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Aims/hypothesis The aim of the study was to examine the association of retinal vessel morphometry with BP, body composition and biochemistry, and to determine whether these associations differ by diabetes status. Methods The UK Biobank ocular assessment included 68,550 participants aged 40-70 years who underwent non-mydriatic retinal photography, BP and body composition measurements, and haematological analysis. A fully automated image analysis program provided measurements of retinal vessel diameter and tortuosity. The associations between retinal vessel morphology and cardiometabolic risk factors by diabetes status were examined using multilevel linear regression, to provide absolute differences in vessel diameter and percentage differences in tortuosity (allowing for within-person clustering). Results A total of 50,233 participants (a reduction from 68,550) were included in these analyses. Overall, those with diabetes had significantly more tortuous venules and wider arteriolar diameters compared with those without. Associations between venular tortuosity and cardiometabolic risk factors differed according to diabetes status (p interaction 1c, C-reactive protein, white cell count and granulocyte count. For example, a unit rise in white cell count was associated with a 0.18% increase (95% CI 0.05, 0.32%) in venular tortuosity for those without diabetes and a 1.48% increase (95% CI 0.90, 2.07%) among those with diabetes. For arteriolar diameter, significant interactions were evident for systolic BP, diastolic BP, mean arterial pressure (MAP) and LDL-cholesterol. For example, a 10 mmHg rise in systolic BP was associated with a −0.92 μm difference (95% CI −0.96 to −0.88 μm) in arteriolar diameter for those without diabetes, and a −0.58 μm difference (95% CI −0.76 to −0.41 μm) among those with diabetes. No interactions were observed for arteriolar tortuosity or venular diameters. Conclusions/interpretation We provide clear evidence of the modifying effect of diabetes on cardiometabolic risk factor associations with retinal microvascular architecture. These observations suggest the occurrence of preclinical disease processes, and may be a sign of impaired autoregulation due to hyperglycaemia, which has been suggested to play a pivotal role in the development of diabetes-related microvascular complications. Data Availability The data supporting the results reported here are available through the UK Biobank (https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). Graphical abstract

Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

Purpose: To investigate the association of commonly used systemic medications with glaucoma and intraocular pressure (IOP) in the European population. Design: Meta-analysis of eleven population-based cohort studies of the European Eye Epidemiology (E3) consortium. Participants: A total of 143240 participants were included in the glaucoma analyses and 47177 participants in the IOP analyses. Methods: We examined associations of four categories of systemic medications (antihypertensive medications: beta-blockers, diuretics, calcium channel blockers [CCBs], alpha-agonists, angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers; lipid-lowering medications; antidepressants; antidiabetic medications) with glaucoma prevalence and IOP. Glaucoma ascertainment and IOP measurement method were according to individual study protocols. Multivariable regression analyses were carried out in each study and results were pooled using random effects meta-analyses. Associations with antidiabetic medications were examined in diabetic participants only. Main Outcome Measures: Glaucoma prevalence and IOP. Results: In the meta-analyses of our maximally-adjusted multivariable models, use of CCBs was associated with a higher prevalence of glaucoma (odds ratio [OR] with corresponding 95% confidence interval [95% CI]: 1.23 [1.08 to 1.39]). This association was stronger for monotherapy of CCBs with direct cardiac effects (OR [95% CI]: 1.96 [1.23 to 3.12]). The use of other antihypertensive medications, lipid-lowering medications, antidepressants or antidiabetic medications were not clearly associated with glaucoma. Use of systemic beta-blockers was associated with a lower IOP (Beta [95% CI]: -0.33 [-0.57 to -0.08] mmHg). Monotherapy of both selective (Beta [95% CI]: -0.45 [-0.74 to -0.16] mmHg) and non-selective (Beta [95% CI]: -0.54 [-0.94 to -0.15] mmHg) systemic beta-blockers was associated with lower IOP. There was a suggestive association between use of high-ceiling diuretics and lower IOP (Beta [95% CI]: -0.30 [-0.47; -0.14] mmHg), but not when used as monotherapy. Use of other antihypertensive medications, lipid-lowering medications, antidepressants, or antidiabetic medications were not associated with IOP. Conclusions: We identified a potentially harmful association between use of CCBs and glaucoma prevalence. Additionally, we observed and quantified the association of lower IOP with systemic beta-blocker use. Both findings are potentially important given that glaucoma patients frequently use systemic antihypertensive medications. Determining whether the CCB association is causal should be a research priority. published

