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.

Association of preoperative retinal microcirculation and perioperative outcomes in patients undergoing congenital cardiac surgery.

BACKGROUND: Microcirculatory dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to investigate the association between preoperative retinal microcirculation evaluated using optical coherence tomography angiography (OCTA) and perioperative outcomes in patients with congenital heart disease (CHD). METHODS: This prospective, observational study was performed from May 2017 to January 2021. OCTA was used to automatically quantify the vessel density (VD) of the superficial capillary plexus, deep capillary plexus (DCP), and radial peripapillary capillary (RPC) preoperatively. The primary outcome was excessive postoperative bleeding, defined as bleeding volume > 75th percentile for 24-hour postoperative chest tube output. The secondary outcome was composite adverse outcomes, including one or more operative mortalities, early postoperative complications, and prolonged length of stay. The association between retinal VD and outcomes was assessed using Poisson regression. RESULTS: In total, 173 CHD patients who underwent cardiac surgery were included (mean age, 26 years). Among them, 43 (24.9%) and 46 (26.6%) developed excessive postoperative bleeding and composite adverse outcomes, respectively. A lower VD of DCP (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.08-1.43; P = 0.003) was independently associated with excessive postoperative bleeding, and a lower VD of RPC (OR, 1.97; 95% CI, 1.08-3.57; P = 0.027), and DCP (OR, 2.17; 95% CI, 1.08-4.37; P = 0.029) were independently associated with the postoperative composite adverse outcomes. CONCLUSION: Preoperative retinal hypoperfusion was independently associated with an increased risk of perioperative adverse outcomes in patients with CHD, suggesting that retinal microcirculation evaluation could provide valuable information about the outcomes of cardiac surgery, thereby aiding physicians in tailoring individualized treatment.

Serum cystatin C for risk stratification of prediabetes and diabetes populations.

BACKGROUND: The association between serum cystatin C level and vascular outcomes has not been fully elucidated in diabetes and is unclear in prediabetes. We aim to evaluate whether cystatin C level predicts future risk for mortality and vascular outcomes in prediabetes and diabetes. METHODS: A total of 85,371 participants with prediabetes and diabetes, and available baseline cystatin C in the UK biobank were included with a 14-year follow-up. Cox hazards models were used to calculate the associations between cystatin C level, mortality (all-cause, cause-specfic mortality) and vascular outcomes (myocardial infarction [MI], stroke, end-stage renal disease [ESRD] and diabetic retinopathy [DR]). The 1136 diabetes subjects in Guangzhou Diabetic Eye Study (GDES) were included for examing the impact of cystatin C on in vivo retinal degeneration and microvascular changes by using SS-OCT and OCTA. RESULTS: The highest cystatin C quartile had increased risks of all-cause (hazard ratio [HR], 2.02; 95% confidence interval [CI] 1.86-2.19), cardiovascular (HR, 2.29; 95% CI 1.97-2.67), cancer (HR, 1.86; 95% CI 1.65-2.10) and other-cause mortality (HR, 2.24; 95% CI 1.90-2.64), MI (HR, 1.40; 95% CI 1.26-1.55), stroke (HR, 1.88; 95% CI, 1.57-2.26), ESRD (HR, 7.33; 95% CI, 5.02-10.71), DR (HR, 1.17; 95% CI 1.03-1.32) than those in the lowest quartile. Adding cystatin C to the conventional model improved C-statistic for all-cause (0.699-0.724), cardiovascular (0.762-0.789), cancer (0.661-0.674) and other-cause mortality (0.675-0.715), MI (0.748-0.750), stroke (0.712-0.718), and ESRD (0.808-0.827). The GDES analysis identified a strong association between increased cystatin C levels and diminished retinal neural layers, as well as microvascular rarefaction in both macular and optic disc regions (all P < 0.05). CONCLUSIONS: Serum cystatin C refines the risk stratification for mortality and vascular outcomes among patients with prediabetes or diabetes.

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.

Longitudinal Changes in Choroidal Structure Following Repeated Low-Level Red-Light Therapy for Myopia Control: Secondary Analysis of a Randomized Controlled Trial.

