Red blood cell fatty acids and age-related macular degeneration in postmenopausal women.

PURPOSE: To evaluate the relationship between red blood cell (RBC) polyunsaturated fatty acid (PUFA) levels, and dietary PUFA and fish intake, with prevalent and incident age-related macular degeneration (AMD) in a US cohort of postmenopausal women. METHODS: This analysis included 1456 postmenopausal women from the Women's Health Initiative (WHI) Clinical Trials. RBC PUFAs were measured from fasting serum samples collected at WHI baseline. Dietary PUFAs and fish intake were assessed via food frequency questionnaires at baseline. There were 240 women who had prevalent AMD and 138 who self-reported AMD development over 9.5 years. Adjusted odds ratios and 95% confidence intervals were estimated for prevalent AMD by RBC PUFA levels, dietary PUFA intake, and frequency of fish consumption. Adjusted hazard ratios and 95% confidence intervals were estimated for incident AMD. A p-for-trend was estimated for continuous measures of dietary PUFA and fish intake. RESULTS: No significant association was found between prevalent or incident AMD and RBC docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA), EPA, DHA, alpha-linolenic acid (ALA), linoleic acid (LA), or arachidonic acid (AA). A positive association was found between dietary intake of AA and odds of prevalent AMD (p-for-trend for continuous AA intake = 0.02) and between intake of LA/ALA and incident AMD (p-for-trend for continuous ratio of LA/ALA intake = 0.03). No statistically significant associations were found between AMD and dietary intake of PUFAs or fish. CONCLUSIONS: RBC PUFAs were not associated with AMD in this cohort. Overall, dietary analyses of PUFAs supported this, excepting dietary AA intake and intake of LA in proportion to ALA of which there were trends of increased risk.

Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake.

25-Hydroxyvitamin D (25(OH)D) concentration is a complex trait with genetic and environmental predictors that may determine how much vitamin D exposure is required to reach optimal concentration. Interactions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultraviolet (UV) radiation (PGS*UV) were evaluated in individuals of African (n = 1,099) or European (n = 8,569) ancestries. Interaction terms and joint effects (main and interaction terms) were tested using one-degree of freedom (1-DF) and 2-DF models, respectively. Models controlled for age, sex, body mass index, cohort, and dietary intake/available UV. In addition, in participants achieving Institute of Medicine (IOM) vitamin D intake recommendations, 25(OH)D was evaluated by level PGS. The 2-DF PGS*intake, 1-DF PGS*UV, and 2-DF PGS*UV results were statistically significant in participants of European ancestry (p = 3.3 × 10-18 , p = 2.1 × 10-2 , and p = 2.4 × 10-19 , respectively), but not in those of African ancestry. In European-ancestry participants reaching IOM vitamin D intake guidelines, the percent of participants achieving adequate 25(OH)D ( >20 ng/ml) increased as genetic risk decreased (72% vs. 89% in highest vs. lowest risk; p = .018). Available UV radiation and vitamin D intake interact with genetics to influence 25(OH)D. Individuals with higher genetic risk may require more vitamin D exposure to maintain optimal 25(OH)D concentrations.

Dietary carotenoids and cognitive function among US adults, NHANES 2011-2014.

Objectives: Dietary carotenoids may limit neuronal damage from free radicals, potentially serving as a modifiable risk factor for cognitive decline. We examined intake of lutein and zeaxanthin (L and Z) in relation to cognitive performance among 2011-2014 National Health and Nutrition Examination Survey participants aged ≥60 years. Methods: L and Z intake from foods and supplements was estimated from two non-consecutive 24-hour diet recalls. Outcomes included the CERAD Word Learning sub-test score, Animal Fluency test score, and Digit Symbol Substitution test score. Regression models were adjusted for survey design variables, year, sex, age, race/ethnicity, body mass index, family income, education, alcohol, and smoking. Results: Among the 2796 participants, higher dietary intake of L and Z was associated with higher score on each test. For example, the highest quartile of L and Z intake was associated with a 2.52 point increase (SE=0.86 points, P=0.01) on the digit symbol score test, compared with the lowest quartile. There were differences by race/ethnicity, with positive associations generally stronger for Black compared to white participants. Discussion: Further research from longitudinal studies is needed, but increasing L and Z intake may help to prevent or slow cognitive decline.

