EBD: an eye biomarker database.

MOTIVATION: Many ophthalmic disease biomarkers have been identified through comprehensive multiomics profiling, and hold significant potential in advancing the diagnosis, prognosis, and management of diseases. Meanwhile, the eye itself serves as a natural biomarker for several systemic diseases including neurological, renal, and cardiovascular systems. We aimed to collect and standardize this eye biomarkers information and construct the eye biomarker database (EBD) to provide ophthalmologists with a platform to search, analyze, and download these eye biomarker data. RESULTS: In this study, we present the EBD , a world-first online compilation comprising 889 biomarkers for 26 ocular diseases and 939 eye biomarkers for 181 systemic diseases. The EBD also includes the information of 78 "nonbiomarkers"-the objects that have been proven cannot be biomarkers. Biological function and network analysis were conducted for these ocular disease biomarkers, and several hub pathways and common network topology characteristics were newly identified, which may promote future ocular disease biomarker discovery and characterizes the landscape of biomarkers for eye diseases at the pathway and network level. The EBD is expected to yield broader utility among developmental biologists and clinical scientists in and outside of the eye field by assisting in the identification of biomarkers linked to eye disorders and related systemic diseases. AVAILABILITY AND IMPLEMENTATION: EBD is available at http://www.eyeseeworld.com/ebd/index.html.

Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables.

OBJECTIVE: Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. METHODS: In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. RESULTS: The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. CONCLUSION: The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

Retinal vasculature-function correlation in non-proliferative diabetic retinopathy.

PURPOSE: To compare and correlate retinal microcirculation and function in patients with non-proliferative diabetic retinopathy (NPDR). METHODS: Thirty-three healthy controls (33 eyes), 36 diabetic patients with no clinically detectable retinopathy (NDR, 36 eyes) and 101 patients (101 eyes) with NPDR (35 mild NPDR, 34 moderate NPDR, 32 severe NPDR) were involved in the study. We used optical coherence tomography angiography (OCTA) to quantify the macular vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP) and foveal density in a 300 µm region around foveal avascular zone. Retinal function was assessed by a mydriasis-free, full-field flicker electroretinogram (FERG) recording device, and the amplitudes and implicit time were recorded. The association between microvascular parameters and FERG results was analyzed with stepwise multiple linear regression model. RESULTS: Decreased amplitudes and delayed implicit time, as well as lower parafoveal/perifoveal VD in both SCP and DCP, were found in NDR group and NPDR groups compared with the control group (all p < 0.05). Specifically, the FERG parameters and microvascular indices were comparable between NDR group and mild NPDR group (all p > 0.05). However, compared to mild NPDR, the reduction in FERG amplitude was more pronounced than the reduction in parafoveal VD (both SCP and DCP) in severe NPDR. Stepwise multiple linear regression analyses showed that delayed implicit time was significantly correlated with increased age and decreased VD of parafoveal region in both SCP and DCP in patients with NPDR. Meanwhile, decreased amplitude was significantly associated with decreased VD of parafoveal region in both SCP and DCP in patients with NPDR. CONCLUSION: Macular VD in both superficial and deep capillary plexus correlated with ERG implicit time and amplitude in mild-to-severe NPDR. OCTA and FERG may both be useful in detection of preclinical DR and early DR, but once the disease deteriorates, FERG may be more sensitive to discern progression of DR.

Screening for diabetic retinopathy in diabetic patients with a mydriasis-free, full-field flicker electroretinogram recording device.

PURPOSE: To investigate the accuracy of the RETeval full-field flicker ERG in the screening of diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) and to determine a suitable range of DR diagnostic reference for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study involving 172 subjects with T2DM, including 71 subjects without clinically detectable DR (NDR), 25 subjects with mild non-proliferative diabetic retinopathy (NPDR), 24 subjects with moderate NPDR, 27 subjects with severe NPDR and 25 subjects with proliferative diabetic retinopathy (PDR). All the subjects underwent a full-field flicker ERG using the RETeval device (DR assessment protocol), which is a mydriasis-free, full-field electroretinogram (ERG) recording system. The performance of the DR assessment protocol in detecting the DR (including mild NPDR, moderate NPDR, severe NPDR and PDR) and VTDR was analyzed with the receiver operating characteristic (ROC) curve. RESULTS: For the detection of DR (mild NPDR, moderate NPDR, severe NPDR, PDR), the area under the ROC curve was 0.867 (p < 0.001, 95% CI 0.814-0.920), and the best cutoff value for DR was determined to be 20.75, with a sensitivity of 80.2% and specificity of 81.7%. Meanwhile, for the detection of VTDR, the area under the ROC curve was 0.965 (p < 0.001, 95% CI 0.941-0.989), and the best cutoff value was set to 23.05, with a sensitivity of 94.6% and a specificity of 88.8%. CONCLUSION: The DR assessment protocol in RETeval device was effective in screening for DR (mild NPDR, moderate NPDR, severe NPDR, PDR) and VTDR in patients with diabetes. It could be helpful in referring and managing patients with T2DM in primary healthcare setting. However, caution should be taken that optimal cutoff value of DR assessment protocol may vary in different ethnic populations.

