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.

Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults.

Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98-2.27; OR, 2.03; 95% CI, 1.86-2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.

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.

Difference of central foveal thickness measurement in patients with macular edema using optical coherence tomography in different display modes.

Purpose: To assess the differences in the measurement of central foveal thickness (CFT) in patients with macular edema (ME) between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT). Design: This is a retrospective, cross-sectional study. Methods: Group A consisted of participants with well-horizontal OCT B-scan images and group B consisted of participants with tilted OCT B-scan. We manually measured the CFT under the two display modes, and the values were compared statistically using the paired t-test. Spearman's test was used to assess the correlations between the OCT image tilting angle (OCT ITA) and the differences in CFT measurement. The area under the curve (AUC) was calculated to define the OCT ITA cutoff for a defined CFT difference. Results: In group A, the mean CFT in the 1:1 pixel display mode was 420.21 ± 130.61 µm, similar to the mean CFT of 415.27 ± 129.85 µm in the 1:1 micron display mode. In group B, the median CFT in the 1:1 pixel display mode is 409.00 µm (IQR: 171.75 µm) and 368.00 µm (IQR: 149.00 µm) in the 1:1 micron display mode. There were significant differences between the two display modes with the median (IQR) absolute difference and median (IQR) relative difference of 38.00 µm (75.00 µm) and 10.19% (21.91%) (all p = 0.01). The differences in CFT measurement between the two display modes were correlated with the OCT ITA (absolute differences, r = 0.88, p < 0.01; relative differences, r = 0.87, p < 0.01). The AUC for a predefined CFT difference was 0.878 (10 µm), 0.933 (20 µm), 0.938 (30 µm), 0.961 (40 µm), 0.962 (50 µm), and 0.970 (60 µm). Conclusion: In patients with DM, when the OCT B-scan images were well-horizontal, manual CFT measurements under the two display modes were similar, but when the B-scan images were tilted, the CFT measurements were different under the two display modes, and the differences were correlated to the OCT ITA.

Alterations of outer retinal reflectivity in diabetic patients without clinically detectable retinopathy.

PURPOSE: This study aimed to investigate alterations of outer retinal reflectivity on spectral-domain optical coherence tomography (OCT) in diabetic patients without clinically detectable retinopathy (NDR). METHODS: In this retrospective study, 64 NDR patients and 71 controls were included. Relative reflectivity (RR) of the ellipsoid zone (EZ), photoreceptor outer segment (OS) and inner segment (IS), and outer nuclear layer (ONL) at the foveola and at 500 µm, 1000 µm, and 2000 µm nasal (N), temporal (T), superior (S), and inferior (I) to the foveola was measured by cross-line OCT and ImageJ. Retinal vessel densities (VD) in fovea, parafovea, and perifovea areas were detected by OCT angiography (OCTA). RESULTS: EZ RR in most retinal locations was significantly lower in NDR eyes compared to controls (all P < 0.05), except the foveola. Compared with controls, NDR eyes also displayed lower RR at N2000, T2000, S1000, and I1000 of OS, at S500 and I500 of IS, and at I500 of ONL (all P < 0.05). Negative correlations could be observed between retinal RR and diabetes duration, HbA1c, and best-corrected visual acuity (BCVA) (r = - 0.303 to - 0.452). Compared to controls, EZ, OS, and IS RR of the NDR eyes showed lower correlation coefficients with whole image SCP and DCP VD of parafovea and perifovea regions. CONCLUSION: Outer retinal reflectivity, along with the coefficients between retinal reflectivity and VD, is reduced in NDR patients and is correlated with diabetes duration, HbA1c, and BCVA. The reduction of outer retinal reflectivity may be a potential biomarker of early retinal alterations in diabetic patients.

Determinants of incident atherosclerotic cardiovascular disease events among individuals with type 2 diabetic microvascular complications in the UK: a prospective cohort study.

OBJECTIVE: To evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications. METHODS: We included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006-2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD. RESULTS: We studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32-0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications. CONCLUSION: HDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up.

