OMEGA-3 FATTY ACIDS ARE ASSOCIATED WITH DECREASED PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY: A Combined Analysis of MESA and GOLDR Cohorts.

PURPOSE: Inflammation is associated with diabetic retinopathy development and progression, and previous studies have demonstrated that omega-3 polyunsaturated fatty acids have anti-inflammatory properties. Therefore, the goal of this study was to determine if omega-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are associated with decreased risk and severity of retinopathy in individuals with type 2 diabetes. METHODS: In a combined population of 1,356 individuals with type 2 diabetes from the Multi-Ethnic Study of Atherosclerosis and Genetics of Latino Diabetic Retinopathy cohorts, odds ratios using logistic regression were determined to assess the association between polyunsaturated fatty acids and retinopathy. RESULTS: In 1,356 participants with type 2 diabetes, individuals in the fourth quartile of DHA were 17% less likely to have retinopathy compared with the first quartile ( P = 0.009, CI: 0.72-0.95). Secondary analysis revealed 38% lower severity of retinopathy in individuals in the fourth quartile compared with the first quartile of DHA ( P = 0.006; CI: 0.44-0.87) and EPA + DHA ( P = 0.004; CI: 0.44-0.85). No significant associations were observed between EPA and retinopathy. CONCLUSION: DHA is inversely associated with the presence and severity of diabetic retinopathy. Increased intake of dietary sources of DHA may provide some protection against retinopathy in individuals with type 2 diabetes and warrants more research as a preventative option.

ASSOCIATION OF PLASMA ω-3 FATTY ACIDS WITH EARLY AGE-RELATED MACULAR DEGENERATION IN THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS.

PURPOSE: To examine the association between omega-3 polyunsaturated fatty acids, docosahexaenoic acid, and eicosapentaenoic acid and age-related macular degeneration (AMD) in the Multi-Ethnic Study of Atherosclerosis cohort. METHODS: Multi-Ethnic Study of Atherosclerosis is a multicenter, prospective cohort study designed to identify risk factors for cardiovascular disease in four ethnic groups. Six thousand eight hundred and fourteen participants of White, African American, Hispanic/Latino, and Chinese descent, aged 45-84 years, were recruited, with those found to have cardiovascular disease excluded. Our study population included all Multi-Ethnic Study of Atherosclerosis participants with baseline polyunsaturated fatty acid measurements and retinal photography at Examination 5 (n = 3,772). Fundus photographs were assessed for AMD using a standard grading protocol. Relative risk regression (log link) determined associations between polyunsaturated fatty acid levels and AMD. RESULTS: There was a significant association between increasing docosahexaenoic acid levels and increasing docosahexaenoic acid + eicosapentaenoic acid levels with reduced risk for early AMD (n = 214 participants with early AMD, of which n = 99 (46.3%) are non-White). Eicosapentaenoic acid levels alone were not significantly associated with AMD. CONCLUSION: Our analysis suggests increasing levels of docosahexaenoic acid are associated with reduced risk for early AMD in a multiethnic cohort. This represents the first racially diverse study demonstrating an association between omega-3 polyunsaturated fatty acids and AMD risk.

Adequate vitamin D status is associated with the reduced odds of prevalent diabetic retinopathy in African Americans and Caucasians.