Adherence to a Mediterranean diet and cognitive function in the Age-Related Eye Disease Studies 1 & 2.

INTRODUCTION: The objective was to determine whether closer adherence to the alternative Mediterranean Diet (aMED) was associated with altered cognitive function. METHODS: Observational analyses of participants (n = 7,756) enrolled in two randomized trials of nutritional supplements for age-related macular degeneration: Age-Related Eye Disease Study (AREDS) and AREDS2. RESULTS: Odds ratios for cognitive impairment, in aMED tertile 3 (vs 1), were 0.36 (P = .0001) for Modified Mini-Mental State (<80) and 0.56 (P = .001) for composite score in AREDS, and 0.56 for Telephone Interview Cognitive Status-Modified (<30) and 0.48 for composite score (each P < .0001) in AREDS2. Fish intake was associated with higher cognitive function. In AREDS2, rate of cognitive decline over 5 to 10 years was not significantly different by aMED but was significantly slower (P = .019) with higher fish intake. DISCUSSION: Closer Mediterranean diet adherence was associated with lower risk of cognitive impairment but not slower decline in cognitive function. Apolipoprotein E (APOE) haplotype did not influence these relationships.

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.

Joint Associations of Diet, Lifestyle, and Genes with Age-Related Macular Degeneration.

PURPOSE: Unhealthy lifestyles have been associated with increased odds for age-related macular degeneration (AMD). Whether this association is modified by genetic risk for AMD is unknown and was investigated. DESIGN: Interactions between healthy lifestyles AMD risk genotypes were studied in relation to the prevalence of AMD, assessed 6 years later. PARTICIPANTS: Women 50 to 79 years of age in the Carotenoids in Age-Related Eye Disease Study with exposure and AMD data (n=1663). METHODS: Healthy lifestyle scores (0-6 points) were assigned based on Healthy Eating Index scores, physical activity (metabolic equivalent of task hours/week), and smoking pack years assessed in 1994 and 1998. Genetic risk was based on Y402H in complement factor H (CFH) and A69S in age-related maculopathy susceptibility locus 2 (ARMS2). Additive and multiplicative interactions in odds ratios were assessed using the synergy index and a multiplicative interaction term, respectively. MAIN OUTCOME MEASURES: AMD presence and severity were assessed from grading of stereoscopic fundus photographs taken in 2001-2004. AMD was present in 337 women, 91% of whom had early AMD. RESULTS: The odds of AMD were 3.3 times greater (95% confidence interval [CI], 1.8-6.1) in women with both low healthy lifestyle score (0-2) and high-risk CFH genotype (CC), relative to those who had low genetic risk (TT) and high healthy lifestyle scores (4-6). There were no significant additive (synergy index [SI], 1.08; 95% CI, 0.70-1.67) or multiplicative (Pinteraction=0.94) interactions in the full sample. However, when limiting the sample to women with stable diets before AMD assessment (n=728) the odds for AMD associated with low healthy lifestyle scores and high-risk CFH genotype were strengthened (odds ratio, 4.6; 95% CI, 1.8-11.6) and the synergy index was significant (SI, 1.34; 95% CI, 1.05-1.70). Adjusting for dietary lutein and zeaxanthin attenuated, and therefore partially explained, the joint association. There were no significant additive or multiplicative interactions for ARMS2 and lifestyle score. CONCLUSIONS: Having unhealthy lifestyles and 2 CFH risk alleles increased AMD risk (primarily in the early stages), in an or additive or greater (synergistic) manner. However, unhealthy lifestyles increased AMD risk regardless of AMD risk genotype.

Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids.

OBJECTIVE: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). DESIGN: A cross-sectional study of healthy adults aged 20 to 70. PARTICIPANTS: We recruited 302 participants after local advertisement. METHODS: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts. MAIN OUTCOME MEASURES: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender. RESULTS: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10(-4)), an SNP in high linkage disequilibrium with rs11057841 (r(2) = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. CONCLUSIONS: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Vitamin D intake and season modify the effects of the GC and CYP2R1 genes on 25-hydroxyvitamin D concentrations.

