalTrials.gov (Identifier: NCT02980445).

Effect of Repeated Low-level Red Light on Myopia Prevention Among Children in China With Premyopia: A Randomized Clinical Trial.

Importance: Myopia is a global concern, but effective prevention measures remain limited. Premyopia is a refractive state in which children are at higher risk of myopia, meriting preventive interventions. Objective: To assess the efficacy and safety of a repeated low-level red-light (RLRL) intervention in preventing incident myopia among children with premyopia. Design, Setting, and Participants: This was a 12-month, parallel-group, school-based randomized clinical trial conducted in 10 primary schools in Shanghai, China. A total of 139 children with premyopia (defined as cycloplegic spherical equivalence refraction [SER] of -0.50 to 0.50 diopter [D] in the more myopic eye and having at least 1 parent with SER ≤-3.00 D) in grades 1 to 4 were enrolled between April 1, 2021, and June 30, 2021; the trial was completed August 31, 2022. Interventions: Children were randomly assigned to 2 groups after grade stratification. Children in the intervention group received RLRL therapy twice per day, 5 days per week, with each session lasting 3 minutes. The intervention was conducted at school during semesters and at home during winter and summer vacations. Children in the control group continued usual activities. Main Outcomes and Measures: The primary outcome was the 12-month incidence rate of myopia (defined as SER ≤-0.50 D). Secondary outcomes included the changes in SER, axial length, vision function, and optical coherence tomography scan results over 12 months. Data from the more myopic eyes were analyzed. Outcomes were analyzed by means of an intention-to-treat method and per-protocol method. The intention-to-treat analysis included participants in both groups at baseline, while the per-protocol analysis included participants in the control group and those in the intervention group who were able to continue the intervention without interruption by the COVID-19 pandemic. Results: There were 139 children (mean [SD] age, 8.3 [1.1] years; 71 boys [51.1%]) in the intervention group and 139 children (mean [SD] age, 8.3 [1.1] years; 68 boys [48.9%]) in the control group. The 12-month incidence of myopia was 40.8% (49 of 120) in the intervention group and 61.3% (68 of 111) in the control group, a relative 33.4% reduction in incidence. For children in the intervention group who did not have treatment interruption secondary to the COVID-19 pandemic, the incidence was 28.1% (9 of 32), a relative 54.1% reduction in incidence. The RLRL intervention significantly reduced the myopic shifts in terms of axial length and SER compared with the control group (mean [SD] axial length, 0.30 [0.27] mm vs 0.47 [0.25] mm; difference, 0.17 mm [95% CI, 0.11-0.23 mm]; mean [SD] SER, -0.35 [0.54] D vs -0.76 [0.60] D; difference, -0.41 D [95% CI, -0.56 to -0.26 D]). No visual acuity or structural damage was noted on optical coherence tomography scans in the intervention group. Conclusions and Relevance: In this randomized clinical trial, RLRL therapy was a novel and effective intervention for myopia prevention, with good user acceptability and up to 54.1% reduction in incident myopia within 12 months among children with premyopia. Trial Registration: ClinicalTrials.gov Identifier: NCT04825769.

Changes of corneal biomechanics in children using orthokeratology and their roles in predicting axial length progression-A prospective 2-year study.

PURPOSE: To determine how orthokeratology (ortho-k) affects corneal biomechanical properties in myopia control and whether corneal biomechanical parameters can predict clinical efficacy of ortho-k. METHODS: A total of 125 children 7-15 years of age using ortho-k lenses were followed in this clinical practice and data of their right eyes were analysed. Corneal biomechanical parameters and most ocular biometry were measured at baseline, 1 week, and at 1, 3, 6, 12, 18 and 24 months. Axial length (AL) was collected every 6 months after baseline measurements. RESULTS: During the 2-year follow up, nine corneal biomechanical parameters, including deformation amplitude maximum (DA), varied between baseline and 1 week (p < 0.05) and stabilized during the rest of wearing period (p > 0.05). The mean AL increased from 25.02 ± 0.84 mm to 25.38 ± 0.81 mm and baseline DA strongly correlated with AL progression (Pearson r = 0.37). In the multiple regression models, baseline age, AL and DA were the independent factors for AL progression (R2 : 0.7849, 0.2180 in low and moderate myopes). The area under the receiver operating characteristic curves using the three variables for predicting excessive AL progression (>0.35 mm during 2 years) in low and moderate myopes was 0.902 and 0.698. CONCLUSIONS: Corneal biomechanics firstly fluctuated before becoming stable with long-term ortho-k use. Corneal biomechanics was associated with AL progression in children wearing ortho-k lenses. DA combined with age and AL at baseline could predict AL progression in low myopes using ortho-k.

