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Purpose To examine associations between retinal vessel morphometry and cardiometabolic risk factors in older British men and women. Design Retinal imaging examination as part of the European Prospective Investigation into Cancer—Norfolk Eye Study. Participants Retinal imaging and clinical assessments were carried out in 7411 participants. Retinal images were analyzed using a fully automated validated computerized system that provides novel measures of vessel morphometry. Methods Associations between cardiometabolic risk factors, chronic disease, and retinal markers were analyzed using multilevel linear regression, adjusted for age, gender, and within-person clustering, to provide percentage differences in tortuosity and absolute differences in width. Main Outcomes Measures Retinal arteriolar and venular tortuosity and width. Results In all, 279 802 arterioles and 285 791 venules from 5947 participants (mean age, 67.6 years; standard deviation [SD], 7.6 years; 57% female) were analyzed. Increased venular tortuosity was associated with higher body mass index (BMI; 2.5%; 95% confidence interval [CI], 1.7%–3.3% per 5 kg/m 2 ), hemoglobin A1c (HbA1c) level (2.2%; 95% CI, 1.0%–3.5% per 1%), and prevalent type 2 diabetes (6.5%; 95% CI, 2.8%–10.4%); wider venules were associated with older age (2.6 μm; 95% CI, 2.2–2.9 μm per decade), higher triglyceride levels (0.6 μm; 95% CI, 0.3–0.9 μm per 1 mmol/l), BMI (0.7 μm; 95% CI, 0.4–1.0 per 5 kg/m 2 ), HbA1c level (0.4 μm; 95% CI, –0.1 to 0.9 per 1%), and being a current smoker (3.0 μm; 95% CI, 1.7–4.3 μm); smoking also was associated with wider arterioles (2.1 μm; 95% CI, 1.3–2.9 μm). Thinner venules were associated with high-density lipoprotein (HDL) (1.4 μm; 95% CI, 0.7–2.2 per 1 mmol/l). Arteriolar tortuosity increased with age (5.4%; 95% CI, 3.8%–7.1% per decade), higher systolic blood pressure (1.2%; 95% CI, 0.5%–1.9% per 10 mmHg), in females (3.8%; 95% CI, 1.4%–6.4%), and in those with prevalent stroke (8.3%; 95% CI, –0.6% to 18%); no association was observed with prevalent myocardial infarction. Narrower arterioles were associated with age (0.8 μm; 95% CI, 0.6–1.0 μm per decade), higher systolic blood pressure (0.5 μm; 95% CI, 0.4–0.6 μm per 10 mmHg), total cholesterol level (0.2 μm; 95% CI, 0.0–0.3 μm per 1 mmol/l), and HDL (1.2 μm; 95% CI, 0.7–1.6 μm per 1 mmol/l). Conclusions Metabolic risk factors showed a graded association with both tortuosity and width of retinal venules, even among people without clinical diabetes, whereas atherosclerotic risk factors correlated more closely with arteriolar width, even excluding those with hypertension and cardiovascular disease. These noninvasive microvasculature measures should be evaluated further as predictors of future cardiometabolic disease.

OBJECTIVE: With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders. DESIGN: Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS. PARTICIPANTS: Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013. METHODS: Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration. MAIN OUTCOME MEASURES: Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome. RESULTS: Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective. CONCLUSIONS: Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings.

With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders.Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS.Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013.Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration.Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome.Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective.Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings.