Vitamin D deficiency {defined by the blood concentration of 25-hydroxyvitamin D [25(OH)D]} has been associated with many adverse health outcomes. Genetic and nongenetic factors account for variation in 25(OH)D, but the role of interactions between these factors is unknown. To assess this, we examined 1204 women of European descent from the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative Observational Study. Twenty-nine single nucleotide polymorphisms (SNPs) in 4 genes, GC, CYP2R1, DHCR7, and CYP24A1, from recent meta-analyses of 25(OH)D genome-wide association studies were genotyped. Associations between these SNPs and 25(OH)D were tested using generalized linear regression under an additive genetic model adjusted for age, blood draw month, and ancestry. Results were stratified by season of blood draw and, separately, vitamin D intake for the 6 SNPs showing a significant association with 25(OH)D at the P < 0.01 level. Two nonsynonymous SNPs in GC and 4 SNPs in CYP2R1 were strongly associated with 25(OH)D in individuals whose blood was drawn in summer (P ≤ 0.002) but not winter months and, independently, in individuals with vitamin D intakes ≥400 (P ≤ 0.004) but not <400 IU/d (10 µg/d). This effect modification, if confirmed, has important implications for the design of genetic studies for all health outcomes and for public health recommendations and clinical practice guidelines regarding the achievement of adequate vitamin D status.

Reticular Pseudodrusen Characteristics and Associations in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2), an Ancillary Study of the Women's Health Initiative.

PURPOSE: To determine the prevalence and morphologic features of reticular pseudodrusen (RPD) and their association with participant demographics and age-related macular degeneration (AMD) status in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) sample, an ancillary study of the Women's Health Initiative Observational Study. DESIGN: Cross-sectional, multicenter, natural history study. PARTICIPANTS: Nine hundred and twenty-seven eyes from 466 postmenopausal women 69 to 101 years of age. METHODS: Multimodal imaging, including spectral-domain (SD) OCT and infrared reflectance (IR), were used to identify RPD characteristics, including location (within or outside the 6-mm diameter circle centered at the macula), presence of peripapillary RPD, pattern of RPD, and RPD area. Age-related macular degeneration features from SD OCT, IR, and color photographs also were assessed and AMD severity was categorized. MAIN OUTCOME MEASURES: Reticular pseudodrusen prevalence using SD OCT and IR imaging and AMD status. RESULTS: Reticular pseudodrusen were present in 130 eyes (14% of eyes, 16% of participants), with increasing prevalence with age: 7% in those younger than 78 years, 14% in those 78 to 83 years of age, and 30% in those older than 83 years. Using clinical classification of AMD with color photography, RPD were seen in 2.4% of eyes with no AMD or aging changes, 11.5% in early AMD, 25.1% in intermediate AMD, and 51.1% in late AMD. Mean RPD area was 17.4 mm2 (standard deviation, 14.7 mm2). Ribbon morphologic RPD (53%) was more common than dot morphologic RPD (36%). Reticular pseudodrusen mostly were located both within and outside the 6-mm circle with primarily superior retinal distribution. Reticular pseudodrusen were visualized with corresponding color fundus photography in only 38 eyes (4% of total eyes). Participants with and without RPD had a visual acuity±standard error of 77.9 ± 1.4 letters and 81.3 ± 0.4 letters, respectively (P = 0.02). CONCLUSIONS: The prevalence of RPD in CAREDS2 increased with age and was associated with AMD severity. Reticular pseudodrusen were detected in eyes without other features of AMD and could represent an earlier disease state. Multimodal imaging with SD OCT and IR has significantly greater sensitivity for visualizing RPD than color fundus photography.

Serum and Macular Carotenoids in Relation to Retinal Vessel Caliber Fifteen Years Later, in the Second Carotenoids in Age-Related Eye Disease Study.

