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Aims: To investigate the associations of genetic variants previously linked to axial length (AL) and spherical equivalent refraction (SE) in adults with refractive error and related endophenotypes in children, at baseline and 3-year follow-up., Methods: 15 candidate single-nucleotide polymorphisms (SNPs), selected from previous Genome-Wide Association Studies and meta-analyses, were genotyped in 2819 Chinese children, who had undergone baseline and 3-year follow-up cycloplegic refraction, ocular biometry and ocular health examinations. Linear regression analyses were conducted to assess the associations of the SNPs with baseline measurements and longitudinal changes in SE, spherical power (SPH), AL, corneal radius of curvature (CR) and AL/CR ratio., Results: SNPs ZMAT4 rs7829127, ZMAT4 rs16890057, TOX rs7837791, GRIA4 rs11601239 and RDH5 rs3138142 were associated with SE (β=0.233, p=4.21×10 -4 ; β=0.221, p=7.87×10 -4 ; β=0.106, p=0.0076; β=0.084, p=0.041; β=0.14, p=0.013, respectively) and SPH (β=0.24, p=2.3×10 -4 ; β=0.232, p=3.8×10 -4 ; β=0.088, p=0.025; β=0.086, p=0.034; β=0.14, p=0.012, respectively). Among them, ZMAT4 rs7829127 and rs16890057, were also associated with AL (β=-0.128, p=5.6×10 -4 ; β=-0.128, p=5.21×10 -4 ) and AL/CR ratio (β=-0.014, p=0.0028; β=-0.014, p=0.0034), whereas TOX rs7837791 was associated with AL (β=-0.062, p=0.0058) and GRIA4 11 601 239 with AL/CR ratio (β=-0.0058, p=0.049). Additionally, CD55 rs1652333 and RDH5 rs3138142 were associated with 3-year longitudinal changes in AL (β=0.062, p=0.018; β=-0.079, p=0.029) and CR (β=0.014, p=0.027; β=-0.018, p=0.035)., Conclusion: Among SNPs previously associated with AL and SE in adults, variants in ZMAT4 , TOX and GRIA4 were associated with AL, SE, SPH, and/or AL/CR ratio, while variants in RDH5 and CD55 showed associations with AL and CR changes in children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5., Design: Randomized, double-masked extended trial., Participants: Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study., Methods: Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups., Main Outcomes Measures: (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5., Results: Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were -1.34 ± 1.40 D, -1.97 ± 1.03 D, and -2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were -0.97 ± 0.82 D and -1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively., Conclusions: Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To systematically review and meta-analyze all reported heritability studies of refractive astigmatism (RA), corneal astigmatism (CA) and corneal curvature (CC), and evaluate the existing genetic associations of RA, CA and CC., Design: Systematic review and meta-analysis (PROSPERO ID: CRD42023447370)., Methods: Studies that reported the heritability and genetic associations of RA, CA and/or CC were identified from PubMed, Web of Science and EMBASE (from inception to October 1, 2023). Newcastle-Ottawa Scale criteria was used to assess the risk of bias. Meta-analyses of heritability were conducted using random-effects model for mean difference. All current genetic associations were catalogued according to level of statistical significance., Results: Pooled heritabilities were moderate for RA (h 2 = 0.46, 95% CI: 0.27-0.65), CA (h 2 = 0.48, 95% CI: 0.38-0.58) and CC (h 2 = 0.64, 95% CI: 0.53-0.76). Subgroup analyses revealed significant differences between analysis methods (CA: P < .01; CC: P = .03) and populations (CA: P < .01; CC: P < .01) in both CA and CC, and between age groups in CA (P < .01). Totally 50 single-nucleotide polymorphisms (SNPs) in 10 genes have been reported with overlapping associations with RA, CA, and/or CC, with BMP3, FMNL2, HERC2, PROX1-AS1, and ZC3H11B associated with RA and CA, FBN1, NHSL1, and PDGFRA with CA and CC, TRAF3IP1 with RA and CC, and CASC15 with RA, CA, and CC., Conclusions: This study confirms moderate heritabilities of RA, CA and CC. Through evaluating overlapping SNPs or genes between these three phenotypes, we prioritized 50 SNPs in 10 genes as candidate variants for further validation. These findings highlight the complex genetic architecture of astigmatism and indicate shared and distinct genetic markers for different astigmatism-related corneal parameters. Future studies in different populations and functional studies evaluating the roles of the involved genes in astigmatism are warranted., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The association between serum vitamin D level and cataract remains controversial. This study aims to evaluate the association between vitamin D level and cataract., Methods: In this study, articles in the PubMed, Web of Science, and EMBASE databases were searched up to 30 August 2023 and 626 articles were screened. Four studies involving a total of 10,928 subjects with cataract and 10,117 control subjects met the inclusion criteria., Results: Decreased serum vitamin D level was associated with higher incidence of cataract (P = 0.047; MD: -4.87; 95%CI: [-9.67, -0.07]). In the subgroup analysis by sex, a significant association was found between serum vitamin D level and cataract in both male (P = 0.01, MD: -2.15,95%CI: [-3.83, -0.46]) and female (P < 0.01; MD: -6.67,95%CI: [-8.20, -5.14]).In the subgroup analysis by the types of cataract, significant association was found between serum vitamin D level and nuclear (P < 0.01; MD: -10.48; 95%CI: [-12.72, -8.24]) and posterior subcapsular cataract (P = 0.02; MD: -6.05; 95%CI: [-11.30, -0.80]) but not in cortical cataract (P = 0.14; MD: -6.74; 95%CI: [-15.70, 2.22])., Conclusion: This meta-analysis revealed potential association between serum vitamin D level and cataract, more significant in female, and the subtypes of nuclear and posterior subcapsular cataract., (© 2024. The Author(s).)

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of -17.8%, 95% CI: -29.4%, -6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children., (© 2024. The Author(s).)

