Supplemental Information

As clinicians await the results of AREDS 2, many seek ways to improve patient compliance.

By René Luthe, Senior Associate Editor

Following up on AREDS's landmark finding about the role of antioxidant supplementation in slowing the progression of AMD in patients with advanced forms of the disease, the National Institute of Health is currently conducting AREDS 2. The main objective is to determine if oral supplementation with xanthophylls and/or omega-3 acids will decrease the risk of progression to advanced AMD, as the original AREDS formulation did by 25%, says retinal specialist Seenu M. Hariprasad, MD, director of ophthalmology clinical research at the University of Chicago.

Yet while physicians wait with great interest to learn researchers' findings, they must still contend with a patient base that sometimes seems to show the "unreliable reception" of the old rabbit-ears televisions when it comes to medical advice regarding vitamins. Preventive therapy is difficult for patients to adopt in their daily routine. Absent any immediate benefit to their health or vision — which would reinforce the value of the intervention — they have to "take it on faith" that it's worth the effort and expense. Here's an update on the important nutrients for ocular health and strategies for addressing patient compliance.

The AREDS 2 Difference

AREDS 2, which commenced in 2008, adds the xanthophylls lutein (10 mg per day) and zeaxanthin (2 mg per day), plus the LCPUFAs docosahexaenoic acid and eicosapentaenoic acid (at a total of 1 g per day) to the original AREDS formulation. Further changes are that AREDS 2 halves the amount of zinc from the original study (from 80 mg to 40 mg) and eliminates betacarotene altogether.

Epidemiologic studies have shown an association between lutein, zeaxanthin and omega-3s and a reduced risk of advanced AMD, points out Dr. Hariprasad.

Ellen Troyer, chief executive officer and chief research officer of supplement manufacturer Biosyntrx, is one of many nutrition experts who believe the additions were sound. "I understand why they weren't included in the first study, because at that point, there had not been enough evidence to support inclusion, but shortly after AREDS was published, a lot of information was published on lutein and zeaxanthin and macular pigment health," Ms. Troyer notes.

Dr. Hariprasad reports that three comparisons will be made at each interim analysis of AREDS 2:

► progression to advanced AMD for lutein/zeaxanthin alone vs placebo
► progression to advanced AMD for DHA/EPA alone vs placebo
► progression to advanced AMD for lutein/zeaxanthin and DHA/EPA vs placebo

Omega-3s are another substance that has received a great deal of attention in the medical and popular press for their supposedly beneficial effects on health; because of this, some manufacturers of ocular vitamins have already begun adding them to their formulations. Other companies, however, are opting for a more conservative approach until the results of AREDS 2 are in (the study is projected to run for five to six years).

"AREDS 2 is an ongoing study and Alcon does not market vitamin formulations based on presumed results of an ongoing study," says Janet Campbell, Alcon's product manager for ocular vitamins in the US. "We are looking at formulas that include ingredients being studied in AREDS 2, and should the study prove those ingredients to be beneficial for patients, we would certainly promote the clinical support of AREDS 2. As a participant in the AREDS 2 trial, we look forward to seeing the results," says Ms. Campbell.

Message Incomplete?

Despite widespread support from the medical community for dietary supplements, and the significant publicity the original AREDS trial results received, many clinicians report compliance problems with the very patient demographic the AREDS formulation demonstrated an ability to slow the rate of advanced AMD by 25%. Clinicians have offered a few theories to explain the compliance problem. Emily Chew, MD, deputy director of the division of ophthalmology and clinical research at the National Eye Institute, points out that the advanced age of the average AMD patient usually means the individual already has a lengthy list of medications to take. "Adding either four tablets or two soft gels of the AREDS supplements may become too onerous for the elderly."

There is also the issue of likely patient confusion given all the information on vitamins in the popular press and from marketing. Patients are probably aware of what the current "wonder nutrients" are, but may not know the correct dosages for various compounds. Patients often seem to be taking a little of this and a little of that — when they think about it.

