AMD: The Role of Genetic Testing in the Use of Ocular Multivitamin Supplements

Vision Preservation and Your DNA

Age-Related Macular Degeneration (AMD) is one of the leading causes of blindness in North America, due to its progressive disease course and its devastating effects on central vision loss.

AMD is classified into two main categories based on damage to the macular area of the retina as dry AMD, seen in patients with early signs of deposits in the retina, and wet AMD, a later, more aggressive stage of the disease characterized by increases in deposits, new blood-vessel growth, bleeding and macular scarring. Please see our article titled “AMD: The Sneak Thief of Vision” for more information about this condition.

Unfortunately, at the present time there is no cure for macular degeneration; the best strategy for treatment is preservation of existing vision and protection from future progression in both eyes but in particular for the fellow eye.

Known risk factors for developing AMD include smoking, age and body mass index, as well as dietary deficiencies in anti-oxidants and certain vitamins and minerals. Healthy eating and nutrition are important in overall treatment of AMD; please see our article “AMD: Healthy Eating Essential,” for more specific information.

The findings of the Age-Related Eye Disease Study (AREDS), a large, multi-year longitudinal research study, resulted in widespread recommended use of ocular nutritional supplements known as the AREDS-Formulation (AF), which contains both anti-oxidants and zinc to be used by all patients with AMD in an effort to slow the progressive nature of this condition. Early results of AREDS, before genetic testing was available, indicated that such supplements were useful in delaying the progression of AMD from its dry to its wet forms, and delayed damage to vision overall.

However...

Recent studies and re-analysis of the AREDS results show that individuals with certain genetic markers should not be using the AREDS-formulation nutritional supplements because they may actually increase the risk of macular damage (emphasis ours), progression and significant vision loss. More specifically, the addition or removal of zinc to the official AREDS formulation was found to be significant.

A paper by Carl C Awh, MD, Steven Hawken, MSc and Brent W. Zanke, MD, PhD, published online September 5, 2014 in the journal Ophthalmology describes seven-year outcomes analysis of 989 AREDS patients and the impact of genotype on response to AREDS-formulation supplements.

Awh, et al., expanded on an earlier report that was based on the presence of Complement Factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2) risk alleles in DNA, revealed by genetic testing as supplied by PGx, the manufacturer of simple mouth-swab DNA collection materials and subsequent typing. Results indicate that using predetermined genotype groups to predict AMD advancement into more severe categories is a valuable tool for decisions about the recommendation of ocular nutritional supplements.

Risk Factor Groups

PGx is a provider of proprietary genetic testing materials which are used to determine the presence or absence of CFH and ARMS2 alleles, so that the genetic risk of advancing AMD and significant further loss of vision might be predicted. For this analysis, the researchers examined genetic risk factors and sorted patients into four groups:

• Patients with high CFH and low ARMS2 [high-low]
• Those with low CFH and high ARMS2 [low-high]
• Patients with low CFH and low ARMS2 [low-low]
• Patients with high CFH and high ARMS2 [high-high]

Results of Treatment or Placebo

Patients in the first group, high-low, progressed 17% with placebo, but got worse with either zinc alone or on the AREDS-formulation, by 43% and 40%, respectively.

The second group, low-high, benefited from zinc alone or in combination with antioxidants, as in the AREDS-formulation. For this group, placebo allowed progression by 43%, but with zinc alone, by 25%. The AREDS-formulation group progressed by 27%. The rate of progression increased slightly with the antioxidants in the AREDS-formulation as opposed to that on zinc alone.

Antioxidants were helpful for patients in the third group, low-low. Progression with placebo was 22%, but with antioxidants progression was only 9%. For this group, the addition or subtraction of zinc apparently had no effect on outcome.

For patients with two high-risk categories in the fourth group, high-high, progression with treatment using any supplement was no better than progression with a placebo, which was approximately 48%.

In other words, in two out of the four groups categorized above, ocular nutritional supplements either had no particular value in slowing the progression of AMD or had the effect of worsening the situation. Only in the second and third group was the rate of progression significantly slowed by using either the AREDS-formulation, which contains zinc, or just the antioxidants alone. Very surprisingly, the first group experienced less progression of their AMD without supplements of any kind, while the fourth group showed now difference in rate of progression whether they used a supplement or not.

Implications

It will be important to follow developments in this area closely, as the implications of this study, especially if they are confirmed by further research are, to say the least, significant. Accurately predicting the result of ocular nutritional supplementation to the diet becomes very much more important, especially in view of the fact that some patients using them got worse than they might have without them.

There are other known risk factors for progressive vision loss in AMD that have been shown to be meaningful, including age, body mass index, history of smoking and the educational level of the individual. These factors are used by PGx in combination with its genetic testing in an attempt to individualize treatment for each patient with AMD and to be more accurate in recommending ocular nutritional supplements, either alone or with zinc.

Also, the formulations of ocular nutritional supplements are undergoing more analysis even now. Best recommendations for supplementation of the diet include vitamins C and E, zinc, copper, lutein, zeanxanthin and meso-zeanxanthin.

Also, people have a tendency to believe that manufactured pharmaceuticals are always harmful and that anything that is “natural” is, by definition, safer for us to use; as a treatment strategy, nutritional supplements are often viewed as a more natural option, as opposed to manufactured pharmaceuticals.

There are some who will view all this with mixed feelings; because we can do genetic testing, does that always mean that we should do it? Will the advantages of knowing how much risk you may have for developing AMD help you change your lifestyle, stop smoking and begin taking the correct vitamin and mineral supplements to help prevent its onset? There is a tendency in Canada and the US for us to think about nutritional supplements of vitamins and minerals in terms of “well, it can’t hurt to take these,” but this may be tragically untrue in the case of age-related macular degeneration.

The more we learn about medicine and genetics, the more questions there are that need answers. As scientists discover more genotypes and more knowledge about specific genes and what they do in the body, it is a given that medical practice must change in response. What is true today may or may not be true tomorrow, as we have just discovered in the area of macular degeneration. We should keep in mind that new information is always just over the horizon.