Associations of genetic variants for refractive error and axial length in adults with ocular endophenotypes in children: a cross-sectional and longitudinal study.

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 (ß=0.233, p=4.21×10-4; ß=0.221, p=7.87×10-4; ß=0.106, p=0.0076; ß=0.084, p=0.041; ß=0.14, p=0.013, respectively) and SPH (ß=0.24, p=2.3×10-4; ß=0.232, p=3.8×10-4; ß=0.088, p=0.025; ß=0.086, p=0.034; ß=0.14, p=0.012, respectively). Among them, ZMAT4 rs7829127 and rs16890057, were also associated with AL (ß=-0.128, p=5.6×10-4; ß=-0.128, p=5.21×10-4) and AL/CR ratio (ß=-0.014, p=0.0028; ß=-0.014, p=0.0034), whereas TOX rs7837791 was associated with AL (ß=-0.062, p=0.0058) and GRIA4 11 601 239 with AL/CR ratio (ß=-0.0058, p=0.049). Additionally, CD55 rs1652333 and RDH5 rs3138142 were associated with 3-year longitudinal changes in AL (ß=0.062, p=0.018; ß=-0.079, p=0.029) and CR (ß=0.014, p=0.027; ß=-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.

Heritability and Genetic Factors of Astigmatism and Corneal Curvature: A Systematic Review and Meta-analysis.

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 (h2 = 0.46, 95% CI: 0.27-0.65), CA (h2 = 0.48, 95% CI: 0.38-0.58) and CC (h2 = 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.

A deep learning system for myopia onset prediction and intervention effectiveness evaluation in children.

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.

Association between vitamin D level and cataract: A systematic review and meta-analysis.

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.

Deep learning-based image quality assessment for optical coherence tomography macular scans: a multicentre study.

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.

A systematic review on the applicability of cell-free DNA level as an obesity biomarker.

Obesity has become a global health concern in recent decades. Utilizing biomarkers presents a promising approach to comprehensively monitor the progress of obesity and its associated health conditions. This review aims to synthesize the available evidence on the correlation between cfDNA level and obesity and to provide insights into the applicability of using cfDNA level as a tool for monitoring progression of obesity. Searches were performed in PubMed and Embase on April 1, 2022. Data and other relevant information were extracted and compiled into a structured table for further analysis. Among 1170 articles screened, 11 articles were included in this review and assessed qualitatively. The results demonstrated that existing evidence mainly focused on three populations, including healthy individuals, cancer patients and pregnant women. Majority of the studies on healthy individuals identified a significant association between cfDNA level and body weight status but not among cancer patients. Varying results were observed among pregnant women at different gestational trimesters. Our review summarized some preliminary evidence on the association between cfDNA level and obesity. More cohort studies in larger scale with comprehensive assessment have to be conducted to examine the applicability of cfDNA as a biomarker for severity and disease progression of obesity.

Etiology including epigenetic defects of retinoblastoma.

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.

Advances in myopia control strategies for children.

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.

Improved accuracy of spectral-domain optical coherence tomography and optical coherence tomography angiography for monitoring myopic macular neovascularisation activity.

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.