Evaluation and application of a Chinese version symptom questionnaire for visual dysfunctions (CSQVD) in school-age children.

Objective: To develop and evaluate a Chinese version of the Symptom Questionnaire for Visual Dysfunctions (CSQVD) to quantify visual dysfunction symptoms in school-age children with various eye diseases, and to explore the relationship between ophthalmological disorders and visual dysfunction symptoms. Methods: Following standard scale adaptation procedures, the Symptom Questionnaire for Visual Dysfunctions (SQVD) was translated into Chinese (CSQVD). We employed random sampling to survey 198 outpatients aged 7-18 to assess the psychometric properties of the CSQVD. Using the reliable and validated questionnaire, we evaluated the determinants of visual dysfunction symptoms among 406 school-age patients at an eye center. The CSQVD scores were correlated with demographic and clinical variables, including gender, age, eye position, refractive power, and best-corrected visual acuity. Univariate analysis identified potential risk factors, followed by binary logistic regression and multiple linear regression analysis on factors with a P-value <0.05. Results: The CSQVD scale's critical ratio (CR) values ranged from 6.028 to 10.604. The Cronbach's Alpha coefficient was 0.779, and Spearman-Brown split-half reliability was also 0.779. The I-CVI varied from 0.83 to 1.000, the S-CVI/Ave was 0.857, and the KMO value was 0.821. Multifactorial regression analysis indicated that high myopia (OR â€‹= â€‹5.744, 95% CI [1.632, 20.218], P â€‹= â€‹0.006) and amblyopia (OR â€‹= â€‹9.302, 95% CI [1.878, 46.058], P â€‹= â€‹0.006) were significant predictors of CSQVD symptoms. Multiple linear regression analysis showed that BCVA of amblyopic eyes (B â€‹= â€‹-5.052, 95% CI [-7.779, 2.325], P â€‹= â€‹0.000) and SE power (B â€‹= â€‹-0.234, 95% CI [-0.375, 0.205], P â€‹= â€‹0.001) significantly affected the CSQVD scale scores. Conclusions: The Chinese version of the SQVD scale (CSQVD) demonstrates good feasibility, discriminatory power, validity, and reliability in assessing Chinese school-aged children. Furthermore, those who have severe myopia and amblyopia reported more visual dysfunction symptoms.

Gender Disparities in the Global Burden of Refractive Disorders in Children: An Analysis From the Global Burden of Disease Study 2019.

PURPOSE: To investigate gender disparities in the global burden of refractive disorders in children younger than 15 years by year, age, and national developmental status using disability-adjusted life years (DALYs). METHODS: Global, regional, and national gender-specific DALY numbers and rates of refractive disorders in children were obtained by year (from 1990 to 2019) and age group (0 to 4, 5 to 9, and 10 to 14 years) from the Global Burden of Disease Study 2019. Data from the Inequality-adjusted Human Development Index in 2019 as an indicator of national developmental status were extracted from the Human Development Report. Pearson correlation and linear regression analyses were performed to explore the association between female-to-male DALY rate ratios and national developmental status. RESULTS: Gender disparities in DALY numbers and rates of refractive disorders in children have persisted and shown little improvement from 1990 to 2019. Girls had a higher burden than boys of the same age, and gender disparities increased with age (1.120 in preschool children aged 0 to 4 years, 1.124 in younger school-aged children aged 5 to 9 years, and 1.135 in older school-aged children aged 10 to 14 years). Female-to-male DALY rate ratios were negatively related to Inequality-adjusted Human Development Index values (standardized b = -0.189, P < .05). CONCLUSIONS: Gender disparities in the global burden of refractive disorders in children have persisted for decades, with girls who are older and from lower-income countries having a higher burden than boys. Gender-specific health policies should be made to manage refractive disorders in children. [J Pediatr Ophthalmol Strabismus. 2024;61(1):51-58.].