ImportanceLaser peripheral iridotomy (LPI) is the most common primary treatment for primary angle closure disease (PACD). However, there are sparse data guiding the longitudinal care of PAC suspect (PACS) eyes after LPI.ObjectiveTo elucidate the anatomic effects of LPI that are associated with a protective outcome against progression from PACS to PAC and acute angle closure (AAC) and to identify biometric factors that predict progression after LPI.Design, Setting, and ParticipantsThis was a retrospective analysis of data from the Zhongshan Angle Closure Prevention (ZAP) trial, a study of mainland Chinese people aged 50 to 70 years with bilateral PACS who received LPI in 1 randomly selected eye. Gonioscopy and anterior-segment optical coherence tomography (AS-OCT) imaging were performed 2 weeks after LPI. Progression was defined as the development of PAC or an acute angle closure (AAC) attack. Cohort A included a random mix of treated and untreated eyes, and cohort B included only eyes treated with LPI. Univariable and multivariable Cox regression models were developed to assess biometric risk factors for progression in cohorts A and B. Data were analyzed from January 4 to December 22, 2022.Main Outcome and MeasureSix-year progression to PAC or AAC.ResultsCohort A included 878 eyes from 878 participants (mean [SD] age, 58.9 [5.0] years; 726 female [82.7%]) of whom 44 experienced progressive disease. In a multivariable analysis, treatment (hazard ratio [HR], 0.67; 95% CI, 0.34-1.33; P = .25) was no longer associated with progression after adjusting for age and trabecular iris space area at 500 μm (TISA at 500 μm) at the 2-week visit. Cohort B included 869 treated eyes from 869 participants (mean [SD] age, 58.9 [5.0] years; 717 female [82.5%]) of whom 19 experienced progressive disease. In multivariable analysis, TISA at 500 μm (HR, 1.33 per 0.01 mm2 smaller; 95% CI, 1.12-1.56; P = .001) and cumulative gonioscopy score (HR, 1.25 per grade smaller; 95% CI, 1.03-1.52; P = .02) at the 2-week visit were associated with progression. Persistent angle narrowing on AS-OCT (TISA at 500 μm ≤0.05 mm2; HR, 9.41; 95% CI, 3.39-26.08; P P =.04) conferred higher risk of progression.Conclusions and RelevanceStudy results suggest that persistent angle narrowing detected by AS-OCT or cumulative gonioscopy score was predictive of disease progression in PACS eyes after LPI. These findings suggest that AS-OCT and gonioscopy may be performed to identify patients at high risk of developing angle closure who may benefit from closer monitoring despite patent LPI.

Purpose To assess baseline ocular biometric risk factors for progression from primary angle closure suspect (PACS) to primary angle closure (PAC) or acute angle closure (AAC). Design Prospective, observational study. Participants Six hundred forty-three mainland Chinese with untreated PACS. Methods Participants underwent baseline clinical examinations, including gonioscopy, anterior segment OCT (AS-OCT) imaging, and A-scan ultrasound biometry as part of the Zhongshan Angle Closure Prevention (ZAP) Trial. Primary angle closure suspect was defined as an inability to visualize pigmented trabecular meshwork in 2 or more quadrants based on static gonioscopy. Primary angle closure was defined as development of intraocular pressure above 24 mmHg or peripheral anterior synechiae. Progression was defined as development of PAC or an AAC attack. Multivariable logistic regression models were developed to assess biometric risk factors for progression. Main Outcome Measures Six-year progression from PACS to PAC or AAC. Results Six hundred forty-three untreated eyes (609 nonprogressors, 34 progressors) of 643 participants were analyzed. In a multivariable model with continuous parameters, narrower horizontal angle opening distance of 500 μm from the scleral spur (AOD500; odds ratio [OR], 1.10 per 0.01-mm decrease; P = 0.03), flatter horizontal iris curvature (IC; OR, 1.96 per 0.1-mm decrease; P = 0.01), and older age (OR, 1.11 per 1-year increase; P = 0.01) at baseline were associated significantly with progression (area under the receiver operating characteristic curve [AUC], 0.73). Smaller cumulative gonioscopy score was not associated with progression (OR, 1.03 per 1-modified Shaffer grade decrease; P = 0.85) when replacing horizontal AOD500 in the multivariable model. In a separate multivariable model with categorical parameters, participants in the lowest quartile of horizontal AOD500 (OR, 3.10; P = 0.002) and IC (OR, 2.48; P = 0.014) measurements and 59 years of age or older (OR, 2.68; P = 0.01) at baseline showed higher odds of progression (AUC, 0.72). Conclusions Ocular biometric measurements can help to risk-stratify patients with early angle closure for more severe disease. Anterior segment OCT measurements of biometric parameters describing the angle and iris are predictive of progression from PACS to PAC or AAC, whereas gonioscopy grades are not.

