Cardiovascular risk factors associated with age-related macular degeneration: the Tromsø Study.

PURPOSE: To examine associations between cardiovascular risk factors and age-related macular degeneration (AMD). METHODS: A population-based, cross-sectional study of Caucasians aged 65-87 years was conducted in Norway in 2007/2008. Retinal photographs were graded for AMD. Multivariable logistic regression analyses were performed based on questionnaires addressing habits of smoking, alcohol consumption, physical activity, health and medication; and physical examination comprising anthropometric measurements, blood pressure and blood sampling. Cardiovascular disease status was obtained from a validated end-point registry. RESULTS: Gradable photographs were available for 2631 participants, of whom 92 (3.5%) subjects had late AMD. In the multivariable analysis of late AMD, significant interactions were found between sex and the variables age, triglyceride level, use of lipid-lowering drugs and physical exercise. Current daily smoking was significantly related to late AMD in both sexes (odds ratio (OR) 4.06, 95% confidence interval (CI) 1.69-9.76 and OR 3.59, 95% CI 1.17-11.04, women and men, respectively) compared with never smokers. Higher number of pack years was associated with the presence of large drusen (>125 µm) (OR 1.04, 95% CI 1.01-1.09 per 5 years). Higher systolic blood pressure (OR 1.06, 95% CI 1.01-1.12 per 5 mmHg), overweight (OR 2.87, 95% CI 1.13-7.29) and obesity (OR 2.92, 95% CI 1.06-8.03), physical exercise duration (OR 0.41, 95% 0.18-0.96 for 30 min or more compared with less) and frequency (OR 0.46, 95% CI 0.23-0.92 for weekly or more often compared to less) were associated with late AMD in women only. CONCLUSIONS: Smoking was strongly associated with AMD, in line with results from other populations. Also, late AMD was related to higher systolic blood pressure, physical inactivity, overweight and obesity in women.

Retinal vascular calibres are significantly associated with cardiovascular risk factors: the Tromsø Eye Study.

PURPOSE: To describe the association between retinal vascular calibres and cardiovascular risk factors. METHODS: Population-based cross-sectional study including 6353 participants of the Tromsø Eye Study in Norway aged 38-87 years. Retinal arteriolar calibre (central retinal artery equivalent) and retinal venular calibre (central retinal vein equivalent) were measured computer-assisted on retinal photographs. Data on blood pressure, body mass index (BMI), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, glycosylated haemoglobin (HbA1c) and smoking were collected. Association between retinal vessel calibre and the cardiovascular risk factors was assessed by multivariable linear and logistic regression analyses. RESULTS: Retinal arteriolar calibre was independently associated with age, blood pressure, HbA1c and smoking in women and men, and with HDL cholesterol in men only. Blood pressure had the strongest effect on arteriolar calibre, with a decrease in calibre of 3.6 µm (women)/4.1 µm (men) per standard deviation increase in mean arterial blood pressure. Retinal venular calibre was independently associated with age, blood pressure, BMI, HDL and LDL cholesterol and smoking in men and women. The effect of BMI and HDL cholesterol on venular calibre was sigifnicantly stronger in men than in women. Current smoking was the most important factor for venular calibre, where smokers had 13.2 µm (women)/15.2 µm (men) wider calibre than nonsmokers. CONCLUSION: All the explored cardiovascular risk factors were independently associated with retinal vascular calibre, with stronger effect of HDL cholesterol and BMI in men than in women. Blood pressure and smoking contributed most to the explained variance.

Lactation, female hormones and age-related macular degeneration: the Tromsø Study.

OBJECTIVE: Some risk factors for age-related macular degeneration (AMD) have been shown to act differently in women and men. The present study aims to investigate this disparity by examining associations between female hormones, reproductive history and AMD. METHODS: Women aged 65-87 years were invited to this cross-sectional, population-based study in Norway. Participants underwent physical examination, retinal photography, answered questionnaires and had blood samples taken. RESULTS: The sample included 1512 women, of whom 48 (3.2%) had late AMD and 378 (25%) had large drusen >125 µm phenotype. Length of breast feeding per child was significantly associated with late AMD (OR per month 0.80, 95% CI 0.68 to 0.94) in multivariable regression analysis. We observed no associations between late AMD or drusen >125 µm and contraceptives, oral hormonal replacement therapy, parity, age at first childbirth, age of menarche, age of menopause, number of menstruating years or the reason for menopause. CONCLUSIONS: Longer duration of lactation was associated with lower frequency of maternal late AMD when controlled for confounders. Other reproductive factors and hormone replacement therapy were not significantly associated with AMD.

Localized changes in retinal vessel caliber after focal/grid laser treatment in patients with diabetic macular edema: a measure of treatment response?

