Welcome to The Age-Related Eye Disease Study 2 (AREDS2) was a multi-center, randomized trial designed to assess the effects of oral. The Age-Related Eye Disease Study 2 (AREDS2) Research Group* . AREDS2 was designed to test whether adding lutein + zeaxanthin, DHA. Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2).
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All participants were also asked to take the original AREDS formulation or accept a secondary randomization to 4 variations of the AREDS formulation, including elimination of beta carotene, lowering of zinc dose, or both. The unit of analyses used was by eye. Comparison with placebo in the primary analyses demonstrated no statistically significant reduction in progression to advanced AMD hazard ratio [HR], 0.
There was no apparent effect of beta carotene elimination or lower-dose zinc on progression to advanced AMD.
More lung cancers were noted in the beta carotene vs no beta carotene group 23 [2. Without more effective ways of slowing progression, the number of persons with advanced AMD is expected to double over the next 20 years, resulting in increasing socioeconomic burden.
A secondary goal was to test the effects of eliminating beta arecs2 and reducing zinc dose in the AREDS formulation. The details of the study design have been reported previously.
Enrollment was restricted to people between the ages of 50 and 85 years at high risk of progression to advanced AMD with either bilateral large drusen or large drusen in 1 eye and advanced AMD in the fellow eye.
Inclusion and exclusion criteria have been published. Likelihood studyy adherence to the study aeeds2 was evaluated during a run-in phase using study placebo and the AREDS formulation. They could not have other ocular diseases such as high myopia, glaucoma, clinically significant diabetic retinopathy 10 or more microaneurysms or retinal hemorrhages arrds2, and other diseases that might confound the assessment of the ocular outcome measurements.
Eyes that had undergone cataract surgery at least 3 months prior to enrollment were eligible; eyes that had undergone other intraocular surgeries were not included. Persons with systemic diseases, including oxalate kidney stones, Wilson disease, hemochromatosis, lung cancer, or other diseases associated with poor 5-year survival, were excluded. Institutional review boards approved the AREDS2 research protocol, and all participants provided written informed consent.
Stusy were able to select more than 1 racial category. Previous dose-ranging studies provided support for the doses used. A second-tier randomization was conducted to evaluate the effect of eliminating beta carotene and lowering the zinc doses in the original AREDS formulation Figure 1. Beta carotene had been used in this formulation because lutein and zeaxanthin were not commercially available at the start of AREDS.
AREDS2 Results Released | Macular Disease Foundation Australia
A zinc dose of 80 mg was used in the original AREDS formulation because it was the dose used in an earlier trial suggesting efficacy. Persons who did not consent to this secondary randomization but who agreed to take the original AREDS supplements, provided they were not current or former smokers within the past arreds2, were allowed to participate in the study.
Participants and study personnel were masked to treatment aredss2 in both randomizations. Follow-up study visits were scheduled annually; follow-up also included telephone contact 3 months after randomization and subsequent telephone contacts at 6 months between ards2 visits.
At each study visit, participants received a comprehensive eye examination, including best-corrected visual acuity using a standardized protocol. Masked graders at a central reading center used a standard protocol to assess the photographs. Adherence to the treatment regimen was stduy by pill count arevs2 each annual visit. Information on AMD treatment and adverse effects was collected by telephone and at annual visits.
The primary outcome was the development of advanced AMD, defined as central geographic atrophy or retinal features of choroidal neovascularization detected on central grading of the stereoscopic fundus photographs or a history of treatment for advanced AMD atudy study enrollment. Treatment for choroidal neovascularization was included in the outcome because treatment might maintain visual acuity in an eye with advanced AMD. Safety outcomes included serious adverse events and mortality.
A previous report detailed the power calculation. All analyses were conducted following the intention-to-treat principle. The unit of analysis for ophthalmic outcomes was by eye. The primary efficacy outcome, time to progression to advanced AMD, was assessed using a Cox proportional hazards model incorporating the method of Wei et al for obtaining robust variance estimates that allows for dependence among multiple event times 1 or 2 study eyes.
AREDS2 Results Released
Participants lost to follow-up or who died during the course of the study were censored at the time of last contact. Hazard ratios HRs and All analyses were conducted using SAS version 9.
A total of participants were enrolled, with a mean age of Baseline characteristics of the AREDS2 cohort were comparable across the 4 treatment groups in the primary randomization Table 1. A total of participants Of the remaining participants, Table 2 reports the distribution of randomization of the variations of the AREDS formulation as well as participants who chose to take the AREDS formulation within each of the treatment groups in the primary randomization.
Distributions were similar across the 4 treatment groups. Participants underwent follow-up for a studyy of 4. These percentages were similar across treatment groups for both randomizations.
