EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.
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78 EW SECONDARY FEATURE February 2011 Retina October 2012 Predicting AMD by Enette Ngoei EyeWorld Contributing Writer "We are analyzing the data now, but we did this test in order to test the hypothesis that since we're looking at DNA and DNA doesn't change, both tests should give us exactly the same result in the same patient," she said. How the tests work For both tests, the inside of the pa- tient's cheek is swabbed at the oph- thalmologist's office, and the swab is placed inside a biohazard bag and sent off to the laboratory. The labo- ratory extracts the DNA from the saliva, analyzes it, and sends a report in 2-5 weeks, Dr. Holekamp said. Macula Risk can be used by optometrists and ophthalmologists, while RetnaGene can be used only by ophthalmologists, she said. In fact, RetnaGene is targeted at retina specialists in particular. Dr. Holekamp explained, "It's EyeWorld explores two DNA tests that assess a patient's risk of developing AMD B y 2020, an estimated 2.9 million Americans will have advanced age-re- lated macular degenera- tion (AMD). Without prevention or cure for the leading cause of vision loss in people over the age of 65, current treatments are targeted at slowing the progression of the disease, making early detec- tion crucial. Scientists studying the patho- genesis of AMD have identified certain genetic risk factors for devel- oping the disease, leading at least two companies to produce commer- cially available DNA tests for assess- ing a person's lifetime risk for developing late-stage neovascular AMD. The two tests are Macula Risk (ArcticDx Inc., Bonita Springs, Fla.) and RetnaGene (Sequenom Center for Molecular Medicine, San Diego). According to Nancy Holekamp, M.D., associate professor of clinical ophthalmology and visual sciences, Washington University School of Medicine, St. Louis, Macula Risk looks at eight genetic markers plus smoking and is based on an algo- rithm that will predict the lifetime risk of any macular degeneration over age 60, while RetnaGene looks at 13 different markers. "So who's right? Is it 13 or eight? What's the magic number? There's general agreement that [ge- netic risk] involves variants in the complement factor H, complement component 3 (C3), and ARMS2/ HTRA1 genes," Dr. Holekamp said. According to Gregory S. Hageman, Ph.D.,executive director, Moran Translational Medicine Cen- ter, University of Utah, two major loci account for the major propor- tion of risk. "It's confusing at times because of all the associations that have been described, to be clear the vast major- ity of risk resides within two major loci. One is on chromosome 1, which includes the complement factor H gene (CFH) and five of the so-called complement factor H- related genes (CFHR1-5). These six genes are aligned on chromosome 1 locus in a row. On chromosome 10, there's a pair of genes, one called ARMS2 and one called HTRA1. The RetnaGene test is based on the CFH and CFB/C2 loci published by Dr. Hageman and his colleagues, including Drs. Rando Allikmets and Michael Dean, as well as studies on the chromosome 10 locus published by Dr. Michael Gorin and colleagues. Macula Risk looks at comple- ment factor H, complement component 3 (C3), ARMS2, and a mitochondrially encoded NADH dehydrogenase 2, while RetnaGene looks at complement factor B, com- plement component 2 and F13B, in addition to complement factor H, complement component 3 (C3), and ARMS2, Dr. Holekamp explained. She and colleagues did a 100 patient, three-center, prospective clinical trial comparing both tests head to head in the same patient. hard to comprehend the genetic risks involved; it's a little bit more sophisticated. Retina specialists are the ones with the most AMD pa- tients in their practice, and they may be more judicious in using it appropriately so that it truly en- hances the management of the patient, so the companies have a different approach to who they are marketing to." The Macula Risk test categorizes people into one of five groups, she explained, group one being the low- est risk and group five being the highest risk. "I had myself swabbed and I came out in group 2; I feel pretty good about that because that's a lower risk group," she said. The other test will give a per- centage of risk, she said; anything above 75% is high risk, anything be- tween 25 and 75% is moderate risk, and anything less than 25% is low risk. "These are just risk profiles—not everyone at high risk is going to get AMD, but they're at high risk to get it," Dr. Holekamp said. Which patients to test? Since one's DNA doesn't change, children could be tested for their risk later in life, Dr. Holekamp said. However, since there's no preven- tion, it doesn't make sense to test children.