BACKGROUND: Vitamin D status has been hypothesized to protect against development of diabetic retinopathy via its anti-inflammatory and anti-angiogenic properties. Additionally, in vitro and in vivo studies suggest vitamin D favorably influences blood pressure and blood glucose control, strong risk factors for diabetic retinopathy. We examined the association between vitamin D status and prevalent diabetic retinopathy in participants with diabetes from a population-based cohort. METHODS: Among participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes at visit 3 (1993-1995), 1339 (906 Caucasians, 433 African Americans) had serum 25-hydroxyvitamin (25[OH]D) concentrations assessed at visit 2 (1989-1992) and nonmydriatic retinal photographs taken at visit 3. Dietary intake of vitamin D was assessed at visit 1 (1987-1989). Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetic retinopathy by categories of season-adjusted 25(OH)D (<30 [referent], 30-<50, 50-<75 and ≥75 nmol/L), by quartile of vitamin D intake (IU/day), and use of vitamin D or fish oil supplements (yes/no). P for trend was estimated using continuous 25(OH)D or vitamin D intake. ORs were adjusted for race, and duration of diabetes. We further adjusted for HBA1c and hypertension to examine if 25(OH)D influenced diabetic retinopathy via its effects on either glycemic control or blood pressure. RESULTS: ORs (95 % CIs) for retinopathy, adjusted for race and duration, were 0.77 (0.45-1.32), 0.64 (0.37-1.10), and 0.39 (0.20-0.75), p for trend = 0.001, for participants with 25(OH)D of 30-<50, 50-<75, and ≥75 nmol/L, respectively. Further adjustment for hypertension minimally influenced results (data not show), but adjustment for HBA1c attenuated the OR among those with 25(OH)D ≥75 (0.47 [0.23-0.96], p for trend = 0.030). No statistically significant association was observed between vitamin D intake from foods or supplements and retinopathy. CONCLUSIONS: 25(OH)D concentrations ≥75 nmol/L were associated with lower odds of any retinopathy assessed 3 years later. We speculate this may be due in part to vitamin D's influence on blood glucose control.

Cross-sectional associations of medication and supplement use with retinal vascular diameter in the Beaver Dam Eye Study.

IMPORTANCE: Retinal vessel diameters are being measured to examine their relationship with ocular and systemic disease and, in some studies, to calculate the risk of disease. Important factors that directly affect retinal vessel diameters, such as medication use, should be considered when estimating these associations. OBJECTIVE: To quantify the association between selected medications and supplements and retinal vessel diameters. DESIGN, SETTING, AND PARTICIPANTS: In a prospective cohort investigation, 4926 participants (aged 43-86 years at baseline) in the Beaver Dam Eye Study were evaluated every 5 years during 20 years of follow-up from 1988 to 2010. MAIN OUTCOMES AND MEASURES: Central retinal arteriolar equivalent and central retinal venular equivalent measured from the Early Treatment Diabetic Retinopathy Study fundus photograph field 1. RESULTS: After Bonferroni correction, the use of any blood pressure medication (ß = 0.75; P = .04), specifically calcium channel blockers (ß = -1.02; P < .001), was significantly associated with wider central retinal arteriolar equivalent adjusting for refraction, photograph focus, age, systolic blood pressure, height, examination phase, educational level, smoking and drinking histories, and presence of diabetes mellitus and emphysema. Use of prostaglandin analogues was marginally associated with narrower central retinal arteriolar equivalent (ß = -2.04; P = .09); ß-blockers (ß = -1.02; P = .10) and oral corticosteroids (ß = 2.13; P = .07) were marginally associated with changes in the central retinal venular equivalent. CONCLUSIONS AND RELEVANCE: Several medications are associated with central retinal arteriolar and venular equivalents. Prostaglandin analogues, calcium channel blockers, and oral corticosteroids have the largest relative effects. After Bonferroni correction was applied, the use of calcium channel blockers was most strongly associated with change in the central retinal arteriolar equivalent. The presence of factors that are associated with retinal vessel diameters should be considered when using retinal vessel diameter as an outcome or when using these measures to assess the risk of systemic or ocular disease.

Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations.