Global research of artificial intelligence in strabismus: a bibliometric analysis.

Purpose: To analyze the global publications on artificial intelligence (AI) in strabismus using a bibliometric approach. Methods: The Web of Science Core Collection (WoSCC) database was used to retrieve all of the publications on AI in strabismus from 2002 to 2023. We analyzed the publication and citation trend and identified highly-cited articles, prolific countries, institutions, authors and journals, relevant research domains and keywords. VOSviewer (software) and Bibliometrix (package) were used for data analysis and visualization. Results: By analyzing a total of 146 relevant publications, this study found an overall increasing trend in the number of annual publications and citations in the last decade. USA was the most productive country with the closest international cooperation. The top 3 research domains were Ophthalmology, Engineering Biomedical and Optics. Journal of AAPOS was the most productive journal in this field. The keywords analysis showed that "deep learning" and "machine learning" may be the hotspots in the future. Conclusion: In recent years, research on the application of AI in strabismus has made remarkable progress. The future trends will be toward optimized technology and algorithms. Our findings help researchers better understand the development of this field and provide valuable clues for future research directions.

Efficacy of augmented-dosed surgery versus botulinum toxin A injection for acute acquired concomitant esotropia: a 2-year follow-up.

BACKGROUND/AIMS: This study aims to evaluate the clinical efficacy of botulinum toxin type A (BTXA) injection and augmented-dosed surgery in the treatment of acute acquired concomitant esotropia (AACE), and explore potential risk factors associated with recurrence. METHODS: A total of 104 patients diagnosed with AACE between October 2020 and January 2021 were included and voluntarily chose to undergo augmented surgery or BTXA injection. The follow-up assessments ended in November 2022. Multivariable linear regression analysis was used to identify potential factors that influence the dose-response of bilateral medial rectus recession (MRrec). Kaplan-Meier survival analyses and Cox proportional hazards models were performed to evaluate rate and risk factors for AACE relapse. RESULTS: A total of 31 AACE patients chose augmented-dosed esotropia surgery, and 73 chose BTXA treatment. During the 2-year follow-up, the surgical group achieved more stable postoperative results with no recurrence of diplopia, while only 68.68% (95% CI 55.31% to 78.79%) patients achieved orthophoria in the BTXA group. For patients undergoing BTXA treatment, hours of near work per day were demonstrated to be a significant risk factor for AACE relapse (HR 1.29, 95% CI 1.00 to 1.67). The dose-response of augmented-dosed bilateral MRrec was positively correlated with preoperative deviation angle (R2=0.833; ß=0.043, 95% CI 0.031 to 0.055; p<0.001). CONCLUSION: Our findings provided quantitative evidence that augmented-dosed surgery would achieve more stable and favourable surgical outcomes for AACE patients compared with BTXA injection. However, BTXA treatment is still proposed for patients with small deviation angles due to its advantages of reduced trauma, operational simplicity, low cost and quick recovery.

Automated photographic analysis of inferior oblique overaction based on deep learning.

Background: Inferior oblique overaction (IOOA) is a common ocular motility disorder. This study aimed to propose a novel deep learning-based approach to automatically evaluate the amount of IOOA. Methods: This prospective study included 106 eyes of 72 consecutive patients attending the strabismus clinic in a tertiary referral hospital. Patients were eligible for inclusion if they were diagnosed with IOOA. IOOA was clinically graded from +1 to +4. Based on photograph in the adducted position, the height difference between the inferior corneal limbus of both eyes was manually measured using ImageJ and automatically measured by our deep learning-based image analysis system with human supervision. Correlation coefficients, Bland-Altman plots and mean absolute deviation (MAD) were analyzed between two different measurements of evaluating IOOA. Results: There were significant correlations between automated photographic measurements and clinical gradings (Kendall's tau: 0.721; 95% confidence interval: 0.652 to 0.779; P<0.001), between automated and manual photographic measurements [intraclass correlation coefficients (ICCs): 0.975; 95% confidence interval: 0.963 to 0.983; P<0.001], and between two-repeated automated photographic measurements (ICCs: 0.998; 95% confidence interval: 0.997 to 0.999; P<0.001). The biases and MADs were 0.10 [95% limits of agreement (LoA): -0.45 to 0.64] mm and 0.26±0.14 mm between automated and manual photographic measurements, and 0.01 (95% LoA: -0.14 to 0.16) mm and 0.07±0.04 mm between two-repeated automated photographic measurements, respectively. Conclusions: The automated photographic measurements of IOOA using deep learning technique were in excellent agreement with manual photographic measurements and clinical gradings. This new approach allows objective, accurate and repeatable measurement of IOOA and could be easily implemented in clinical practice using only photographs.

