Global, regional, and national burden of blindness and vision loss attributable to high fasting plasma glucose from 1990 to 2019, and forecasts to 2030: A systematic analysis for the Global Burden of Disease Study 2019.

AIMS: To systematically clarify the spatiotemporal trends, and age-sex-specific blindness and vision loss (BVL) burden due to high fasting plasma glucose (HFPG) from 1990 to 2019, and project this burden over the next decade. MATERIALS AND METHODS: We obtained the number and rate of years lived with disability (YLDs) for the BVL burden attributable to HFPG by age, sex, socio-demographic index (SDI), and location between 1990 and 2019 from the Global Burden of Disease (GBD) 2019 database. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of HFPG-attributable BVL burden. The Bayesian age-period-cohort model was used to predict the HFPG-attributable BVL burden. RESULTS: In 2019, the global number and age-standardized rate (ASR) for YLDs of BVL attributable to HFPG were 673.13 (95% UI: 159.52 to 1565.34) thousand and 8.44 (95% UI: 2.00 to 19.63) per 100,000 people, respectively. The highest burdens were found in Oceania, South Asia, and Southeast Asia, and the BVL burden due to HFPG was higher in the elderly and lower SDI regions. From 1990 to 2019, the global ASR of HFPG-attributable BVL gradually increased with AAPC (95% CI) being 0.80 (0.74 to 0.86). In addition, the HFPG-attributable BVL burden will slightly increase in the future decade. CONCLUSIONS: The HFPG remains the important cause of BVL worldwide, placing a substantial disease burden. From 1990 to 2019, the age-standardized burden of BVL due to HFPG increased, and will consistently increase in the future decade, particularly in the elderly and in regions with middle SDI or below.

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.

Shared genetic aetiology of Alzheimer's disease and age-related macular degeneration by APOC1 and APOE genes.

Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) share similar pathological features, suggesting common genetic aetiologies between the two. Investigating gene associations between AD and AMD may provide useful insights into the underlying pathogenesis and inform integrated prevention and treatment for both diseases. Methods: A stratified quantile-quantile (QQ) plot was constructed to detect the pleiotropy among AD and AMD based on genome-wide association studies data from 17 008 patients with AD and 30 178 patients with AMD. A Bayesian conditional false discovery rate-based (cFDR) method was used to identify pleiotropic genes. UK Biobank was used to verify the pleiotropy analysis. Biological network and enrichment analysis were conducted to explain the biological reason for pleiotropy phenomena. A diagnostic test based on gene expression data was used to predict biomarkers for AD and AMD based on pleiotropic genes and their regulators. Results: Significant pleiotropy was found between AD and AMD (significant leftward shift on QQ plots). APOC1 and APOE were identified as pleiotropic genes for AD-AMD (cFDR <0.01). Network analysis revealed that APOC1 and APOE occupied borderline positions on the gene co-expression networks. Both APOC1 and APOE genes were enriched on the herpes simplex virus 1 infection pathway. Further, machine learning-based diagnostic tests identified that APOC1, APOE (areas under the curve (AUCs) >0.65) and their upstream regulators, especially ZNF131, ADNP2 and HINFP, could be potential biomarkers for both AD and AMD (AUCs >0.8). Conclusion: In this study, we confirmed the genetic pleiotropy between AD and AMD and identified APOC1 and APOE as pleiotropic genes. Further, the integration of multiomics data identified ZNF131, ADNP2 and HINFP as novel diagnostic biomarkers for AD and AMD.

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.

Global burden of all cause-specific injuries among children and adolescents from 1990 to 2019: a prospective cohort study.