Aims: To compare and rank the myopia control effects of different light wavelengths in children using a systematic review and Bayesian network meta-analysis (Bayesian NMA)., Methods: The review protocol was registered with PROSPERO. We searched PubMed, EMBASE and MEDLINE for relevant clinical and animal studies published as of 2 February 2023. We included studies comparing red, violet or full-spectrum light with controls. Data extracted included descriptive statistics and study outcomes (axial length (AL) elongation and progression of spherical equivalent (SE) refraction). After quality assessment, estimates of treatment effect outcomes (mean differences (MDs) and 95% CIs) were first pooled for the animal and clinical studies in a traditional meta-analysis. To compare and rank the different light wavelengths, the Bayesian NMA was then conducted for all the included clinical studies (12 studies) and separately for only randomised controlled trials (8 studies). MDs, 95% credible intervals (CrIs) and ranks of the various light wavelengths were estimated in the Bayesian NMA., Results: When all clinical studies were included in the Bayesian NMA (12 studies), only red-light significantly slowed AL elongation, MD (95% CrI), -0.38 mm (-0.59 mm to -0.16 mm)/year and SE refraction progression, 0.72D (0.35D to 1.10D)/year compared with controls. It remained the only significant intervention when effect sizes from only RCTs (eight studies) were separately combined, (-0.28 mm (-0.40 mm to -0.15 mm)/year and 0.57D (0.22D to 0.92D)/year, for AL and SE refraction, respectively)., Conclusion: Myopia control efficacy varied among different wavelengths of light, with red light ranked as the most effective., Prospero Registration Number: Clinical studies: CRD42022368998; animal studies: CRD42022368671., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: To develop and externally test deep learning (DL) models for assessing the image quality of three-dimensional (3D) macular scans from Cirrus and Spectralis optical coherence tomography devices., Methods: We retrospectively collected two data sets including 2277 Cirrus 3D scans and 1557 Spectralis 3D scans, respectively, for training (70%), fine-tuning (10%) and internal validation (20%) from electronic medical and research records at The Chinese University of Hong Kong Eye Centre and the Hong Kong Eye Hospital. Scans with various eye diseases (eg, diabetic macular oedema, age-related macular degeneration, polypoidal choroidal vasculopathy and pathological myopia), and scans of normal eyes from adults and children were included. Two graders labelled each 3D scan as gradable or ungradable, according to standardised criteria. We used a 3D version of the residual network (ResNet)-18 for Cirrus 3D scans and a multiple-instance learning pipline with ResNet-18 for Spectralis 3D scans. Two deep learning (DL) models were further tested via three unseen Cirrus data sets from Singapore and five unseen Spectralis data sets from India, Australia and Hong Kong, respectively., Results: In the internal validation, the models achieved the area under curves (AUCs) of 0.930 (0.885-0.976) and 0.906 (0.863-0.948) for assessing the Cirrus 3D scans and Spectralis 3D scans, respectively. In the external testing, the models showed robust performance with AUCs ranging from 0.832 (0.730-0.934) to 0.930 (0.906-0.953) and 0.891 (0.836-0.945) to 0.962 (0.918-1.000), respectively., Conclusions: Our models could be used for filtering out ungradable 3D scans and further incorporated with a disease-detection DL model, allowing a fully automated eye disease detection workflow., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Limited research has been conducted to examine the factors during early childhood that may contribute to conduct problems in later stages of life. This study aimed to investigate the relationship between family and school environments during early childhood and conduct problems in adolescence. In Wave 1 (W1), the study recruited 502 participants, aged 5-6 years, from Hong Kong local kindergartens, with 51.4% boys. One of their parents provided information about family socioeconomic status (SES), parent-child recreational activities, and child screen time, whereas the class teacher rated their school readiness using the Chinese version of the Early Development Instrument. Data on the number of special facilities were obtained from the kindergartens. In Wave 2 (W2), the same parents of 395 participants were asked about their involvement in their children's education. Finally, in Wave 3 (W3), the parents of 206 participants completed the Conduct Problem scale of the Strength and Difficulties Questionnaire to evaluate the level of conduct problems in the participants. The results of the path analysis revealed that higher W1 family SES was associated with fewer W3 conduct problems through an increase in W1 and W2 parental involvement in children's learning and play activities. Findings have implications for understanding the impact of early-life family and school environments on adolescent conduct problems. Early childhood interventions that promote family resources and positive parent-child interactions have the potential to reduce adolescent conduct problems., (© 2024 The Author(s). Family Process published by Wiley Periodicals LLC on behalf of Family Process Institute.)

