Gerry Belgraver responds:

Issue: January 2018

There has been an increasing amount of confusion and frustration among all parties in the debate over the gene-AREDS interaction and the role of genetics in the selection of the ideal patients for AREDS prophylaxis. Everyone wants to know if the AREDS formulation is safe and effective for all patients. The two sides to this debate include Arctic (the genetic testing company) and the NIH, which holds a royalty-bearing license issued to Bausch + Lomb for its patented Age-Related Eye Disease Study supplement.

Much of the confusion is fueled by the fact that the bulk of these gene-AREDS interaction studies incorrectly measured both clinical endpoints for advanced AMD (wet AMD and geographic atrophy) as pooled results. For example, in the recent publication by Assel and colleagues, 55% of patients analyzed progressed to geographic atrophy even though AREDS has no impact on it. The use of geographic atrophy as a clinical endpoint dilutes the data analysis, disguises the reality of the gene-AREDS interaction and confuses everyone.

AREDS is only effective when used as prophylaxis against progression to wet AMD (AREDS report no. 8). Seddon and colleagues taught us that this is also true regardless of genetics. She demonstrated that AREDS as prophylaxis for wet AMD is not effective in 31% of patients, but it works much better than expected in two-thirds of patients; 13.5% of her patients analyzed experienced an 85% risk reduction against progression to wet AMD. That is an excellent performance from AREDS that many doctors and patients should know about.

The Medicare reviewers at Palmetto GBa, who have been asked to provide patient access within Medicare, have, no doubt, experienced frustration in that the main rebuttal publication has conflicting conclusions, some of which are unsupported by the researchers’ own data (Chew et al., 2014).

Nearly 5,000 patients and doctors wrote letters asking Palmetto to approve patient access to genetic testing for doctors who want to use the test. The Palmetto adjudicators issued a positive reimbursement decision on May 25, which was taken back a few weeks later when the manuscript by Assel and colleagues was submitted for review, as Dr. Rapp correctly points out. It was unfortunate that an unpublished manuscript, which focused on the wrong disease, could overturn the decision to reimburse.

However, the newest work from Vavvas and colleagues, slated to be published in the Proceedings of the National Academy of Sciences, appropriately analyzed the gene-AREDS interaction against progression to wet AMD, confirming the risk in the suspect genotype in two separate cohorts. Now Palmetto can finally decide what is best for patients.

References:
Age-related Eye Disease Study Research Group. Arch Ophthalmology. 2001;119(10):1417-1436.
Assel M, et al. Ophthalmology. 2017;doi.org/10.1016/j.ophtha.2017.09.008
Awh CC, et al. Ophthalmology. 2013;doi:10.1016/j.ophtha.2013.07.039.
Awh, C, et al. Ophthalmology. 2015;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. 2015;doi.org/10.1016/j.ophtha.2014.10.012.
Klein ML, et al. Ophthalmology. 2008;doi:10.1016/j.ophtha.2008.01.036.
Seddon JM, et al. Br J Ophthalmol. 2016;doi:10.1136/bjophthalmol-2016-308624

Disclosure: Belgraver is employed by Arctic.