Purpose To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). Design Prospective, randomized controlled trial. Participants This multicenter, randomized controlled trial ( ClinicalTrials.gov identifier, NCT00347178 ) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). Methods Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. Main Outcome Measures The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. Results Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37–0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03–1.10; P Conclusions In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.

Background/aimsMarkers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness.MethodsLeveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also used to determine: (1) the relationship between: (A) glycated haemoglobin (HbA1c) irrespective of diabetes diagnosis and pRNFL thickness, (B) diabetes and pRNFL thickness and (2) which quadrants of pRNFL may be affected in participants with diabetes and in relation to HbA1c.Results7076 participants were included. After controlling for covariates, inferior pRNFL thickness was 0.94 µm lower (95% CI −1.28 µm to −0.60 µm), superior pRNFL thickness was 0.83 µm lower (95% CI −1.17 µm to −0.49 µm) and temporal pRNFL thickness was 1.33 µm higher (95% CI 0.99 µm to 1.67 µm) per unit increase in HbA1c. Nasal pRNFL thickness was not significantly associated with HbA1c (p=0.23). Similar trends were noted when diabetes was used as the predictor.ConclusionSuperior and inferior pRNFL was significantly thinner among those with higher HbA1c levels and/or diabetes, representing areas of the pRNFL that may be most affected by diabetes.

We report the sensitivity and specificity of van Herick (VH) grading in detecting gonioscopically-defined primary angle closure suspects (PACS) among subjects screened for participation in a population-based trial in southern China. A cut-off of VH≤25% was found to have sensitivity and specificity rates of 98.2% and 25.9%, respectively. Rates were adjusted for missing gonioscopy data, resulting in a sensitivity and specificity of 92.5% and 61.5%, respectively.

PURPOSE: To assess anatomic changes after laser peripheral iridotomy (LPI) and predictors of angle widening based on anterior segment (AS) OCT and angle opening based on gonioscopy. DESIGN: Prospective observational study. PARTICIPANTS: Primary angle-closure suspects (PACSs) 50 to 70 years of age. METHODS: Participants of the Zhongshan Angle Closure Prevention (ZAP) Trial underwent gonioscopy and AS-OCT imaging at baseline and 2 weeks after LPI. Primary angle-closure suspect was defined as the inability to visualize pigmented trabecular meshwork in 2 or more quadrants on static gonioscopy. Laser peripheral iridotomy was performed on 1 eye per patient in superior (between 11 and 1 o'clock) or temporal or nasal locations (at or below 10:30 or 1:30 o'clock). Biometric parameters in horizontal and vertical AS-OCT scans were measured and averaged. Linear and logistic regression modeling were performed to determine predictors of angle widening, defined as change in mean angle opening distance measured at 750 μm from the scleral spur (AOD750); poor angle widening, defined as the lowest quintile of change in mean AOD750; and poor angle opening, defined as residual PACS after LPI based on gonioscopy. MAIN OUTCOME MEASURES: Anatomic changes and predictors of angle widening and opening after LPI. RESULTS: Four hundred fifty-four patients were included in the analysis. Two hundred nineteen underwent superior LPI and 235 underwent temporal or nasal LPI. Significant changes were found among most biometric parameters (P < 0.006) after LPI, including greater AOD750 (P < 0.001). One hundred twenty eyes (26.4%) showed residual PACS after LPI. In multivariate regression analysis, superior LPI location (P = 0.004), smaller AOD750 (P < 0.001), and greater iris curvature (P < 0.001), were predictive of greater angle widening. Temporal or nasal LPI locations (odds ratio [OR], 2.60, P < 0.001) was predictive of poor angle widening. Smaller mean gonioscopy grade (OR, 0.34, 1-grade increment) was predictive of poor angle opening. CONCLUSIONS: Superior LPI location results in significantly greater angle widening compared with temporal or nasal locations in a Chinese population with PACS. This supports consideration of superior LPI locations to optimize anatomic changes after LPI.