Cell Wall Destruction and Internal Cascade Synergistic Antifungal Strategy for Fungal Keratitis.

Fungal keratitis is one of the most common blindness-causing diseases, but clinical antifungal treatment remains a challenge. The fungal cell wall and biofilm matrix which severely confine the drug preparation are the critical obstructive factors to therapeutic effects. Herein, we report ethylenediaminetetraacetic acid (EDTA) modified AgCu2O nanoparticles (AgCuE NPs) to disrupt the cell wall and then eradicate C. albicans through the internal cascade synergistic effects of ion-released chemotherapy, chemodynamic therapy, photodynamic therapy, and mild photothermal therapy. AgCuE NPs exhibited excellent antifungal activity both in preventing biofilm formation and in destroying mature biofilms. Furthermore, AgCuE NP based gel formulations were topically applied to kill fungi, reduce inflammation, and promote wound healing, using optical coherence tomography and photoacoustic imaging to monitor nanogel retention and therapeutic effects on the infected murine cornea model. The AgCuE NP gel showed good biosafety and no obvious ophthalmic and systemic side effects. This study suggests that the AgCuE NP gel is an effective and safe antifungal strategy for fungal keratitis with a favorable prognosis and potential for clinical translation.

TP53INP2 Contributes to TGF-ß2-Induced Autophagy during the Epithelial-Mesenchymal Transition in Posterior Capsular Opacification Development.

BACKGROUND: Posterior capsule opacification (PCO) is the most common complication after cataract surgery, in which increased levels of transforming growth factor-beta 2 (TGF-ß2) accelerate PCO formation; however, the pathological mechanisms are not fully understood. This study aims to explore the regulation mechanism of TGF-ß2 in PCO formation via its autophagic functions. METHODS: The autophagic effect of TGF-ß2 was detected by transmission electron microscopy (TEM), Western blotting, and immunofluorescence analysis. The association between autophagy and the epithelial-mesenchymal transition (EMT) was evaluated by qPCR and Western blotting. The transcriptome analysis was used to uncover the molecular mechanism of TGF-ß2-induced PCO formation. RESULTS: TGF-ß2 specifically promotes autophagy flux in human lens epithelial cells. The activation of autophagy by rapamycin can promote EMT marker synthesis and improve cell migration. However, the inhibition of autophagy by 3-MA attenuates EMT. To uncover the molecular mechanisms, we performed RNA sequencing and found that TGF-ß2 elevated tumor protein p53-inducible nuclear protein2 (TP53INP2) expression, which was accompanied by a nuclear-to-cytoplasm translocation. Moreover, the knockdown of TP53INP2 blocked the TGF-ß2-induced autophagy and EMT processes, revealing that TP53INP2 plays an important role in TGF-ß2-induced autophagy during EMT. CONCLUSIONS: Taken together, the results of this study suggested that TP53INP2 was a novel regulator of PCO development by TGF-ß2, and notably, TP53INP2, may be a potential target for the pharmacological treatment of PCO.

Automated Measurement of Ocular Movements Using Deep Learning-Based Image Analysis.