Comprehensive analysis of vitreous chemokines involved in ischemic retinal vein occlusion.

Purpose: To investigate vitreous levels of chemokines in eyes with ischemic retinal vein occlusion (RVO). Methods: The vitreous humor was collected at the start of 23-gauge pars plana vitrectomy from patients with ischemic RVO and patients with idiopathic preretinal membranes (PRMs) and idiopathic macular holes (IMHs). The levels of 40 different chemokines were measured using magnetic color-bead-based multiplex assay. The chi-square test was performed for clinical variables such as sex, and the Mann-Whitney U test was performed to evaluate the differences in the chemokine levels between the RVO group and the control group. Results: Vitreous humor was collected from 20 controls and 25 subjects with ischemic RVO. C-C motif ligand 17 (CCL17) was unmeasurable in more than 70% of the samples. The levels of 29 of 39 chemokines were statistically significantly elevated in the RVO group compared with the control group, including CCL21, C-X-C motif ligand (CXCL) 13, CCL27, CCL24, CX3CL1, CXCL6, interferon-gamma (IFN-γ), interleukin (IL) 1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-16, CXCL10, CXCL11, CCL8, CCL7, CCL13, CCL22, macrophage migration inhibitory factor (MIF), CXCL9, CCL3, CCL15, CCL20, CCL19, CCL23, CCL25, and tumor necrosis factor-alpha (TNF-α). Among the 29 elevated chemokines, we found that the levels of three chemokines (IL-8, CXCL9, and TNF-α) showed a more than six-fold increase in the RVO eyes versus controls, and CXCL9 expression showed the greatest change of all tested chemokines. Conclusions: Dozens of chemokines were found to be elevated in the vitreous of RVO eyes complicated with vitreous hemorrhage, suggesting that inflammation is severe in the ischemic retina. The knowledge of specific upregulation of chemokines in ischemic RVO could allow more targeted future therapies.

Evaluation of the Observational Associations and Shared Genetics Between Glaucoma With Depression and Anxiety.

Purpose: Glaucoma, a leading cause of blindness worldwide, is suspected to exhibit a notable association with psychological disturbances. This study aimed to investigate epidemiological associations and explore shared genetic architecture between glaucoma and mental traits, including depression and anxiety. Methods: Multivariable logistic regression and Cox proportional hazards regression models were employed to investigate longitudinal associations based on UK Biobank. A stepwise approach was used to explore the shared genetic architecture. First, linkage disequilibrium score regression inferred global genetic correlations. Second, MiXeR analysis quantified the number of shared causal variants. Third, specific shared loci were detected through conditional/conjunctional false discovery rate (condFDR/conjFDR) analysis and characterized for biological insights. Finally, two-sample Mendelian randomization (MR) was conducted to investigate bidirectional causal associations. Results: Glaucoma was significantly associated with elevated risks of hospitalized depression (hazard ratio [HR] = 1.54; 95% confidence interval [CI], 1.01-2.34) and anxiety (HR = 2.61; 95% CI, 1.70-4.01) compared to healthy controls. Despite the absence of global genetic correlations, MiXeR analysis revealed 300 variants shared between glaucoma and depression, and 500 variants shared between glaucoma and anxiety. Subsequent condFDR/conjFDR analysis discovered 906 single-nucleotide polymorphisms (SNPs) jointly associated with glaucoma and depression and two associated with glaucoma and anxiety. The MR analysis did not support robust causal associations but indicated the existence of pleiotropic genetic variants influencing both glaucoma and depression. Conclusions: Our study enhances the existing epidemiological evidence and underscores the polygenic overlap between glaucoma and mental traits. This observation suggests a correlation shaped by pleiotropic genetic variants rather than being indicative of direct causal relationships.