PURPOSE: To compare retinal vessel caliber changes at the macula region and surrounding the optic disk after focal/grid laser treatment for diabetic macular edema. METHODS: The study included 69 eyes from 46 patients treated with focal/grid laser for diabetic macular edema. Retinal photographs were taken <6 months before and 2 months and 12 months after focal/grid photocoagulation treatment. The diameters of retinal vessels around macula and the optic disk were measured separately before and after treatment. Optic disk and macular diameters were summarized into central retinal arteriolar and venular equivalent and macular retinal arteriolar and venular equivalent. RESULTS: Median age and duration of diabetes was 60 years and 13 years. There was a statistically significant decrease in diameter of the macular arterioles (macular retinal arteriolar equivalent 73.5 vs. 72.0 µm, P = 0.04) and venules (macular retinal venular equivalent 63.5 vs. 62.4 µm, P = 0.02) after treatment but no difference in central retinal arteriolar equivalent or central retinal venular equivalent before and after treatment. Retinal vascular calibers in control eyes did not change throughout the study. CONCLUSION: The diameters of macular vessels decreased after focal/grid laser treatment in most eyes. In contrast, vessel calibers at the optic disk did not change. Quantitative measurement of macular vessels may allow physicians to monitor the progress and success of diabetic macular edema treatment.

The Tromsø Eye Study: study design, methodology and results on visual acuity and refractive errors.

PURPOSE: To describe the study design and methodology of the Tromsø Eye Study (TES), and to describe visual acuity and refractive error in the study population. METHODS: The Tromsø Eye Study is a sub-study of the Tromsø Study, a population-based multipurpose longitudinal study in the municipality of Tromsø, Norway. The Tromsø Eye Study was a part of the sixth survey of the Tromsø Study, conducted from October 2007 through December 2008. The eye examination included information on self-reported eye diseases, assessment of visual acuity and refractive errors, retinal photography and optical coherence tomography. Retinal images were graded for diabetic retinopathy and age-related macular degeneration, and with computer-assisted measurements of arteriolar and venular diameters. In addition, TES researchers have access to the large comprehensive Tromsø Study database including physical examination results, carotid artery ultrasound, electrocardiogram, bone densitometry, cognitive tests, questionnaires, DNA, blood and urine samples and more from the present and the five previous surveys. RESULTS: Visual acuity was assessed in 6459 subjects and refraction in 6566 subjects aged 38-87 years. Snellen visual acuity <20/60 was found in 1.2% (95% CI 0.95-1.5) of the participants and there was no gender difference. Visual impairment increased with age, and in the age group 80-87 years, the overall visual acuity <20/60 was 7.3% (95% CI 3.3-11.2). Spherical equivalent showed an increasing trend with age and there was no clinically relevant difference between men and women. Retinal photography was performed in 6540 subjects. CONCLUSION: Prevalence of visual impairment was low but increased with age. There was a trend towards hyperopia with age and no clinically relevant difference in refraction between the sexes. TES aims to provide epidemiological research on several eye and eye-related diseases. Owing to a comprehensive data collection, it has the opportunity to explore issues related to environmental factors, cognition and their interaction with diseases in this community.

Prevalence of age-related macular degeneration in elderly Caucasians: the Tromsø Eye Study.

PURPOSE: To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Caucasian adults aged 65 to 87 years from the 6th Tromsø Study, a population-based study conducted in 2007-2008 in the municipality of Tromsø, Norway. METHODS: Digital color fundus photographs were graded for predominant phenotype based on drusen size, geographic atrophy, and neovascular AMD. MAIN OUTCOME MEASURES: Age-related macular degeneration. RESULTS: A total of 3025 subjects participated; 89% of those were invited to the eye examinations. Gradable photographs were available for 2631 persons (mean age 72.3 years). Drusen 63-125 µm as the predominant phenotype were found in 34.9% of participants (95% confidence interval [CI], 33.1-36.8), drusen >125 µm were found in 24.1% (95% CI, 22.5-25.8), geographic atrophy was found in 1.0% of participants (95% CI, 0.6-1.4), and neovascular AMD was found in 2.5% of participants (95% CI, 1.9-3.1). Bilateral involvement of late AMD was present in 1.1% of the sample. Eyes with late AMD had a significantly lower refractive error (spherical equivalent 0.078 vs. 0.99 diopters, P<0.0001), and 42.5% of eyes had Snellen visual acuity ≤ 0.32. CONCLUSIONS: The prevalence of AMD among the elderly persons in this study was similar to rates in other Caucasian populations. Late AMD was present in 10.9% of subjects aged 80 years or more. No sex differences in prevalence rates of large drusen or late AMD were observed. Lower refractive error was observed in eyes with late AMD than in eyes without late AMD.

Cataract surgery in a population-based cohort of patients with type 1 diabetes: long-term incidence and risk factors.

