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.

Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3.

IMPORTANCE: The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina. OBJECTIVE: To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. DESIGN, SETTING, PARTICIPANTS: The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye. INTERVENTIONS: In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination. MAIN OUTCOMES AND MEASURE: S Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P = .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P = .91) for central geographic atrophy. CONCLUSION AND RELEVANCE: The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4.

IMPORTANCE: Age-related cataract is a leading cause of visual impairment in the United States. The prevalence of age-related cataract is increasing, with an estimated 30.1 million Americans likely to be affected by 2020. OBJECTIVE: To determine whether daily oral supplementation with lutein/zeaxanthin affects the risk for cataract surgery. DESIGN, SETTING, AND PATIENTS: The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, double-masked clinical trial, enrolled 4203 participants, aged 50 to 85 years, at risk for progression to advanced age-related macular degeneration. INTERVENTIONS: Participants were randomly assigned to daily placebo; lutein/zeaxanthin, 10mg/2mg; omega-3 long-chain polyunsaturated fatty acids, 1 g; or a combination to evaluate the effects on the primary outcome of progression to advanced age-related macular degeneration. MAIN OUTCOMES AND MEASURES: Cataract surgery was documented at annual study examination with the presence of pseudophakia or aphakia, or reported during telephone calls at 6-month intervals between study visits. Annual best-corrected visual acuity testing was performed. A secondary outcome of AREDS2 was to evaluate the effects of lutein/zeaxanthin on the subsequent need for cataract surgery. RESULTS: A total of 3159 AREDS2 participants were phakic in at least 1 eye and 1389 of 6027 study eyes underwent cataract surgery during the study, with median follow-up of 4.7 years. The 5-year probability of progression to cataract surgery in the no lutein/zeaxanthin group was 24%. For lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratios for progression to cataract surgery was 0.96 (95% CI, 0.84-1.10; P = .54). For participants in the lowest quintile of dietary intake of lutein/zeaxanthin, the hazard ratio comparing lutein/zeaxanthin vs no lutein/zeaxanthin for progression to cataract surgery was 0.68 (95% CI, 0.48-0.96; P = .03). The hazard ratio for 3 or more lines of vision loss was 1.03 (95% CI, 0.93-1.13; P = .61 for lutein/zeaxanthin vs no lutein/zeaxanthin). CONCLUSIONS AND RELEVANCE: Daily supplementation with lutein/zeaxanthin had no statistically significant overall effect on rates of cataract surgery or vision loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

Vitamin D status and early age-related macular degeneration in postmenopausal women.

OBJECTIVE: The relationship between serum 25-hydroxyvitamin D (25[OH]D) concentrations (nmol/L) and the prevalence of early age-related macular degeneration (AMD) was investigated in participants of the Carotenoids in Age-Related Eye Disease Study. METHODS: Stereoscopic fundus photographs, taken from 2001 to 2004, assessed AMD status. Baseline (1994-1998) serum samples were available for 25(OH)D assays in 1313 women with complete ocular and risk factor data. Odds ratios (ORs) and 95% confidence intervals (CIs) for early AMD (n = 241) of 1287 without advanced disease were estimated with logistic regression and adjusted for age, smoking, iris pigmentation, family history of AMD, cardiovascular disease, diabetes, and hormone therapy use. RESULTS: In multivariate models, no significant relationship was observed between early AMD and 25(OH)D (OR for quintile 5 vs 1, 0.79; 95% CI, 0.50-1.24; P for trend = .47). A significant age interaction (P = .002) suggested selective mortality bias in women aged 75 years and older: serum 25(OH)D was associated with decreased odds of early AMD in women younger than 75 years (n = 968) and increased odds in women aged 75 years or older (n = 319) (OR for quintile 5 vs 1, 0.52; 95% CI, 0.29-0.91; P for trend = .02 and OR, 1.76; 95% CI, 0.77-4.13; P for trend = .05, respectively). Further adjustment for body mass index and recreational physical activity, predictors of 25(OH)D, attenuated the observed association in women younger than 75 years. Additionally, among women younger than 75 years, intake of vitamin D from foods and supplements was related to decreased odds of early AMD in multivariate models; no relationship was observed with self-reported time spent in direct sunlight. CONCLUSIONS: High serum 25(OH)D concentrations may protect against early AMD in women younger than 75 years.