Association of hyperopia with incident clinically significant depression: epidemiological and genetic evidence in the middle-aged and older population.

AIMS: To investigate the association between hyperopia and clinically significant depression (CSD) in middle-aged and older individuals. The effect of genetic determinants of hyperopia on incident CSD was also explored. METHODS: We included participants who had available data on mean spherical equivalent (MSE) and were free of depression at baseline from the UK Biobank. For the phenotypic association, hyperopia was defined as MSE of+2.00 dioptres (D) or greater, and was divided into mild, moderate and high groups. Diagnosis of CSD across follow-up was determined based on electronic hospital inpatients records. For the genetic association analysis, the association between hyperopia Polygenic Risk Score and incident CSD was assessed. Mendelian randomisation was assessed for causality association. RESULTS: Over a median follow-up of 11.11 years (IQR: 10.92-11.38), hyperopia was significantly associated with incident CSD independent of genetic risk (HR 1.29, 95% CI 1.05 to 1.59) compared with emmetropia participants, especially in those hyperopic patients without optical correction (HR 1.38, 95% CI 1.07 to 1.76). In addition, participants in the high degree of hyperopia were more likely to have incident CSD than participants in the mild degree of hyperopia (P for trend=0.009). Genetic analyses did not show any significant associations between hyperopia and incident CSD (p≥0.1). CONCLUSIONS: Hyperopia was significantly associated with an increased risk of incident CSD. This was independent of genetic predisposition to hyperopia, emphasising the importance of regular vision screening and correction of hyperopia to reduce the risk of CSD regardless of genetic risk.

The associations and mediators between visual disabilities and anxiety disorders in middle-aged and older adults: A population-based study.

Visual disabilities significantly impact an individual's mental health. Little is known about the prospective relationship between visual disabilities and anxiety disorders and the underlying effects of modifiable risk factors. Our analysis was based on 117,252 participants from the U.K. Biobank, with baseline data collected between 2006 and 2010. Habitual visual acuity was measured by a standardized logarithmic chart, and ocular disorders reported using questionnaires were collected at baseline. Incident hospitalized anxiety recorded using longitudinal linkage with hospital inpatient data, lifetime anxiety disorder, and current anxiety symptoms assessed by a comprehensive online mental health questionnaire were identified over a 10-year follow-up. After adjustments for confounding factors, one-line worse visual acuity (0.1 logarithm of the minimum angle of resolution [logMAR]) was associated with an increased risk of incident hospitalized anxiety (HR = 1.05, 95% CI = 1.01-1.08), lifetime anxiety disorder (OR = 1.07, 95% CI [1.01-1.12]), and current anxiety scores (ß = 0.028, 95% CI [0.002-0.054]). Besides poorer visual acuity, the longitudinal analysis also supported that each ocular disorder (including cataracts, glaucoma, macular degeneration, and diabetes-related eye disease) was significantly associated with at least two anxiety outcomes. Mediation analyses highlighted that subsequent onsets of eye diseases, especially cataracts, and lower socioeconomic status (SES) partly mediated the association between poorer visual acuity and anxiety disorders. This study demonstrates an overall association between visual disabilities and anxiety disorders in middle-aged and older adults. In particular, early interventions involving treatments for visual disabilities and effective psychological counseling services sensitive to socioeconomic status may help prevent anxiety in those living with poor vision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Measurement of Foveal Retinal Thickness in Myopic Patients Using Different Display Modes on Optical Coherence Tomography: A Retrospective, Cross-Sectional Study.

INTRODUCTION: The aim of this work is to investigate the differences in the measurement of foveal retinal thickness in myopic patients between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT). METHODS: Horizontal OCT line scan through the central fovea was used for manual measurement of foveal retinal thickness under the two display modes, and the values were compared using Wilcoxon signed-rank test. Correlations between the OCT image tilting angle (OCT ITA) and differences in OCT measurement were analyzed by Spearman's test. RESULTS: 127 participants with a median age of 28 years, a median spherical equivalent (SE) of - 8.5 D, and a median axial length (AL) of 27.04 mm. There were significant differences between the two display modes, with a median absolute difference (median relative difference) of 13.33 µm (2.75%) for the central foveal thickness (CFT), 5.33 µm (1.28%) for the Henle fiber and outer nuclear layer thickness (HFL + ONL), 3 µm (6.47%) for the external limiting membrane to ellipsoid zone distance (ELM-EZ), and 4 µm (8.77%) for the ellipsoid zone to retinal pigment epithelium distance (EZ-RPE) (all p < 0.05). The differences in foveal retinal thickness between the two display modes were significantly correlated with the OCT ITA (r = 0.732 for CFT, 0.561 for HFL + ONL, 0.642 for ELM-EZ, and 0.471 for EZ-RPE, all p < 0.05). CONCLUSIONS: Disparities between the two display modes were found in the manual measurement of foveal retinal thickness and correlated to the OCT ITA.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank.

