The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts in the Age-Related Eye Disease Study: AREDS Report No. 37.

PURPOSE: To evaluate whether dietary intake of luteiin/zeaxanthin and B vitamins is associated with cataract prevalence and incidence. DESIGN: Clinic-based, baseline cross-sectional and prospective cohort study designs. PARTICIPANTS: Three thousand one hundred fifteen patients (6129 eyes) enrolled in the Age-Related Eye Disease Study 55 to 80 years of age followed up for mean of 9.6 years. METHODS: Participants completed baseline food frequency questionnaires. Baseline and annual lens photographs were graded centrally. Multivariate models controlling for previously identified risk factors for cataracts tested for the association of cataracts with reported dietary intake, using the lowest quintile as reference. MAIN OUTCOME MEASURES: Cataract surgery, cataract status (type and severity) at baseline, and development of cataracts. RESULTS: At baseline, increased dietary riboflavin and B12 were associated inversely with nuclear and cortical lens opacities. In comparisons of persons with and without cataract, persons with the highest riboflavin intake versus those with the lowest intake had the following associations: mild nuclear cataract: odds ratio (OR), 0.78; 95% confidence interval (CI), 0.63-0.97; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43-0.90; and mild cortical cataract: OR, 0.80; 95% CI, 0.65-0.99. For B12, the results were: mild nuclear cataract: OR, 0.78; 95% CI, 0.63-0.96; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43-0.88; and mild cortical cataract: OR, 0.77; 95% CI, 0.63-0.95. Highest dietary B6 intake was associated with a decreased risk of moderate nuclear lens opacity developing compared with the lowest quintile (OR, 0.67; 95% CI, 0.45-0.99). Highest dietary intake levels of niacin and B12 were associated with a decreased risk of development of mild nuclear or mild cortical cataracts in participants not taking Centrum (Pfizer, New York, NY) multivitamins. For participants taking multivitamins during the study, the highest intake of dietary folate was associated with an increased risk of mild posterior subcapsular lens opacity development. No statistically significant associations were found between lutein plus zeaxanthin intake and presence at baseline or development of nuclear or cortical lens opacity outcomes. CONCLUSIONS: These findings are consistent with earlier studies suggesting that dietary intake of B vitamins may affect the occurrence of age-related lens opacities. Further investigations are warranted.

Treatment of geographic atrophy with subconjunctival sirolimus: results of a phase I/II clinical trial.

PURPOSE: To investigate the safety and effects of subconjunctival sirolimus, an mTOR inhibitor and immunosuppressive agent, for the treatment of geographic atrophy (GA). METHODS: The study was a single-center, open-label phase II trial, enrolling 11 participants with bilateral GA; eight participants completed 24 months of follow-up. Sirolimus (440 µg) was administered every 3 months as a subconjunctival injection in only one randomly assigned eye in each participant for 24 months. Fellow eyes served as untreated controls. The primary efficacy outcome measure was the change in the total GA area at 24 months. Secondary outcomes included changes in visual acuity, macular sensitivity, central retinal thickness, and total drusen area. RESULTS: The study drug was well tolerated with few symptoms and related adverse events. Study treatment in study eyes was not associated with structural or functional benefits relative to the control fellow eyes. At month 24, mean GA area increased by 54.5% and 39.7% in study and fellow eyes, respectively (P = 0.41), whereas mean visual acuity decreased by 21.0 letters and 3.0 letters in study and fellow eyes, respectively (P = 0.03). Substantial differences in mean changes in drusen area, central retinal thickness, and macular sensitivity were not detected for all analysis time points up to 24 months. CONCLUSIONS: Repeated subconjunctival sirolimus was well-tolerated in patients with GA, although no positive anatomic or functional effects were identified. Subconjunctival sirolimus may not be beneficial in the prevention of GA progression, and may potentially be associated with effects detrimental to visual acuity. (ClinicalTrials.gov number, NCT00766649.).