Machine Learning-Based Integration of Metabolomics Characterisation Predicts Progression of Myopic Retinopathy in Children and Adolescents.

Myopic retinopathy is an important cause of irreversible vision loss and blindness. As metabolomics has recently been successfully applied in myopia research, this study sought to characterize the serum metabolic profile of myopic retinopathy in children and adolescents (4-18 years) and to develop a diagnostic model that combines clinical and metabolic features. We selected clinical and serum metabolic data from children and adolescents at different time points as the training set (n = 516) and the validation set (n = 60). All participants underwent an ophthalmologic examination. Untargeted metabolomics analysis of serum was performed. Three machine learning (ML) models were trained by combining metabolic features and conventional clinical factors that were screened for significance in discrimination. The better-performing model was validated in an independent point-in-time cohort and risk nomograms were developed. Retinopathy was present in 34.2% of participants (n = 185) in the training set, including 109 (28.61%) with mild to moderate myopia. A total of 27 metabolites showed significant variation between groups. After combining Lasso and random forest (RF), 12 modelled metabolites (mainly those involved in energy metabolism) were screened. Both the logistic regression and extreme Gradient Boosting (XGBoost) algorithms showed good discriminatory ability. In the time-validation cohort, logistic regression (AUC 0.842, 95% CI 0.724-0.96) and XGBoost (AUC 0.897, 95% CI 0.807-0.986) also showed good prediction accuracy and had well-fitted calibration curves. Three clinical characteristic coefficients remained significant in the multivariate joint model (p < 0.05), as did 8/12 metabolic characteristic coefficients. Myopic retinopathy may have abnormal energy metabolism. Machine learning models based on metabolic profiles and clinical data demonstrate good predictive performance and facilitate the development of individual interventions for myopia in children and adolescents.

Higher-order aberrations and their association with axial elongation in highly myopic children and adolescents.

BACKGROUND: Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. METHODS: Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤-5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. RESULTS: Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. CONCLUSION: In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

Normative data and percentile curves for axial length and axial length/corneal curvature in Chinese children and adolescents aged 4-18 years.

PURPOSE: To develop age-specific and gender-specific reference percentile charts for axial length (AL) and AL/corneal radius of curvature (AL/CR) and, to use percentiles to determine probability of myopia and estimate refractive error (RE). METHODS: Analysis of AL, cycloplegic RE and CR of 14 127 Chinese participants aged 4-18 years from 3 studies. AL and AL/CR percentiles estimated using Lambda-Mu-Sigma method and compared for agreement using intraclass correlation (ICC). Logistic regression was used to model risk of myopia based on age, gender, AL and AL/CR percentiles. Accuracy of AL progression and RE estimated using percentiles was validated using an independent sample of 5742 eyes of children aged 7-10 years. RESULTS: Age-specific and gender-specific AL and AL/CR (3rd, 5th, 10th, 25th, 50th, 75th, 90th and 95th) percentiles are presented. Concordance between AL and AL/CR percentiles improved with age (0.13 at 4 years to >0.75 from 13 years) and a year-to-year change was observed for all except <10th percentile from 15 years. Increasing age, AL and AL/CR was associated with a more myopic RE (r2=0.45,0.70 and 0.83, respectively). The sensitivity and specificity of the model to estimate probability of myopia was 86.0% and 84.5%, respectively. Estimation of 1-year change in AL using percentiles correlated highly with actual AL (ICC=0.98). Concordance of estimated to actual RE was high (ICC=0.80) and within ±0.50D and ±1.0D of actual RE for 47.4% and 78.9% of eyes, respectively. CONCLUSION: Age-specific and gender-specific AL and AL/CR percentiles provide reference data, aid in identifying and monitoring individuals at risk of myopia and have utility in screening for myopia. AL/CR percentiles were more accurate in estimating probability of myopia in younger children.