BACKGROUND: To assess the burden and change in incidence, death, and disability-adjusted life years (DALYs) for all-cause-specific injuries among children and adolescents in 204 countries and territories between 1990 and 2019. MATERIALS AND METHODS: Data were extracted from the Global Burden of Disease, Injury, and Risk Factor Study 2019 (GBD 2019). Global, regional, and country-level age-standardized rate (per 100 000) of incidence (ASRI), mortality (ASRM), and DALYs (ASRD) with 95% uncertainty interval (95% UI) of injuries were estimated by age, sex, socio-demographic index (SDI), and all-cause-specific injuries from 1990 to 2019. RESULTS: Overall, the ASRI, ASRM, and ASRD of injury were 9006.18 (95% UI: 7459.74-10 918.04), 23.04 (20.00-26.50), and 2020.19 (1759.47-2318.64) among children and adolescents worldwide in 2019, respectively. All the above indicators showed a downward trend from 1990 to 2019. In level 2 cause of injury, both the global transport injury and unintentional injury declined during the study years, while self-harm and interpersonal violence-related injury showed an increasing trend. High SDI regions had higher ASRI of injuries, but low SDI regions had higher ASRM and ASRD of injuries globally in 2019. Males had a higher burden of injuries than those in females. The ASRI of injuries is higher in adolescents aged 15-19 years, whereas the mortality and DALYs rate are higher among children under 5 years old. Moreover, adolescents aged 15-19 years and individuals living in Central Asia, Middle East, and Africa had higher ASRI, ASRM, and ASRD of injuries owing to self-harm and interpersonal violence. Generally, falls and road traffic injuries are the leading cause of injury among the population aged 0-19 years worldwide, but self-harm, interpersonal violence, and conflict and terrorism are also leading types of injuries in some regions, particularly in Low-Income Countries and Middle-Income Countries. CONCLUSIONS: Injury remains a major global public health problem among children and adolescents, although its burden at the worldwide level showed a decreasing trend from 1990 to 2019. Of concern, the burden of injuries caused by transport injuries, and unintentional injuries has shown a downward trend in most countries, while the burden caused by self-harm and interpersonal violence has shown an upward trend in most countries. These findings suggest that more targeted and specific strategies to prevent the burden of injuries should be reoriented, and our study provides important findings for decision-makers and healthcare providers to reduce injury burden among children and adolescents.

Metabolomic age and risk of 50 chronic diseases in community-dwelling adults: A prospective cohort study.

It is unclear how metabolomic age is associated with the risk of a wide range of chronic diseases. Our analysis included 110,692 participants (training: n = 27,673; testing: n = 27,673; validating: n = 55,346) aged 39-71 years at baseline (2006-2010) from the UK Biobank. Incident chronic diseases were identified using inpatient records, or death registers until January 2021. Predicted metabolomic age was trained and tested based on 168 metabolomics. Metabolomic age was linked to the risk of 50 diseases in the validation dataset. The median follow-up duration for individual diseases ranged from 11.2 years to 11.9 years. After controlling for false discovery rate, chronological age-adjusted age gap (CAAG) was significantly associated with the incidence of 25 out of 50 chronic diseases. After adjustment for full covariates, associations with 15 chronic diseases remained significant. Greater CAAG was associated with increased risk of eight cardiometabolic disorders (including cardiovascular diseases and diabetes), some cancers, alcohol use disorder, chronic obstructive pulmonary disease, chronic kidney disease, chronic liver disease and age-related macular degeneration. The association between CAAG and risk of peripheral vascular disease, other cardiac diseases, fracture, cataract and thyroid disorder was stronger among individuals with unhealthy diet than in those with healthy diet. The association between CAAG and risk of some conditions was stronger in younger individuals, those with metabolic disorders or low education. Metabolomic age plays an important role in the development of multiple chronic diseases. Healthy diet and high education may mitigate the risk for some chronic diseases due to metabolomic age acceleration.

Global, regional and national burden of retinopathy of prematurity among childhood and adolescent: a spatiotemporal analysis based on the Global Burden of Disease Study 2019.