PURPOSE: Repeated low-level red-light (RLRL) therapy has been confirmed as a novel intervention for myopia control in children. This study aims to investigate longitudinal changes in choroidal structure in myopic children following 12-month RLRL treatment. MATERIALS AND METHODS: The current study is a secondary analysis from a multicenter, randomized controlled trial (NCT04073238). Choroidal parameters were derived from baseline and follow-up swept-source optical coherence tomography scans taken at 1, 3, 6, and 12 months. These parameters included the luminal area (LA), stromal area (SA), total choroidal area (TCA; a combination of LA and SA), and choroidal vascularity index (CVI; ratio of LA to TCA), which were automatically measured by a validated custom choroidal structure assessment tool. RESULTS: A total of 143 children (88.3% of all participants) with sufficient image quality were included in the analysis (n=67 in the RLRL and n=76 in the control groups). At the 12-month visit, all choroidal parameters increased in the RLRL group, with changes from baseline of 11.70×10 3  µm 2 (95% CI: 4.14-19.26×10 3  µm 2 ), 3.92×10 3  µm 2 (95% CI: 0.56-7.27×10 3  µm 2 ), 15.61×10 3  µm 2 (95% CI: 5.02-26.20×10 3  µm 2 ), and 0.21% (95% CI: -0.09% to 0.51%) for LA, SA, TCA, and CVI, respectively, whereas these parameters reduced in the control group. CONCLUSIONS: Following RLRL therapy, the choroidal thickening was found to be accompanied by increases in both the vessel LA and SA, with the increase in LA being greater than that of SA. In the control group, with myopia progression, both the LA and SA decreased over time.

Associations of concomitant retinopathy and depression with mortality in a nationally representative population.

OBJECTIVE: To evaluate the interaction effects between retinopathy and depression on mortality risks in genral population and subpopulation with diabetes. METHODS: Prospective analyses were conducted on data from the National Health and Nutrition Examination Surveys study. Associations of retinopathy, depression and their interaction with all-cause, cardiovascular disease (CVD)-specific, cancer-specific and other-specific mortality risk were estimated using Kaplan-Meier curves and multivariate Cox proportional hazards models. RESULTS: Among 5367 participants, the weighted prevalence of retinopathy and depression was 9.6 % and 7.1 %, respectively. After a follow-up period of 12.1 years, 1295 deaths (17.3 %) occurred. Retinopathy was associated with an increased risk of all-cause (hazard ratio [HR]; 95 % confidence interval [CI]) (1.47; 1.27-1.71), CVD-specific (1.87; 1.45-2.41), and other-specific (1.43; 1.14-1.79) mortality. Similar relationship was observed between depression and all-cause mortality (1.24; 1.02-1.52). Retinopathy and depression had a positive multiplicative and additive interaction effect on all-cause (Pinteraction = 0.015; relative excess risk of interaction [RERI] 1.30; 95 % CI 0.15-2.45) and CVD-specific mortality (Pinteraction = 0.042; RERI 2.65; 95 % CI -0.12-5.42). Concomitant retinopathy and depression was more markedly associated with all-cause (2.86; 1.91-4.28), CVD-specific (4.70; 2.57-8.62), and other-specific mortality risks (2.18; 1.14-4.15) compared to those without retinopathy and depression. These associations were more pronounced in the diabetic participants. CONCLUSIONS: The co-occurrence of retinopathy and depression increases the risk of all-cause and CVD-specific mortality among middle-aged and older adults in the United States, especially in population with diabetes. Focus on diabetic patients and active evaluation and intervention of retinopathy with depression may improve their quality of life and mortality outcomes.

Association between cardiovascular health metrics and retinal ageing.

The study aims to investigate associations between cardiovascular health (CVH) metrics and retinal ageing indexed by retinal age gap. A total of 26,354 participants from the UK Biobank study with available CVH metrics and qualified retinal imaging were included in the present analysis. CVH included 7 metrics (smoking, physical activity, diet, body mass index [BMI], total cholesterol, blood pressure [BP], blood glucose). These were summarized to classify the overall CVH as poor (0-7), intermediate (8-10) or ideal (11-14). Retinal age gap was defined as the difference between biological age predicted by fundus images and chronological age. Accelerated and non-accelerated retinal ageing was defined if retinal age gap was in the upper or lower 50% quantiles of the study population, respectively. Linear and logistic regression models estimated the association of overall CVH and each metric of CVH with retinal age gap respectively. Our results showed that in the fully adjusted model, each one-unit score increase in overall CVH was negatively associated with retinal age gap (odds ratio [OR] = 0.89, 95% confidence interval [CI]: 0.87-0.92, P < 0.001). Compared with poor overall CVH, people with intermediate and ideal overall CVH had significantly lower retinal age gap (OR = 0.76, 95%CI: 0.67-0.85, P < 0.001; OR = 0.58, 95%CI: 0.50-0.67, P < 0.001). Similar associations were found between overall CVH and accelerated retinal ageing. CVH metrics including smoking, BMI, BP, and blood glucose were also significantly associated with higher retinal age gap. Taken together, we found a significant and inverse dose-response association between CVH metrics and retinal age gap, indicating that maintaining healthy metrics especially smoking, BMI, BP, and blood glucose may be crucial to slow down biological ageing.

