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Carl C Awh, Brent Zanke; Treatment Response to AREDS Components as a Function of CFH and ARMS2 Risk in Patients with AMD. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2994.
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© ARVO (1962-2015); The Authors (2016-present)
To use observed outcomes of patients followed in the Age Related Eye Disease Study (AREDS) to support published findings that response to components of the AREDS formulation is influenced by CFH and ARMS2 risk alleles.
DNA from white AREDS participants (988) with AREDS category (cat) 3 disease in at least one eye was genotyped at CFH and ARMS2 loci. Patients were divided into 4 groups: 1) those with CFH risk but no ARMS2 risk; 2) those with ARMS2 risk but no CFH risk; 3) those with both CFH and ARMS2 risk; and 4) those without CFH or ARMS2 risk. AMD progression was defined as development of AREDS cat 4 disease in any eye with cat 1-3 disease at study entry. Time to progression was determined from AREDS data available from dbGAP. Progression at 10 years was compared for AREDS-assigned treatment vs placebo for the entire study population and for each risk group. Odds ratios (OR) for progression were calculated and statistical significance determined using the Chi Square statistic.
Consistent with AREDS results, overall reduction in 10-year AMD progression was observed for AREDS formulation-treated patients (OR 0.66, p=0.02). However, this was not shown in each genetic risk group. For patients with only CFH risk (n=352), zinc-only treatment was associated with increased AMD progression (OR 1.88, p=0.049) while antioxidants-alone was associated with decreased progression (OR 0.51, p=0.027) and AREDS formulation was not shown to significantly alter AMD progression. Patients with only ARMS2 risk (n=62) trended toward decreased progression (OR 0.29, p=0.07) if treated with zinc-only, but had no demonstrated progression change with either antioxidant-containing regimen. Patients with both CFH and ARMS2 risk (n=516) treated with either antioxidants or AREDS formulation had reduced AMD progression (OR 0.55, p<0.03 or 0.02, respectively). Patients without CFH or ARMS2 risk (n=58) had no demonstrated significant alteration in progression with any treatment.
Outcomes analysis of AREDS patients with different CFH and ARMS2 risk profiles reveals statistically significant effects (consistent with published Cox modeling) of CFH and ARMS2 genetic risk on response to zinc and antioxidants, respectively. Patients with only CFH risk fared best with antioxidant-only treatment. Genotype-directed nutritional therapy may benefit white patients with moderate AMD.
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