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.

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.

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.

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.

Corrigendum: Risk factors of falls in elderly patients with visual impairment.

[This corrects the article DOI: 10.3389/fpubh.2022.984199.].

Associations of vision impairment and eye diseases with frailty in community-dwelling older adults: a nationwide longitudinal study in China.

AIMS: To test whether vision impairment and major ophthalmic conditions are predictive of frailty. METHODS: The analysis included 5321 participants aged 60-95 years at baseline from the China Health and Retirement Longitudinal Study. Participants were enrolled in 2011 and followed up in 2013, and 2015 through a face-to-face interview. Distance/near vision impairment was defined by reporting poor eyesight and reporting excellent, very good, good or fair eyesight was used as the reference. A history of cataract surgery and glaucoma were also self-reported. Frailty was defined as the presence of ≥3 of the five components of the Fried phenotype: weakness, slowness, exhaustion, inactivity and shrinking. RESULTS: In the cross-sectional analysis, both near (odds ratio [OR] (95% confidence interval [CI]): 1.62 (1.30 to 2.00)) and distance (1.59 (1.30 to 1.96)) vision impairment was associated with a higher prevalence of frailty independent of confounders. In the longitudinal analysis, the multivariable-adjusted OR (95% CI) for incident frailty associated with glaucoma, distance vision impairment, near vision impairment and vision problem was 3.41 (1.46 to 7.99), 1.59 (1.17 to 2.17), 1.62 (1.17 to 2.23) and 2.11 (1.41 to 3.15), respectively. Vision problem was associated with decreased handgrip strength (ß (95% CI): -1.47 (-2.20 to -0.75) kg) during follow-up. Individuals with glaucoma (-0.11 (-0.16 to -0.05) m/s), distance vision impairment (-0.02 (-0.03 to 0.00) m/s) or vision problem (-0.02 (-0.05 to 0.00) m/s) had decreased gait speed compared with the control group. CONCLUSIONS: Vision problem, vision impairment and glaucoma are important predictors of frailty in older adults.

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.

Risk factors of falls in elderly patients with visual impairment.

Objective: To examine the risk factors for falls in elderly patients with visual impairment (VI) and assess the predictive performance of these factors. Methods: Between January 2019 and March 2021, a total of 251 elderly patients aged 65-92 years with VI were enrolled and then prospectively followed up for 12 months to evaluate outcomes of accidental falls via telephone interviews. Information of demographics and lifestyle, gait and balance deficits, and ophthalmic and systemic conditions were collected during baseline visits. Forward stepwise multivariable logistic regression analysis was performed to identify independent risk factors of falls in elderly patients with VI, and a derived nomogram was constructed. Results: A total of 143 falls were reported in 251 elderly patients during follow-up, with an incidence of 56.97%. The risk factors for falls in elderly patients with VI identified by multivariable logistic regression were women [odds ratio (OR), 95% confidence interval (CI): 2.71, 1.40-5.27], smoking (3.57, 1.34-9.48), outdoor activities/3 months (1.31, 1.08-1.59), waking up frequently during the night (2.08, 1.15-3.79), disorders of balance and gait (2.60, 1.29-5.24), glaucoma (3.12, 1.15-8.44), other retinal degenerations (3.31, 1.16-9.43) and best-corrected visual acuity (BCVA) of the better eye (1.79, 1.10-2.91). A nomogram was developed based on the abovementioned multivariate analysis results. The area under receiver operating characteristic curve of the predictive model was 0.779. Conclusions: Gender, smoking, outdoor activities, waking up at night, disorders of balance and gait, glaucoma, other retinal degeneration and BCVA of the better eye were independent risk factors for falls in elderly patients with VI. The predictive model and derived nomogram achieved a satisfying prediction of fall risk in these individuals.

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.

Retinal Neurovascular Changes in Patients With Ischemic Stroke Investigated by Optical Coherence Tomography Angiography.

