Yumeng Shi

Purpose: To investigate the causal relationship between type 1 diabetes (T1D) and cataracts and to explore the mediating role of serum metabolites. Methods: This study employed bidirectional Mendelian randomization (MR) using genetic variants as instrumental variables to infer causality in both directions: from T1D to cataracts and cataracts to T1D. Genetic data for T1D, its complications, and cataracts were sourced from independent genome-wide association study (GWAS) datasets. A two-step multivariable MR combined with mediation analysis was conducted to evaluate the indirect effects of serum metabolites in the causal pathway from T1D to cataracts. Results: The MR analysis demonstrated a significant causal association between T1D and an increased risk of cataracts (OR = 1.01–1.05; p < 0.05). Further analysis showed that patients with T1D complications such as coma, ketoacidosis, nephropathy, and retinopathy exhibited a significantly higher risk of developing cataracts compared to those without complications. Sensitivity analyses upheld the robustness of these findings, with no evidence of heterogeneity or pleiotropy. Additionally, 102 serum metabolites were found to exhibit statistically significant mediation effects on cataract risk, with four (13-HODE + 9-HODE, 2-naphthol sulfate, docosadienoate (22:2n6), and X-12906) showing significant mediation effects. Specifically, 13-HODE + 9-HODE had a protective effect, while the other three metabolites were linked to an increased cataract risk. Conclusions: This study provides strong evidence of a causal link between T1D and cataracts, highlighting the mediating role of specific serum metabolites. These findings underscore the importance of early detection and management of cataracts in patients with T1D and suggest potential therapeutic targets for mitigating cataract risk. Further research should focus on replicating these findings in diverse populations and exploring the underlying metabolic pathways in greater detail.

Background/objectives To evaluate the diagnostic performance of B-scan kinetic ultrasonography (USG), standard ultra-widefield (UWF) imaging, and indirect ophthalmoscopy (IDO) in retinal break detection in cataractous eyes. Subjects/methods We consecutively enrolled 126 cataract patients (including 246 eyes) with no comorbidities that could decrease best corrected visual acuity (BCVA). Three index tests (USG, nonmydriatic UWF, and mydriatic IDO) were performed preoperatively to screen for retinal breaks. One week after cataract extraction, a dilated IDO examination was repeated for the definitive diagnosis of retinal break as the reference standard. The sensitivity, specificity, Youden index (YI), and predictive values of each index test were calculated according to postoperative ophthalmoscopic findings. A deep-learning nomogram was developed to quantify the risk of retinal break presence using patients’ baseline data and findings reported from preoperative ophthalmic tests. Results Fifty-two eyes (21%) were excluded from appropriate preoperative UWF imaging because of massive lens opacity. The BCVA cutoff point with maximum YI indicating UWF applicability was 0.6 logMAR (YI = 0.3; area under curve [AUC] = 0.7). Among all 246 eyes, preoperative IDO, USG, and UWF showed fair interobserver agreement (all κ > 0.2). According to postoperative IDO findings, the index tests with the highest sensitivity and specificity were USG (100%) and preoperative IDO (99%), respectively. Conclusions For cataractous eyes without vision-impairing comorbidities, a BCVA better than 0.6 logMAR (Snellen acuity, 20/80) allows for appropriate nonmydriatic standard UWF imaging. In a high-volume clinic equipped with skilled ophthalmic examiners, screening with USG followed by directed IDO allows the efficient identification of retinal breaks in cataractous eyes.

Ectopia lentis is a hallmark of Marfan syndrome (MFS), a genetic connective tissue disorder affecting 1/5000 to 1/10 000 individuals worldwide. Early detection in ophthalmology clinics and timely intervention of cardiovascular complications can be lifesaving. In this study, a modified proteomics workflow with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS)‐based data‐independent acquisition (DIA) and field asymmetric ion mobility spectrometry (FAIMS) to profile the proteomes of aqueous humor (AH) and lens tissue from MFS children with ectopia lentis is utilized. Over 2300 and 2938 comparable proteins are identified in AH and the lens capsule, respectively. Functional enrichment analyses uncovered dysregulation of complement and coagulation‐related pathways, collagen binding, and cell adhesion in MFS. Through weighted correlation network analysis (WGCNA) and machine learning, distinct modules associated with clinical traits are constructed and a unique biomarker panel (Q14376, Q99972, P02760, Q07507; gene names: GALE, MYOC, AMBP, DPT) is defined. These biomarkers are further validated using advanced parallel reaction monitoring (PRM) in an independent patient cohort. The results provide novel insights into the proteome characterization of ectopia lentis and offer a promising approach for developing a valuable biomarker panel to aid in the early diagnosis of Marfan syndrome via AH proteome.