Purpose: Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP). Design: Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts. Participants: We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009. Methods: Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc). Main Outcome Measures: Corneal-compensated IOP. Results: Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06–0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08–0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05–0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07–0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03–0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06–0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (–0.05 mmHg; 95% CI, –0.08 to –0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30). Conclusions: Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

AimsTo assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects.MethodsParticipants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression.ResultsA mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement).ConclusionA smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease.Trial registration numberISRCTN45213099.

To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts.Longitudinal, observational study.We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years.Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status.Incident cataract surgery.There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively.Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.

Background/aimsTo investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population.MethodsWe included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis.ResultsBetween studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication.ConclusionOur study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD.

AimsWe examine whether inclusion of Artificial Intelligence (AI)-enabled retinal vasculometry (RV) improves existing risk algorithms for incident stroke, myocardial infarction (MI) and circulatory mortality.MethodsAI-enabled retinal vessel image analysis processed images from 88,052 UK Biobank (UKB) participants (aged 40-69 years at image capture) and 7,411 EPIC-Norfolk participants (aged 48-92). Retinal arteriolar and venular width, tortuosity and area were extracted. Prediction models were developed in UKB using multivariable Cox proportional hazards regression for circulatory mortality, incident stroke and MI, and externally validated in EPIC-Norfolk. Model performance was assessed using optimism adjusted calibration, C- and R2 statistics. Performance of Framingham risk scores (FRS) for incident stroke and incident MI, with addition of RV to FRS, were compared with a simpler model based on RV, age, smoking status and medical history (antihypertensive/cholesterol lowering medication, diabetes, prevalent stroke/MI).ResultsUKB prognostic models were developed on 65,144 participants (mean age 56.8; median follow-up 7.7 years) and validated in 5,862 EPIC-Norfolk participants (67.6, 9.1 years respectively). Prediction models for circulatory mortality in men and women had optimism adjusted C- and R2 statistics between 0.75-0.77 and 0.33-0.44 respectively. For incident stroke and MI, addition of RV to FRS did not improve model performance in either cohort. However, the simpler RV model performed equally or better than FRS.ConclusionRV offers an alternative predictive biomarker to traditional risk-scores for vascular health, without the need for blood sampling or blood pressure measurement. Further work is needed to examine RV in population screening to triage individuals at high-risk. (250 words)HIGHLIGHTSWhat is already known on this topicPopulation screening for MI and stroke using risk prediction tools exist but have limited uptake; risk scores for circulator mortality do not exist.What this study addsRisk models developed in UK Biobank (validated in EPIC-Norfolk) using Artificial Intelligence (AI)-enabled retinal vasculometry (RV), age, history of cardiovascular disease, use of hypertensive medication and smoking yielded high predictive test performance for circulatory mortality.Risk scores for MI and stroke performed similarly to established risk scores.How this study might affect research, practice or policyAI-enabled RV extraction offers a non-invasive prognostic biomarker of vascular health that does not require blood sampling or blood pressure measurement, and potentially has greater community reach to identify individuals at medium-high risk requiring further clinical assessment.SYNOPSIS/PRECISRisk models developed in UK Biobank (validated in EPIC-Norfolk) using Artificial Intelligence enabled retinal vasculometry indices, age, history of cardiovascular disease, use of hypertensive medication and smoking yielded high predictive test performance for circulatory mortality. Risk scores for MI and stroke performed similarly to established risk scores.