OBJECTIVE: To examine effect modification between genetic susceptibility to age-related macular degeneration (AMD) and dietary antioxidant or fish consumption on AMD risk. DESIGN: Pooled data analysis of population-based cohorts. PARTICIPANTS: Participants from the Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). METHODS: Dietary intakes of antioxidants (lutein/zeaxanthin [LZ], ß-carotene, and vitamin C), long-chain omega-3 polyunsaturated fatty acids, and zinc were estimated from food frequency questionnaires. The AMD genetic risk was classified according to the number of risk alleles of CFH (rs1061170) or ARMS2 (rs10490924) as low (no or 1 risk allele) or high (≥ 2 risk alleles). Interactions between dietary intake and genetic risk levels were assessed. Associations between dietary intake and AMD risk were assessed comparing the highest with the 2 lower intake tertiles by genetic risk subgroups using discrete logistic regression, conducted in each study separately and then using pooled data. Participants without AMD lesions at any visit were controls. We adjusted for age and sex in analyses of each cohort sample and for smoking status and study site in pooled-data analyses. MAIN OUTCOME MEASURES: All 15-year incident late AMD cases were confirmed by chief investigators of the Beaver Dam Eye Study, BMES, and RS. Intergrader reproducibility was assessed in an early AMD subsample, with 86.4% agreement between BMES and RS graders, allowing for a 1-step difference on a 5-step AMD severity scale. RESULTS: In pooled data analyses, we found significant interaction between AMD genetic risk status and LZ intake (P=0.0009) but nonsignificant interactions between genetic risk status and weekly fish consumption (P=0.05) for risk of any AMD. Among participants with high genetic risk, the highest intake tertile of LZ was associated with a >20% reduced risk of early AMD, and weekly consumption of fish was associated with a 40% reduced risk of late AMD. No similar association was evident among participants with low genetic risk. No interaction was detected between ß-carotene or vitamin C and genetic risk status. CONCLUSIONS: Protection against AMD from greater LZ and fish consumption in persons with high genetic risk based on 2 major AMD genes raises the possibility of personalized preventive interventions.

Risk of advanced age-related macular degeneration after cataract surgery in the Age-Related Eye Disease Study: AREDS report 25.

PURPOSE: To assess the risk of advanced age-related macular degeneration (AMD) developing after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Four thousand five hundred seventy-seven participants (8050 eyes) from a multicenter, controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS). METHODS: Development of advanced AMD, either neovascular (NV) AMD or geographic atrophy (GA), was evaluated with annual fundus photographs, and history of cataract surgery was assessed every 6 months. Cox proportional hazard models with time-dependent covariates were conducted for NV AMD and GA separately. MAIN OUTCOME MEASURES: Neovascular AMD, GA, and central GA (CGA; involving the center of the macula). RESULTS: The Cox proportional hazards model of right eyes showed nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82-1.75) for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49) for CGA. CONCLUSIONS: The AREDS results showed no clear effect of cataract surgery on the risk of progression to advanced AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study.

OBJECTIVES: To describe the 15-year incidence of retinal vein occlusion (central retinal vein occlusion and branch retinal vein occlusion) and associated risk factors. METHODS: A population-based study where branch retinal vein occlusion and central retinal vein occlusion were detected at baseline (n = 4068, 1988-1990) and three 5-year follow-up examinations by grading 30 degrees color fundus photographs. RESULTS: The 15-year cumulative incidences of branch retinal vein occlusion and central retinal vein occlusion were 1.8% and 0.5%, respectively. Using a generalized estimating equation model, incident retinal vein occlusion was related to baseline age (odds ratio [OR] per 10 years, 1.70; 95% confidence interval [CI], 1.36-2.12), history of barbiturate use (OR, 5.30; 95% CI, 2.28-12.31), focal retinal arteriolar narrowing (OR, 2.45; 95% CI, 1.29-4.66), glaucoma (OR, 3.17; 95% CI, 1.50-6.69), serum ionized calcium level (OR per 0.4 mg/dL, 0.43; 95% CI, 0.23-0.79), serum phosphorus level (OR per 0.3 mg/dL, 1.15; 95% CI, 1.01-1.30), and serum creatinine level (OR for > or = 1.4 vs < 1.4 mg/dL, 1.61; 95% CI, 1.00-2.59). Migraine headache history was associated with branch retinal vein occlusion (OR, 1.99; 95% CI, 1.08-3.67). Diabetes history was associated with central retinal vein occlusion (OR, 6.35; 95% CI, 1.90-21.27). CONCLUSIONS: Incident retinal vein occlusion is not infrequent in the population, especially after age 65 years. The relationships of barbiturate use, serum creatinine level, serum ionized calcium level, and serum phosphorus level with incident retinal vein occlusion require further assessment in other large population-based studies.

Supplements and age-related eye conditions the beaver dam eye study.