The prevalence of diabetes mellitus is increasing in resource limited settings. Simultaneously, there has been an increase in the number of novel therapies for the management of diabetes mellitus. However, use of novel antidiabetic therapies is limited because of major market access challenges in resource limited settings. Niching products to those patients with the highest absolute risk for major adverse cardiovascular outcomes, and thus most likely to benefit from the therapy, are less likely to have negative budget impact for funders. To improve access, and reduce morbidity and mortality, requires alignment amongst key stakeholders including patient advocacy groups, health care professional councils, national departments of health, the pharmaceutical industry, treasury and finance departments.

SIGNIFICANCE: The ethnic differences in myopia rates, ocular dimensions, and risk factors between Han and non‐Han schoolchildren observed in this study may help fill the knowledge gap about ethnic minorities and are important for China and other countries to address vision‐related health inequalities among different ethnic groups. PURPOSE: This study aimed to investigate the risk factors of juvenile myopia and elucidate the disparities of risk factors among Han and non‐Han school students in Xinjiang, China. METHODS: A population‐based cross‐sectional study of 876 schoolchildren from grades 1 to 9 was conducted in the Anjihai Middle School in Shawan, Xinjiang Uygur Autonomous Region, China. Visual acuity and ocular biometry were assessed, and personal information, including behavior, birth status, and familial factors, was collected using self‐made standardized questionnaires. RESULTS: The myopia rate among students of Han ethnicity (50.5%) was the highest, followed by Hui (41.3%) and Uygur et al. (32.0%, P <. 001). Similar patterns were observed for mean axial length. The mean axial lengths are 23.7, 23.4, and 23.3 mm, respectively ( P =. 01). Overall, performing high‐quality eye exercises, longer sleep duration, being born in summer, parental smoking, and consuming more food containing anthocyanins were all associated with a lower incidence of myopia. Meanwhile, Han ethnicity, intensive near task, bad eye habits, and myopic mothers were associated with higher odds of myopia. After adjusting for environmental influences pertaining to myopia, the variation in myopia prevalence between Han and Uygur et al. remained significant, whereas it changed to not significant between Han and Hui ethnicities. CONCLUSIONS: Significant disparities were found in the prevalence of myopia among various ethnic groups in Shawan, Xinjiang. Life habits, birth status, and familial factors may contribute to such variance and play different roles in the occurrence of juvenile myopia among various ethnicities.

Cataract is a common disease in the aging population. Gap junction has been considered a central component in maintaining homeostasis for preventing cataract formation. Gap junction channels consist of connexin proteins with more than 20 members. Three genes including GJA1, GJA3, and GJA8, that encode protein Cx43 (connexin43), Cx46 (connexin46), and Cx50 (connexin50), respectively, have been identified in human and rodent lens. Cx46 together with Cx50 have been detected in lens fiber cells with high expression, whereas Cx43 is mainly expressed in lens epithelial cells. Disrupted expression of the two connexin proteins Cx46 and Cx50 is directly related to the development of severe cataract in human and mice. In this review article, we describe the main role of Cx46 and Cx50 connexin proteins in the lens and the relationship between mutations of Cx46 or Cx50 and hereditary cataracts. Furthermore, the latest progress in the fundamental research of lens connexin and the mechanism of cataract formation caused by lens connexin dysfunction are summarized. Overall, targeting connexin could be a novel approach for the treatment of cataract.

To illustrate the expression profile of lncRNAs and mRNAs in diabetic cataract (DC) and explore their potential role in the pathogenesis of DC.LncRNA and mRNA microarray were conducted using the le...