Objective To obtain prevalence estimates of age-related macular degeneration (AMD; late, geographic atrophy, neovascular) by age and gender amongst populations of European ancestry taking into account study design and time trends. Design Systematic review of population-based studies published by September 2010 with quantitative estimates of geographic atrophy (GA), neovascular (NV), and late AMD prevalence. Studies were identified by a literature search of MEDLINE (from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases. Participants Data from 25 published studies (57 173 subjects: 455 with GA, 464 with NVAMD, and 1571 with late AMD). Methods Bayesian meta-regression of the log odds of AMD with age, gender, and year of study allowing for differences in study design characteristics, to estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals (CrI). Main Outcome Measures Log odds and prevalence of AMD. Results There was considerable heterogeneity in prevalence rates between studies; for late AMD, 20% of the variability in prevalence rates was explained by differences in age and 50% by study characteristics. The prevalence of AMD increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI, 3.8–4.6), which did not differ by gender. There was some evidence to suggest higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0–1.5). Compared with studies using fundus imaging and international classification systems, studies using fundus imaging with alternative classifications were more likely (OR, 2.7; 95% CrI, 1.1–2.8), and studies using alternative classifications without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI, 1.3–7.8). There was no good evidence of trends in AMD prevalence over time. Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%–2.0%) at 70 years of age, rising to 5.6% (95% CrI, 3.9%–7.7%) at age 80 and 20% (95% CrI, 14%–27%) at age 90. Conclusions Studies using recognized classifications systems with fundus photography reported the lowest prevalences of AMD taking account of age and gender, and were stable over time, with a potentially higher risk of NVAMD for women. These prevalence estimates can be used to guide health service provision in populations of European ancestry. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Diabetes is associated with loss of capillaries and macrovessel dilation in the conjunctiva, similar to well-known vessel changes in the retina. However, little is known about the effect of diabetes on the tortuosity of vessels of the conjunctiva. The authors examined the tortuosity of conjunctival vessels in participants with and without diabetes.Case-control study.Fifty-three patients with diabetes (17 with type 1 diabetes, 36 with type 2 diabetes) and 60 controls (all aged 20-94 years).Digital red-free images of conjunctivae were analyzed using an automated computer algorithm to identify vessel axes and to quantify vessel tortuosity. Differences in vessel tortuosity were adjusted for age, gender, blood pressure, and smoking status.Tortuosity was expressed in units of curve energy (the square of the radian angular change between subsequent locations identified by the algorithm, standardized by vessel length).A longer duration of diabetes was associated with a reduction in overall vessel tortuosity (-2.8%; 95% confidence interval [CI], -4.3% to -1.3% per decade). This inverse association was driven by changes in larger vessels (40 microm in width or more), whereas increased tortuosity was observed in capillary sized vessels (25 microm, 4.0%; 95% CI, -0.2% to 8.2% per decade). Compared with controls, those with type 1 diabetes (median duration of disease, 26 years) showed a 17.9% increase (95% CI, 4.7% to -31.0%) in capillary tortuosity. Conversely, those with type 1 diabetes showed a 7% decrease (95% CI, -11.8% to -2.3%) in tortuosity among vessels 40 to 80 microm or less in size and a 26.8% decrease (95% CI, -66.2% to 12.7%) in the fewer number of vessels more than 80 microm in size compared with controls. Similar, but smaller differences were seen in those with type 2 diabetes with shorter duration of diabetes (median, 7 years).Macrovessel dilation associated with diabetes may result in vessel engorgement and straightening, especially among those with longer durations of disease. Increased tortuosity associated with diabetes among conjunctival capillaries mirrors established vessel changes observed in the retina. Conjunctival angiopathy associated with diabetes may contribute to susceptibility to anterior eye disease among patients with diabetes.

Objective To investigate the relationship between the absolute area of certain optic disc parameters and a number of ocular dimensional characteristics and demographic factors in young, healthy subjects. Design Cross-sectional study. Participants One hundred twenty-one subjects, aged 16.5 to 35.4 years participated, encompassing a wide range of refractive error from +4 diopters (D) to −25.75 D. One eye from each subject was randomly selected for examination. Main outcome measures Absolute size of the optic disc parameters: optic disc area (DA), neuroretinal rim area (NRA), optic cup area (CA), and peripapillary atrophy area (PA). Methods Absolute sizes of optic disc parameters were determined from digitized photographic color transparencies, taking into consideration the magnification of the fundus camera and human eye. Relationships between the absolute size of the optic disc features and axial length, crystalline lens thickness, anterior chamber depth, ocular refraction, front surface keratometry, age, and gender were examined. Results Axial length, lens thickness, front surface keratometry, and age demonstrated positive associations with all optic disc parameters, and anterior chamber depth and ocular refraction demonstrated negative associations in all cases. Multiple regression analysis revealed that the associations observed univariately for age, anterior chamber depth, lens thickness, front surface keratometry, and ocular refraction were confounded by axial length for all disc parameters. After taking logs, DA and NRA exhibit an exponential relationship with axial length, whereas PA and CA exhibit a linear relationship with axial length. DA and NRA increase by approximately 3% per millimeter increase in axial length at 20 mm and up to 40% for DA and 50% for NRA at an axial length of 35 mm. PA and CA are estimated to increase by 26% (10%–44%) and 10% (5%–16%), respectively, per millimeter increase in axial length. Females have approximately 5% smaller DA and 7% smaller NRA than males, but these effects are not statistically significant ( P > 0.2). From the multiple regression analysis, females have 31% larger optic cup areas (1%–57%, P = 0.03) and 24% smaller PA (42% smaller to 5% larger P = 0.06) than males, but these effects are of borderline statistical significance at 5%. Conclusions Of the ocular biometric factors considered, axial length seems to be the most important predictor of the absolute area of the optic disc parameters. No association exists between any disc parameter and age in this sample of subjects less than 40 years of age. Females exhibited smaller values for DA, NRA, and PA than did males, differences that were not statistically significant, and larger CA ( P = 0.03).

