Background/Purpose. Recent findings suggest that an objective assessment of retinal vessel caliber from fundus photographs provide information about the association of microvascular characteristics with macrovascular disease. Current methods used to quantify retinal vessel caliber, introduced by Parr(1,2) and Hubbard,(3) are not independent of scale and are affected by the number of vessels. To improve upon these methods we introduce revised formulas for quantifying vessel caliber. Methods. Revised formulas were estimated using retinal vessel measurements from 44 young adults free of hypertension and diabetes. Comparisons between the two methods were done using digitized photographs from 4926 participants at the baseline examination of the Beaver Dam Eye Study (BDES), an ongoing population-based cohort study initiated in 1987. Individual arterioles and venules were measured using semi-automated computer software from which summary measures were calculated. Results. Correlation coefficients between the Parr-Hubbard and revised formulas were high (Pearson correlation coefficients ranging from 0.94 to 0.98). Both arteriolar and venular caliber significantly increased with an increasing number of vessels measured using the Parr-Hubbard formulas (p < 0.001), which in turn affected the relationship to mean arterial blood pressure. To the contrary, the revised formulas were not affected by the number of measured vessels (p > 0.50). Conclusions. We describe revised formulas for summarizing retinal vessel diameters measured from fundus photographs to be used in future studies and analyses. The revised formulas correlate highly with the previously used Parr-Hubbard formulas, but offer the advantages of being more robust against variability in the number of vessels observed, being independent of image scale, and being easier to implement.

Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10−8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10−8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD.

Objective To examine the 25-year cumulative incidence of macular edema (ME) and its relation to various risk factors. Design Population-based study. Participants Nine hundred and fifty-five insulin-taking persons living in an 11-county area in southern Wisconsin with type 1 diabetes diagnosed before age 30 years who participated at baseline (1980-1982) and at least one of 4 follow-up (4-, 10-, 14-, and 25-year) examinations (n=891) or died before the first follow-up examination (n=64). Methods Stereoscopic color fundus photographs were graded using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. Competing risk of death was included in statistical models. Main Outcome Measures Incidence of ME and clinically significant ME (CSME). Results The 25-year cumulative incidence of ME was 29% and for CSME it was 17%. Annualized incidence of ME were 2.3, 2.1, 2.3, and 0.9%, respectively, in the 1st, 2nd, 3rd, and 4th follow-up periods of the study. In univariate analyses, the incidence of ME was associated with more severe diabetic retinopathy, being male, having higher glycosylated hemoglobin, proteinuria, higher systolic and diastolic blood pressure, and having smoked more pack years. Multivariate analyses showed that the incidence of ME was related to higher baseline glycosylated hemoglobin (Hazard Ratio [HR] per 1% 1.17, 95% Confidence Interval [CI] 1.10, 1.25, P<0.001) and higher systolic blood pressure (HR per 10 mmHg 1.15, 95% CI 1.04, 1.26, P=0.004) and marginally to proteinuria (HR 1.43, 95% CI 0.99, 2.08, P=0.06). Conclusions These data show that relatively high 25-year cumulative rates of incidence of ME were related to glycemia and blood pressure. The lower risk of incident ME in the last period of the study may reflect recent improvement in care.

OBJECTIVE—To determine whether components of the metabolic syndrome precede the 5-year incidence of cardiovascular disease and diabetes. RESEARCH DESIGN AND METHODS—A population of individuals aged 43–84 years was evaluated from 1988 to 1990 and again 5 years later. Medical history, blood pressure, and laboratory measures were obtained at both examinations following the same protocols. Subjects without diabetes were classified according to level of glycemia, high blood pressure, high-risk lipid levels, high uric acid levels, and proteinuria at baseline. History of incident myocardial infarction, angina, stroke, and diabetes was obtained at follow-up. RESULTS—Of the 4,423 subjects without diabetes, 6.9% had elevated levels of glycemia, 18.4% had high blood pressure, 82.7% had high-risk lipid levels (either high serum total cholesterol or low HDL cholesterol or high ratio of these two levels), 27% had elevated uric acid levels, 33.2% had high BMI, and 3.3% had proteinuria (≥30 mg/dl). The risk of incident cardiovascular disease 5 years later increased with the number of the components present; 2.5% of those with one component developed cardiovascular disease, whereas 14.9% of those with four or more components developed cardiovascular disease. Of those with one component, diabetes developed in 1.1% 5 years later, whereas diabetes developed in 17.9% of those with four or more components. CONCLUSIONS—Components of the metabolic syndrome are common and are associated with incident cardiovascular disease and diabetes after 5 years. Interventions to alter BMI, lipid levels, and blood pressure may decrease incident diabetes and cardiovascular disease.