AREDS: providing quantitative data for treating macular degeneration

In October 2001, the National Eye Institute released the long-awaited results of the Age-Related Eye Disease Study. This landmark study was designed so researchers could learn more about the natural history and risk factors of age-related macular degeneration and cataract and to assess the effect of high doses of antioxidants and zinc on the progression of these conditions.

Results from the AREDS showed that high levels of antioxidants and zinc significantly reduce the risk of advanced AMD and its associated vision loss. These same nutrients had no significant effect on the development or progression of cataract.

Today, the findings of AREDS continue to be evaluated for their long-term implications and are often used as guidelines for treatment regimens.

“Practitioners have embraced AREDS,” said Jeffry D. Gerson, OD, FAAO, a practitioner based in Kansas City, Mo. “It gives us some quantitative data to be able to refer to when discussing AMD with our patients.”

Treatment recommendations

Many practitioners have adjusted their recommendations for AMD treatment in order to adhere to the AREDS findings. In particular, this is reflected through the recommendation of the AREDS formula vitamins for certain patients.

“We recommend the AREDS formulation to most of our AMD patients,” Dr. Gerson told Primary Care Optometry News. “Although the study did not show that the AREDS formula definitely helps those with low-risk AMD, we are still using it in those patients. We often have our lower-risk patients taking half of the AREDS dose along with a multivitamin to make sure that they are getting all of the vitamins and minerals they need from a systemic perspective.”

Dr. Gerson said that patients are often hesitant to add another pill to those they currently take. However, he said, many patients are already taking vitamin C and vitamin E, which will be not needed once the eye-specific vitamin is started.

Dr. Gerson said he found it interesting that the zinc-only group in the AREDS did nearly as well as the antioxidant group. “This helps us to be able to feel comfortable discussing formulations without beta carotene,” he said.

John W. Potter, OD, FAAO, a Primary Care Optometry News Editorial Board member based in Dallas, discussed for whom the AREDS formula supplementation works best.

“Over the study period in AREDS Report No. 8, patients with soft, confluent drusen who used the supplements were better off than those who did not in two key areas,” Dr. Potter said in an interview. “First, there was a bit less loss of visual acuity or an improvement for some patients. Second, and actually more importantly, fewer soft, confluent drusen patients on supplementation developed the more severe neovascular macular degeneration. Lutein has been demonstrated in the LAST [Lutein Antioxidant Supplementation Trial] study to be a valuable addition to our supplementation.”

Deciding who needs supplementation

According to Stuart P. Richer, OD, MS, PhD, FAAO, chief of the Optometry Department at the Department of Veterans Affairs, Medical Eye Clinic in North Chicago, it is important for the non-retinal practitioner to be able to distinguish which high-risk AMD patients to place on an AREDS-type formulation.

He cited patients with the following characteristics:

• 1 large drusen (>125 µm in diameter)
• 15 or more intermediate drusen (between 63 and 125 µm in diameter)
• non-central geographic atrophy
• loss of vision from AMD in the fellow eye
• advanced AMD
• non-smokers

For high-risk smokers, Dr. Richer told Primary Care Optometry News that he currently recommends Ocuvite PreserVision with Lutein gel caps (Bausch & Lomb, Rochester, N.Y.) or an equivalent product twice per day. Another option, he said, would be to add spinach or 10 mg of lutein to the older four-times-a-day PreserVision product or use a comprehensive lutein-based multivitamin/multimineral product such as Whole Body (Medical Ophthalmics, Tarpon Springs, Fla.)

“Quite frankly, there isn’t a single AMD patient who doesn’t walk out of my examination room with a recommendation of either daily spinach (as long as the patient is not on Coumadin [warfarin, DuPont]) or 10 mg of lutein per day,” he said. “This is based upon the epidemiological 1994 Eye Disease Case Control Study by Seddon and colleagues (JAMA. 1995;272:1413-1420, 6212.) and recent AREDS II re-evaluation, which both suggest that spinach intake reduces the risk of advanced AMD.”

For ‘at risk’ patients

Dr. Potter said patients with soft, confluent drusen in one or both eyes are at greater risk for vision loss than are other patients with other forms of drusen.

“As a result of the AREDS reports and the LAST study, it is clear that certain supplements can benefit these patients,” he said. “It is, however, not possible to predict which specific patient will benefit from supplementation, which is a challenge for clinicians and their patients.”

What is clear, Dr. Potter said, is that as a group, patients with soft, confluent drusen in one or both eyes who use AREDS supplementation are more likely to have slightly better visual acuity and less neovascular degeneration over time than those who do not.

Dr. Richer said he basically applies the NEI/NIH AREDS guidelines along with lutein for at-risk patients. “I also recommend omega-3 fatty acids or cod liver oil based upon research,” he said. “This is important, as more than four servings of fish per week are associated with a 35% lower risk of developing AMD, and AREDS II post-hoc analysis found that heart-healthy fish and nuts were protective, while manufactured food was detrimental.”

Dr. Richer said sardines are particularly useful, because they are low in mercury and PCB and are inexpensive, widely available and storable. “There also is biologic plausibility that the extra vitamin D found in sardines, for example, has anti-angiogenic properties,” he added.