PURPOSE: Clinical assessment of ocular movements is essential for the diagnosis and management of ocular motility disorders. This study aimed to propose a deep learning-based image analysis to automatically measure ocular movements based on photographs and to investigate the relationship between ocular movements and age. METHODS: 207 healthy volunteers (414 eyes) aged 5-60 years were enrolled in this study. Photographs were taken in the cardinal gaze positions. Ocular movements were manually measured based on a modified limbus test using ImageJ and automatically measured by our deep learning-based image analysis. Correlation analyses and Bland-Altman analyses were conducted to assess the agreement between manual and automated measurements. The relationship between ocular movements and age were analyzed using generalized estimating equations. RESULTS: The intraclass correlation coefficients between manual and automated measurements of six extraocular muscles ranged from 0.802 to 0.848 (P < 0.001), and the bias ranged from -0.63 mm to 0.71 mm. The average measurements were 8.62 ± 1.07 mm for superior rectus, 7.77 ± 1.24 mm for inferior oblique, 6.99 ± 1.23 mm for lateral rectus, 6.71 ± 1.22 mm for medial rectus, 6.81 ± 1.20 mm for inferior rectus, and 6.63 ± 1.37 mm for superior oblique, respectively. Ocular movements in each cardinal gaze position were negatively related to age (P < 0.05). CONCLUSIONS: The automated measurements of ocular movements using a deep learning-based approach were in excellent agreement with the manual measurements. This new approach allows objective assessment of ocular movements and shows great potential in the diagnosis and management of ocular motility disorders.

Necroptosis contributes to airborne particulate matter-induced ocular surface injury.

In this study, we explored the role of necroptosis in the pathogenesis of ocular surface injury caused by airborne particulate matter (PM). Human corneal epithelial (HCE) cells and mouse ocular surface were treated with PM exposure and compared with non-exposed groups. The expression of necroptosis-related proteins was measured by immunoblotting in HCE cell groups. Cell damages were detected using CCK-8, flow cytometry, and immunofluorescence staining. In the mouse model, hematoxylin and eosin (H&E) staining and corneal fluorescein sodium staining were assessed. In addition, the expression of inflammatory cytokines and mucin were examined via Enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and/or quantitative RT -PCR (qRT-PCR), both in vitro and in vivo. Our research showed that PM exposure may trigger HCE cell damage via necroptosis. Necrostatin-1(Nec-1), one of the specific inhibitors of necroptosis, can markedly reduce PM-induced HCE cell damage. HCE cell damage markers included decreased cell viability, increased intracellular reactive oxygen species (ROS) levels, and loss of mitochondrial membrane potential. At the same time, Nec-1 inhibited the increased inflammatory cytokines and the decreased mucin expression caused by PM exposure in HCE cells. Nec-1 also reduced corneal inflammation and mucin underproduction in mouse ocular surface after PM exposure. Our study demonstrated that necroptosis is involved in the pathogenesis of PM exposure-related ocular surface injury, including inflammation and insufficient mucin production in the cornea, which can be rescued by inhibitor Nec-1. This suggests Nec-1 could be a novel therapeutic target for ocular surface disorders, especially dry eye disease, which is caused by the exacerbation of airborne PM pollution.

Rapamycin relieves the cataract caused by ablation of Gja8b through stimulating autophagy in zebrafish.