This study aims to describe the grading methods and baseline characteristics for UK Biobank (UKBB) participants who underwent retinal imaging in 2009-2010, and to characterise individuals with retinal features suggestive of age-related macular degeneration (AMD), glaucoma and retinopathy.Non-mydriatic colour fundus photographs and macular optical coherence tomography (OCT) scans were manually graded by Central Administrative Research Facility certified graders and quality assured by clinicians of the Network of Ophthalmic Reading Centres UK. Captured retinal features included those associated with AMD (≥1 drusen, pigmentary changes, geographic atrophy or exudative AMD; either imaging modality), glaucoma (≥0.7 cup-disc ratio, ≥0.2 cup-disc ratio difference between eyes, other abnormal disc features; photographs only) and retinopathy (characteristic features of diabetic retinopathy with or without microaneurysms; either imaging modality). Suspected cases of these conditions were characterised with reference to diagnostic records, physical and biochemical measurements.Among 68,514 UKBB participants who underwent retinal imaging, the mean age was 57.3 years (standard deviation 8.2), 45.7% were men and 90.6% were of White ethnicity. A total of 64,367 participants had gradable colour fundus photographs and 68,281 had gradable OCT scans in at least one eye. Retinal features suggestive of AMD and glaucoma were identified in 15,176 and 2184 participants, of whom 125 (0.8%) and 188 (8.6%), respectively, had a recorded diagnosis. Of 264 participants identified to have retinopathy with microaneurysms, 251 (95.1%) had either diabetes or hypertension.This dataset represents a valuable addition to what is currently available in UKBB, providing important insights to both ocular and systemic health.

This systematic review and meta-analysis summarizes evidence relating to the prevalence of diabetic retinopathy (DR) among Indigenous and non-Indigenous Australians.Indigenous Australians suffer disproportionately from diabetes-related complications. Exploring ethnic variation in disease is important for equitable distribution of resources and may lead to identification of ethnic-specific modifiable risk factors. Existing DR prevalence studies comparing Indigenous and non-Indigenous Australians have shown conflicting results.This study was conducted following Joanna Briggs Institute guidance on systematic reviews of prevalence studies (PROSPERO ID: CRD42022259048). We performed searches of Medline (Ovid), EMBASE, and Web of Science until October 2021, using a strategy designed by an information specialist. We included studies reporting DR prevalence among diabetic patients in Indigenous and non-Indigenous Australian populations. Two independent reviewers performed quality assessments using a 9-item appraisal tool. Meta-analysis and meta-regression were performed using double arcsine transformation and a random-effects model comparing Indigenous and non-Indigenous subgroups.Fifteen studies with 8219 participants met criteria for inclusion. The Indigenous subgroup scored lower on the appraisal tool than the non-Indigenous subgroup (mean score 50% vs. 72%, P = 0.04). In the unadjusted meta-analysis, DR prevalence in the Indigenous subgroup (30.2%; 95% confidence interval [CI], 24.9-35.7) did not differ significantly (P = 0.17) from the non-Indigenous subgroup (23.7%; 95% CI, 16.8-31.4). After adjusting for age and quality, DR prevalence was higher in the Indigenous subgroup (P0.01), with prevalence ratio point estimates ranging from 1.72 to 2.58, depending on the meta-regression model. For the secondary outcomes, prevalence estimates were higher in the Indigenous subgroup for diabetic macular edema (DME) (8.7% vs. 2.7%, P = 0.02) and vision-threatening DR (VTDR) (8.6% vs. 3.0%, P = 0.03) but not for proliferative DR (2.5% vs. 0.8%, P = 0.07).Indigenous studies scored lower for methodological quality, raising the possibility that systematic differences in research practices may be leading to underestimation of disease burden. After adjusting for age and quality, we found a higher DR prevalence in the Indigenous subgroup. This contrasts with a previous review that reported the opposite finding of lower DR prevalence using unadjusted pooled estimates. Future epidemiological work exploring DR burden in Indigenous communities should aim to address methodological weaknesses identified by this review.