Purpose: We investigated whether dietary carotenoids lutein and zeaxanthin (L/Z) in the serum and macula were associated with central retinal arteriole and venule calibers in a follow-up ancillary study among older women in the Women's Health Initiative. Methods: Among 390 women who participated in Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2) (2016-2019), we investigated associations between serum L/Z at Women's Health Initiative baseline (1994-1998), and macular pigment optical density (MPOD) at CAREDS baseline (2001-2004), with central retinal vessel caliber in CAREDS2. MPOD was measured using heterochromatic flicker photometry (0.5° from the foveal center) in CAREDS baseline and CAREDS2. Vessel calibers were measured from fundus photographs (CAREDS2). We also explored associations in women with stable MPOD (±0.10 optical density units) over 15 years (n = 106), given the long-term increases in MPOD related to diet patterns and supplement use. Associations were investigated using linear modeling. Results: In the full sample (n = 390), higher serum L/Z (tertile 3 vs. 1) was positively associated with arteriole caliber (mean ± SE, 145.0 ± 1.4 µm vs. 140.8 ± 1.4 µm; P = 0.05) and venule caliber (214.6 ± 2.2 µm vs. 207.5 ± 2.2 µm; P = 0.03). MPOD was also associated with wider vessel calibers (tertile 3 vs. 1), but the trend was only statistically significant for venules (144.4 ± 1.4 µm vs. 141.1 ± 1.4 µm [P = 0.12] and 213.3 ± 2.1 µm vs. 206.0 ± 2.1 µm [P = 0.02], respectively.) Most associations were strengthened in women with stable MPOD over 15 years, including between MPOD and arteriole caliber (149.8 ± 2.6 µm vs.135.8 ± 3.0 µm; P = 0.001). Conclusions: Higher L/Z status in serum and retina was associated with larger central retinal vessel calibers. Prospective studies and clinical trials are needed to elucidate whether L/Z supplementation prevents vision loss through increasing blood flow.

Association of Macular Thickness With Age and Age-Related Macular Degeneration in the Carotenoids in Age-Related Eye Disease Study 2 (CAREDS2), An Ancillary Study of the Women's Health Initiative.

Purpose: To evaluate the relationship of retinal layer thickness with age and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study 2. Methods: Total retinal thickness within the macular area, and individual layer thickness was determined for CAREDS2 participants (n = 906 eyes, 473 women) from the Women's Health Initiative using Heidelberg optical coherence tomography (OCT). Mean measurements within the OCT grid were compared across age tertiles (69-78, 78-83, and 83-101 years) and AMD outcomes. Results: Mean retinal thickness in the central circle, inner ring, and outer ring were 277 ± 34 µm, 326 ± 20 µm, and 282 ± 15 µm, respectively. Thickness did not vary by age in the central circle, but decreased with age in the inner and outer circles (P ≤ 0.004). Specifically, ganglion cell (GCL), inner plexiform, and outer nuclear (ONL) layer thickness decreased with age (P ≤ 0.003). Age-adjusted retinal thickness in all three circles did not vary by AMD outcomes (486 without AMD and 413 with AMD). However, individual layers showed changes with GCL and photoreceptor thinning and retinal pigment epithelial thicknening in eyes with late AMD. After controlling for age and AMD, higher ONL thickness was associated with better visual acuity. Conclusions: In this cohort of older women, a decrease in perifoveal thickness was associated with increasing age, particularly in the inner retinal layers. Variabilty in thickness in AMD eyes was primarily due to outer retinal layers. Among all retinal layers, the ONL plays an important role in preserving visual acuity. Translational Relevance: The study provides a deeper understanding of age related changes to the retinal layers and their effect on visual loss.

Women's Health Initiative diet intervention did not increase macular pigment optical density in an ancillary study of a subsample of the Women's Health Initiative.

In this study, we examined the impact of long-term (>8 y), low-fat, high-fruit and -vegetable diets on levels of lutein and zeaxanthin in the macula of the retina, as indicated by the OD of macular pigment. Macular pigment OD, measured by heterochromatic flicker photometry, was compared in women aged 60-87 y, who, 7-18 mo earlier (median 12 mo), had been in the dietary modification intervention (n = 158) or comparison (n = 236) groups of the Women's Health Initiative (WHI) at the Madison, WI site for a mean of 8.5 y. Women in the intervention group ate more fruits and vegetables (mean +/- SEM) (6.1 +/- 0.2 vs. 4.6 +/- 0.2 servings/d; P < 0.0001) and had higher intakes of lutein and zeaxanthin from foods and supplements (2.7 +/- 0.2 vs. 2.1 +/- 0.1 mg/d; P = 0.0003) than the comparison group. However, macular pigment density did not differ between the intervention (0.36 +/- 0.02 OD units) and comparison (0.35 +/- 0.01 OD units) groups. It tended to be higher (11%; P = 0.11) in women consuming lutein and zeaxanthin in the highest compared with the lowest quintile (median 6.4 vs. 1.1 mg/d). The increase in fruit and vegetable intake among dietary modification participants of this WHI subsample was not of sufficient magnitude to alter the mean density of retinal carotenoids, given other existing dietary conditions in this sample.