Myopia has long been a global threat to public health. Timely interventions are likely to reduce the risk of vision-threatening complications. There are both established and rapidly evolving therapeutic approaches to slow myopia progression and/or delay its onset. The effective methods for slowing myopia progression include atropine eye-drops, defocus incorporated multiple segments (DIMS) spectacle lenses, spectacle lenses with highly aspherical lenslets target (HALT), diffusion optics technology (DOT) spectacle lenses, red light therapy (RLT), multifocal soft contact lenses and orthokeratology. Among these, 0.05% atropine, HALT lenses, RLT and +3.00 peripheral addition soft contact lenses yield over 60% reduction in myopia progression, whereas DIMS, DOT and MiSight contact lenses demonstrate at least 50% myopia control efficacy. 0.05% atropine demonstrates a more optimal balance of efficacy and safety than 0.01%. The efficacy of 0.01% atropine has not been consistent and requires further validation across diverse ethnicities. Combining atropine 0.01% with orthokeratology or DIMS spectacles yields better outcomes than using these interventions as monotherapies. Increased outdoor time is an effective public health strategy for myopia prevention while recent studies suggest that 0.05% low-concentration atropine and RLT therapy have promising potential as clinical myopia prevention interventions for high-risk groups. Myopia control spectacle lenses, being the least invasive, are safe for long-term use. However, when considering other approaches, it is essential to ensure proper instruction and regular follow-ups to maintain safety and monitor any potential complications. Ultimately, significant advances have been made in myopia control strategies, many of which have shown meaningful clinical outcomes. However, regular use and adequate safety monitoring over extended durations are imperative to foster confidence that can only come from extensive clinical experience., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To evaluate the diagnostic accuracy of spectral-domain optical coherence tomography (SD OCT) combined with OCT angiography (OCTA) for myopic myopic macular neovascularisation (MNV) activity., Methods: Both eyes of patients with myopic MNV diagnosed with fluorescein angiography (FA), SD OCT and OCTA were assessed by unmasked investigators. The images were deidentified and randomised before graded by masked investigators, who determined the presence of active myopic MNV by using SD OCT together with OCTA without FA and by FA alone, respectively. The findings of masked investigators were compared with unmasked investigators., Results: 213 eyes of 110 patients comprising 499 imaging episodes were eligible for grading. For diagnosing new-onset myopic MNV without FA, combined use of SD OCT and OCTA had a sensitivity of 0.94, specificity of 0.84 and area under the curve (AUC) of 0.92. FA had a sensitivity of 0.52 (p<0.01), specificity of 0.80 (p=0.38) and AUC of 0.66 (p<0.01). For recurrent myopic MNV, the combination of SD OCT and OCTA had a sensitivity of 0.98, specificity of 0.78 and AUC of 0.88. FA had a sensitivity of 0.50 (p=0.04), specificity of 0.76 (p=0.85) and AUC of 0.63 (p=0.01). Myopic traction maculopathy was more frequently associated with recurrent myopic MNV (p<0.01)., Conclusion: SD OCT with dense volumetric scan was highly sensitive for diagnosing myopic MNV. The addition of OCTA improved the diagnostic specificity without FA. Monitoring of the longitudinal changes on SD OCT and judicious use of FA is a reliable surveillance strategy for myopic MNV., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate the associations of the TIE2 gene with diabetic retinopathy (DR) and diabetic macular edema (DME)., Methods: This study included a Chinese cohort of 285 non-proliferative DR patients and 433 healthy controls. The DR patients were classified further into those with or without DME. Thirty haplotype-tagging single-nucleotide polymorphisms (SNPs) in TIE2 were genotyped using TaqMan technology. Associations of DR and subtypes were analyzed by logistic regression adjusted for age and sex. Stratification association analysis by sex was performed., Results: TIE2 rs625767 showed a nominal but consistent association with DR [odds ratio (OR) = 0.71, P = 0.005] and subtypes (DR without DME: OR = 0.69, P = 0.016; DME: OR = 0.73, P = 0.045). SNP rs652010 was consistently associated with overall DR (OR = 0.74, P = 0.011) and DR without DME (OR = 0.70, P = 0.016), but not with DME. Moreover, SNPs rs669441, rs10967760, rs549099 and rs639225 showed associations with overall DR, whilst rs17761403, rs664461 and rs1413825 with DR without DME. In stratification analysis, three SNPs, rs625767 (OR = 0.62, P = 0.005), rs669441 (OR = 0.63, P = 0.006) and rs652010 (OR = 0.64, P = 0.007), were associated with DR in females, but not in males. Moreover, one haplotype T-T defined by rs625767 and rs669441 was significantly associated with DR in females only., Conclusions: This study revealed TIE2 as a susceptibility gene for DR and DME in Chinese, with a sex-specific association in females. Further validation should be warranted., Competing Interests: Conflict of interest The authors declare no conflict of interest including any financial, personal, or other relationships with other people or organizations that might influence or be perceived to influence their work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Effects of genetic variants on primary angle-closure disease remained uncertain., Objective: To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression., Data Sources: Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen., Study Selection: Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression., Data Extraction and Synthesis: PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics., Main Outcomes and Measures: SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized., Results: Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified., Conclusions and Relevance: This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1 is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1 mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1 biallelic loss are rare, yet epigenetic changes driven by RB1 loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To review the effects of firsthand tobacco smoking on central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) of firsthand tobacco smokers., Methods: We performed a search on EMBASE and PubMed for studies up to 15 th July 2022. Two independent reviewers selected studies with baseline data of CRAE and CRVE of current smokers, nonsmokers, and former smokers. Initial search identified 893 studies, of which 10 were included in the meta-analysis. Two independent reviewers extracted data from the included studies. The quality of studies was assessed by the Newcastle-Ottawa Scale., Results: In this meta-analysis, 7431 nonsmokers, 2448 current smokers and 5786 former smokers, as well as 7404 nonsmokers, 2430 current smokers and 5763 former smokers were included in CRAE and CRVE analysis respectively. Nonsmokers had narrower CRVE (Weighted mean difference [WMD], -12.15; 95% CI, -17.33 - -6.96) and CRAE (WMD, -4.77; 95% CI, -7.96 - -1.57) than current smokers, and narrower CRVE (WMD, -3.08; 95% CI, -6.06 - -0.11) than former smokers. Current smokers had wider CRVE (WMD, 10.42; 95% CI, 7.80 - 13.04) and CRAE (WMD, 7.05; 95% CI, 6.65 - 7.46) than former smokers. Subgroup analysis and sensitivity analysis were performed., Conclusion: Firsthand tobacco smoking resulted in wider CRAE and CRVE in current and former smokers, particularly in CRVE, and such changes may not be reversible after smoking cessation. Therefore, retinal vessel caliber may reflect the effects of firsthand tobacco smoking and be used to estimate the risk of cardiovascular diseases., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3-5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P 50 and P 95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese., (© 2024. The Author(s).)