Importance: Understanding the effects of modifiable risk factors on risk for multiple sclerosis (MS) and associated neurodegeneration is important to guide clinical counseling. Objective: To investigate associations of alcohol use, smoking, and obesity with odds of MS diagnosis and macular ganglion cell layer and inner plexiform layer (mGCIPL) thickness. Design, Setting, and Participants: This cross-sectional study analyzed data from the community-based UK Biobank study on health behaviors and retinal thickness (measured by optical coherence tomography in both eyes) in individuals aged 40 to 69 years examined from December 1, 2009, to December 31, 2010. Risk factors were identified with multivariable logistic regression analyses. To adjust for intereye correlations, multivariable generalized estimating equations were used to explore associations of alcohol use and smoking with mGCIPL thickness. Finally, interaction models explored whether the correlations of alcohol and smoking with mGCIPL thickness differed for individuals with MS. Data were analyzed from February 1 to July 1, 2021. Exposures: Smoking status (never, previous, or current), alcohol intake (never or special occasions only [low], once per month to ≤4 times per week [moderate], or daily/almost daily [high]), and body mass index. Main Outcomes and Measures: Multiple sclerosis case status and mGCIPL thickness. Results: A total of 71 981 individuals (38 685 women [53.7%] and 33 296 men [46.3%]; mean [SD] age, 56.7 [8.0] years) were included in the analysis (20 065 healthy control individuals, 51 737 control individuals with comorbidities, and 179 individuals with MS). Modifiable risk factors significantly associated with MS case status were current smoking (odds ratio [OR], 3.05 [95% CI, 1.95-4.64]), moderate alcohol intake (OR, 0.62 [95% CI, 0.43-0.91]), and obesity (OR, 1.72 [95% CI, 1.15-2.56]) compared with healthy control individuals. Compared with the control individuals with comorbidities, only smoking was associated with case status (OR, 2.30 [95% CI, 1.48-3.51]). High alcohol intake was associated with a thinner mGCIPL in individuals with MS (adjusted β = -3.09 [95% CI, -5.70 to -0.48] μm; P = .02). In the alcohol interaction model, high alcohol intake was associated with thinner mGCIPL in control individuals (β = -0.93 [95% CI, -1.07 to -0.79] μm; P

The aim of this study was to assess whether adiposity or body composition relates to microvascular characteristics of the retina, indicative of cardiometabolic function. A fully automated QUARTZ software processed retinal images from 68,550 UK Biobank participants (aged 40-69 years). Differences in retinal vessel diameter and tortuosity with body composition measures from the Tanita analyzer were obtained by using multilevel regression analyses adjusted for age, sex, ethnicity, clinic, smoking, and Townsend deprivation index. Venular tortuosity and diameter increased by approximately 2% (P

Background/AimsThis work aimed to study the effect of long-term intraocular pressure (IOP) fluctuation on visual field (VF) progression 8 years post-trabeculectomy in Asian eyes.MethodsThis was a retrospective analysis of 8-year post-trabeculectomy data from The Singapore 5-Fluorouracil (5-FU) Study. VFs were analysed using Progressor software (Medisoft, Leeds, UK). Outcome measures included mean slope for VF per year, number of progressing points and mean slope for progressing points per year. Multivariate regression analyses were performed adjusting for age, gender, ethnicity, glaucoma type, intraoperative 5-FU, diabetes mellitus, hypertension, best pre-trabeculectomy VF mean deviation, post-trabeculectomy mean IOP, IOP reduction and IOP fluctuation (SD of IOPs at 6-monthly timepoints).Results127 (52.3%) subjects completed 8-year follow-up with ≥5 reliable VFs and ≥8 6-monthly IOP measurements. Mean age was 61.8±9.6 years. Post-operatively, mean IOP was 14.2±2.8 mm Hg and mean IOP fluctuation was 2.53±1.20 mm Hg. Higher IOP fluctuation was associated with greater mean slope for field (B=−0.071; p=0.013), number of progressing points (B=0.963; p=0.014) and VF progression as defined by ≥1 progressing point (OR=1.585; p=0.029). There was also a trend towards eyes with higher IOP fluctuation having ≥3 adjacent progressing points in the same hemifield (OR=1.489; p=0.055). Greater mean IOP reduction post-trabeculectomy was associated only with a lower mean slope for progressing points per year (B=−0.026; p=0.028). There was no significant effect of intra-operative 5-FU compared with placebo for all outcome measures.ConclusionIn post-trabeculectomy Asian eyes with well-controlled IOP, higher long-term IOP fluctuation may be associated with greater VF progression.