Serum 25-Hydroxyvitamin D Concentrations and Incidence of Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study.

Purpose: To investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentrations at visit 2 (1990-1992) and the 18-year incidence of age-related macular degeneration (AMD) between visit 3 (1993-1995) and visit 5 (2011-2013). Methods: This prospective analysis was conducted in a subset of participants (n = 1225) from the Atherosclerosis Risk in Communities Study. We evaluated the incidence of any, early, and late AMD from visit 3 to 5. The 25(OH)D concentrations were assessed in 2012-2013 by using stored serum from visit 2. Retinal fundus photographs taken at both visits were graded side by side to determine the incidence of AMD. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for incident AMD outcomes during 18 years of follow-up (1993-1995 to 2011-2013) by tertile of 25(OH)D adjusted for age, race, and smoking status. P for linear trend was estimated by using continuous 25(OH)D concentrations. Sensitivity analyses applied inverse probability weights to account for selection to have eye photographs, death, and loss to follow-up. Results: There was a decreased odds of any incident AMD (n = 139) and large, soft drusen (n = 80) in 25(OH)D tertile 3 versus 1, with OR (95% CI) = 0.57 (0.36-0.90), P trend = 0.11 and with 0.52 (0.28-0.93), P trend = 0.18, respectively. Applying sampling weights attenuated these results to 0.66 (0.38-1.16), P trend = 0.32 (any incident AMD) and 0.54 (0.27-1.09), P trend = 0.36 (large, soft drusen), respectively, suggesting these associations may be biased by loss to follow-up and sampling for retinal photographs at visit 5. No statistically significant results were observed with pigmentary abnormalities (n = 46) or incident late AMD (n = 26). Conclusions: High 25(OH)D concentrations, approximately >70 nM, may be associated with decreased odds of incident early AMD.

Macular pigment density and age-related maculopathy in the Carotenoids in Age-Related Eye Disease Study. An ancillary study of the women's health initiative.

PURPOSE: To examine the association between intermediate age-related macular degeneration (AMD) and the optical density of macular pigment (MPOD), which is composed of lutein and zeaxanthin from the diet. DESIGN: Cross-sectional cohort study. PARTICIPANTS: We included 1698 of 2005 women ages 54 to 86 years and participating in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative. METHODS: The MPOD was measured noninvasively by heterochromatic flicker photometry. Fundus photographs were taken to document prevalent AMD. MAIN OUTCOME MEASURES: Intermediate AMD (n = 305) and two subtypes-large drusen (n = 233) and pigmentary abnormalities (n = 157). RESULTS: After adjusting for covariates, the odds ratio (OR) and 95% confidence interval (CI) for AMD among women in quintile (Q) 5 (n = 339) versus 1 (n = 340) for MPOD was 1.4 (0.9, 2.1). However, after excluding women with possible unstable diets and recent supplement use due to chronic disease history, associations reversed (OR Q2-5 vs. 1, 0.8; 95% CI, 0.5-1.2), but remained nonsignificant. Associations also differed between middle-aged (54-69 years) and older (> or =70 years) women (P-interaction = 0.09), but less so, after excluding women who were likely to have unstable diets: adjusted ORs (95% CI) were 0.5 (0.3-1.0; P = 0.08) for intermediate AMD among middle-aged women (n = 516) with MPOD in Q2 to Q5 versus 1 and 1.0 (0.5-2.0; P = 0.90) for older women (n = 422). CONCLUSIONS: The MPOD is not cross-sectionally associated with AMD. The inconsistency of relationships across age groups and in subgroups of women who are likely to have more stable diets suggests that cross-sectional associations may be biased and highlights the need to study these relationships prospectively.

Associations between age-related nuclear cataract and lutein and zeaxanthin in the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an Ancillary Study of the Women's Health Initiative.