The baseline serum levels of study nutrients were balanced xtudy the treatment groups; the levels achieved during the study are reported in eTables Baseline dietary intake of the study nutrients, including those in the AREDS supplements, was balanced across treatment groups. Primary Randomization A total of participants had experienced at least 1 advanced AMD event by the end of the study events in study eyes.
In the primary analyses, comparisons with placebo demonstrated no statistically significant reductions in progression to advanced AMD HR, 0.
These analyses were performed with stratification by the secondary interventions. The analyses conducted without the stratification showed essentially similar results. Main Effects of Primary Randomization. The results presented were also analyzed with stratification by the secondary interventions. The results from analyses without the stratification by secondary interventions ares2 very similar to these results.
The exploratory analyses of the secondary randomization were restricted to participants randomized to the 4 variations of the AREDS supplements. The secondary randomization analyses showed that lowering zinc dose and eliminating beta carotene had no statistically significant effect on progression to advanced AMD HR, 1.
Additional analyses stratified by tertiles, quartiles, and deciles eFigure 1 showed similar results, with the lowest stratum demonstrating a protective effect compared with the remaining strata. The HRs were 0.
None of the nutrients affected development of moderate or worse vision loss, defined as a reduction of 15 or more letters from baseline or ards2 for neovascular AMD. Compared with placebo, the HRs for development of moderate or worse vision loss were 0.
No apparent effect on vision of eliminating beta carotene and reducing zinc dose was observed. No clinically or statistically significant differences in reported serious adverse events, including rates of development of neoplasms, were noted across the treatment groups in the primary randomization Table 3.
However, secondary randomization excluding participants who were smokers showed more lung cancers in the beta carotene group than in the no beta carotene group sgudy [2. In the original AREDS report, gastrointestinal conditions and hospitalizations for genitourinary diseases were significantly more common in participants randomized to receive zinc 80 mg than to receive placebo.
Rates of wreds2 gastrointestinal disorders and hospitalizations for genitourinary diseases were similar in the 2 sstudy assigned groups high-dose zinc, low-dose zinc in AREDS2. No clinically or statistically significant differences in reported serious adverse events were found in the analyses of the secondary randomization Table 4. These analyses included all the participants randomly assigned to the variations of the AREDS supplement, including smokers.
There also were no differences for zinc main effect low-dose zinc vs high-dose zinc HR, 1. Because of the potential for increased risk of mortality with beta carotene, analyses for competing risk were performed. These results showed little change from the original findings on mortality. These null results may be attributable to the true lack of efficacy. Other factors to consider include inadequate dose, inadequate duration of treatment, or both. The form of omega-3 long-chain polyunsaturated fatty acids ethyl ester and the DHA: Specifically, the nutritional status of the AREDS2 cohort and the competitive absorption of carotenoids require further assessments.
Similar findings were seen when the arrds2 were divided into tertiles, quartiles, and deciles. This hypothesis requires further study. Two randomized controlled clinical trials of beta carotene reported an increase in lung cancer rates and associated mortality in cigarette smokers assigned to receive beta carotene.
This formulation was given as a mixture of antioxidant vitamins and minerals. It is not known whether a single specific ingredient is important or if the combination is essential for its therapeutic effect.
In these analyses we assumed that there would be little interaction between the various nutrients tested. However, when we conducted the analyses with and without stratification for the secondary interventions, the results were almost identical.
We also have not tested for equivalency between low-dose zinc and high-dose zinc and between no beta carotene and beta carotene.
Age-Related Eye Disease Study 2 (AREDS2) | National Eye Institute
Another limitation would be our inability to assess the effect of the potential increased risk of lung cancer associated with beta carotene on our analyses of mortality.
The number of lung cancers was small, and the analyses of competing risk showed essentially no change in our mortality results. These study results may not be generalizable, because arfds2 study population is a highly selected group of highly educated and well-nourished people. The strengths of this study include the low rates of loss to follow-up and consistently good adherence to the treatment regimen.
Comparison of low-dose zinc vs high-dose zinc showed no evidence of a statistically significant effect, and there is insufficient evidence to provide areda2 clinical recommendation. Drs Chew and Clemons had full access to all of the data in the study and areds22 responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Analysis and interpretation of data: Critical revision of the manuscript for important intellectual content: Administrative, technical, or material support: Conflict of Interest Disclosures: Dr Ruby reported receiving payment for lectures from Genentech. Dr Fish reported receiving grant and travel support from Texas Retina Associates. No other authors reported disclosures. Funds were generously contributed to these contracts by the following NIH institutes: Role of the Sponsor: The staff of the National Eye Institute and their contractors, led by Dr Chew, had complete control of the design and conduct of the study; the collection, management, analysis, and interpretation of the data; and the preparation, review, or approval of the manuscript.