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Report: Nutritional supplement beneficial regardless of genotype
Analyses failed to find a detrimental effect of the AREDS supplementation or zinc in patients with age-related macular degeneration.
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Genetic testing should be relegated to research and not used to determine the suitability or efficacy of AREDS nutritional supplementation in patients with age-related macular degeneration, according to a report.
In Ophthalmology, Emily Y. Chew, MD, and colleagues published a report showing that the AREDS formulation was beneficial, regardless of genotype.
“Genetic testing should be for research purposes, not for clinical care,” Chew told Ocular Surgery News.
Emily Y. Chew
The report supported the findings of AREDS Report 38, in which Chew was the lead author.
AREDS Report 38, published in Ophthalmology in 2014, showed that AREDS supplements reduced the rate of AMD progression in all genotype groups and that genotypes at the complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) loci had an insignificant effect on the supplement’s efficacy.
AREDS Report 38
AREDS Report 38 followed a study published in Ophthalmology in which Awh et al found that patients with one or two CFH risk alleles and zero ARMS2 risk alleles received the maximum benefit from antioxidant-only supplementation and that treatment with zinc was associated with increased progression to advanced AMD.
In an overall analysis, Chew and colleagues found an insignificant relationship between genotype and response to AREDS supplementation.
“[We] looked at the entire dataset using everybody to see whether there were genotype changes that would have an influence on the response to AREDS supplements. We found no statistically significant interaction,” Chew said.
Chew and colleagues also conducted a subgroup analysis in an effort to replicate Awh’s findings.
“The subgroup analysis should never have been done because, overall, it was not statistically significant,” Chew said. “We did the subgroup [analysis] because we wanted to mimic and see whether we would find anything that Dr. Awh found.”
The subgroup analysis also showed an insignificant relationship between genotype and response to AREDS supplementation, Chew said.
“The overall message from Report 38 is that there was no influence of the genotype on the response to AREDS supplements,” she said.
Residual cohort analysis
In another study of 7-year outcomes of 989 AREDS patients assigned to four genotype subgroups chosen from nine different genetic subgroups, Awh et al found that patients in one genotype group had a favorable response to AREDS supplementation and that patients in three genotype groups had neutral or unfavorable responses.
In their report, Chew and colleagues set out to replicate Awh’s subgroup analysis by analyzing 526 patients from a residual cohort of AREDS patients who were not included in Awh’s study.
Chew et al were unable to replicate Awh’s subgroup analysis. Additionally, the Awh and Chew subgroup analyses yielded dramatically different results. For example, Awh’s analysis of the group with two CFH risk alleles and one or two ARMS2 risk alleles, the highest risk, showed a harmful treatment effect from zinc or the AREDS formulation. Chew’s analysis showed that supplementation had a beneficial effect for both zinc by itself and the AREDS formulation.
“The [genotype groups] that had harmful effects in response to zinc and the AREDS formulation in Dr. Awh’s analyses, we found the opposite. Their analyses were never statistically significant in the first place,” Chew said.
Chew attributed the differences in results to subgroup selection. Subgroup definitions in the Awh study were guided by the same data that were used to gauge their effectiveness. Awh’s subgroup analysis was biased because the nine genetic subgroups were not pre-specified and were organized retrospectively based on rates of progression, according to Chew.
“You can subdivide people based upon the outcome. You know what the outcome is. It’s what we call a post hoc analysis. You already know what the results are,” Chew said.
In an editorial published in Ophthalmology, Janet Wittes, PhD, and David C. Musch, PhD, MPH, supported Chew’s findings that every genetic subgroup benefited from AREDS supplementation. – by Matt Hasson
Editor’s note: Read another article written by OSN writer Matt Hasson on this topic in the Dec. 25, 2014 issue.
References:
Awh CC, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2013.07.039.Awh CC, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.07.049.
Chew EY, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.05.008.
Chew EY, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.10.012.
Wittes J, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.10.023.
For more information:
Emily Y. Chew, MD, can be reached at National Eye Institute, 31 Center Drive, Bethesda, MD 20892-2510; 301-496-6583; email: echew@nei.nih.gov.Disclosure: Chew has no relevant financial disclosures.