Healthy diets and the subsequent prevalence of nuclear cataract in women.

OBJECTIVE: To assess the association between healthy diet scores and prevalence of nuclear cataract in women. METHODS: The association between healthy diet scores, which reflect adherence to the US dietary guidelines, and prevalence of nuclear cataract determined 4 to 7 years later was assessed in a sample of Women's Health Initiative Observational Study participants (aged 50-79 years) residing in Iowa, Wisconsin, and Oregon. Scores on the 1995 Healthy Eating Index, which reflect adherence to 1990 guidelines, were assigned from responses to food frequency questionnaires at the Women's Health Initiative baseline (1994-1998). Presence of nuclear cataract was determined from slitlamp photographs and self-reports of cataract extractions were assessed from May 1, 2001, to January 31, 2004, in 1808 women participating in the Carotenoids in Age-Related Eye Disease Study. RESULTS: Having a high 1995 Healthy Eating Index score was the strongest modifiable predictor of low prevalence of nuclear cataract among numerous risk factors investigated in this sample. The multivariate-adjusted odds ratio for high vs low quintile for diet score was 0.63 (95% confidence interval, 0.43-0.91). Higher prevalence of nuclear cataract was also associated with other modifiable factors (smoking and marked obesity) and nonmodifiable factors (having brown eyes, myopia, and high pulse pressure). Vitamin supplement use was not related to cataract. CONCLUSION: These data add to the body of evidence suggesting that eating foods rich in a variety of vitamins and minerals may contribute to postponing the occurrence of the most common type of cataract in the United States.

Association between dietary fat intake and age-related macular degeneration in the Carotenoids in Age-Related Eye Disease Study (CAREDS): an ancillary study of the Women's Health Initiative.

OBJECTIVE: To evaluate the relationships between the amount and type of dietary fat and intermediate age-related macular degeneration (AMD). DESIGN: Women aged 50 to 79 years with high and low lutein intake from 3 sites of the Women's Health Initiative Observational Study were recruited into the Carotenoids in Age-Related Eye Disease Study. Fat intake from 1994 through 1998 was estimated using food frequency questionnaires, and AMD was assessed photographically from 2001 through 2004. RESULTS: Intakes of omega-6 and omega-3 polyunsaturated fatty acids, which were highly correlated (r = 0.8), were associated with approximately 2-fold higher prevalence of intermediate AMD in high vs low quintiles. However, monounsaturated fatty acid intake was associated with lower prevalence. Age interactions were often observed. In women younger than 75 years (n = 1325), total fat and saturated fatty acid intakes were associated with increased prevalence of AMD (multivariate adjusted odds ratios [95% confidence interval] for intermediate AMD, 1.7 [1.0-2.7] for quintile 5 vs quintile 1 for total fat [P = .10 for trend] and 1.6 [0.7-3.6] for saturated fatty acids [P = .23 for trend]). The associations were reversed in older women. CONCLUSIONS: These results support a growing body of evidence suggesting that diets high in several types of fat may contribute to the risk of intermediate AMD and that diets high in monounsaturated fatty acids may be protective.

Nutritional supplements in the prevention of age-related macular degeneration.

The benefit of the AREDS study and of nutritional supplements in reducing the onset or progression of end-stage AMD in those known to be at risk is a step forward in our understanding of what can be a blinding and debilitating disease. Nutritional supplements are not without risks, and their effects must be diligently and accurately monitored. However, they pose a viable complement in the venue of treating ocular disease and conditions.