He said he recommends that patients decrease smoking, avoid obesity, exercise, avoid exposure to bright sunlight, avoid or control hypertension and avoid multivitamins containing iron as well. He also recommends decreased meat consumption and recommends that patients give blood three times a year.

“Also especially helpful for high-risk patients are banana and orange intake (another recent epidemiologic study) and soy genistein (preferably fermented tofu or miso soup), which has antiangiogenic properties,” Dr. Richer continued. “Bioflavonoids found in red wine and blueberries are likely helpful as well.”

Dr. Gerson said he recommends the AREDS formula vitamins for “at risk” AMD patients. “Of course, we need to watch out for those who are smokers, because they cannot take beta carotene, as the general population can,” he said. “This presents another problem, because so many of our AMD patients are smokers. For these patients, we are recommending a lutein formula, such as ICaps Lutein and Zeaxanthin Formula [Alcon] or Ocuvite PreserVision with Lutein instead of the AREDS formula.”

Importance of lutein

Another key finding from AREDS was the importance of lutein in the prevention and management of AMD. Dr. Richer said the average American intake is approximately 2 mg per day.

“I am recommending at least 10 mg a day for high-risk patients, based upon the most up-to-date biologic data from the 2005 ARVO meeting,” he said. “One can obtain this amount from a daily cup of spinach, lightly cooked in oil, which increases lutein bioavailability by a factor of 4. Kale, collard greens and lutein-containing eggs are also great sources.”

According to Dr. Potter, it is probably best to follow the dosage used in the LAST study for the time being. “We may learn more about how to use lutein more effectively in the future, but for now, the recommended dose is probably best,” he said.

Dr. Gerson said it is important to educate patients about the need for lutein beyond what is supplied in a multivitamin. “Many of our patients are taking a multivitamin even before they come in to see us,” he said. “These vitamins often have ‘with lutein’ on the label, so people think they are already ‘taking’ lutein. The problem is that the dose in these multivitamins is often only 500 µg. This is well below what anybody really feels is beneficial.”

Dr. Gerson said the best source of lutein is green leafy vegetables, such as spinach and kale. When recommending lutein, he has patients take a multivitamin that contains a sufficient amount of lutein, as in most of the eye-specific vitamins.

“There is a multivitamin coming to market that will essentially contain the AREDS formula without beta carotene, but with lutein and also other vitamins and minerals,” he said. “This will be a good option for patients wanting to take one type of vitamin to meet all of their needs.”

AOA and AREDS

While the American Optometric Association does not officially endorse AREDS in its Clinical Practice Guidelines, members of this organization have generally recognized the usefulness of the study results.

“Our members have likely embraced AREDS as reinforcement to what they have been practicing for years,” said Jeffrey L. Weaver, OD,MS, FAAO, director of the AOA’s Clinical Care Group, in an interview. “Optometrists, led by experts in the field such as Dr. Richer, embraced the use of antioxidants for their likely prophylactic and treatment value on certain eye diseases long before the definitive AREDS trial was begun.”

Dr. Weaver said the AOA Optometric Clinical Practice Guideline on Care of the Patient with Age-Related Macular Degeneration had its last major revision in 1999. “I would certainly expect our Consensus Panel to include AREDS as a major reference in the update,” he said.

While AREDS does offer a proven dosage of ingredients, Dr. Weaver said AOA members may not be convinced that this is the only formula that may be successful in their patients. “A lot of quality products contain critical antioxidants while not exactly in the same formula that AREDS used,” he said.

Dr. Weaver said lutein and zeaxanthin could certainly be recommended as components of a formula that may prevent or slow the progression of macular degeneration.

“At this point, we are leaving the dosing of lutein up to the professional judgment of the provider,” he said. “Nothing may be better for either of these carotenoids than increasing one’s diet of green, leafy vegetables. I personally have increased my consumption of spinach from none to near-Popeye quantities.”

For Your Information:

• Jeffry D. Gerson, OD, FAAO, is a practitioner based in Kansas City, Mo. He can be reached at 4321 Washington Blvd., Ste. 5000, Kansas City, MO 64111; (816) 756-5900; fax: (816) 756-5457; e-mail: jgerson@hotmail.com. Dr. Gerson has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• John W. Potter, OD, FAAO, is a Primary Care Optometry News Editorial Board member and vice president for clinical services for TLC Laser Eye Centers. He can be reached at 18352 Dallas Pkwy., Ste. 136, Dallas, TX 75287; (972) 818-1239; fax: (972) 818-1240; e-mail: john.potter@tlcvision.com. Dr. Potter has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
• Stuart P. Richer, OD, MS, PhD, FAAO, is Chief of the Optometry Department at the Department of Veterans Affairs, Medical Eye Clinic in North Chicago. He can be reached at 3001 Green Bay Rd., North Chicago, IL 60064-3095; (847) 688-1900, ext. 85406; fax: (847) 578-6924; e-mail: Stuart.Richer1@Med.VA.gov. Dr. Richer is a paid consultant for Bausch & Lomb and Medical Ophthalmics.
• Jeffrey L. Weaver, OD, MS, FAAO is director of the AOA’s clinical care group. He can be reached at 243 N. Lindebergh St., Saint Louis, MO 63141; (314) 991-4100; fax: (314) 991-4101; e-mail: JLWeaver@aoa.org. Dr. Weaver has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.