BACKGROUND: This study aimed to provide a comprehensive assessment of burden estimates and the secular trend of vision loss due to retinopathy of prematurity (ROP) among people younger than 20 years, at the global, regional and national levels. METHODS: Data were obtained from the Global Burden of Disease Study 2019 database. The average annual percentage change (AAPC) was calculated to quantify the temporal trends in the measures of vision loss. RESULTS: In 2019, the global age-standardised rates (ASRs) of prevalence per 100 000 population was 86.4 for vision loss, specifically, 35 for moderate vision loss, 19.9 for severe vision loss, 31.6 for blindness due to ROP among people younger than 20 years. Moreover, the ASR of years lived with disability per 100 000 was 10.6 for vision loss, specifically, 1.1 for moderate vision loss, 3.6 for severe vision loss, 5.9 for blindness, respectively. From 1990 to 2019, the ASR of prevalence of blindness and vision loss due to ROP significantly increased, while its burden slightly decreased. Males showed higher ASR of prevalence than females in 2019, whereas females have larger increasing trend than males from 1990 to 2019. The global highest ASR of disease burden was observed in South Asia and Southern sub-Saharan Africa, as well as low sociodemographic index (SDI) regions in 2019. CONCLUSIONS: Globally, although the burden decreased, the prevalence of childhood and adulthood vision loss due to ROP continues to increase. Reasonable resource allocation and advanced intervention are recommended to prevent and control the vision loss due to ROP.

Mapping the global, regional, and national burden of diarrheal diseases attributable to unsafe water.

Background: Diarrheal diseases are major contributors to deaths. Data on global and country-specific levels and trends of diarrheal diseases resulting from unsafe water are essential for policymakers to allocate resources. Aims: This study aimed to describe the global, regional, and national spatiotemporal burden of diarrheal diseases resulting from unsafe water exposure. Methods: According to the Global Burden of Disease (GBD) 2019 dataset, deaths, disability-adjusted life years (DALYs) of diarrheal diseases, and their age-standardized rates (ASRs) were analyzed by age and sex in 204 countries and territories. Moreover, the average annual percentage change (AAPC) was estimated by a log-linear regression model to reflect the time trend. The association between ASR of diarrheal diseases due to unsafe water and socio-demographic index (SDI) levels was also analyzed. Results: From 1990 to 2019, the number of deaths and DALYs of diarrheal diseases resulting from unsafe water decreased by 50 and 59%, respectively. Moreover, the ASR of deaths and DALYs also decreased during the study period, with AAPCs of -3.69 (95% CI [95% confidence interval]: -3.91 to -3.47) and - 3.66 (95% CI: -3.8 to -3.52), respectively. High diarrheal diseases resulting from unsafe water occurred mainly in low SDI regions and Africa. Males exhibited greater diarrheal deaths attributable to unsafe water than females, which was contrary to the condition in terms of DALYs. The age-specific burden of diarrheal deaths attributable to unsafe water is concentrated in children younger than 5 years. The AAPCs of the ASR of both deaths and DALYs showed a strong negative correlation with the SDI levels. Conclusion: The current study indicated that the global burden of unsafe water exposure-related diarrheal diseases decreased from 1990 to 2019 and varied significantly according to age, sex, and geographical location. Effective health promotion and health communication strategies and policies should be adopted to prevent and control diarrheal diseases resulting from unsafe water exposure.

Translation of Color Fundus Photography into Fluorescein Angiography Using Deep Learning for Enhanced Diabetic Retinopathy Screening.