Introduction: Examining the retina represents a non-invasive method to evaluate abnormalities pertaining to the nervous and cardiovascular systems. Evidence indicates that physical activity is a non-pharmacological intervention to enhance the nervous and cardiovascular systems. However, little is unknown about its effects on ocular characteristics in children and adolescents. The purpose of this study was to examine the effects of physical activity interventions on ocular characteristics in children and adolescents., Method: The electronic bases Web of Science, Embase, Cochrane Library, PubMed, SPORTDiscus, CINAHL, and ERIC were searched from inception to May 2023. Incorporated were randomized controlled trials or quasi-experimental designs that had implemented acute or chronic physical activity interventions among children and adolescents to evaluate various eye-related attributes via clinical examinations or surveys. Two authors independently performed the data extraction and risk of bias assessment, utilizing the Physiotherapy Evidence Database checklist., Results: A total of 474 articles were identified, of which eight articles underwent a systematic review, and six were chosen for meta-analysis. Chronic physical activity interventions positively impacted central retinal artery equivalent (CRAE) with a small to moderate effect (SMD = 0.21; 95% CI 0.04 to 0.39, p = 0.034, I 2  = 0%) and central retinal venular equivalent (CRVE) with a small effect (SMD = 0.098; 95% CI 0.08 to 0.11; p = 0.008, I 2  = 0%). Intraocular pressure, kinetic visual acuity, and eye strain also improved significantly after physical activity interventions., Discussion: Participating in chronic physical activity programs appear to impact children and adolescents' eye-related attributes positively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the genetic associations of different subtypes of central serous chorioretinopathy (CSCR), neovascular age-related macular degeneration (nAMD), and polypoidal choroidal vasculopathy (PCV)., Design: A case-control genetic association study., Methods: This study enrolled 217 CSCR, 341 nAMD, 288 PCV patients, and 1380 controls. The CSCR patients were classified into those with focal or diffuse leakage, with or without pigment epithelial detachment (PED), and with or without macular neovascularization (MNV). Associations between 11 variants from 8 genes, ADAMTS9, ANGPT2, ARMS2, CFH, NR3C2, PGF, TNFRSF10A and VIPR2, and diseases/subtypes were analyzed by logistic regression analysis adjusted for age and sex, and inter-phenotype comparison by heterogeneity test., Results: The CFH rs800292-A conferred a protective effect for CSCR with MNV (OR=0.44, P = 0.002) and a risk effect for CSCR without MNV (OR=1.31, P = 0.023). CSCR patients carrying rs800292-G had a 3.23-fold of increased risk towards developing secondary MNV (P = 1.45 ×10 -4 ). CFH rs3753394, rs800292 and rs1329428 showed similar effects among CSCR with MNV, nAMD and PCV, but opposite effects on CSCR without MNV. TNFRSF10A rs13278062-T was associated with overall CSCR but not with CSCR subtypes, nAMD or PCV. Moreover, CFH and ARMS2 SNPs showed heterogeneous effects in CSCR without MNV against CSCR with MNV, nAMD and PCV., Conclusions: Genetic associations of CSCR with MNV resembled nAMD and PCV compared to CSCR without MNV, indicating differential genetic effects on neovascularization and choroidopathy. Further investigation of the functional roles of CFH, ARMS2, and TNFRSF10A in CSCR, nAMD and PCV should help elucidate the mechanisms of these maculopathies., Competing Interests: Declaration of Competing Interest No conflicting relationship exists for any author., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To determine whether health-related physical fitness and body mass index (BMI) status differed before and after school closure from the COVID-19 pandemic in a population-based cohort of Hong Kong primary schoolchildren., Study Design: We examined the BMI z score, BMI status, and physical fitness z scores including (i) upper limb muscle strength, (ii) 1-minute sit-up test, (iii) sit-and-reach test, and (iv) endurance run tests, among 3 epochs: prepandemic (September 2018-August 2019), before school closure (September 2019-January 2020), and partial school reopening (September 2021-August 2022), using a repeated cross-sectional approach., Results: A total of 137 752 primary schoolchildren aged 6-12 years were recruited over 3 academic years. Obesity increased significantly from 25.9% in 2018/19 to 31.0% in 2021/22, while underweight increased slightly from 6.1% to 6.5%. All tested parameters were adversely affected by the pandemic. The negative trend over time was far more pronounced in all 4 physical fitness scores in the underweight group, although performance in handgrip strength had no significance between 2018/19 and 2021/22., Conclusions: Schoolchildren who are both underweight and overweight/obese are vulnerable to adverse changes in physical fitness during the COVID-19 pandemic. To eliminate the negative health and fitness outcomes, it is urgent to develop strategies for assisting schoolchildren in achieving a healthy weight, especially in the postpandemic era., Competing Interests: Declaration of Competing Interest This study was funded by the Collaborative Research Fund, University Grants Committee (Reference No.: C7149-20 GF, Project Title: Impact of COVID-19 pandemic on Hong Kong children and support to families during crisis). The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: This study is to evaluate if there is any difference in the balance between incidence of and remission from overweight/obesity in Hong Kong school-age children before and during the COVID-19 pandemic over three years., Methods: This is a retrospective longitudinal study that involved children aged 6-16 years from a database of the School Physical Fitness Award Scheme., Results: 2765 students were longitudinally followed up for two years. The prevalence of childhood overweight/obesity was increased between the 2019 and 2021 academic years (P < 0.001). During the COVID-19 pandemic, the rate of obesity remission significantly reduced by 7.9 % (P = 0.003), at a background of a plateau of obesity among children and adolescents., Conclusions: Our study provides evidence on the impact of school closure and home confinement as a standard infection control measure for the prevention of COVID-19, which are likely to break the balance between incidence of and remission from childhood obesity., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Generative pretrained transformer-4 (GPT-4) has gained widespread attention from society, and its potential has been extensively evaluated in many areas. However, investigation of GPT-4's use in medicine, especially in the ophthalmology field, is still limited. This study aims to evaluate GPT-4's capability to identify rare ophthalmic diseases in three simulated scenarios for different end-users, including patients, family physicians, and junior ophthalmologists., Methods: We selected ten treatable rare ophthalmic disease cases from the publicly available EyeRounds service. We gradually increased the amount of information fed into GPT-4 to simulate the scenarios of patient, family physician, and junior ophthalmologist using GPT-4. GPT-4's responses were evaluated from two aspects: suitability (appropriate or inappropriate) and accuracy (right or wrong) by senior ophthalmologists (> 10 years' experiences)., Results: Among the 30 responses, 83.3% were considered "appropriate" by senior ophthalmologists. In the scenarios of simulated patient, family physician, and junior ophthalmologist, seven (70%), ten (100%), and eight (80%) responses were graded as "appropriate" by senior ophthalmologists. However, compared to the ground truth, GPT-4 could only output several possible diseases generally without "right" responses in the simulated patient scenarios. In contrast, in the simulated family physician scenario, 50% of GPT-4's responses were "right," and in the simulated junior ophthalmologist scenario, the model achieved a higher "right" rate of 90%., Conclusion: To our knowledge, this is the first proof-of-concept study that evaluates GPT-4's capacity to identify rare eye diseases in simulated scenarios involving patients, family physicians, and junior ophthalmologists. The results indicate that GPT-4 has the potential to serve as a consultation assisting tool for patients and family physicians to receive referral suggestions and an assisting tool for junior ophthalmologists to diagnose rare eye diseases. However, it is important to approach GPT-4 with caution and acknowledge the need for verification and careful referrals in clinical settings., (© 2023. The Author(s).)