OBJECTIVE: To investigate the association of use of vitamin, mineral, and nonvitamin nonmineral supplements with common age-related eye diseases. DESIGN: Population-based prospective study with incidence data. PARTICIPANTS: Subjects were participants in the Beaver Dam Eye Study who contributed data in 1988 to 1990 (n = 4926), 1993 to 1995 (n = 3722), 1998 to 2000 (n = 2962), and 2003 to 2005 (n = 2375). METHODS: Use of all medications and supplements were collected from study participants at each of 4 examinations. Intraocular pressure (IOP) measurement and fundus and lens photography were done at each visit. Visual field data are available only from baseline. Photographs of the lenses, retina, and discs were graded using standard protocols by trained graders. MAIN OUTCOME MEASURES: Incidence of age-related cataracts, macular degeneration (AMD), and high IOP for one set of analyses and incidence of supplement use for the second set of analyses. RESULTS: There was little evidence of any significant associations between supplement use and incident ocular outcomes except for a small protective effect for cortical cataracts by vitamins A and D, zinc, and multivitamins and increased odds of late AMD. Late AMD was associated with incident use of vitamins A, C, and E and zinc. CONCLUSIONS: Age-related macular degeneration seems to precede use of vitamins A, C, and E and zinc. This may reflect advice by family, friends, and health care providers about the benefits of Age-Related Eye Disease Study-like supplements.

Lifestyle exposures and eye diseases in adults.

PURPOSE: To provide a perspective of observed associations between lifestyle exposures and eye diseases in adults. DESIGN: Summary of recent epidemiologic studies. METHODS: Nonsystematic review of the literature. RESULTS: Data suggest that some lifestyle exposures (e.g., smoking) are significantly associated with risk of several different diseases, suggesting that altering behaviors may decrease risk. Where risk is inherent to an occupational or recreational activity, eye protection is likely to decrease risk. CONCLUSIONS: Although data are imperfect, it seems that some lifestyle alterations may decrease the risk of eye diseases at little or no risk to the individual.

A longitudinal study of nonvitamin, nonmineral supplement use: prevalence, associations, and survival in an aging population.

PURPOSE: We sought to describe population and survival characteristics in nonvitamin, nonmineral (NVNM) supplement users in a population-based cohort study. METHODS: People from 43 to 86 years of age living in Beaver Dam, Wisconsin, participated in a baseline examination from 1988 to 1990 (n = 4,926) and three follow-up examinations at 5-year intervals (n = 3,722, 2,962, 2,375 at each successive examination). Medication and supplement use, medical and lifestyle factors were collected during the examination and survival was monitored through 2002. RESULTS: NVNM supplement use increased from 5% at baseline, to 6% at the second, to 21% at the third to 30% at the fourth examination. In general, younger age, vitamin or mineral use, and taking more medications was directly related to NVNM supplement use, while current smoking and history of other systemic diseases (e.g., cardiovascular disease, cancer) was inversely related to NVNM supplement use. After adjusting for age, sex, and other medical and lifestyle factors, users of NVNM supplements had lower mortality (hazard ratio, 0.74; 95% confidence interval, 0.57-0.95, p = 0.02) than nonusers. CONCLUSIONS: NVNM supplement users had a healthier lifestyle and fewer co-morbid medical conditions and were more likely to survive after adjusting for these factors than non-users.

The relationship of optic disk cupping to retinal vein occlusion: the Beaver Dam Eye Study.

PURPOSE: To examine the association between optic disk cupping and retinal vein occlusion (RVO). DESIGN: Prospective epidemiologic study. METHODS: setting: Population-based prospective study in Beaver Dam, Wisconsin. study population: Adults aged 43 to 86 years at baseline (n = 4926). observation procedures: Optic disk cupping and RVO were determined from retinal photographs. A standardized medical examination and questionnaire were administered. main outcome measure: Ten-year cumulative incidence of RVO. RESULTS: There were 58 persons who developed incident RVO at 5 (n = 31) or 10 (n = 27) years after the baseline examination. Those sustaining RVO were older, had higher intraocular pressure (IOP), and were more likely to have definite or probable glaucoma at the baseline examination. The odds of having an incident RVO increased with increasing cup-to-disk ratio at baseline (odds ratio [OR] = 1.29/0.1 increase in cup-to-disk ratio, 95% confidence interval 1.07, 1.56), while controlling for age, systolic blood pressure, current smoking, diabetes status, and IOP. A similar OR was found after excluding those with glaucoma. Excluding persons with central (as opposed to branch) vein occlusion did not have a significant effect on the OR. CONCLUSION: Cup-to-disk ratio is a significant predictor of risk of incident RVO.