Macroautophagy/autophagy is known to be important for intracellular quality control in the lens. GJA8 is a major gap junction protein in vertebrate lenses. Mutations in GJA8 cause cataracts in humans. The well-known cataractogenesis mechanism is that mutated GJA8 leads to abnormal assembly of gap junctions, resulting in defects in intercellular communication among lens cells. In this study, we observed that ablation of Gja8b (a homolog of mammalian GJA8) in zebrafish led to severe defects in organelle degradation, an important cause of cataractogenesis in developing lens. The role of autophagy in organelle degradation in lens remains disputable. Intriguingly, we also observed that ablation of Gja8b induced deficient autophagy in the lens. More importantly, in vivo treatment of zebrafish with rapamycin, an autophagy activator that inhibits MAPK/JNK and MTORC1 signaling, stimulated autophagy in the lens and relieved the defects in organelle degradation, resulting in the mitigation of cataracts in gja8b mutant zebrafish. Conversely, inhibition of autophagy by treatment with the chemical reagent 3-MA blocked these recovery effects, suggesting the important roles of autophagy in organelle degradation in the lens in gja8b mutant zebrafish. Further studies in HLE cells revealed that GJA8 interacted with ATG proteins. Overexpression of GJA8 stimulated autophagy in HLE cells. These data suggest an unrecognized cataractogenesis mechanism caused by ablation of Gja8b and a potential treatment for cataracts by stimulating autophagy in the lens.Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy related; AV: autophagic vacuoles; Dpf: days post fertilization; GJA1: gap junction protein alpha 1; GJA3: gap junction protein alpha 3; GJA8: gap junction protein alpha 8; Hpf: hours post fertilization; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; WT: wild type.

Functional acute acquired comitant esotropia: clinical characteristics and efficacy of single Botulinum toxin type A injection.

BACKGROUND: To examine the clinical features of acute acquired comitant esotropia (AACE) and to evaluate the clinical effectiveness of a single injection of botulinum toxin type A (BTXA) on binocular visual function (BVF). METHODS: This retrospective, observational case series study enrolled patients with AACE examined from October 2018-May 2019. BTXA was injected into the both medial rectus muscles. The refractive error, best-corrected visual acuity (BCVA), stereoacuity, vergence, accommodation, the horizontal angle of deviation, and the gradient accommodative convergence/accommodation (AC/A) ratio were measured pre- and post-BTXA injection. Data pre- and postinjection were compared by the Wilcoxon signed-rank test. A Spearman correlation coefficient was calculated to explore the relationships between demographic characteristics and BVF. RESULTS: Twenty-two AACE cases were included. Compared with preinjection deviation, the postinjection deviation in the primary position was smaller for near (p < 0.001) and distance (p < 0.001) fixation at 3 months after injection (BTXA). Furthermore, convergence was better for near (p = 0.003) and distance (p < 0.001) fixation, divergence was better for near (p = 0.021) and distance (p < 0.001) fixation, accommodation was better in the right (p = 0.011) and left (p = 0.004) eyes, and the gradient AC/A ratio was better at the third month after injection (p = 0.001). Stereoacuity was improved in 11 (50%), unchanged in 5 (22.73%) and decreased in 6 (27.27%) patients. The preinjection stereoacuity (p = 0.013, r = 0.522) and preinjection deviation for near (p = 0.015 r, = - 0.512) and distance (p = 0.009, r = - 0.541) were significantly associated with patient age. CONCLUSIONS: AACE is characterized by a high AC/A ratio and low accommodation. A single injection of BTXA is effective for AACE. Deviation, stereoacuity, and the therapeutic effect of BTXA may be correlated with patient age.

Interplay of MPP5a with Rab11 synergistically builds epithelial apical polarity and zonula adherens.

Adherens junction remodeling regulated by apical polarity proteins constitutes a major driving force for tissue morphogenesis, although the precise mechanism remains inconclusive. Here, we report that, in zebrafish, the Crumbs complex component MPP5a interacts with small GTPase Rab11 in Golgi to transport cadherin and Crumbs components synergistically to the apical domain, thus establishing apical epithelial polarity and adherens junctions. In contrast, Par complex recruited by MPP5a is incapable of interacting with Rab11 but might assemble cytoskeleton to facilitate cadherin exocytosis. In accordance, dysfunction of MPP5a induces an invasive migration of epithelial cells. This adherens junction remodeling pattern is frequently observed in zebrafish lens epithelial cells and neuroepithelial cells. The data identify an unrecognized MPP5a-Rab11 complex and describe its essential role in guiding apical polarization and zonula adherens formation in epithelial cells.