The Association between Dietary Iron Intake and Incidence of Dementia in Adults Aged 60 Years or over in the UK Biobank.

Background Several studies have investigated the association between dietary iron intake and cognitive impairment, but little is known about the relationship between iron intake and dementia incidence. Objectives This study explored the association between dietary iron intake and incident dementia in males and females. Whether this association was modified by factors such as age and medical diseases was also examined. Methods We included 41,213 males and 48,892 females aged 60 years or over, from the UK-Biobank cohort. Dietary iron intake was measured using a web-based 24-h dietary recall questionnaire from between 2009 and 2012. Incident dementia was ascertained using hospital inpatient records and death registers until April 2021. Cox proportional regression models examined the association between iron intake and incident dementia, and hazard ratio curves were constructed with knots from the analysis indicating insufficient or excessive iron intake. Results During a mean follow-up of 11.8 years, 560 males and 492 females developed dementia. A non-linear relationship between iron intake and incident dementia was observed in both males and females. The lowest incidence rates were observed in the higher iron intake quintile (Q4: ≥15.73, <17.57 mg/day) for males, and the intermediate iron intake quintile (Q3: ≥12.4, <13.71 mg/day) for females. Among those aged 60 and above, all-cause dementia in males was associated with deficient iron intake (Q1 versus Q4: Hazard ratio [HR]: 1.37, 95% Confidence interval [95%CI]: 1.01−1.86, p = 0.042) and excessive iron intake (Q5 versus Q4: HR: 1.49, 95%CI: 1.14−1.96, p = 0.003), whilst significant associations between all-cause dementia and deficient iron intake were only observed in females without hypertension. Smoking status was a significant moderator (p-value for trend = 0.017) for dementia in males only. Conclusions Excessive iron intake (≥17.57 mg/day) is associated with a higher incidence of all-cause dementia in males and smoking status modified this association amongst males. Deficient iron intake (<10.93 mg/day) was associated with a higher incidence of all-cause dementia in females without a history of hypertension.

From bench to clinic: Emerging therapies for corneal scarring.

Corneal diseases are one of the leading causes of moderate-to-severe visual impairment and blindness worldwide, after glaucoma, cataract, and retinal disease in overall importance. Given its tendency to affect people at a younger age than other blinding conditions such as cataract and glaucoma, corneal scarring poses a huge burden both on the individuals and society. Furthermore, corneal scarring and fibrosis disproportionately affects people in poorer and remote areas, making it a significant ophthalmic public health problem. Traditional medical strategies, such as topical corticosteroids, are not effective in preventing fibrosis or scars. Corneal transplantation, the only effective sight-restoring treatment for corneal scars, is curbed by challenges including a severe shortage of tissue, graft rejection, secondary conditions, cultural barriers, the lack of well-trained surgeons, operating rooms, and well-equipped infrastructures. Thanks to tremendous research efforts, emerging therapeutic options including gene therapy, protein therapy, cell therapy and novel molecules are in development to prevent the progression of corneal scarring and compliment the surgical options currently available for treating established corneal scars in clinics. In this article, we summarise the most relevant preclinical and clinical studies on emerging therapies for corneal scarring in recent years, showing how these approaches may prevent scarring in its early development.

Retinal age gap as a predictive biomarker for mortality risk.