PURPOSE: Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD). METHODS: Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality. RESULTS: We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10 U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, Pnonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (Pnonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD. CONCLUSIONS: Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.

Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors.

Crown ether fused anilinoquinazoline analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities in an in vitro EGFR kinase assay and an EGFR-mediated intracellular tyrosine phosphorylation assay. The synthesis and preliminary biological, physical, and pharmacokinetic evaluation of these fused quinazoline compounds is reported.

Matching Biomedical Ontologies via a Hybrid Graph Attention Network.

Biomedical ontologies have been used extensively to formally define and organize biomedical terminologies, and these ontologies are typically manually created by biomedical experts. With more biomedical ontologies being built independently, matching them to address the problem of heterogeneity and interoperability has become a critical challenge in many biomedical applications. Existing matching methods have mostly focused on capturing features of terminological, structural, and contextual semantics in ontologies. However, these feature engineering-based techniques are not only labor-intensive but also ignore the hidden semantic relations in ontologies. In this study, we propose an alternative biomedical ontology-matching framework BioHAN via a hybrid graph attention network, and that consists of three techniques. First, we propose an effective ontology-enriching method that refines and enriches the ontologies through axioms and external resources. Subsequently, we use hyperbolic graph attention layers to encode hierarchical concepts in a unified hyperbolic space. Finally, we aggregate the features of both the direct and distant neighbors with a graph attention network. Experimental results on real-world biomedical ontologies demonstrate that BioHAN is competitive with the state-of-the-art ontology matching methods.

Causes and Risk Factors of Repeated Hospitalization among Patients with Diabetic Retinopathy.

Purpose: To identify the causes and risk factors of repeated hospitalization among patients with diabetic retinopathy (DR). Methods: Our study retrospectively examined the data of DR patients who were readmitted for treatments to the Department of Ophthalmology, Guangdong Provincial People's Hospital between January 2012 and July 2021. We first analyzed the main causes of repeated admissions and then divided the patients into three groups according to the times of readmissions. Ordinal logistic regression was performed to determine the impact of patients' demographic and clinical characteristics. Moreover, comparisons of the length of stay and the hospitalization cost of DR patients with repeated admission causes were conducted. Results: Among 2592 hospital discharges of 827 patients who experienced at least two hospitalizations, the major causes of repeated hospitalization were macular edema (30.83%), vitreous hemorrhage (29.09%), cataract (22.76%), proliferative membrane formation (6.91%), silicone oil removal (4.71%), retinal detachment (4.44%), and glaucoma (4.17%). The results of ordinal logistic regression showed that younger patients with medical insurance and local residence have a higher risk of repeated hospitalization (p < 0.05). Furthermore, patients readmitted for vitreous hemorrhage, proliferative membrane formation, and retinal detachment experienced longer length of hospital stay and higher hospitalization cost (p < 0.001). Conclusions: Multiple causes and risk factors contribute to repeated hospitalization, imposing a substantial physical and economic burden on DR patients. A better understanding of these causes and risk factors of readmission may lead to lowering such risks and alleviating patients' burden.

Evaluation of short-term intraocular pressure changes after intravitreal injection of Conbercept in patients with diabetic macular edema.