Dystrophia canthorum in Waardenburg syndrome with a novel MITF mutation.

AIM: To reveal a novel MITF gene mutation in Waardenburg syndrome (WS), which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes, hair and skin. METHODS: The genetic analysis of the Chinese family was conducted by whole-exome sequencing, then the results were confirmed by Sanger sequencing. RESULTS: WS is classified into type I to IV, which are identified by the W index, clinical characteristics and additional features. The MITF gene mostly accounts for WS type II. In this study, a de novo heterozygous mutation in the MITF gene, c.638A>G in exon 7, was identified in the patient diagnosed with WS type I features, as the W index was 2.17 (over 2.10), with dystrophia canthorum, congenital bilateral profound hearing loss, bilateral heterochromia irides, premature greying of the hair, and excessive freckling on the face at birth. She also underwent refractive errors and esotropia, reduced pigmentation of the choroid and visible choroid vessels. The mutation was not found in previous studies or mutation databases. CONCLUSION: The novel mutation in the MITF gene, which altered the protein in amino acids 213 from the glutamic acid to glycine, is the genetic pathological cause for WS features in the patient. Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS, which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities. Moreover, ocular symptoms should be emphasized in all types of WS patients.

Cytoprotective role of humanin in lens epithelial cell oxidative stress­induced injury.

Oxidative stress-induced injury and apoptosis of human lens epithelial cells (HLECs) are early events in the development of age­related cataracts (ARCs). Humanin (HN) is a mitochondrial­related peptide that serves a cytoprotective role in various cell types and animal models. Following HN knockdown or overexpression, the level of reactive oxygen species (ROS), mitochondrial membrane potential and mitochondrial DNA copy number, cell viability, LDH activity and apoptosis of HLECs under oxidative stress were detected, and apoptosis and autophagy were detected via transmission electron microscopy. The results suggested that HN may be involved in the response of HLECs to oxidative stress, and that HN expression was significantly upregulated under oxidative stress conditions. Furthermore, exogenous HN reduced intracellular ROS content and mitochondrial damage, and enhanced mitochondrial biosynthesis; however, this protection was lost in an endogenous HN knockdown cell model. In addition, to the best of our knowledge, the present study was the first to identify that HN increased mitochondrial autophagy, which was involved in reducing ROS production under oxidative stress. The present study indicated a potential mechanism underlying the anti­oxidative damage and apoptotic effects of HN under oxidative stress. In conclusion, HN may be a potential therapeutic target for ARCs as it has a significant cellular protective effect on HLECs under oxidative stress; therefore, further study is required to investigate its role in the occurrence and development of ARCs.

Development of mucoadhesive cationic polypeptide micelles for sustained cabozantinib release and inhibition of corneal neovascularization.

Corneal neovascularization (CNV) is one of the leading risk factors for vision loss. Anti-angiogenic drugs can theoretically be extended to the treatment of CNV. However, the application of these drugs is often hindered by traditional administration methods, e.g., eye drops, which is ascribed to the unique structure of the cornea and tear film. In this study, cationic polypeptide nanoparticles with mucoadhesive ability that carry lipophilic cabozantinib (a tyrosine kinase inhibitor), called Cabo-NPs, were developed for sustained cabozantinib release and inhibition of CNV. The polypeptides were synthesized via N-carboxyanhydride ring-opening polymerization and could self-assemble into micelles with cabozantinib in aqueous solution. The Cabo-NPs possessed good biocompatibility both in corneal epithelial cells and mouse corneas. More importantly, in vitro angiogenesis assays demonstrated the strong inhibitory effect of Cabo-NPs on cell migration and tube formation. Furthermore, the Cabo-NPs exerted superior anti-angiogenic effects with remarkable reductions in the neovascular area, which were as effective as the clinical dexamethasone but without apparent side effects. The therapeutic mechanism of the Cabo-NPs is closely related to the significant decrease in proangiogenic and proinflammatory factors, suppressing neovascularization and inflammation. Overall, cationic Cabo-NPs offer a new prospect for safe and effective CNV treatment via enhancing the bioavailability of lipophilic cabozantinib.