AIM: To develop a deep learning (DL) model that predicts age from fundus images (retinal age) and to investigate the association between retinal age gap (retinal age predicted by DL model minus chronological age) and mortality risk. METHODS: A total of 80 169 fundus images taken from 46 969 participants in the UK Biobank with reasonable quality were included in this study. Of these, 19 200 fundus images from 11 052 participants without prior medical history at the baseline examination were used to train and validate the DL model for age prediction using fivefold cross-validation. A total of 35 913 of the remaining 35 917 participants had available mortality data and were used to investigate the association between retinal age gap and mortality. RESULTS: The DL model achieved a strong correlation of 0.81 (p<0·001) between retinal age and chronological age, and an overall mean absolute error of 3.55 years. Cox regression models showed that each 1 year increase in the retinal age gap was associated with a 2% increase in risk of all-cause mortality (hazard ratio (HR)=1.02, 95% CI 1.00 to 1.03, p=0.020) and a 3% increase in risk of cause-specific mortality attributable to non-cardiovascular and non-cancer disease (HR=1.03, 95% CI 1.00 to 1.05, p=0.041) after multivariable adjustments. No significant association was identified between retinal age gap and cardiovascular- or cancer-related mortality. CONCLUSIONS: Our findings indicate that retinal age gap might be a potential biomarker of ageing that is closely related to risk of mortality, implying the potential of retinal image as a screening tool for risk stratification and delivery of tailored interventions.

Self-reported cataract surgery and 10-year all-cause and cause-specific mortality: findings from the National Health and Nutrition Examination Survey.

PURPOSE: To investigate the association of self-reported cataract surgery with all-cause and cause-specific mortality using a large-scale population-based sample. METHODS: Data from the 1999-2008 cycles of the National Health and Nutrition Examination Survey were used. A self-reported history of cataract surgery was considered a surrogate for the presence of clinically significant cataract surgery. Mortality data were ascertained from National Death Index records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for survival were estimated using Cox proportional hazards regression models. RESULTS: A total of 14 918 participants were included in the analysis. During a median follow-up of 10.8 (Interquartile range, IQR, 8.25-13.7) years, 3966 (19.1%) participants died. Participants with self-reported cataract surgery were more likely to die from all causes and specific causes (vascular disease, cancer, accident, Alzheimer's disease, respiratory disease, renal disease and others) compared with those without (all Ps <0.05). The association between self-reported cataract surgery and all-cause mortality remained significant after multiple adjustments (HR=1.13; 95% CI 1.01 to 1.26). For cause-specific mortality, multivariable Cox models showed that self-reported cataract surgery predicted a 36% higher risk of vascular-related mortality (HR=1.36; 95% CI 1.01 to 1.82). The association with other specific causes of mortality did not reach statistical significance after multiple adjustments. CONCLUSIONS: This study found significant associations of self-reported cataract surgery with all-cause and vascular mortalities. Our findings provide potential insights into the pathogenic pathways underlying cataract.

Parapapillary Choroidal Microvasculature Predicts Diabetic Retinopathy Progression and Diabetic Macular Edema Development: A Three-Year Prospective Study.

PURPOSE: To determine the predictive value of the microcirculation of the optic nerve head by swept-source optical coherence tomography angiography for identifying individuals with high risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. DESIGN: Prospective observational cohort study. METHODS: A total of 946 patients (1879 eyes) with type 2 diabetes mellitus were recruited who had no DR or mild nonproliferative DR at baseline, and no DME. All subjects underwent 3 × 3 mm swept-source optical coherence tomography angiography centered on the optic nerve head to generate angiograms in 4 layers: radial peripapillary plexus, superficial retinal capillary plexus (SCP), deep retinal capillary plexus, and choriocapillaris (CC). The CC flow deficit percentage (CC FD%), vessel density (VD), and perfusion density (PD) were quantified. RESULTS: During the 3 consecutive years of follow-up, 312 eyes (16.60%) experienced DR progression and 115 eyes (6.12%) developed DME. The DR progression was related to a lower VD of the SCP (relative risk per standard deviation decrease, 95% confidence interval): 1.30, 1.14-1.48; P < .001), a lower PD of the SCP (1.41, 1.24-1.60; P < .001), a lower VD of the radial peripapillary plexus (1.23, 1.08-1.40; P = .002), and an elevated CC FD% (1.62, 1.40-1.88; P < .001). The DME occurrence was associated with a lower VD of SCP (1.35, 1.09-1.66; P = .005), a lower PD of SCP (1.29, 1.05-1.59; P = .016), and a higher CC FD% (1.29, 1.03-1.61; P < .001). The CC FD% significantly improved the predictive power, with the increase of the C-statistic for DR progression and DME occurrence by 3.83% (P = .002) and 5.24% (P < .001), respectively. CONCLUSIONS: This study provides the first longitudinal evidence suggesting that peripapillary CC FD% can improve the prediction of DR progression and DME development beyond traditional risk factors.

Choriocapillaris Flow Deficit as a Biomarker for Diabetic Retinopathy and Diabetic Macular Edema: 3-Year Longitudinal Cohort.