Background: The study concerning the influence of Conbercept, which is an anti-Vascular endothelial growth factor (VEGF) agent, in intraocular pressure (IOP) spike is limited and warrants further investigation. The current study aimed to investigate the changes of intraocular pressure after intravitreal injection (IVI) of Conbercept and evaluate the risk factors associated with intraocular pressure spikes. Methods: Patients with diabetic macular edema receiving intravitreal injection of 0.05 ml (0.5 mg) Conbercept were involved in the study. All patients underwent slit lamp examination to determine the status of phakia/pseudophakia. The axial length was measured using IOL Master 500 before intravitreal injection. Patients underwent a Conbercept intravitreal injection with a 30-gauge needle in a standard fashion. The intraocular pressure was measured 2 min before injection, and 2, 10, 30 min, 1, 2, 5, 24 h after injection using a rebound tonometer. The changes of intraocular pressure and the relevant risk factors were evaluated. Patients were subdivided into phakic group and pseudophakic group to analyze the effect of lens status on intraocular pressure changes. Results: Forty patients with a mean age of 62.48 ± 12.22 years were included in the study. The mean intraocular pressure values at baseline and 2, 10, 30 min, 1, 2, 5, 24 h after injection were 14.81 ± 3.13 mmHg, 26.80 ± 9.43 mmHg, 18.76 ± 6.16 mmHg, 16.54 ± 5.94 mmHg, 15.64 ± 3.75 mmHg, 14.46 ± 3.03 mmHg, 14.10 ± 1.88 mmHg, 14.23 ± 2.71 mmHg respectively. The intraocular pressure after injection for 2, 10 min was significantly higher than baseline (p < 0.001, p = 0.001, respectively). The intraocular pressure between baseline and post-injection for 30 min or beyond were comparable (all p > 0.05). No significant difference was found between the phakic group and pseudophakic group (p = 0.422). The changes of intraocular pressure were positively correlated with age (r = 0.329, p = 0.038), but negatively with axial length (r = -0.472, p = 0.002). Conclusion: intravitreal injection of Conbercept may cause rapid spike of intraocular pressure, but is safe with respect to short-term changes. The intraocular pressure in patients with older age and shorter axial length is more likely to be higher after intravitreal injection.

Association of Visual Health With Depressive Symptoms and Brain Imaging Phenotypes Among Middle-Aged and Older Adults.

Importance: Vision loss and depression are common conditions with major health implications. However, mechanisms of the association of visual health (across the full acuity spectrum) with depression remain unclear. Objective: To characterize the association between visual health and depression and investigate the association between depression and brain microstructure and macrostructure in subgroups divided by visual acuity. Design, Setting, and Participants: In the UK Biobank Study cohort, 114 583 volunteers were included at baseline from March to June 2006 to July 2010. Habitual distance visual acuity was examined using the logarithm of the minimum angle of resolution (LogMAR) characters. Depression was identified based on Patient Health Questionnaire (PHQ) or through an interview-based psychiatric diagnosis. Subgroup participants completed multimodal magnetic resonance imaging (MRI) of the brain and PHQ evaluation during the imaging visit after 2014. Data were analyzed from May 5 to August 9, 2022. Main Outcomes and Measures: Depression, depressive symptoms, and imaging-derived phenotypes from T1-weighted and diffusion MRI. Results: Of the 114 583 participants from the UK Biobank Study, 62 401 (54.5%) were women, and the mean (SD) age was 56.8 (8.1) years (range, 39-72 years). A 1-line worse visual acuity (0.1 LogMAR increase) was associated with 5% higher odds of depression (odds ratio, 1.05 [95% CI, 1.04-1.07]) after adjustment for age, sex, race and ethnicity, Townsend index, educational qualifications, smoking, alcohol consumption, obesity, physical activity, history of hypertension, diabetes, hyperlipidemia, and family history of depression. Of the 7844 participants eligible for MRI analysis, there were linear associations between PHQ score and the left volume of gray matter in supracalcarine cortex (coefficient, 7.61 [95% CI, 3.90-11.31]) and mean isotropic volume fraction (ISOVF) in the right fornix (cres) and/or stria terminalis (coefficient, 0.003 [95% CI, 0.001-0.004]) after correction for multiple comparison. In addition, their association could be moderated by visual acuity, whereby increased PHQ score was associated with higher ISOVF levels only among those with poorer visual acuity (P = .02 for interaction). Conclusions and Relevance: This study suggests an association between visual health and depression and that the diffusion characteristic of ISOVF in the fornix (cres) and/or stria terminalis is associated with depressive symptoms in participants with poorer visual acuity.

Shared genetic architecture between the two neurodegenerative diseases: Alzheimer's disease and glaucoma.