PURPOSE: To estimate the long-term cumulative incidence of cataract surgery and associated risk factors in a 25-year follow-up of a population-based cohort of patients with type 1 diabetes. METHODS: Based on insulin prescriptions, a population-based cohort of 727 patients with type 1 diabetes was identified in 1973. In 1981-1982 diabetic retinopathy was graded and other markers of diabetes were measured in 573 patients who participated in a clinical baseline examination. Based on data from the Danish National Patient Registry, patients were followed until November 2006 and cataract surgery was evaluated during follow-up. RESULTS: The 25-year crude cumulative incidence of cataract surgery was 20.8% (117 of 562 patients at risk), corresponding to a mortality-adjusted incidence of 29.4% [95% confidence interval (CI) 25.6-33.1%]. Median age and duration of diabetes at the time of surgery were 59.3 and 42 years, respectively. Cataract surgery in the cohort took place approximately 20 years earlier compared to non-diabetic persons. In a multivariate regression analysis, baseline age [hazard ratio (HR) 1.89 per 10 years, 95% CI 1.46-2.27] and maculopathy (HR 1.89, 95% CI 1.05-3.40) were the only statistically significant predictors of cataract surgery. Duration of diabetes, gender, glycaemic regulation, proteinuria, smoking, blood pressure and level of retinopathy were not associated with cataract surgery. CONCLUSION: Type 1 diabetes is associated with a high long-term incidence of cataract surgery. The association between maculopathy and subsequent cataract surgery is a novel finding and should be addressed in future studies.

N-terminal pro brain natriuretic peptide reflects long-term complications in type 1 diabetes.

PURPOSE: To evaluate N-terminal pro brain natriuretic peptide (NT-proBNP) as a marker of long-term micro- and macrovascular complications in type 1 diabetes. METHODS: This was a cross-sectional study of 208 long-term surviving type 1 diabetic patients from a population-based cohort from Fyn County, Denmark. In a clinical examination in 2007-2008, NT-proBNP was measured and related to proliferative diabetic retinopathy (PDR), nephropathy, neuropathy and macrovascular disease. RESULTS: Median age and duration of diabetes was 58.7 and 43 years, respectively. Median NT-proBNP concentration was 78 pg/ml (10th-90th percentile 25-653 pg/ml). The NT-proBNP level (89 vs. 71 pg/ml, p = 0.02) was higher in women. In univariate analyses, NT-proBNP was associated with age, duration of diabetes, diastolic blood pressure (inversely), nephropathy, neuropathy and macrovascular disease. For instance, median NT-proBNP concentrations were 70, 91 and 486 pg/ml for patients with normo-, micro- and macroalbuminuria, respectively (p < 0.01). When adjusted for age, sex, duration of diabetes, high sensitivity CRP, HbA(1c), diastolic blood pressure and smoking, higher NT-proBNP concentrations (4th vs. 1st quartile) were related to nephropathy (odds ratio [OR] 5.03; 95% confidence interval [CI] 1.77-14.25), neuropathy (OR 4.08; 95% CI 1.52-10.97) and macrovascular disease (OR 5.84; 95% CI 1.65-20.74). There was no association with PDR. CONCLUSIONS: NT-proBNP has traditionally been described as a marker of heart failure and left ventricular dysfunction. In this study of long-term surviving type 1 diabetic patients, we found NT-proBNP associated with nephropathy, neuropathy and macrovascular disease. If confirmed by prospective studies, NT-proBNP might be a useful prognostic marker of diabetes-related complications.

Does osteoprotegerin relate to micro- and macrovascular complications in long-term type 1 diabetes?

PURPOSE: Markers of micro- and macrovascular disease are needed in type 1 diabetes in order to identify patients at risk of severe complications. Osteoprotegerin (OPG) is expressed in vascular myocytes, and increasing levels have been reported in type 1 diabetes. Consequently, we investigated OPG as a non-invasive marker of micro- and macrovascular complications in long-term type 1 diabetic patients. METHODS: This was a cross-sectional study of 200 type 1 diabetic patients with long diabetes duration from a population-based cohort from Fyn County, Denmark. Patients were examined in 2007-2008, and OPG was measured and correlated to diabetes-associated complications: retinopathy, nephropathy, neuropathy and macrovascular disease. RESULTS: Median age and duration of diabetes was 58.7 years (range 37.7-84.4 years) and 43 years (range 34-70 years), respectively. Median level of OPG was 1257 pg/ml (range 379-5706 pg/ml). In univariate analyses, OPG was related to age, duration of diabetes, female gender, nephropathy and inversely to diastolic blood pressure. In an age- and sex-adjusted model, higher levels of OPG were associated with a higher risk of nephropathy (OR 2.54, 95% confidence interval 1.09-5.90 for third vs. first tertile). Statistical significance was, however, lost in a multivariate model, and proliferative diabetic retinopathy, neuropathy and macrovascular disease was not associated with OPG in either model. CONCLUSIONS: Some associations of OPG and nephropathy were found in a long-term type 1 diabetic cohort. Prospective studies are needed in order to determine whether OPG can be used to predict nephropathy.