OBJECTIVE: To evaluate associations between nuclear cataract (determined from slitlamp photographs between May 2001 and January 2004) and lutein and zeaxanthin in the diet and serum in patients between 1994 and 1998 and macula between 2001 and 2004. DESIGN: A total of 1802 women aged 50 to 79 years in Iowa, Wisconsin, and Oregon with intakes of lutein and zeaxanthin above the 78th (high) and below the 28th (low) percentiles in the Women's Health Initiative Observational Study (1994-1998) were recruited 4 to 7 years later (2001-2004) into the Carotenoids in Age-Related Eye Disease Study. RESULTS: Women in the group with high dietary levels of lutein and zeaxanthin had a 23% lower prevalence of nuclear cataract (age-adjusted odds ratio, 0.77; 95% confidence interval, 0.62-0.96) compared with those with low levels. Multivariable adjustment slightly attenuated the association (odds ratio, 0.81; 95% confidence interval, 0.65-1.01). Women in the highest quintile category of diet or serum levels of lutein and zeaxanthin as compared with those in the lowest quintile category were 32% less likely to have nuclear cataract (multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.97; P for trend = .04; and multivariable-adjusted odds ratio, 0.68; 95% confidence interval, 0.47-0.98; P for trend = .01, respectively). Cross-sectional associations with macular pigment density were inverse but not statistically significant. CONCLUSIONS: Diets rich in lutein and zeaxanthin are moderately associated with decreased prevalence of nuclear cataract in older women. However, other protective aspects of such diets may in part explain these relationships.

Racial Differences in the Effects of Hormone Therapy on Incident Open-Angle Glaucoma in a Randomized Trial.

PURPOSE: We conducted a secondary analysis of a randomized, placebo-controlled trial to test if hormone therapy (HT) altered the risk of open-angle glaucoma (OAG), and if the risk reduction varied by race. DESIGN: Secondary analysis of randomized controlled trial data. METHODS: We linked Medicare claims data to 25 535 women in the Women's Health Initiative. Women without a uterus were randomized to receive either oral conjugated equine estrogens (CEE 0.625 mg/day) or placebo, and women with a uterus received oral CEE and medroxyprogesterone acetate (CEE 0.625 mg/day + MPA 2.5 mg/day) or placebo. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence interval. RESULTS: After exclusion of women with prevalent glaucoma or without claims for eye care provider visits, the final analysis included 8102 women (mean age = 68.5 ± 4.8 years). The OAG incidence was 7.6% (mean follow-up = 11.5 ± 5.2 years; mean HT duration = 4.4 ± 2.3 years). Increased age (P trend = .01) and African-American race (HR = 2.69, 95% CI = 2.13-3.42; white as a reference) were significant risk factors for incident OAG. We found no overall benefit of HT in reducing incident OAG (HR = 1.01, 95% CI = 0.79-1.29 in the CEE trial, and HR = 1.05, 95% CI = 0.85-1.29 in the CEE + MPA trial). However, race modified the relationship between CEE use and OAG risk (P interaction = .01), and risk was reduced in African-American women treated with CEE (HR = 0.49, 95% CI = 0.27-0.88), compared to placebo. Race did not modify the relation between CEE + MPA use and OAG risk (P interaction = .68). CONCLUSIONS: Analysis suggests that HT containing estrogen, but not a combination of estrogen and progesterone, reduces the risk of incident OAG among African-American women. Further investigation is needed.

Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994.

OBJECTIVE: To evaluate the associations between levels of vitamin D (25-hydroxyvitamin D) in serum and prevalent age-related macular degeneration (AMD). METHODS AND DESIGN: Cross-sectional associations of serum vitamin D and early and advanced AMD, assessed from nonmydriatic fundus photographs, were evaluated in the third National Health and Nutrition Examination Survey, a multistage nationally representative probability sample of noninstitutionalized individuals (N = 7752; 11% with AMD). RESULTS: Levels of serum vitamin D were inversely associated with early AMD but not advanced AMD. The odds ratio (OR) and 95% confidence interval (CI) for early AMD among participants in the highest vs lowest quintile of serum vitamin D was 0.64 (95% CI, 0.5-0.8; P trend <.001). Exploratory analyses were conducted to evaluate associations with important food and supplemental sources of vitamin D. Milk intake was inversely associated with early AMD (OR, 0.75; 95% CI, 0.6-0.9). Fish intake was inversely associated with advanced AMD (OR, 0.41; 95% CI, 0.2-0.9). Consistent use vs nonuse of vitamin D from supplements was inversely associated with early AMD only in individuals who did not consume milk daily (early AMD: OR, 0.67; 95% CI, 0.5-0.9). CONCLUSION: This study provides evidence that vitamin D may protect against AMD. Additional studies are needed to confirm these findings.