Background: To investigate retinal neurovascular structural changes in patients with ischemic stroke (IS) using optical coherence tomography angiography (OCTA). Materials and Methods: The cross-sectional study was conducted in Guangdong Provincial People's Hospital, China, consisting of 159 eyes from IS patients and 109 eyes from age-matched control subjects. Retinal microvascular parameters including the vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and radial peripapillary capillary (RPC), and neural parameters such as ganglion cell complex thickness (GCCt) and retinal nerve fibre layer thickness (RNFLt) were measured by OCTA. Results: The VD of SCP and DCP in the macular area were significantly reduced in IS patients compared to the control group (all p < 0.001). The VD of RPC at the optic disc was also significantly reduced in IS patients (all p < 0.05). IS patients showed reduced GCCt and RNFLt and increased GCC focal loss volume and global loss volume compared with the controls (all p < 0.05). Among patients with IS, the parafovea SCP VD was positively correlated with GCCt (r = 0.346-0.408, all p < 0.001) but not with DCP VD (all p > 0.1). In the optic disc region, the whole image RPC VD was positively correlated with mean RNFLt (r = 0.467-0.548, all p < 0.001). Conclusion: Reduction of retinal VD, GCCt and RNFLt was observed in patients with IS. The parafovea SCP VD and RPC VD were positively correlated with GCCt and RNFLt, respectively.

The Distribution Pattern of Ocular Residual Astigmatism in Chinese Myopic Patients.

Purpose: We aimed to investigate the distribution of ocular residual astigmatism (ORA) and its associations with age, gender, manifest refraction, and other ocular indicators in Chinese patients with myopia. Design: This is a multi-center retrospective cross-sectional study. Method: The study included 7,893 patients with myopia (7,893 eyes) aged 18-40 years from five ophthalmic centers. Anterior segment biometrics of the eyes were collected from the Pentacam. ORA and its summated vector mean were calculated using Alpins vector analysis. Compensation factor (CF) was used to evaluate the relation between ORA and corneal astigmatism. ORA in different age, gender, and refraction groups was compared. The Spearman correlation was adopted to reveal multiple ocular indicators associated with ORA, which were integrated into a multiple linear regression model to predict ORA. Results: Distribution of ORA was slightly positively skewed (Skewness= 2.111, Kurtosis = 19.660, KS P < 0.0001). Mean ORA was 0.74 ± 0.39 D (95% normal range: 0.14-1.54 D). Among all the subjects, 22.4% of the eyes had an ORA magnitude of 1.0 D or more. Undercompensation or full-compensation of anterior corneal astigmatism (ACA) by ORA prevailed in both J0 (76.99%) and J45 (58.48%). Women had higher ORA power than men (0.77 ± 0.36 D vs. 0.73 ± 0.41 D, P < 0.0001). Participants with less negative spherical equivalent (SE) or higher manifest astigmatism (MA) also had higher ORA (all P < 0.0001). ORA was significantly correlated with ACA (r = 0.405) and posterior corneal astigmatism (PCA, r = 0.356). The multivariate logistic regression analysis showed strong predictability of ORA magnitude >1.0 D using anterior segment parameters (area under the receiver operating characteristic curve: 0.739). Conclusion: ORA is present in Chinese adults with myopia and is affected by multiple ocular factors. Our findings may provide valuable information about ORA distribution in candidates for refractive surgery, helping optimize the outcome of astigmatism correction.

Retinal Neurovascular Impairment in Non-diabetic and Non-dialytic Chronic Kidney Disease Patients.