Age-related macular degeneration and optic disk cupping: the Beaver Dam Eye Study.

PURPOSE: To examine the association between presence, severity, and extent of lesions of age-related macular degeneration (AMD) and optic disk and cup diameters in a general population. DESIGN: Cross-sectional study. METHODS: setting: Population-based. study population: Adults aged 43 to 86 years participating in the Beaver Dam Eye Study. observation procedures: Fundus photographs were graded for lesions of AMD using standard protocols. The photographs were obtained during the baseline examination of the Beaver Dam Eye Study. main outcome measure: Optic disk cupping as related to presence, severity, and extent of lesions of AMD. RESULTS: There were no significant differences in the vertical optic disk and cup measurements or in the vertical cup to disk ratios by severity of lesions of AMD (P values all greater than .10). In those eyes with late lesions of AMD, there was no association of the size of the lesions or their distribution in the fundus and the extent of cupping. CONCLUSIONS: From a population perspective, there is no relationship of the presence or severity of AMD and optic disk cupping.

Does the intraocular pressure effect on optic disc cupping differ by age?

PURPOSE: To investigate whether age influences optic disc cupping in addition to the effects of intraocular pressure (IOP). METHODS: Population-based study (N = 4,926 at baseline). All measures including fundus photography were done according to standard protocols. Stereoscopic images of the optic disc were graded in masked fashion. RESULTS: Cup-to-disc ratios (C/D) were directly related to IOP at baseline. Age of 75 years or older was associated with increase in cupping at a given level of IOP, but the age association was attenuated when including refraction in multivariable models. Change in C/D between baseline and 15-year follow-up was also influenced by age such that those 75 years of age or older were at increased risk of cupping. When refraction was included in this model, age was still significant. CONCLUSIONS: People who are at least 75 years of age are at greater risk of developing optic disc cupping, which is associated with greater IOP.

Relations of serum ascorbic acid and alpha-tocopherol to diabetic retinopathy in the Third National Health and Nutrition Examination Survey.

The protective relation of ascorbic acid and alpha-tocopherol to the development of diabetic retinopathy has not been thoroughly evaluated in epidemiologic studies. The association of prevalent diabetic retinopathy with serum ascorbic acid and alpha-tocopherol was studied among participants with type 2 diabetes (>or=40 years) (n = 998) in the Third National Health and Nutrition Examination Survey (1988-1994); 20% of the sample (n = 199) had prevalent retinopathy. The overall odds ratio for retinopathy among participants in quartile 4 compared with quartile 1 for serum ascorbic acid was 1.3 (95% confidence interval: 0.8, 2.3), with a p for trend = 0.60 after adjustment for the confounders of smoking, race, waist/hip ratio, hypertension, and duration of diabetes. The overall odds ratio for retinopathy among participants in quartile 4 compared with quartile 1 for serum alpha-tocopherol was 2.7 (95% confidence interval: 1.6, 4.6), with a p for trend = 0.14 after adjustment for confounders. After removal of supplement users of vitamin C (n = 307) or vitamin E (n = 298), the odds ratio changed direction or was attenuated: adjusted odds ratios for retinopathy among participants in quartile 4 compared with quartile 1 for serum ascorbic acid and alpha-tocopherol = 0.7 (95% confidence interval: 0.3, 1.4) and 1.6 (95% confidence interval: 0.9, 2.9), respectively. In summary, no significant associations were observed between serum levels of major dietary antioxidants and retinopathy. Recent use of supplements for treatment of complications of diabetes may explain the direct associations.