Background: Considered as the representatives of neurodegenerative diseases, Alzheimer's disease (AD) and glaucoma are complex progressive neuropathies affected by both genetic and environmental risk factors and cause irreversible damages. Current research indicates that there are common features between AD and glaucoma in terms of epidemiology and pathophysiology. However, the understandings and explanations of their comorbidity and potential genetic overlaps are still limited and insufficient. Method: Genetic pleiotropy analysis was performed using large genome-wide association studies summary statistics of AD and glaucoma, with an independent cohort of glaucoma for replication. Conditional and conjunctional false discovery rate methods were applied to identify the shared loci. Biological function and network analysis, as well as the expression level analysis were performed to investigate the significance of the shared genes. Results: A significant positive genetic correlation between AD and glaucoma was identified, indicating that there were significant polygenetic overlaps. Forty-nine shared loci were identified and mapped to 11 shared protein-coding genes. Functional genomic analyses of the shared genes indicate their modulation of critical physiological processes in human cells, including those occurring in the mitochondria, nucleus, and cellular membranes. Most of the shared genes indicated a potential modulation of metabolic processes in human cells and tissues. Furthermore, human protein-protein interaction network analyses revealed that some of the shared genes, especially MTCH2, NDUFS3, and PTPMT1, as well as SPI1 and MYBPC3, may function concordantly. The modulation of their expressions may be related to metabolic dysfunction and pathogenic processes. Conclusion: Our study identified a shared genetic architecture between AD and glaucoma, which may explain their shared features in epidemiology and pathophysiology. The potential involvement of these shared genes in molecular and cellular processes reflects the "inter-organ crosstalk" between AD and glaucoma. These results may serve as a genetic basis for the development of innovative and effective therapeutics for AD, glaucoma, and other neurodegenerative diseases.

Matching Biomedical Ontologies: Construction of Matching Clues and Systematic Evaluation of Different Combinations of Matchers.

BACKGROUND: Ontology matching seeks to find semantic correspondences between ontologies. With an increasing number of biomedical ontologies being developed independently, matching these ontologies to solve the interoperability problem has become a critical task in biomedical applications. However, some challenges remain. First, extracting and constructing matching clues from biomedical ontologies is a nontrivial problem. Second, it is unknown whether there are dominant matchers while matching biomedical ontologies. Finally, ontology matching also suffers from computational complexity owing to the large-scale sizes of biomedical ontologies. OBJECTIVE: To investigate the effectiveness of matching clues and composite match approaches, this paper presents a spectrum of matchers with different combination strategies and empirically studies their influence on matching biomedical ontologies. Besides, extended reduction anchors are introduced to effectively decrease the time complexity while matching large biomedical ontologies. METHODS: In this paper, atomic and composite matching clues are first constructed in 4 dimensions: terminology, structure, external knowledge, and representation learning. Then, a spectrum of matchers based on a flexible combination of atomic clues are designed and utilized to comprehensively study the effectiveness. Besides, we carry out a systematic comparative evaluation of different combinations of matchers. Finally, extended reduction anchor is proposed to significantly alleviate the time complexity for matching large-scale biomedical ontologies. RESULTS: Experimental results show that considering distinguishable matching clues in biomedical ontologies leads to a substantial improvement in all available information. Besides, incorporating different types of matchers with reliability results in a marked improvement, which is comparative to the state-of-the-art methods. The dominant matchers achieve F1 measures of 0.9271, 0.8218, and 0.5 on Anatomy, FMA-NCI (Foundation Model of Anatomy-National Cancer Institute), and FMA-SNOMED data sets, respectively. Extended reduction anchor is able to solve the scalability problem of matching large biomedical ontologies. It achieves a significant reduction in time complexity with little loss of F1 measure at the same time, with a 0.21% decrease on the Anatomy data set and 0.84% decrease on the FMA-NCI data set, but with a 2.65% increase on the FMA-SNOMED data set. CONCLUSIONS: This paper systematically analyzes and compares the effectiveness of different matching clues, matchers, and combination strategies. Multiple empirical studies demonstrate that distinguishing clues have significant implications for matching biomedical ontologies. In contrast to the matchers with single clue, those combining multiple clues exhibit more stable and accurate performance. In addition, our results provide evidence that the approach based on extended reduction anchors performs well for large ontology matching tasks, demonstrating an effective solution for the problem.

Comparisons of Ocular Anatomic Differences of Lens-Subluxated Eye with or without Acute Angle Closure: A Retrospective Study.