Objective To compare the magnification properties of 11 different fundus cameras (including 1 stereo fundus camera), a Rodenstock (infrared) scanning laser ophthalmoscope (SLO), the Heidelberg Laser Tomographic Scanner (LTS), and the Heidelberg Retina Tomograph (HRT). Design A cross-sectional study of the relationship between the true size of a fundus feature and its photographic-computer image in 14 different fundus imaging devices. This relationship was evaluated for each instrument using a model eye adjusted for axial ametropia between +11 diopter (D) and −14 D. To simulate refractive ametropia, the "crystalline lens" was removed to render the model eye aphakic, and the axial length was adjusted to give aphakic ametropia from emmetropia to +20 D. Main outcome measures A correction factor (p) was calculated for each instrument, which can be used in calculations for determining true retinal size. Results The following were found to be of telecentric construction, Zeiss Oberkochen (WS240 Heidelberg), Zeiss Oberkochen (UK), Zeiss Oberkochen (Cologne), Nikon NF505, Kowa RCXV, SLO prototype (UK), LTS, and the HRT, and each exhibited a constant relationship between p and degree of ametropia of the model eye. The Canon CF6OU, Canon CF6OS, Canon CR4-45NM, Nidek 3-DX, Olympus GRCW, and Carl Zeiss Jena Retinophot were found not to be telecentric and exhibited a linear relationship between p and degree of ametropia of the model eye. For all instruments, p remained unchanged for axial and refractive ametropias of the same degree. Conclusions The study has shown that not all fundus imaging systems are telecentric, so the use of a single magnification correction value may not be appropriate. These findings have important implications for the way in which true retinal size calculations are performed. Examples are given to show how the tabulated values of correction factors can be used for both telecentric and nontelecentric cameras in image size calculations.

Retinovascular changes associated with diabetes have been clearly documented; changes in vessels of the conjunctiva are less well described. We examined changes in conjunctival vessel morphologic features in participants with and without diabetes.Case-control study.Fifty-three patients with diabetes (17 with type 1 diabetes, 36 with type 2 diabetes) and 60 controls (all aged 20-94 years).Digital red-free conjunctival images were captured and an automated computer algorithm was used to derive indices that describe the morphologic features of vessels of the conjunctiva. Percentage differences in vessel indices were adjusted for age, gender, blood pressure, and smoking status.Mean vessel diameter (micrometers) and vessel density (square millimeters of vessel per square centimeter of bulbar conjunctiva).A strong positive association between the duration of diabetes and overall mean vessel width was observed (P0.001), resulting from changes in larger vessels (80 mum in width). Conversely, the duration of diabetes showed a strong inverse association with vessel area (P0.001) that appeared to be driven by the trend observed in smaller vessels (40 mum in width). A 25% reduction (95% confidence interval [CI], -35% to -13%; P0.001) in vessel density in those with type 1 diabetes and a 14% reduction (95% CI, -24% to -3%; P = 0.016) in those with type 2 diabetes, compared with controls, was observed. Mean vessel widths were 11% (95% CI, 4%-17%; P = 0.001) wider in type 1 and 5% (95% CI, 0%-10%; P = 0.073) wider in those with type 2 diabetes compared with controls. The difference in magnitude of effect for type 1 and type 2 diabetes compared with controls was explained by duration of diabetes. Grade of diabetic retinopathy and elevated blood pressure showed similar but less strong associations with vessel indices.Loss of capillaries and macrovessel dilation in the conjunctiva associated with diabetes compares with well-known vessel changes in the retina. Associations between morphologic changes in the conjunctiva and elevated blood pressure were similar but less strong; this may show that diabetic angiopathy predominates in those with both diabetes and elevated blood pressure.