PURPOSE: To investigate the relationship between choriocapillaris flow deficit percentage (CC FD%) by swept-source optical coherence tomography angiography (SS-OCTA) and 3-year risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. DESIGN: Prospective, observational cohort study. METHODS: A total of 903 participants with type 2 diabetes mellitus (T2DM) without DR or with mild nonproliferative DR (NPDR) free of DME at baseline were followed up annually for 3 years. All participants underwent standard 7-field fundus photography and spectral-domain OCT. SS-OCTA was used for retinal and choriocapillaris imaging and 3 × 3-mm2 macular CC FD% was quantified. Univariate and multivariate logistic models were used to evaluate the association between CC FD% and 2 or more steps of DR progression and DME development. The additional predictive value of CC FD% for outcome events was assessed using C statistic, net reclassification index (NRI), and integrated discrimination improvement index (IDI). RESULTS: Over 3 years, 295 of 1805 eyes (16.34%) developed DR progression, and 118 eyes (6.54%) developed DME. A higher average CC FD% was correlated with DR progression (odds ratio [OR], 3.41 per SD increase, 95% CI: 2.65-4.39, P < .001) and DME development (OR, 1.37 per SD increase, 95% CI: 1.06-1.77, P = .016) after adjusting for confounders. In the ETDRS regions, increased CC FD% in all fields was associated with DR progression; however, increased CC FD% in the inferior field was associated with DME development. Compared with the models based on established risk factors, the addition of average CC FD% significantly improved the C statistics for DR progression (0.712 to 0.777, P < .001) and DME occurrence (0.743 to 0.773, P = .044). The estimated NRIs and IDIs (all >0) indicated that the addition of CC FD% led to a significant improvement in the discriminative performance for end points. CONCLUSION: CC FD% is independently associated with DR progression and DME development in the Chinese T2DM population and provides incremental predictive value beyond traditional risk factors and retinal microvascular parameters. Further inclusion of CC FD% in DR prediction models helps guide population-based screening and personalized management.

Association of antioxidants use with the risk of dementia among community-dwelling adults in the United Kingdom biobank.

Background: Data regarding the association between antioxidant supplementation and incident dementia are limited. Methods: We included 494,632 adults (54.5% females) aged 40-71 years at baseline from the United Kingdom Biobank in the final analysis. Incident dementia was ascertained using hospital inpatient and death records up to January 2021. Results: Over a median follow-up of 11.9 years, 7,128 new cases of all-cause dementia, 2,772 cases of Alzheimer's disease, and 1,397 cases of vascular dementia were recorded. The hazard ratio (95% CI) for incident dementia associated with zinc supplementation was 0.84 (0.74-0.96), and the association remained significant after adjusting for all confounders (0.84 (0.74-0.96)). In the full model, zinc supplementation was associated with a reduced risk of Alzheimer's disease [HR (95% CI): 0.71 (0.57-0.88)]. There was no significant association between zinc supplementation and the risk of vascular dementia. No significant associations with incident dementia were observed for other antioxidant supplementation. The association between zinc supplementation and incident dementia was significant among individuals with [HR (95% CI): 0.34 (0.15-0.77)] and without cataract [0.87 (0.77-0.99)] but it was stronger among those with cataract (p value for interaction = 0.0271). Conclusion: Our findings suggest that zinc supplementation may help reduce the risk of all-cause dementia and Alzheimer's disease in middle-aged or older adults, especially among those with cataracts.

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.

Diabetes mellitus and incident glaucoma in Australia: a 10-year cohort study from the 45 and Up Study.

Background: Understanding the relationship between diabetes mellitus (DM) and the severity of glaucoma is important for the primary prevention of incident glaucoma. This paper aims to examine the association between DM and incident glaucoma. Methods: The 45 and Up Study is a prospective cohort study where Australians aged ≥45 years old were enrolled. The incident of glaucoma at follow-up is the main outcome measured. Glaucoma incidence was identified as those with recorded glaucoma-related medication from the Pharmaceutical Benefits Scheme or surgery recorded in the Medicare Benefits Schedule. Patients with glaucoma were classified into the medical glaucoma group (with glaucoma-related medication but not surgery) and the surgical glaucoma group (with glaucoma-related surgery). A Cox regression model was used to calculate the hazard ratios (HRs) to examine the association between baseline DM and the risk of developing glaucoma during the follow-up period. The reference groups are as follows: (I) non-DM participant; (II) participant with DM, duration between 0 and 5 years; (III) participant uses insulin. Results: A total of 255,547 eligible participants, with no glaucoma diagnosis at baseline, were included. During the follow-up period, 7,667 patients (3.0%) were identified as medical glaucoma only and 2,326 patients (0.9%) underwent glaucoma surgery. After controlling for confounders, baseline DM was associated with an increased risk of glaucoma in the medical glaucoma group only [hazard ratio (HR) =1.36, 95% confidence interval (CI) =1.07-1.72, P=0.002]. However, baseline DM (HR =0.97, 95% CI =0.57-1.65, P=0.979) was not associated with an increased risk of surgical glaucoma. Conclusions: DM was associated with an increased risk of medical glaucoma only, there was no association identified with surgical glaucoma in the Australian population recruited in the 45 and Up Study.