Background and Objectives: The usual recommended intake of vitamin D for healthy infants is 400 international unit (IU) daily. However, a high dose of vitamin D at 2000-3000 IU daily is needed for those with vitamin D deficiency (VDD). This study aimed to assess the natural history of a group of healthy infants with VDD and the associated factors for persistent VDD., Methods and Study Design: Healthy infants detected to have VDD (25OHD <25 nmol/L) in a population study were followed, and their demographics and clinical data were collected., Results: One hundred and thirty-one subjects (boys = 66%) were included. Their first serum 25OHD was taken at a median age of 87.5 days. None were treated with high-dose vitamin D supplements, but some have been given vitamin D at 400 IU daily. They were assessed again at the median age of 252.5 days when 15 remained to have VDD and 26 were in the insufficient range (25 - 49.9nmol/L). All persistent VDD children were on exclusive breastfeeding. Exclusive breastfeeding and no vitamin D supplementation were significant risk factors for persistent vitamin D insufficiency (<50nmol/L)., Conclusions: Persistent VDD is common among infants exclusively breastfeeding and those who did not receive vitamin D supplementation., Competing Interests: All authors have disclosed no conflicts of interest

Introduction: The aim of this work is to determine the interocular differences in peripapillary retinal nerve fiber layer (p-RNFL) thickness and its associations among school children in Hong Kong., Methods: We conducted a population-based study including 4034 children aged 6-8 years from the Hong Kong Children Eye Study (HKCES). All participants received comprehensive ocular examinations where p-RNFL thickness was measured using spectral-domain optical coherence tomography (SD-OCT). The degree of symmetry between both eyes was analyzed and represented by intraclass correlation coefficient (ICC) values. Multivariable linear regression analysis was used to investigate the associations between ocular and systemic factors with p-RNFL thickness difference., Results: The study included 4034 children with a mean age of 7.61 ± 0.98 years. The mean global p-RNFL thickness was 106.60 ± 9.41 μm in right eyes and 105.99 ± 9.30 μm in left eyes. The ICC for global p-RNFL difference was 0.866 (95% CI 0.858-0.873, p < 0.001). The symmetry displayed the largest values in nasal inferior quadrant with the ICC value of 0.736 (95% CI 0.721-0.749); and the smallest degree of symmetry was found to be in the superior temporal quadrant with the ICC value of 0.567 (95% CI 0.546-0.588). Axial length (AL) difference was found to have more pronounced correlation to interocular symmetry in p-RNFL thickness with the coefficient of 0.514 (p < 0.001)., Conclusions: Normal variation in interocular symmetry exists in children. Our results can contribute to the establishment of a standard reference for interocular differences in OCT parameters in children. The interocular differences in AL should be considered in the interpretation of RNFL symmetry, in terms of identifying children at risk of developing glaucoma or other ocular disorders., (© 2023. The Author(s).)