"In any drug store or supermarket, patients are going to see many ‘AMD vitamins’ on the shelf with all kinds of claims that may or may not be accurate, since vitamins don't have a stringent regulatory pathway that prescribed pharmaceuticals do," says Dr. Hariprasad. However, from a clinician's perspective, he notes that there is no good science to back up the use of any vitamins for AMD except the specific AREDS formulations. "We really need to stick to where the science is," he emphasizes. It falls to ophthalmologists to make sure their patients know which vitamins and claims are backed by science.

Dr. Chew agrees that increased patient education is required to achieve better understanding of the formulation and dosage of the AREDS trial.

Some supplement manufacturers are doing their part in helping get the message across. Bausch + Lomb, maker of PreserVision Eye Vitamins, the product tested in the original AREDS, shares the concern about patient compliance, but observes that it is hardly unique.

"We know that compliance is not great even with the most critical of medicines," says Scott Chapman, executive director of B+L's OTC business. "People don't always stick to the prescribed dose according to the label or even to their doctor's wishes." In an effort to help AMD patients, B+L has developed a program called Joy of Sight. "The Internetbased program currently supports approximately 400,000 AMD patients, providing them with information on the disease, dietary suggestions, tools on how to manage the disease with their physician and tips on how to remain compliant with their PreserVision AREDS vitamin regimen."

Ride the Supplement Wave

The good news is that ophthalmologists can use the public's abiding interest in nutrition as a health aid to their advantage. Increasingly, physicians report that patients are coming in initiating conversations about how they can prevent disease through diet and nutrition.

Jonathan Stein, MD, reports that in his practice in suburban Connecticut, a more affluent and better-educated patient base is aware that nutrients can help them preserve their health and are eager to learn more from their physicians.

"I even have a couple of friends who live in my town that started vitamin supplement companies," Dr. Stein notes. "So it's obviously a huge industry. People are, at least in my area, coming in asking about that."

The highly publicized connections between nutrition and health mean that many patients are already taking supplements for other conditions, or know other people who are doing so.

"If the patient has blepharitis, a lot of times a discussion about supplements is initiated because of that, or dry eye syndrome," Dr. Stein explains. "If they say, ‘My eyes are really bothering me — they're crusty in the morning and my eyes are dry,’ I will ask if they are taking any vitamin supplements. If the answer is something along the lines of, ‘I have some fish oil capsules that I take once in a while,’ then I start educating them about some of the better products that are out there." Further discussions of supplements to support ocular health are usually easy.

Again, Dr. Hariprasad says it is crucial that patients un der stand that the dosing of the AREDS formulation is the only one that has been proven to slow the progression of AMD.

Diet is Not Enough

More broadly, Dr. Stein believes that multivitamins are a good thing for people to incorporate, provided that they are calibrated to the appropriate gender and life stage. A former nutrition major in college, he notes that while it is preferable to get one's nutrients from food, that is usually difficult to achieve in real life. Patients may need to hear this from their physicians. A supplement such as Macutrition (Advanced Vision Research) may be aimed at patients with retinal conditions, but he points out that the supplement contains many substances, such as green tea and vitamin C, that are beneficial to good health.

"I think supplementation is actually important, especially when you have detrimental medical processes running around through your body," Dr. Stein says.

Ms. Troyer agrees. "I've just gotten some of the early data back from Healthy People 2010 [the US Depar tment of Health and Human Services' program of disease prevention and health promotion goals for the nation], and they found that fewer than 10% of the population even consumes five fruits and vegetables a day," she says. "The new recommendation is nine to 13 servings of fruits and vegetables a day. That means 90% of the people who walk into an eye doctor's office are most likely nutritionally deficient. So do I think everyone should take a multiple? You bet I do."

The Science — And Support — Are There

In the CE courses she teaches around the country, Ms. Troyer says that she is seeing increasing interest on the part of physicians.

"I was one of the founders of the Ocular Nutrition Society," she says. "Although it started as an optometric group, more and more MDs are starting to join. They didn't have a lot of nutrition science/biochemistry in their formal educations, but they are starting to become far more fascinated with it at this point. So I was delighted when the society voted to change the name to make it more inclusive."

Both clinicians and supplement makers attribute the growing acceptance of vitamins among the ophthalmic community to AREDS. "The study was a real breakthrough regarding vitamins and health. Before that, you didn't have the clinical proof. Well, the study changed that," says B+L's Mr. Chapman. OM