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Age-Related Macular Degeneration: The Role of Genetic Testing in the Use of Ocular Multivitamin Supplements



Age-Related Macular Degeneration: The Role of Genetic Testing in the Use of Ocular Multivitamin Supplements


Age-Related Macular Degeneration (AMD or ARMD) 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.

The findings of the Age-Related Eye Disease Study (AREDS), over the course of longitudinal research, 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.


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 formulation is also 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:

1. Patients with high CFH and low ARMS2 [high-low]

2. Those with low CFH and high ARMS2 [low-high]

3. Patients with low CFH and low ARMS2 [low-low]

4. 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 three 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 third group was the rate of progression significantly slowed by using either the AREDS-formulation, which contains zinc, or just the antioxidants alone.


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 macular risk factors are used by PGx in combination with its genetic testing to individualize treatment for each patient with AMD and in an attempt to be more accurate in recommending ocular nutritional supplements, either alone or with zinc.

There is a tendency in Canada and the US for most of us to think about nutritional supplements of vitamins and minerals in terms of "well, it can't hurt to take these," but it this may be tragically untrue in the case of age-related macular degeneration. 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.

Additionally, the more is learned 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.

Diagnosis Codes

ICD-9 ICD-10*
362.50 Senile macular degeneration, unspecified H35.30
362.51 Non-exudative senile macular degeneration H35.31
362.52 Exudative senile macular degeneration H35.32
362.57 Drusen, degenerative) of macula, unspecified H35.369

*In the US, ICD-9 diagnosis codes will change to ICD-10 codes on Oct. 1, 2015.