Geographical Inequality on Cataract Surgery Uptake in 200,000 Australians: Findings from the "45 and Up Study".

Using a geographical information system (GIS), we investigated the spatiotemporal evolution of a cataract surgery service and its association with socioeconomic factors and private insurance, based on 10-year real-world medical claim data in an Australian population. The data collected cover a decade (2007-2016) from the "45 and Up Study". A total of 234,201 participants within the cataract surgery service were grouped into 88 Statistical Area Level 3 (SA3s) according to their residential postcodes in New South Wales Australia. We analyzed the spatiotemporal variations and geographical distribution inequality in cataract surgery incidence and its respect to socioeconomic status (SES) and private health insurance coverage by Spearman correlation analysis and Moran's I test. Then these variations were intuitive displayed by six-quartile maps and a local indicator of spatial association (LISA) maps based on GIS. The average cumulative age-gender-standardized of the incidence of cataract surgery (ICS) was 8.85% (95% CI, 5.33-15.6). Spatial variation was significant (univariate Moran's I = 0.45, P = 0.001) with incidence gradually decreasing from the coastal regions to the north-western inland regions, suggesting inequality in the cataract surgery service across the state of New South Wales. Notably, clustering of the low incidence areas had gradually disappeared over the decade, suggesting that the cataract surgery service has improved over time. Low scores on the "index of socioeconomic disadvantages" (IRSD) and high private health insurance coverage were significantly associated with a higher incidence of cataract surgery (bivariate Moran's I = -0.13 and 0.23, P < 0.01; Spearman correlation r = 0.25 and -0.25, P = 0.02), which is displayed on the map visually and obviously. Spatiotemporal variations in the incidence of cataract surgery are significant, but the low incidence area had gradually disappeared over time. High socioeconomic status and private insurance contribute to a higher incidence of cataract surgery in Australia.

Association of Myopia With Risk of Incident Metabolic Syndrome: Findings From the UK Biobank Study Cohort of 91,591 Participants.

Purpose: To investigate the association between myopia and risk of metabolic syndrome (MetS) in a prospective cohort from the UK Biobank Study. Methods: Volunteers (aged 40 years and above) free of baseline MetS and cataract included from the UK Biobank Study, a prospective follow-up cohort. Myopia was defined using uncycloplegic autorefraction, self-report-myopia, and medical records for refractive error at baseline. MetS as well as components of MetS were diagnosed based on health records, blood biochemistry, and questionnaires. Questionnaires determined the status of smoking, drinking, physical activity and dietary supplements, as well as ethnicity and education. Results: A total of 91,591 participants were available in the analysis, with a mean age of 55.37 ± 8.07 years at baseline and a median follow-up years of 11.16 years. The proportion of myopia was 49.7%, and a total of 937 (1.0%) participants were identified as having incident MetS (0.09/100 person years). Subjects with myopia were more likely to have MetS compared with non-myopic subjects (0.82 vs. 0.21%, Log-rank test P < 0.001). Mopes had greater risk of incident MetS (Hazard ratio [HR] = 4.19, 95% confidence interval [CI] 3.57-4.93, P < 0.001) adjusting for baseline age, gender, education and ethnicity. After further controlling for lifestyle factors (smoking, drinking, physical activity, and fish oil supplement) or baseline metabolic disorders, the risk of incident MetS were 3.88- and 4.06-fold greater in myopic subjects than those without myopia, respectively (P < 0.001 for both models). The severity of myopia was not significantly correlated to incident MetS in multivariate-adjusted models. Conclusions: An increased risk of incident MetS among the elderly is associated with myopia, but not the degree of myopia. These findings highlighted the need of prevention of MetS among older adults with myopia.