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.

An Association Between Large Optic Cupping and Total and Regional Brain Volume: The Women's Health Initiative.

PURPOSE: To investigate the relationships between optic nerve cupping and total and regional brain volumes. DESIGN: Secondary analysis of randomized clinical trial data. METHODS: Women 65 to 79 years of age without glaucoma with cup-to-disc ratio (CDR) measurements from the Women's Health Initiative (WHI) Sight Examination study and magnetic resonance imaging (MRI)-based total and regional brain volumes from the WHI Memory Study MRI-1 were included. Large CDR was defined as 0.6 or greater in either eye. Generalized estimating equation models were used to account for intra-brain correlations between the right and left sides. The final analysis was adjusted for demographic and clinical characteristics and for total brain volume (for regional analyses). RESULTS: Final analyses included 471 women, with the mean age ± SD was 69.2 ± 3.6 years; 92.8% of the subjects were white. Of 471 women, 34 (7.2%) had large CDR. Controlling for total brain volume and for demographic and clinical characteristics, lateral ventricle volume was 3.01 cc larger for subjects with large CDR compared to those without large CDR (95% CI = 0.02 to 5.99; P = .048). Furthermore, frontal lobe volume was 4.78 cc lower for subjects with large CDR compared to those without (95% CI = -8.71, -0.84; P = 0.02), and occipital lobe volume was 1.86 cc lower for those with large CDR compared to those without (95% CI = -3.39, -0.3; P =.02). CONCLUSIONS: Our analysis suggests that in women aged 65 years or more, large CDR is associated with lower relative total brain volume and absolute regional volume in the frontal and occipital lobes. Enlarged CDR in individuals without glaucoma may represent a sign of optic nerve and brain aging, although more longitudinal data are needed.

Association between cognitive function and large optic nerve cupping, accounting for cup-disc-ratio genetic risk score.

PURPOSE: To investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women. DESIGN: This was a retrospective study using data from the Women's Health Initiative. METHODS: Patients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics. RESULTS: Final analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007). CONCLUSIONS: Independent of the CDR GRS, women with large CDR had a lower cognitive function.

An Association Between Large Optic Nerve Cupping and Cognitive Function.

PURPOSE: To determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension. METHODS: We used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy. RESULTS: Analyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04). CONCLUSIONS: Postmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Supplementation with three different macular carotenoid formulations in patients with early age-related macular degeneration.

PURPOSE: To investigate the impact of three different macular carotenoid formulations on macular pigment optical density and visual performance in subjects with early age-related macular degeneration. METHODS: Fifty-two subjects were supplemented and followed for 12 months, 17 of them were in intervention Group 1 (20 mg/day lutein and 2 mg/day zeaxanthin); 21 in Group 2 (10 mg/day meso-zeaxanthin, 10 mg/day lutein, and 2 mg/day zeaxanthin); and 14 in Group 3 (17 mg/day meso-zeaxanthin, 3 mg/day lutein, and 2 mg/day zeaxanthin). The macular pigment optical density was measured using customized heterochromatic flicker photometry, and visual function was assessed using corrected distance visual acuity and by letter contrast sensitivity. RESULTS: A statistically significant increase in the macular pigment optical density was observed at all measured eccentricities in Group 2 (P ≤ 0.005) and in Group 3 (P < 0.05, for all), but only at 1.75° in Group 1 (P = 0.018). Statistically significant (P < 0.05) improvements in letter contrast sensitivity were seen at all spatial frequencies (except 1.2 cycles per degree) in Group 3, and at low spatial frequencies in Groups 1 and 2. CONCLUSION: Augmentation of the macular pigment optical density across its spatial profile and enhancements in contrast sensitivity were best achieved after supplementation with a formulation containing high doses of meso-zeaxanthin in combination with lutein and zeaxanthin.

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.

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.

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.