Peer Reviewed Science
Scientific studies as recent as 2018 and 2019 serve as clear evidence of the relationship between a specific genetic group and long-term use of zinc (such as the AREDS formulations), which increase progression of the disease to wet AMD (nvAMD) in patients with dry AMD. This recent research is built upon years of prior scientific genetic discoveries in AMD.
The largest and most complete validation of the clinical utility of the Macula Risk test was performed by an international group of investigators led by Dr. Demetrios Vavvas MD (Harvard University and the Massachusetts Eye and Ear Infirmary), which showed that 15% of patients carried a genetic profile that increased progression to wet AMD after chronic exposure to zinc. This genetic profile is defined as 2 complement factor H risk variants combined with an absence of risk markers at the ARMS2 locus. These are the two major genes associated with AMD risk. These patients had almost three times the risk of progression to nvAMD compared to those not receiving supplements.
Summary overview of the science that supports the Macula Risk product
Foundational Research
The Arctic Medical Laboratories 2012 research program resulted in a pioneering discovery by retina specialist and recipient of the Senior Achievement Award of the American Academy of Ophthalmology, Dr. Carl Awh and Dr. Brent Zanke, Arctic Medical Labs co-founder, MD, PhD and geneticist. This study pointed to a potentially negative interaction between the genetic profile of some patients and the AREDS eye vitamin and mineral formulation. The importance and uniqueness of this finding was recognized with a United States patent.
Read Awh’s and Zanke’s original published research:
AREDS Formulation and Wet AMD
Since the publication of Awh and Zanke’s original research, there have been multiple supporting publications. The most significant studies were published in 2016 and beyond. Dr. Johanna Seddon and her colleagues from Tufts and Harvard Universities noted that the genetic interaction with the AREDS formulation was only related to wet AMD and not the other form of advanced AMD called geographic atrophy (GA). These appear to be two different pathological processes. Dr. Seddon pointed out that the AREDS formulation only had an effect to delay or prevent wet AMD, not geographic atrophy.
Dr. Seddon’s work was validated in another large and comprehensive study published in 2018 by Dr. Demetrios Vavvas, MD, PhD, assistant professor of ophthalmology at Harvard Medical School’s Department of Ophthalmology and others, including renowned data scientists from Stanford University.
Their publication in the journal, Proceedings of the National Academy of Sciences, U.S.A (PNAS) confirmed the interaction of genetic variants with the AREDS formulation on the progression risk to neovascular AMD.
“Patients with the C2A0 genotype (2 CFH high risk alleles and 0 ARMS2 high risk alleles) experience increased risk of progression to nvAMD (Wet AMD) with the AREDS formulation compared with placebo”.
Genetics, Zinc, and Neovascular AMD
In an earlier study by Assel et al., published online in 2018, both wet AMD and geographic atrophy were combined as endpoints, and no interaction was observed.
A published re-analysis of the exact same data in which wet AMD and geographic atrophy were separated as outcomes showed that the AREDS formulation only affects wet AMD, having no effect on geographic atrophy. In this study, patients with an adverse genetic profile are more likely to develop wet AMD if receiving chronic AREDS supplementation. This re-analysis confirms the relationship between genetics, zinc and neovascular AMD.
B. Zanke – re: Assel et al.: Genetic polymorphisms of CFH and ARMS2 do not predict response to antioxidants and zinc in patients with age-related macular degeneration (Ophthalmology. 2018;125:391-397)
“New patient data provided by the National Institutes of Health in conjunction with the work by Assel et al. that underscores the distinction between GA and choroidal neovascularization (CNV) as distinct progression phenotypes validates previous observations. The GA endpoint is not relevant for AREDS prophylaxis and should be removed from the statistical analyses. Some patients benefit (GTG3) and some may be harmed (GTG2).”
Incidence of progression in those with gene variant
Dr. Stephen Kaufman, a board-certified ophthalmologist and assistant professor at the Case Western University School of Medicine, was the principal investigator of a multi-center, independent research project designed to determine whether there is an interaction between AREDS-formulation (AREDS-F) vitamins and wet AMD. The study included 266 patients with wet AMD and a reliable history of AREDS-F vitamin use.
Dr. Pradeepa Yoganathan presented the research findings in July, 2019 at the annual scientific meeting of the American Society of Retina Specialists.
The study showed that patients with wet AMD and the high-risk genotype (testing positive on Macula Risk) were four times more likely to have taken the AREDS formulation when compared to the genotype group that appears to respond favourably to AREDS.
Kaufman notes that the study confirms a strong interaction between genetics and AREDS use. Further, the results agree with reports by Seddon et al. (2016) and Vavvas et al. (2018), which found AREDS-F protects patients with one genotype from developing wet AMD while increasing the risk of wet AMD for patients with a different genotype.
The above studies provide a volume of research that serve as scientific evidence for the harmful effects of the AREDS formulation in individuals with defined genetic variations.
Peer Reviewed Science
There are hundreds of publications representing more than 150,000 patients behind the genetic discoveries in Macula Risk®. These studies recognize the strong role of genetics in this disease as well as the unmet medical need to detect vision loss earlier for better outcomes.
Leaders in the field from Boston MA studied 2560 AMD patients with an average follow up of 10.3 years. The parameters used to predict outcome were the 12 genes and the non-genetic risk factors included in the Macula Risk® test. The prediction tool was 89.5% accurate in predicting progression by 10 years and 88.3% at 5 years. This research was further validated in a separate publication.
Prospective assessment of genetic effects on progression to different stages of age-related macular degeneration using multistate Markov models
Validation of a Prediction Algorithm for Progression to Advanced Macular Degeneration Subtypes.