Regional differences in the global burden of age-related macular degeneration.

BACKGROUND: Age-related Macular Degeneration (AMD) is the leading cause of blindness. This study aims to analyze regional differences on the global burden of AMD and help direct related policy making. METHODS: Disability-adjusted life years (DALY) data were collected from the Global Burden of Disease Study (GBD) 2017 to estimate the AMD burden. Mean education years, human development index (HDI) and Public Health Expenditure were extracted from the Human Development Report 2018, and latitude data were obtained from the Google Earth. These four factors were analyzed to see their importance in regional differences of AMD burden, using Kruskal-Wallis test, Dunn's multiple comparisons test as well as regression analysis. RESULTS: Global age-standardized DALY rates have decreased since 2011. Based on the WHO region system, age-standardized DALY rates in African and Eastern Mediterranean region were significantly lower than those of other four regions. Linear regression analysis indicated that age-standardized DALY rates were inversely related to HDI and mean education years. CONCLUSIONS: The age-standardized AMD burden had a decreasing tendency recently. Lower socioeconomic status and fewer education years were associated with higher AMD burden. The finding of this study may highlight the importance of national development and education on relieving AMD burden.

Association of IGF1R polymorphisms (rs1546713) with susceptibility to age-related cataract in a Han Chinese population.

AIM: To explore the susceptible association between the insulin-like growth factor-1 receptor (IGF1R) single nucleotide polymorphism (SNP) and age-related cataract (ARC), and investigate the underlying mechanisms in human lens epithelium (HLE) cells. METHODS: Totally 1190 unrelated participants, comprising 690 ARC patients and 500 healthy individuals in Han Chinese population were recruited and genotyped for target SNP. The χ 2-test was used to detect genotypic distribution between the patient and control groups and the logistic regression was performed to adjust the age and gender. Meanwhile, different biological experimental methods, such as cell counting kit 8 (CCK-8) assay, flow cytometry, quantitative real time polymerase chain reaction (Q-PCR) and Western blot, were used to detect cell viability, cell cycle progression and apoptosis in HLE cells or IGF1R knockdown HLE cells. RESULTS: The rs1546713 in IGF1R gene was identified (P=0.046, OR: 1.606, 95%CI: 1.245-2.071), which shown a significant relevance with ARC risk under the dominant model. The results demonstrated that IGF1R knockdown inhibited cell proliferation by inducing cell cycle arrested at S phase and promoting apoptosis. Mechanistically, the cell cycle blocked at S phase was linked with the alterations of cyclin A, cyclin B, cyclin E and P21. The pro-apoptosis function of IGF1R may related with stimulating the activation of Caspase-3 and altering the expression levels of apoptotic proteins, including Bcl-2, Bax and Caspase-3. CONCLUSION: This study first report that IGF1R polymorphisms may affect susceptibility to ARCs in Han Chinese population and provide new clues to understand the pathogenic mechanism of ARCs. Notably, IGF1R is likely a potential target for ARC prevention and treatment.

Socioeconomic inequality in the global burden of refraction disorders: results from the Global Burden of Diseases Study 2017.