Association between Dietary Xanthophyll (Lutein and Zeaxanthin) Intake and Early Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study.

PURPOSE: To examine the association between xanthophyll intake and prevalent early age-related macular degeneration (AMD) using data from the Atherosclerosis Risk in Communities Study (n = 10,295). Potential effect modification by genetic polymorphisms and biomarkers of high-density lipoprotein (HDL) metabolism was explored. METHODS: Xanthophyll intake was assessed at visit 1 (1987-1989) using food frequency questionnaires. Prevalent early AMD was assessed at visit 3 (1993-1995) via retinal photographs. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for AMD by quintiles of xanthophyll intake, adjusted for age, sex, race, field center, and pack-years of smoking. To evaluate effect modification, the association between tertiles (T) of xanthophyll intake and AMD was stratified by complement factor H (CFH) rs1061170 and age-related maculopathy susceptibility 2 (ARMS2) rs10490924 genotypes, as well as by median cutpoints of HDL biomarkers. RESULTS: Xanthophyll intake was not associated with AMD in the overall sample, Caucasians (n = 8257), or African-Americans (n = 2038). Exploratory analyses observed that the association between xanthophyll intake and AMD varied statistically significantly by CFH rs1061170 genotype among Caucasians (p for interaction = 0.045) but not African Americans. No interactions were observed between xanthophyll intake and ARMS2 rs10490924. Moreover, higher xanthophyll intake was associated with decreased odds of AMD among participants with lower HDL (OR = 0.79, 95% CI 0.57-1.09) but not higher HDL (p for interaction = 0.048). CONCLUSION: Xanthophyll intake was not associated with early AMD. Further studies to investigate this association by genetic susceptibility or variations in HDL metabolism are needed.

Predictors of optical density of lutein and zeaxanthin in retinas of older women in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative.

BACKGROUND: Lifestyle, diet, and physical and health predictors of xanthophyll carotenoids in the retina are poorly understood. OBJECTIVE: We aimed to investigate the predictors of the density of lutein and zeaxanthin in the macula of the retina. DESIGN: Macular pigment optical density (MPOD) was measured by heterochromatic flicker photometry. Relations to dietary lutein and zeaxanthin and to other predictors were measured in 1698 women aged 53-86 y. The women were members of observational study cohorts of the Women's Health Initiative at Iowa City, IA, Madison, WI, or Portland, OR, and participated in the Carotenoids in Age-Related Eye Disease Study (2001-2004). RESULTS: MPOD at 0.5 degrees from the foveal center was 30% higher in women in the highest quintile for lutein and zeaxanthin intake [x (+/-SD): 0.40 +/- 0.21] than in women in the lowest quintile (0.31 +/- 0.21) and 20% higher after adjustment for other predictors. Dietary intake of lutein, zeaxanthin, fiber, and polyunsaturated fatty acids (% of energy) together explained 3% of the variability in MPOD. Higher waist circumference and diabetes, which are related to lower MPOD, together with study site explained an additional 5% of variation. The total explained variability increased to 12% when lutein and zexanthin concentrations obtained from the serum, which were collected 4-7 y earlier, were added to the model. CONCLUSIONS: MPOD is directly related to dietary intake of lutein and zeaxanthin but even more strongly to serum concentrations, which may reflect unmeasured physical and medical factors that influence the uptake, distribution, and utilization of lutein and zeaxanthin. Higher abdominal body fat and diabetes are related to lower MPOD. Unknown predictors of retinal carotenoids remain.

Macular pigment: a review of current knowledge.

The existence of the macula lutea of the human retina has been known for more than 200 years. It is established that the xanthophylls lutein and zeaxanthin are responsible for the yellow color. The effect of macular photopigments on blue-light filtration and color perception is well established. It has been postulated that the pigment might serve to reduce chromatic aberration and to improve visual acuity. The antioxidant capabilities of these xanthophylls combined with their ability to trap short-wavelength light may serve to protect the outer retina, retinal pigment epithelium, and choriocapillaris from oxidative damage. Current ideas on the pathophysiology of age-related macular degeneration may be compatible with the proposed function of lutein and zeaxanthin. This review will summarize our knowledge about macular pigment regarding current efforts in research and the epidemiology of age-related eye disease.