Purpose: To develop and validate a deep learning model that can transform color fundus (CF) photography into corresponding venous and late-phase fundus fluorescein angiography (FFA) images. Design: Cross-sectional study. Participants: We included 51 370 CF-venous FFA pairs and 14 644 CF-late FFA pairs from 4438 patients for model development. External testing involved 50 eyes with CF-FFA pairs and 2 public datasets for diabetic retinopathy (DR) classification, with 86 952 CF from EyePACs, and 1744 CF from MESSIDOR2. Methods: We trained a deep-learning model to transform CF into corresponding venous and late-phase FFA images. The translated FFA images' quality was evaluated quantitatively on the internal test set and subjectively on 100 eyes with CF-FFA paired images (50 from external), based on the realisticity of the global image, anatomical landmarks (macula, optic disc, and vessels), and lesions. Moreover, we validated the clinical utility of the translated FFA for classifying 5-class DR and diabetic macular edema (DME) in the EyePACs and MESSIDOR2 datasets. Main Outcome Measures: Image generation was quantitatively assessed by structural similarity measures (SSIM), and subjectively by 2 clinical experts on a 5-point scale (1 refers real FFA); intragrader agreement was assessed by kappa. The DR classification accuracy was assessed by area under the receiver operating characteristic curve. Results: The SSIM of the translated FFA images were > 0.6, and the subjective quality scores ranged from 1.37 to 2.60. Both experts reported similar quality scores with substantial agreement (all kappas > 0.8). Adding the generated FFA on top of CF improved DR classification in the EyePACs and MESSIDOR2 datasets, with the area under the receiver operating characteristic curve increased from 0.912 to 0.939 on the EyePACs dataset and from 0.952 to 0.972 on the MESSIDOR2 dataset. The DME area under the receiver operating characteristic curve also increased from 0.927 to 0.974 in the MESSIDOR2 dataset. Conclusions: Our CF-to-FFA framework produced realistic FFA images. Moreover, adding the translated FFA images on top of CF improved the accuracy of DR screening. These results suggest that CF-to-FFA translation could be used as a surrogate method when FFA examination is not feasible and as a simple add-on to improve DR screening. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Healthy dietary patterns and the risk of individual chronic diseases in community-dwelling adults.

It is unclear regarding associations of dietary patterns with a wide range of chronic diseases and which dietary score is more predictive of major chronic diseases. Using the UK Biobank, we examine associations of four individual healthy dietary scores with the risk of 48 individual chronic diseases. Higher Alternate Mediterranean Diet score is associated with a lower risk of 32 (all 8 cardiometabolic disorders, 3 out of 10 types of cancers, 7 out of 10 psychological/neurological disorders, 5 out of 6 digestive disorders, and 9 out of 14 other chronic diseases). Alternate Healthy Eating Index-2010 and Healthful Plant-based Diet Index are inversely associated with the risk of 29 and 23 individual chronic diseases, respectively. A higher Anti-Empirical Dietary Inflammatory Index is associated with a lower risk of 14 individual chronic diseases and a higher incidence of two diseases. Our findings support dietary guidelines for the prevention of most chronic diseases.

The global incidence and disability of eye injury: an analysis from the Global Burden of Disease Study 2019.

Background: The aim of the present study was to estimate the incidence, years lived with disability (YLDs), and cause of eye injury at global, regional, and national levels by age and sex based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods: This is a retrospective demographic analysis based on aggregated data. GBD 2019 included the burden of eye injury worldwide and its temporal and spatial characteristics in the past three decades. The Bayesian meta-regression tool and DisMod-MR 2.1 were used to analyse the estimates based on a linear regression mode of the age-standardised rates (ASR). Average annual percent change (AAPC) was calculated to represent the temporal trends of the ASR. Findings: Globally, there were 59,933.29 thousand (95% uncertainty interval [UI]: 45,772.34-77,084.03) incident cases and 438.4 thousand (95% UI: 132.44-898.38) YLDs of eye injury in 2019. Both the ASR of incidence and YLDs decreased from 1990 to 2019, with AAPC -0.46 (95% confidence interval [CI]: -0.52 to -0.39) and -0.45 (95% CI: -0.52 to -0.39), respectively. Males had higher rates of incidence and YLDs in all age groups. Young and middle-aged adults had higher disease burdens. Regionally, Australasia had the highest ASR of YLDs to be 9.51 (95% UI: 3.00-19.58) per 100,000. Nationally, New Zealand had the highest burden of eye injury to be 11.33 (95% UI: 3.57-23.10) per 100,000. Foreign bodies, exposure to mechanical forces, and falls were the main causes of global eye injury burden in 2019, and there was an increased worldwide burden due to road injuries and executions and police conflict compared with 1990. Interpretation: Our findings suggest that the incidence and burden of eye injury have decreased over the last 30 years, while the absolute number of eye injuries has substantially increased, representing a major public health concern. Males and young adults were affected to a greater degree than females and elder individuals. More attention should be paid to road injuries and executions and police conflict in order to prevent eye injury. Funding: Guangdong Provincial People's Hospital (GDPH) Supporting Fund for Talent Program (KY0120220263).