PURPOSE: To explore socioeconomic inequality in global burden of refraction disorders using disability-adjusted life years (DALYs). METHODS: World Bank categorical and national DALY numbers, crude rates and age-standardized rates caused by refraction disorders between 1990 and 2017 were obtained. Gini coefficient and concentration index were computed to assess trends in global health inequality in refraction disorders burden. RESULTS: Lower middle-income countries had the highest burden of refraction disorders and greatest decline in age-standardized DALY rates of 15.9% (171.0 in 1990; 143.8 in 2017), followed by upper middle-income countries, with a 9.7% decline (103.7 in 1990; 93.7 in 2017). High-income countries had the lowest age-standardized DALY rates (70.4 in 1990; 65.7 in 2017), while low-income countries had the lowest DALY numbers. Between-country inequality decreased, with Gini coefficient declining from 0.203 in 1990 to 0.184 in 2017. Socioeconomic-associated inequality also decreased, with concentration index changing from -0.060 in 1990 to -0.041 in 2017. Small peaks of DALY numbers and crude rates occurred in the age group of 5-9 years in countries with different income levels. An earlier occurrence of high peaks of DALY estimates in older adults had been observed in countries with lower income. CONCLUSION: Middle-income countries are more burdened with refraction disorders but have achieved great progress in the last few decades. The global health improvement in refraction disorders has been accompanied by narrowing inequality. Older adults in lower income countries tend to suffer from refraction disorders at an earlier age, compared with older adults in higher income countries.

The impact of GJA3 SNPs on susceptibility to age-related cataract.

AIM: To determine the association of gap junction protein alpha 3 (GJA3) gene tag single-nucleotide polymorphisms (SNPs) with susceptibility to age-related cataract (ARC). METHODS: In total, 486 ARC patients were matched with 500 healthy controls. All the participants underwent complete ophthalmic examinations. Haplotype-tagging SNPs of GJA3 gene were selected from the HapMap Beijing Han Chinese population. Genomic DNA was extracted from the peripheral blood leukocytes of all the subjects. Under three different genetic models: dominant, recessive, and additive, the association between SNPs and ARC was examined. After adjusting for age and sex, the genetic effects of the GJA3 SNPs were evaluated with logistic regression analysis. RESULTS: Four tag GJA3 SNPs (rs6490519, rs9506430, rs9509053, and rs9552089) were included in the present study. None of the SNPs showed a significant relationship with an altered risk of total ARC under the dominant, recessive, or additive models. In the subgroup analysis, rs9506430 had a significant effect on the formation of a posterior subcapsular cataract (P=0.002, OR: 0.227, 95%CI: 0.088-0.590) under the recessive model. CONCLUSION: Our study indicates that GJA3 variants may influence the development of posterior subcapsular cataracts. Further studies need to be designed to confirm this possibility.

Gender Inequality in Global Burden of Uncorrected Refractive Error.

PURPOSE: To explore gender inequality in global burden of uncorrected refractive error (URE) by year, age, and socioeconomic status using disability-adjusted life years (DALYs). DESIGN: International, comparative burden-of-disease study. METHODS: Global, regional, and national gender-specific DALY numbers; crude DALY rates; and age-standardized DALY rates caused by URE, by year and age, were extracted from the Global Burden of Disease Study 2015. Human development index (HDI) in 2015 as an indicator of national socioeconomic status was extracted from the Human Development Report. Pearson correlation and linear regression analyses were conducted to investigate the association between socioeconomic status and gender inequality. RESULTS: Gender inequality in global URE burden has persisted since 1990, through 2015, with little improvement over the decades. Age-standardized DALY rates were 189.8 among male subjects vs 223.0 among female subjects in 1990 and 188.4 vs 225.2 in 2015. Female subjects had higher burden than male subjects of the same age, and gender inequality increased with age. Female-minus-male difference in age-standardized DALY rates (r = -0.562, P < .001; standardized ß = -0.562, P < .001) and female-to-male age-standardized DALY rate ratios (r = -0.258, P < .001; standardized ß = -0.258, P < .001) were negatively related to HDI. CONCLUSIONS: Gender inequality in global URE burden has persisted over the past few decades, with female individuals bearing more burden than male individuals. Older age and lower socioeconomic status are related to greater gender inequality. These findings highlight the importance of making gender-sensitive health policy to manage global vision loss caused by URE.