Aims: To explore the prevalence and risk factors for myopia and uncorrected myopia in schoolchildren in southern China., Methods: The government-led Shantou Myopia Study was conducted from September 2020 to June 2021. Non-cycloplegic refraction was performed. Uncorrected visual acuity (UCVA) was measured along with presenting visual acuity if participants wore spectacles. Spherical equivalent refraction (SER) is defined as the spherical dioptres added to half of the cylindrical dioptres. Myopia is defined as SER <-0.50 dioptre with UCVA of <20/20 in at least one eye., Results: This study enrolled 724 828 schoolchildren (77.8% of all schoolchildren in Shantou) from 901 schools. Data from 721 032 schoolchildren (99.5%) were analysed (mean age 11.53±3.13 years, 6-20 years, 373 230 boys and 347 802 girls). Among them, 373 459 (51.8%) had myopia: 37.1% of 465 696 children in primary schools, 75.4% of 170 164 children in junior high schools and 84.8% of 85 172 children in senior high schools. The prevalence of myopia increases non-linearly with age. Older age, female and urban living environment were independently associated with myopia prevalence and myopic SER. Among the 373 459 children with myopia, 60.0% had no refractive correction: 74.9%, 53.9% and 35.5% in primary, junior high and senior high schools, respectively., Conclusion: The overall prevalence of myopia among schoolchildren in Shantou was 51.8%, higher than the national average in China. The proportion of uncorrected myopia is high, especially in primary schools. Our results indicate the need for public education on eye care among schoolchildren even in a municipal city., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The toxicology of secondhand smoke (SHS), along with the harm of its exposure to human health, has been generally acknowledged; however, specific evidence is lacking on the association between SHS exposure and ocular health. In this systematic review (PROSPERO registration number: CRD42022247992), we included 55 original articles published by 12 May 2023, which dealt with SHS exposure and ocular disorders, such as eye irritation, conjunctivitis, dry eye diseases, uveitis, myopia, astigmatism, contact lens discomfort, age-related macular degeneration, glaucoma, and thyroid eye disease that addressed the ocular neurovascular structures of the macular, retinal nerve fiber layer, choroid, and corneal biomechanical parameters. We found compelling correlational evidence for eye irritation, conjunctivitis, and dry eye symptoms-supporting that SHS exposure was positively associated with inflammatory and allergic changes in the eyes. Yet, evidence about the associations between SHS exposure and other ocular disorders, structures, and parameters is still limited or controversial. Given the limitations of existing literature, more investigations with high quality and rigorous design are warranted to elucidate the potentially harmful effects of SHS exposure on ocular health., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article. This study was supported in part by the General Research Fund (GRF), Research Grants Council, Hong Kong (14111515 and 14103419 [JCY]); the Collaborative Research Fund (C7149–20 G [JCY]); the Health and Medical Research Fund (HMRF), Hong Kong (5160836 [LJC] and 07180826 [XJZ]), and the Direct Grants of the Chinese University of Hong Kong (4054193 [LJC], 4054121, 4054199, and 178662514 [JCY], and 4054634 [XJZ]); the Innovation and Technology Fund (7010590 [JCY]); the UBS Optimus Foundation Grant 8984 (JCY); the Centaline Myopia Fund [JCY]; the National Natural Science Foundation of China (8217040098 [JCY]); the CUHK Jockey Club Children’s Eye Care Programme, and the CUHK Jockey Club Myopia Prevention Programme. The sponsor or funding organization had no role in the design or conduct of this research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared., Objective: To determine cost-effective options for controlling myopia progression in children., Design, Setting, and Participants: In this cost-effectiveness analysis, a Markov model was designed to compare the cost-effectiveness of interventions for controlling myopia progression over 5 years from a societal perspective in a simulated hypothetical cohort of patients aged 10 years with myopia. Myopia interventions considered included atropine eye drops, 0.05% and 0.01%, defocus incorporated multiple segment spectacles, outdoor activity, soft contact lenses (daily disposable and multifocal), rigid gas-permeable contact lenses, progressive addition lenses, bifocal spectacle lenses, orthokeratology, highly aspherical lenslets (HALs), and red light therapy; all interventions were compared with single-vision lenses. Deterministic and probabilistic sensitivity analysis determined the association of model uncertainties with the cost-effectiveness. Costs were obtained from the charges of the Hospital Authority of Hong Kong and The Chinese University of Hong Kong Eye Center., Main Outcome and Measures: The mean costs (in US dollars) per child included the cost of hospital visits, medications, and optical lenses. The outcomes of effectiveness were the annual spherical equivalent refraction (SER) and axial length (AL) reductions. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy relative to single-vision lenses over a time horizon of 5 years., Results: Outdoor activity, atropine (0.05%), red light therapy, HALs, and orthokeratology were cost-effective. The ICER of atropine, 0.05%, was US $220/SER reduction; red light therapy, US $846/SER reduction; and HALs, US $448/SER reduction. Outdoor activity yielded a savings of US $5/SER reduction and US $8/AL reduction. Orthokeratology resulted in an ICER of US $2376/AL reduction., Conclusions and Relevance: These findings suggest that atropine eye drops, 0.05%, and outdoor activity are cost-effective for controlling myopia progression in children. Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective. The use of these interventions may help to control myopia in a cost-effective way.

Myopic choroidal neovascularization (CNV) is a vision-threatening complication of high myopia. Here, we systematically review cohort, case-control, and cross-sectional studies in PubMed, Embase, and Web of Science, and summarize the associated factors of myopic CNV using meta-analysis where applicable. Among 1,333 records assessed, 50 were found eligible, all having a low-to-moderate risk of bias. Highly myopic eyes with CNV had a higher risk of lacquer cracks (odds ratio = 2.88) and patchy chorioretinal atrophy (odds ratio = 3.43) than those without. The mean posterior staphyloma height (µm) was greater in myopic CNV eyes than in highly myopic eyes without CNV (mean difference = 82.03). The thinning of choroidal thickness (µm) between myopic eyes with and without CNV differed significantly (mean difference = -47.76). The level of vascular endothelial growth factor (pg/ml) in the aqueous humor of myopic CNV eyes was significantly higher than in highly myopic eyes without CNV (mean difference = 24.98), the same as interleukin-8 (IL-8) (pg/ml, mean difference = 7.73). Single-nucleotide polymorphisms in the vascular endothelial growth factor, complement factor I, and collagen type VIII alpha 1 genes were associated with myopic CNV. We found that myopic CNV eyes have a higher ratio of lacquer cracks and patchy chorioretinal atrophy, thinner choroid, greater posterior staphyloma height, and a higher level of vascular endothelial growth factor and IL-8 in aqueous. Structural predisposing lesions, hemodynamic, genetic, and systemic factors are also associated with myopic CNV., Competing Interests: Declaration of Competing Interest No conflicts of interest exist for any of the authors., (Copyright © 2023. Published by Elsevier Inc.)