Purpose To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell–inner plexiform layer (GCIPL) thicknesses in a large cohort. Design Cross-sectional study. Participants We included 42 044 participants in the UK Biobank. The mean age was 56 years. Methods Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Main Outcome Measures Thicknesses of mRNFL, GCC, and GCIPL. Results We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: –0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61–0.30]; P = 1.1×10–8), greater social deprivation (most significant for GCIPL: –0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, –0.42 to –0.14]; P = 6.6×10–5), lower educational attainment (most significant for mRNFL: –0.36 μm for less than O level compared with degree level [95% CI, –0.45 to 0.26]; P = 2.3×10–14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: –1.65 μm [95% CI, –1.86 to –1.43]; P = 2.4×10–50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (–0.04 μm/mmHg [95% CI, –0.05 to –0.03]; P = 4.0×10–10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, –0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). Conclusions The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

Purpose To examine retinal vasculometry associations with different glaucomas in older British people. Design Cross-sectional study. Methods A total of 8,623 European Prospective Investigation into Cancer-Norfolk Eye study participants were examined, who underwent retinal imaging, ocular biometry assessment, and clinical ascertainment of ocular hypertensive or glaucoma status (including glaucoma suspect [GS], high-tension open-angle glaucoma [HTG], and normal-tension glaucoma [NTG]). Automated measures of arteriolar and venular tortuosity, area, and width from retinal images were obtained. MainOutcomeMeasures: Associations between glaucoma and retinal vasculometry outcomes were analyzed using multilevel linear regression, adjusted for age, sex, height, axial length, intraocular and systemic blood pressure, and within-person clustering, to provide absolute differences in width and area, and percentage differences in vessel tortuosity. Presence or absence of within-person-between-eye differences in retinal vasculometry by diagnoses were examined. Results A total of 565,593 vessel segments from 5,947 participants (mean age 67.6 years, SD 7.6 years, 57% women) were included; numbers with HTG, NTG, and GS in at least 1 eye were 87, 82, and 439, respectively. Thinner arterioles (−3.2 μm; 95% confidence interval [CI] −4.4 μm, −1.9 μm) and venules (−2.7 μm; 95% CI −4.9 μm, −0.5 μm) were associated with HTG. Reduced venular area was associated with HTG (−0.2 mm2; 95% CI −0.3 mm2, −0.1 mm2) and NTG (−0.2 mm2; 95% CI −0.3 mm2, −0.0 mm2). Less tortuous retinal arterioles and venules were associated with all glaucomas, but only significantly for GS (−3.9%; 95% CI −7.7%, −0.1% and −4.8%; 95% CI −7.4%, −2.1%, respectively). There was no evidence of within-person-between-eye differences in retinal vasculometry associations by diagnoses. Conclusions Retinal vessel width associations with glaucoma and novel associations with vessel area and tortuosity, together with no evidence of within-person-between-eye differences in retinal vasculometry, suggest a vascular cause of glaucoma., Highlights • Retinal vessel measurements, including (as a first report) vessel tortuosity and area, were associated with high-tension glaucoma and other glaucoma-related outcomes. • Novel analyses showing that within-person-between-eye glaucoma diagnoses, intraocular pressure, and retinal vasculometry were uncorrelated provides further evidence that systemic microvascular changes may cause glaucoma.

Despite recent advances, our understanding of the aetiological mechanisms underlying glaucoma remains incomplete. Heavy metals toxicity has been linked to the development of neurodegenerative diseases and various ocular pathologies. Given the similarities in pathophysiology between glaucoma and some neurodegenerative disorders, it is plausible that heavy metal toxicity may play a role in the development of glaucoma. Heavy metal exposure may be occupational, or through water or dietary contamination. In this report, we review mechanisms for systemic and neurotoxicity for arsenic, cadmium, chromium, cobalt, lead, mercury, and manganese, and weigh the evidence for an association between glaucoma and the accumulation of heavy metals either in ocular tissues or in the central nervous system.摘要: 尽管近年来关于青光眼的发病机制的研究有所进展, 但我们对其认识仍不全面。已发现重金属毒性与神经的退行性病变与多种眼部疾病发生具有相关性。由于青光眼与一些退行性神经病变的病理生理机制相似, 因此推测重金属毒性可能与青光眼的发展有关。重金属暴露可能是职业性的原因, 也可能通过水及食物的污染。在这篇报道中我们分析了砷, 镉, 铬, 钴, 铅, 汞和锰对于全身和神经系统毒性的病理发病机制, 评估了重金属在眼部与中枢神经系统中的蓄积与青光眼发病之间的相关性。.