PURPOSE: To compare ocular anatomy differences of lens subluxation between eyes with or without acute angle closure (AAC). METHODS: This is a retrospective and case-control study. Sixty cases with mild lens subluxation were recruited. Among them, 30 eyes with acute angle closure were assigned to the AAC group and 30 eyes without AAC were assigned to the non-AAC group. The anterior segment was quantitatively evaluated by ultrasound biomicroscopy (UBM). The axial length (AL) was measured with IOL Master. All patients underwent lens extraction surgery and were followed up for six months. RESULTS: The history of blunt trauma accounted for 22 (73.3%) cases in the AAC group and 21 (70%) cases in the non-AAC group. Fifteen (50%) patients in the AAC group had iridotomy history, and high intraocular pressure recurred. The UBM analysis showed that the average central chamber depth of the affected eyes in the AAC group was 1.82 mm, which was significantly shallower than that in the fellow eyes (2.58 mm, P < 0.05) or both eyes in the non-AAC group.Both eyes in the AAC group presented a shorter AL and shallower anterior chamber than the eyes in the non-AAC group. CONCLUSIONS: An asymmetrical anterior chamber between bilateral eyes is an important feature in lens subluxation-induced AAC. The crowded anterior chamber and shorter AL might be the anatomic basis for the eye with lens subluxation-induced AAC.

Comparison of expression profiling of circular RNAs in vitreous humour between diabetic retinopathy and non-diabetes mellitus patients.

AIMS: To compare circular (circRNA) expression levels in the vitreous humour between PDR (proliferative diabetic retinopathy) and the control groups. METHODS: The present study collected vitreous humour samples of both the PDR group and the control group (composed of rhegmatogenous retinal detachment, idiopathic macular hole and idiopathic macular epiretinal membrane). All the samples were subjected to circRNA and mRNA sequencing as well as bioinformatic analysis. RESULTS: The vitreous humour of the PDR and control groups was collected during PPV surgery. Compared to the control group, 122 upregulated and 9 downregulated circRNAs, and 818 upregulated mRNAs and 864 downregulated mRNAs were identified. We further selected 12 circRNAs to validate the RNA expression level by qPCR; results showed that with the exception of 2 downregulated circRNAs the remaining were significantly upregulated in the PDR group, which was consistent with RNA sequencing results. Bioinformatic analysis was conducted to predict possible miRNAs absorbed by circRNAs. Each circRNA could interact with at least five miRNAs. We randomly chose three miRNAs to test the expression level in the vitreous humour by qPCR and found these miRNAs were significantly downregulated in the PDR group. CONCLUSIONS: The changed profiling of circRNAs in the vitreous humour was reliable and may become a promising biomarker of DR and the circRNA-miRNA-mRNA network. It may also play an important role in the progression of DR.

Comprehensive analysis of vitreous humor chemokines in type 2 diabetic patients with and without diabetic retinopathy.

AIMS: To compare the vitreous levels of chemokines in diabetic patients with and without retinopathy. To find the relationship between stages of diabetic retinopathy (DR) and levels of vitreous chemokines. METHODS: The study involved 20 non-diabetic and 20 diabetic patients without clinical signs of DR (NDR) and 40 diabetic patients with proliferative diabetic retinopathy (PDR). The vitreous humor was collected and the levels of 40 chemokines were measured using magnetic color-bead-based multiplex assay. RESULTS: The control group, NDR group, PDR with vitreous hemorrhage (VH) group, and PDR with tractional retinal detachment group comprised 20, 20, 21, and 19 eyes, respectively. Only the concentration of CCL3 was significantly higher in the NDR group compared with the controls (p = 0.038). Twenty-five types of chemokines were statistically higher in the PDR with VH group in comparison to NDR group (all p < 0.05). All chemokines were statistically higher in the PDR with TRD group in comparison to NDR group (all p < 0.05) apart from 3 chemokines: GM-CSF, MIF, and CCL3(p = 0.086, p = 0.109, p = 0.094, respectively). The concentration of CCL21, CCL15 in PDR with TRD group was significantly higher compared with PDR with VH group, while other 36 chemokines were not significantly different between PDR with VH group and PDR with TRD group. CONCLUSIONS: The inflammation gradually worsen with the progression of DR. CCL3 may be associated with the onset of early diabetic retinal damage, and CCL15 and CCL21 may be closely related to the formation of fibrovascular membrane and the progression of the end stage of DR.