Background: A recent prospective demonstrated that cardiovascular risk factors in early childhood were associated with later cardiovascular events. However, the impact of secondhand smoke (SHS) on children is unclear. The aims of this study is to determine the effects of SHS exposure on the retinal vasculature of children., Methods: This is a population-based cross-sectional study of children aged 6 to 8 years. All participants received comprehensive ophthalmic examinations and retinal photography. Data on SHS exposure was derived from a validated questionnaire. A validated deep-learning system was used to automatically estimate retinal arteriolar and venular calibers from retinal photographs. Associations of quantitative retinal vessel caliber values with SHS exposure, number of smokers in the household, and total number of cigarettes smoked were determined by analyses of covariance (ANCOVA) after adjusting for potential confounders. Test of trend was determined by treating categorical risk factors as continuous ordinal variables., Results: Here we show children exposed to SHS have wider retinal arteriolar (CRAE 152.1 µm vs. 151.3 µm, p < 0.001) and venular (CRVE 216.7 µm vs. 215.5 µm, p < 0.001) calibers compared to those in smoke-free homes, after adjustment for different factors. Wider arteriolar and venular calibers are also associated with increasing number of smokers in the family (p trend < 0.001) and more cigarettes smoked among family smokers (p trend<0.001)., Conclusions: Exposure to SHS at home is associated with changes in retinal vasculature among children. This reinforces the adverse effect of secondhand smoking around children though further research incorporating comprehensive assessment of potential confounders is necessary., (© 2023. The Author(s).)

Background/aims: To identify normative values and determinants for Bruch's membrane opening (BMO) and the minimum rim width of BMO (BMO-MRW) among healthy children., Methods: A population-based cross-sectional study from the Hong Kong Children Eye Study, recruiting 1, 226 children aged 6-8 years. Spherical refractive error, axial length (AL), body mass index and intraocular pressure (IOP) were measured. The optic nerve head and the peripapillary retinal nerve fibre layer (p-RNFL) were imaged through spectral domain-optical coherence tomography, using 24 equally spaced radial B-scans. Global and sectoral BMO-MRW values, BMO area and fovea-to-BMO (FoBMO) angle were calculated. Multiple regression analysis was performed to define the determinants of BMO area and BMO-MRW in relation to demographic and ocular parameters., Results: The mean values for global BMO-MRW, BMO area and FoBMO angle among children were 345.76±54.08 µm, 2.34±0.49 mm 2 and -5.45±4.36°, respectively. Global and sectoral values for BMO-MRW correlated with p-RNFL thickness (r=0.11-0.35, p<0.001). After adjusting for demographic and ocular parameters, global BMO-MRW increased with age (β=6.4, p<0.001) and greater global p-RNFL thickness (β=1.41, p<0.001), but decreased with larger BMO area (β=-47.46, p<0.001) and higher IOP (β=-1.73, p<0.001). Global BMO-MRW did not associate with AL, whereas both BMO area and FoBMO angle associated with AL (β=0.04, p=0.02 and β=0.31, p=0.03, respectively), but not with age., Conclusion: We observed that BMO-MRW increases with age among children. Our results provide normative values and the determinants of BMO parameters among Chinese children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: TYW declares that he is the inventor, patent holder, and co-founder of start-up companies EyRiS and Visre, which have interests in developing digital solutions for eye diseases, including diabetic retinopathy. He also receives consultancy fee from Aldropika Therapeutic, Bayer, Boehringer Ingelheim, Genetech, Iveric Bio, Novartis, Oxurion, Plano, Roche, Sanofi, and Shanghai Henlius. Other authors declared no competing interest related to this manuscript.

Purpose: Association of SIX1-SIX6 variants with peripapillary retinal nerve fibre layer (p-RNFL) thickness had been reported in adults. This study aimed to investigate these associations in children, with further explorations by spatial, age and sex stratifications., Methods: 2878 school children aged between 6 and 9 years were enrolled from the Hong Kong Children Eye Study. Three single-nucleotide polymorphisms (SNPs) at the SIX1-SIX6 locus were genotyped. The association of each SNP with p-RNFL thickness (including global and sectoral thickness) were evaluated using multiple linear regression., Results: SNPs rs33912345 (p=7.7×10 -4 ) and rs10483727 (p=0.0013) showed significant associations with temporal-inferior p-RNFL thickness. The C allele of rs33912345 was associated with a thinner temporal-inferior p-RNFL by an average of 2.44 µm, while rs10483727-T was associated with a thinner temporal-inferior p-RNFL by 2.32 µm. The association with temporal-inferior p-RNFL was the strongest in the 8-9 year-old group for rs33912345 (p=5.2×10 -4 ) and rs10483727 (p=3.3×10 -4 ). Both SNPs were significantly associated with temporal-inferior p-RNFL thickness in boys (p<0.0017), but not in girls (p>0.05). In contrast, rs12436579-C (β=1.66; p=0.0059), but not rs33912345-C (β=1.31; p=0.052) or rs10483727-T (β=1.19; p=0.078), was nominally associated with a thicker nasal-inferior p-RNFL., Conclusions: Both rs33912345 and rs10483727 at SIX1-SIX6 were associated with p-RNFL thickness in children, especially at the temporal-inferior sector, with age-dependent and sex-specific effects. SNP rs12436579 was associated with nasal-inferior p-RNFL thickness. Our findings suggested a role of SIX1-SIX6 in RNFL variation during neural retina development in childhood., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To identify gene variants associated with anisometropia development in children., Methods: This is a population-based, cross-sectional, and longitudinal genetic association study involving 1057 children aged 6 to 10 years with both baseline and 3-year follow-up data. Six single nucleotide polymorphisms (SNPs), ZC3H11B rs4373767, ZFHX1B rs13382811, KCNQ5 rs7744813, SNTB1 rs7839488, PAX6 rs644242, and GJD2 rs524952 were analyzed in all children. Anisometropia was defined by an interocular difference in SE of ≥1 diopter (D) (Aniso-SE) and an interocular difference in axial length (AL) of ≥0.3 mm (Aniso-AL), respectively. Genetic associations of individual SNPs and joint SNP effects were analyzed., Results: ZFHX1B rs13382811 was associated nominally with Aniso-AL (odds ratio [OR], 1.66; P = 0.003) at baseline. At 3 years, rs13382811 was significantly associated with Aniso-AL (OR, 1.49; P = 0.001) and became nominally associated with Aniso-SE (OR, 1.40; P = 0.01). In addition, PAX6 rs644242 was significantly associated with Aniso-AL at 3 years (OR, 1.45; P = 0.002). At the 3-year follow-up, PAX6 rs644242 was associated significantly with Aniso-AL development (OR, 1.61; P = 0.0003) and nominally with Aniso-SE development (P = 0.03) in children who were not anisometropic at baseline, whereas ZFHX1B rs13382811 was associated nominally with Aniso-AL development (P = 0.02). An additive SNP analysis indicated children carrying the risk allele T of ZFHX1B rs13382811 and allele A of PAX6 rs644242 might have a 4.33- and 6.90-fold of increased risk of Aniso-SE and Aniso-AL development by 3 years, respectively., Conclusions: This study identified two susceptible gene variants, ZFHX1B rs13382811 and PAX6 rs644242, for anisometropia development in Hong Kong Chinese children, implicating their role in imbalanced refractive change and axial elongation between both eyes.