Many physiological and pathophysiological processes in cells or tissues are involved in mechanical stretch, which induces the gap junction gene expression and cytokine TGF beta changes. However, the underlying mechanisms of the gap junction gene expression remain unknown. Here, we showed that the mRNA and protein levels of Cx43 in human umbilical vein endothelial cells (HUVECs) were significantly increased after 24 h stretch stimulation, and TGF beta1 (not TGF beta2) expression was also upregulated. Administration of TGF beta1 into HUVECs without stretch also induced upregulation of Cx43 expression. However, SB431542, a specific inhibitor of the TGF beta1 receptor, blocked the Cx43 protein upregulation caused by TGF beta1. Further, the increase of Cx43 protein expression under the stretch condition was partially blocked by SB431542; it was also partially blocked by simultaneous administration of anti-TGF beta1 monoclonal neutralization antibody. Importantly, the upregulation of Cx43 induced by stretch was blocked by the administration of actin and microtubule inhibitors, while NEDD4, a key element in mediating Cx43 protein ubiquitination and degradation, was not changed under the stretch condition. In conclusion, upregulation of Cx43 expression under the 24 h stretch condition is mediated via TGF beta1 receptor signaling pathway, and it also involves the actin and microtubule cytoskeletal network.

Objectives: To describe and compare the prevalence of refractive error and its associated ocular biometric parameters in a large multi-racial sample of schoolchildren from Xinjiang. Methods: A total of 67,102 school children of five ethnicity groups aged 6–23 years from 46 schools in Xinjiang participated in this study. The children underwent a comprehensive eye examination for vision screening, including uncorrected visual acuity and standardized refraction. Refractive error was determined by autorefractors and subjective refraction. Refraction was recorded in spherical equivalent (SE). The age- and sex- adjusted prevalence of myopia (SE ≤ −0.5 D), low myopia (−6 D < SE ≤ −0.5 D), high myopia (SE ≤ −6.0 D), astigmatism (cylinder < −0.5 D), and anisometropia (difference in SE between two eyes of 1.0 D) in the five ethnic groups were calculated. Ocular biometric parameters including axial length (AL) and corneal radius of curvature (CR) were measured by AL-scan optical biometer. Results: The age- and sex- adjusted prevalence of myopia in the Han, Hui, Uyghur, Kyrgyz and Kazakh were 65.8% (95% confidence interval [CI] 65.4, 66.3); 59.1% (95% CI 57.8, 60.4); 30.1% (95% CI 29.2, 30.9); 30.2 (95% CI 28.9, 31.4); and 30.0% (95% CI 27.6, 32.3), respectively. The Han and Hui children also had longer ALs (Han, 23.8; Hui, 23.6, Uyghur, 23.1; Kyrgyz, 23.1; Kazakh, 23.3 mm) and larger AL/CR (Han, 3.04; Hui, 3.00; Uyghur, 2.95; Kyrgyz, 2.96; Kazakh, 2.97) values than the other three minorities (P < 0.01). Overall, girls had shorter ALs, steeper corneas, and smaller AL/CR values than boys (P < 0.01). Conclusions: Significant ethnic difference in the prevalence of myopia was observed in this study on school-aged children in Xinjiang (Han > Hui > Kyrgyz > Uyghur > Kazakh). This study among different ethnic groups in a multiethnic population is valuable for enriching the ethnical information resources for refractive errors and ocular biometry parameters, as well as facilitating further research on myopia-related diseases and risks.

Background/Aims . To investigate the long‐term efficacy and rotational stability of toric intraocular lenses (IOLs) implanted for the correction of moderate‐to‐high corneal astigmatism. Methods . A total of 57 cataract patients (57 eyes) with regular corneal astigmatism (≥2.57 D) were enrolled in this retrospective cohort study. Phacoemulsification with toric IOL implantation was performed for all patients. The uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) were recorded before and one year after surgery, and statistical analysis of preoperative corneal astigmatism, postoperative residual astigmatism, aberrations, IOL rotation, and related factors was performed to evaluate the efficacy, safety, and stability of toric IOLs in correcting moderate‐to‐high corneal astigmatism. Results . One year after surgery, visual acuity was significantly improved compared with that before surgery (preoperative log MAR 0.87 ± 0.34 vs. postoperative log MAR 0.31 ± 0.26, p < 0.001), and the self‐reported spectacle independence rate was 68.42%. The total residual astigmatism was 1.18 ± 0.85 D, which was significantly less than the preoperative value (3.41 ± 0.99 D) ( p < 0.001). The degree of toric IOL rotation was 4.93 ± 3.02°, and 54.39% of patients had a lens rotation of less than 5°. The IOLs of 5.26% (3 eyes) of patients rotated more than 10°, and these patients received glasses instead of undergoing IOL repositioning. Conclusions . Toric IOL implantation provided optimal vision outcomes and low spectacle dependence during a one‐year follow‐up period. The results from our study show that toric IOL implantation is a safe and effective option for cataract patients with moderate‐to‐high corneal astigmatism.