The original Age-Related Eye Disease Study (AREDS), first launched in 1992, was a major clinical trial sponsored by the National Eye Institute to (a) learn more about the history of, and risk factors for, age-related macular degeneration (AMD) and cataract and (b) evaluate the effect of high doses of antioxidants and zinc on the progression of AMD and cataract.
Since that time, the ongoing AREDS trials have produced a number of breakthrough discoveries, including last year’s clarification of the role of supplements in preventing advanced AMD.
Last month, however, the AREDS Study Group released a sobering new report, indicating, in part, that (a) the risk of progression to advanced AMD increased with increasing age and severity of drusen; and (b) women and current smokers were at increased risk of neovascular, or “wet” AMD. In other words, despite encouraging developments in treatment, advanced AMD remains – for now – an intractable foe.
[Editor’s note: Drusen are the hallmark of “dry” AMD. Drusen are small yellow deposits beneath the retina that are a buildup of waste materials, composed of cholesterol, protein, and fats. They are a risk factor for progressing to vision loss.]
The AREDS Study Group report, entitled Ten-Year Follow-up of Age-Related Macular Degeneration in the Age-Related Eye Disease Study: AREDS Report No. 36, was published “online first” in the January 2, 2014 edition of JAMA Ophthalmology (formerly Archives of Ophthalmology). JAMA Ophthalmology is an international peer-reviewed journal published monthly by the American Medical Association.
The authors are Emily Y. Chew, Traci E. Clemons, Elvira Agrón, Robert D. Sperduto, John Paul SanGiovanni, Matthew D. Davis, and Frederick L. Ferris III, who represent the following institutions: the National Eye Institute, National Institutes of Health; the EMMES Corporation, Rockville, Maryland; and the University of Wisconsin.
More about the Age-Related Eye Disease Study
The Original AREDS Trial
The first Age-Related Eye Disease Study (AREDS) was a major clinical trial sponsored by the National Eye Institute to:
- Learn more about the history of, and risk factors for, age-related macular degeneration (AMD) and cataract;
- Evaluate the effect of high doses of antioxidants and zinc on the progression of AMD and cataract.
The original AREDS trial involved 4,757 participants, age 55-80 at the time of enrollment. Of 4,203 surviving participants, 3,549 (about 84 percent) took part in the follow-up AREDS2 trial.
Results from the first AREDS trial, which were reported in October 2001, indicated that five years of supplementation with high doses of antioxidant vitamins, copper, and zinc reduced the risk of developing advanced AMD in 30% of individuals in the study who took the supplements and had already-existing moderate to advanced dry or wet AMD.
The Second AREDS Trial (AREDS2)
In May 2013, The National Eye Institute concluded the Age-Related Eye Disease Study 2, which tested several changes to the original AREDS formulation:
- The primary goal of the AREDS2 study was to determine if (a) adding omega-3 fatty acids or (b) lutein and zeaxanthin (the anti-oxidants found in dark green leafy vegetables) to the original AREDS formulation would make it more effective for reducing the risk of advanced AMD and cataract.
- The AREDS2 research group also substituted lutein and zeaxanthin for beta-carotene, which prior studies had associated with an increased risk of lung cancer in smokers.
Because the original AREDS trial established that the formulation does not benefit people with no AMD or early AMD, the AREDS2 trial was limited to people with intermediate AMD in both eyes, or intermediate AMD in one eye and advanced AMD in the other eye.
The researchers concluded that while omega-3 fatty acids had no effect on the formulation, lutein and zeaxanthin together appeared to be a safe and effective alternative to beta-carotene. Therefore, the addition of lutein and zeaxanthin to, and the subtraction of beta carotene from, the original AREDS supplement formula was recommended by AREDS2.
The AREDS2 formulation now includes:
- 500 milligrams (mg) of vitamin C
- 400 international units of vitamin E
- 80 mg zinc as zinc oxide
- 2 mg copper as cupric oxide (to avoid anemia with high zinc intake)
- 10 mg lutein
- 2 mg zeaxanthin
More about the AREDS Study from JAMA Ophthalmology
From the article abstract:
Importance: Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials.
Objective: To describe 10-year progression rates to intermediate or advanced AMD.
Design, Setting, and Participants: We observed the Age-Related Eye Disease Study (AREDS) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. Participants aged 55 to 80 years with no AMD or AMD of varying severity (n=4757) were followed up in the AREDS trial for a median duration of 6.5 years. When the trial ended, 3549 of the 4203 surviving participants were followed for 5 additional years.
Results: The risk of progression to advanced AMD increased with increasing age and the severity of drusen. Women and current smokers were at increased risk of neovascular [i.e., wet] AMD. In the oldest participants with the most severe AMD status at [the beginning of the study], the risks of developing neovascular AMD … by 10 years were 48.1%.
Similarly, rates of progression to large drusen increased with increasing severity of drusen at [the beginning of the study], with 70.9% of participants with bilateral [i.e., both eyes] medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at [the beginning of the study] but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200.
Conclusions: The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD.
Additional Information about AMD
- February is National AMD Awareness Month
- Read about developments in AMD treatments on the VisionAware blog.