Background: Widespread neural and microvascular injuries are common in chronic kidney disease (CKD), increasing risks of neurovascular complications and mortality. Early detection of such changes helps assess the risks of neurovascular complications for CKD patients. As an extension of central nervous system, the retina provides a characteristic window to observe neurovascular alterations in CKD. This study aimed to determine the presence of retinal neurovascular impairment in different stages of CKD. Methods: One hundred fifteen non-diabetic and non-dialytic CKD patients of all stages and a control group of 35 healthy subjects were included. Retinal neural and microvascular parameters were obtained by optical coherence tomography angiography (OCTA) examination. Results: CKD 1-2 group (versus control group) had greater odds of having decreased retinal ganglion cell-inner plexiform layer thickness (GC-IPLt) (odds ratio [OR]: 0.92; 95% confidence interval [CI]: 0.86-0.98), increased ganglion cell complex-focal loss volume (GCC-FLV) (OR: 3.51; 95% CI: 1.27-9.67), and GCC-global loss volume (GCC-GLV) (OR: 2.48; 95% CI: 1.27-4.82). The presence of advanced stages of CKD (CKD 3-5 group versus CKD 1-2 group) had greater odds of having decreased retinal vessel density in superficial vascular plexus (SVP)-WholeImage (OR: 0.77, 95% CI: 0.63-0.92), SVP-ParaFovea (OR: 0.83, 95% CI: 0.71-0.97), SVP-ParaFovea (OR: 0.76, 95% CI: 0.63-0.91), deep vascular plexus (DVP)-WholeImage (OR: 0.89, 95% CI: 0.81-0.98), DVP-ParaFovea (OR: 0.88, 95% CI: 0.78-0.99), and DVP-PeriFovea (OR: 0.90, 95% CI: 0.83-0.98). Besides, stepwise multivariate linear regression among CKD patients showed that ß2-microglobulin was negatively associated with GC-IPLt (ß: -0.294; 95% CI: -0.469 ∼ -0.118), and parathyroid hormone was positively associated with increased GCC-FLV (ß: 0.004; 95% CI: 0.002∼0.006) and GCC-GLV (ß: 0.007; 95% CI: 0.004∼0.01). Urine protein to creatinine ratio was positively associated with increased GCC-FLV (ß: 0.003; 95% CI: 0.001∼0.004) and GCC-GLV (ß: 0.003; 95% CI: 0.001∼0.006). Conclusion: Retinal neuronal impairment is present in early stages of CKD (stages 1-2), and it is associated with accumulation of uremic toxins and higher UACR, while retinal microvascular hypoperfusion, which is associated with worse eGFR, was only observed in relatively advanced stages of CKD (stages 3-5). The results highlight the importance of monitoring retinal neurovascular impairment in different stages of CKD.

Distribution of White-to-White Corneal Diameter and Anterior Chamber Depth in Chinese Myopic Patients.

Purpose: To investigate the distribution of white-to-white (WTW) corneal diameter and anterior chamber depth (ACD) in Chinese myopia patients. Methods: This was a cross-sectional observational study conducted at five ophthalmic centers. Anterior segment biometry was performed in 7,893 eyes of the 7,893 myopic patients using Pentacam, and the WTW and ACD were recorded. The distribution patterns of WTW and ACD were evaluated and the correlation between WTW and ACD was analyzed statistically. Results: There were 4416 (55.95%) males and 3477 (44.05%) females. The age of the study population was 25.14 ± 5.41 years. Distribution of WTW was slightly positively skewed (Skewness = 0.0076, Kurtosis = 0.3944, KS P = 0.020) with a mean of 11.65 ± 0.38 mm and a 95% normal range of 10.91-12.39 mm. A significant difference in WTW was found among different myopia groups (P < 0.001). The ACD was normally distributed (Skewness = 0.899, Kurtosis = 0.027, KS P = 0.086). The mean ACD was 3.25 ± 0.26 mm and the 95% normal range of was 2.74-3.75 mm. A significant difference in ACD was also found among different myopia groups (P = 0.030). There was a significant correlation between WTW and ACD (r = 0.460, P < 0.001). Conclusions: In our study, 95% of the Chinese myopic patients had a WTW within 10.91-12.39 mm and an ACD within 2.74-3.75 mm. ACD and WTW were significantly different among different myopia, gender and age groups. WTW was positively correlated with ACD.