Prevalence, incidence, deaths, and disability-adjusted life-years of drug use disorders for 204 countries and territories during the past 30 years.

Drug use disorders are increasingly recognized as the main cause of public health issues worldwide. The current analysis aims to provide the most comprehensive, updated estimates of the burden from drug use disorders at global, regional, and national levels during the past three decades. Prevalence, incidence, deaths, and disability-adjusted life-years (DALYs) were estimated from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 by age and sex for drug use disorder as well as its four main categories (opioid use disorders, cocaine use disorders, amphetamine use disorders, and cannabis use disorders) in 204 countries and territories between 1990 and 2019. DisMod-MR 2.1, and Bayesian meta-regression were used to analyze prevalence and incidence, while the Cause of Death Ensemble model (CODEm) was used to estimate death of diseases. Globally, the burden of drug use disorders, as measured by the average annual percentage change (AAPC) of deaths and DALYs, continues to increase. The patterns by regions of DALYs due to drug use disorders varied significantly, and it is mainly in developed countries and concentrated among young people and males. Programs for drug use disorders management should be improved, particularly in opioid use disorders. Governments will face increasing demand for treatment and support services, and effective prevention as well as control strategies are required to reduce the burden from these causes.

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.

Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms.

Objective: Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from retinal fundus images can reflect systemic vascular properties and therefore were hypothesized to provide valuable information on detecting the risk of aneurysms. By integrating oculomics with genomics, this study aimed to (i) identify predictive RVFs as imaging biomarkers for aneurysms and (ii) evaluate the value of these RVFs in supporting early detection of aneurysms in the context of predictive, preventive and personalized medicine (PPPM). Methods: This study involved 51,597 UK Biobank participants who had retinal images available to extract oculomics of RVFs. Phenome-wide association analyses (PheWASs) were conducted to identify RVFs associated with the genetic risks of the main types of aneurysms, including abdominal aortic aneurysm (AAA), thoracic aneurysm (TAA), intracranial aneurysm (ICA) and Marfan syndrome (MFS). An aneurysm-RVF model was then developed to predict future aneurysms. The performance of the model was assessed in both derivation and validation cohorts and was compared with other models employing clinical risk factors. An RVF risk score was derived from our aneurysm-RVF model to identify patients with an increased risk of aneurysms. Results: PheWAS identified a total of 32 RVFs that were significantly associated with the genetic risks of aneurysms. Of these, the number of vessels in the optic disc ('ntreeA') was associated with both AAA (ß = -0.36, P = 6.75e-10) and ICA (ß = -0.11, P = 5.51e-06). In addition, the mean angles between each artery branch ('curveangle_mean_a') were commonly associated with 4 MFS genes (FBN1: ß = -0.10, P = 1.63e-12; COL16A1: ß = -0.07, P = 3.14e-09; LOC105373592: ß = -0.06, P = 1.89e-05; C8orf81/LOC441376: ß = 0.07, P = 1.02e-05). The developed aneurysm-RVF model showed good discrimination ability in predicting the risks of aneurysms. In the derivation cohort, the C-index of the aneurysm-RVF model was 0.809 [95% CI: 0.780-0.838], which was similar to the clinical risk model (0.806 [0.778-0.834]) but higher than the baseline model (0.739 [0.733-0.746]). Similar performance was observed in the validation cohort, with a C-index of 0.798 (0.727-0.869) for the aneurysm-RVF model, 0.795 (0.718-0.871) for the clinical risk model and 0.719 (0.620-0.816) for the baseline model. An aneurysm risk score was derived from the aneurysm-RVF model for each study participant. The individuals in the upper tertile of the aneurysm risk score had a significantly higher risk of aneurysm compared to those in the lower tertile (hazard ratio = 17.8 [6.5-48.8], P = 1.02e-05). Conclusion: We identified a significant association between certain RVFs and the risk of aneurysms and revealed the impressive capability of using RVFs to predict the future risk of aneurysms by a PPPM approach. Our finds have great potential to support not only the predictive diagnosis of aneurysms but also a preventive and more personalized screening plan which may benefit both patients and the healthcare system. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00315-7.

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).

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.