GENETIC SELF TESTING

Athough genetic research suggests new potential treatment targets for glaucoma, genetic testing today is currently seldom needed for clinical diagnosis or treatment, Wallace LM Alward MD told Glaucoma Day at the 2014 American Academy of Ophthalmology annual meeting in Chicago. Indiscriminate testing can even do harm, said Dr Alward, of the University of Iowa, Iowa City, Iowa, US. Commercial genetic self-tests can be especially troublesome, he said, as they often confront patients with “risk” information that is almost meaningless outside a specific clinical context. The results can range from causing needless worry to generating unnecessary tests or even ill-advised prophylactic treatment, Dr Alward said. Therefore, he advised adhering to the AAO genetic testing task force recommendation to avoid routine testing for genetically complex disorders, including late-onset open-angle glaucoma (Ophthalmology 2012; 119: 2408-2410). Risks … Most glaucoma genetic markers were discovered through genome-wide association studies of large populations. So most are associated with increased disease risk rather than directly causing glaucoma, Dr Alward explained. But even when the association is strong, it may not be clinically relevant, Dr Alward added. For example, a gene association study of pseudoexfoliation found that patients homozygous for the highest risk variant of the lysyl oxidase-like 1, or LOXL1, gene were 700 times more likely to develop exfoliation glaucoma than those with the lowest risk (Thorleifsson et al. Science 317:1397-1400, 2007). “That’s pretty exciting – except that 25 per cent of the population is homozygous for the highest risk alleles.” And since most will never get pseudoexfoliation, testing is not very helpful, Dr Alward said. Indeed, research suggests multiple genetic and environmental factors contribute to pseudoexfoliation and most other glaucomatous conditions. But many factors and their interactions are unknown. So conventional clinical signs remain much more powerful glaucoma predictors than genetic tests in most cases, Dr Alward said. … And causes However, a few genes apparently do cause glaucoma. These include myocilin for juvenile onset or primary open-angle glaucomas; optineurin and TBK1 for normal-tension glaucoma; CYP1B1 and LTBP2 for primary congenital glaucoma; and PITX2 and FOXC1 for Axenfeld-Rieger syndrome. “If you have these genes you are at very high risk for getting these diseases,” Dr Alward said. But these rare conditions combined make up only about five per cent of glaucoma cases – and are often evident without genetic tests, Dr Alward said. Genetic tests may be most useful in borderline cases, such as confirming PAX6 mutation in a patient with some but not all aniridia features, or screening offspring of patients with known genetic disease, he said. Wallace LM Alward: wallace-alward@uiowa.edu