The purpose of this study was to explore the findings from the Hong Kong Children Eye Study and the Low Concentration Atropine for Myopia Progression (LAMP-1) Study. The incidence of myopia among schoolchildren in Hong Kong more than doubled during the COVID-19 pandemic, with outdoor time decreased significantly and screen time increased. The change in lifestyle during the COVID-19 pandemic aggravated myopia development. Low-concentration atropine (0.05%, 0.025% and 0.01%) is effective in reducing myopia progression with a concentration-related response. This concentration-dependent response was maintained throughout a 3-year follow-up period, and all low concentrations were well tolerated. An age-dependent effect was observed in each treatment group with 0.05%, 0.025% and 0.01% atropine. Younger age was associated with a poor treatment response to low-concentration atropine. Additionally, low-concentration atropine induced choroidal thickening along a concentration-dependent response throughout the treatment period. During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. Stopping treatment at an older age and receiving lower concentration were associated with a smaller rebound effect. However, differences in the rebound effect were clinically small across all the three concentrations studied., (© 2023 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Importance: Secondhand smoke (SHS) exposure potentially threatens ocular health; however, its association with myopia is unknown., Objective: To examine the association between SHS exposure and childhood myopia., Design, Setting, and Participants: Cross-sectional data from the population-based Hong Kong Children Eye Study were used. Data were collected from March 5, 2015, to September 12, 2021, at The Chinese University of Hong Kong Eye Center. Participants included children aged 6 to 8 years. Secondhand smoke exposure was evaluated using a validated questionnaire. All participants underwent comprehensive ophthalmic and physical examinations., Exposure: Secondhand smoke exposure., Main Outcomes and Measures: Generalized estimating equations were constructed to examine the association of SHS exposure with spherical equivalent and axial length; logistic regression models, with myopia rate; and linear regression models, with myopia onset., Results: A total of 12 630 children (mean [SD] age, 7.37 [0.88] years; 53.2% boys) were included in the analysis. Among the participants, 4092 (32.4%) had SHS exposure. After adjusting for age, sex, parental myopia, body mass index, near-work time, outdoor time, and family income, SHS exposure was associated with greater myopic refraction (β = -0.09 [95% CI, -0.14 to -0.03]) and longer axial length (β = 0.05 [95% CI, 0.02-0.08]). Children with SHS exposure were more likely to develop moderate (odds ratio [OR], 1.30 [95% CI, 1.06-1.59]) and high myopia (OR, 2.64 [95% CI, 1.48-4.69]). The association of SHS exposure with spherical equivalence and axial length was magnified in younger children. For each younger year of a child's exposure to SHS, SHS exposure was associated with a 0.07-D decrease in spherical equivalence (β = 0.07 [95% CI, 0.01-0.13]) and a 0.05-mm increase in axial length (β = -0.05 [95% CI, -0.08 to -0.01]). Exposure to SHS was associated with an earlier mean (SD) age at onset of myopia (72.8 [0.9] vs 74.6 [0.6] months; P = .01). Every increase in SHS exposure in units of 10 cigarettes per day was associated with greater myopic refraction (β = -0.07 [95% CI, -0.11 to -0.02]), axial length (β = 0.04 [95% CI, 0.01-0.06]), and likelihood of developing moderate (OR, 1.23 [95% CI, 1.05-1.44]) and high myopia (OR, 1.75 [95% CI, 1.20-2.56]), and earlier myopia onset (β = -1.30 [95% CI, -2.32 to -0.27])., Conclusions and Relevance: The findings of this cross-sectional study suggest that SHS exposure was associated with greater myopic refraction, longer axial length, greater likelihood of developing moderate and high myopia, and earlier myopia onset. The larger the quantity of SHS exposure and the younger the child, the more advanced myopia development and progression with which SHS exposure is associated.

EZH2, acting as a catalytic subunit of PRC2 to catalyze lysine 27 in histone H3, induces the suppression of gene expression. EZH2 can regulate cell proliferation and differentiation of retinal progenitors, which are required for physiological retinal development. Meanwhile, an abnormal level of EZH2 has been observed in ocular tumors and other pathological tissues. This review summarizes the current knowledge on EZH2 in retinal development and ocular diseases, including inherited retinal diseases, ocular tumors, corneal injury, cataract, glaucoma, diabetic retinopathy and age-related retinal degeneration. We highlight the potential of targeting EZH2 as a precision therapeutic target in ocular diseases.