Is there any value in DIY genetic testing for glaucoma?


Do-it-yourself testing for glaucoma, if and when available, is of limited diagnostic value to clinicians, explained one physician familiar with the technology.


Take-home message: Do-it-yourself testing for glaucoma, if and when available, is of limited diagnostic value to clinicians, explained one physician familiar with the technology.



By Nancy Groves; Reviewed by Wallace L.M. Alward, MD

Iowa City, IA-Genetic testing for glaucoma is useful in some cases, but is most likely to yield clinically valuable information when ordered by a physician and performed by a certified laboratory.

Do-it-yourself genetic testing, if available, is of little benefit since no one, including physicians, is certain how to interpret risk genes discovered out of context, said Wallace L.M. Alward, MD.

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For now, ophthalmologists do not need to worry about how to respond to patients who are concerned with the results of a test they had performed through a personal genome service since these companies have been blocked from marketing their products for medical purposes. Test providers, such as 23andMe, can provide customers with information about their genetic makeup based on blood tests but cannot provide disease risk profiles pending FDA regulatory approval.

 “I’m enthusiastic that understanding glaucoma genetics will one day have a huge impact on diagnosis and therapeutics, but self-testing [in 2015] doesn’t hold promise for glaucoma diagnosis,” said Dr. Alward, the Frederick C. Blodi Chair in Ophthalmology; vice chairman, ophthalmology; director, Glaucoma Service; and professor of ophthalmology and visual sciences, University of Iowa Carver College of Medicine, Iowa City.

NEXT: Glaucoma genes


Dr. Alward discussed genetic testing, emphasizing the distinction between the two major types of glaucoma genes: those in which a single genetic change causes glaucoma, and those in which a change slightly increases the risk of developing glaucoma.

Disease-causing genes have typically been discovered through family studies. These include myocilin for juvenile-onset open-angle glaucoma and primary open-angle glaucoma; CYP1B1 and LTBP2 for primary congenital glaucoma; optineurin and TBK1 for normal tension glaucoma; PAX6 for aniridia; and PITX2 and FOXC1 for Axenfeld-Rieger Syndrome. A family member who carries one of these genes is at high risk to develop the associated form of glaucoma.

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Fee-for-service testing is available for almost all of these genes; offers a list of all the labs that provide testing. If a clinician believes that a patient may have the myocilin mutation, for example, the test can be ordered for about $200 with results available in 12 to 14 weeks. Answering this question may be very important to patients and their families.

“Unfortunately, all of the known glaucoma genes today only cause about 5% of glaucoma,” Dr. Alward said.

Further, the diagnosis can often be made with a slit lamp exam, and a lab test would not be crucial.

That said, genetic testing makes sense in some cases.

“If you have somebody who has all of the features of aniridia but still has an iris, you might want to test for PAX6 mutations,” Dr. Alward said. “I think myocilin testing is useful to do in someone with the classic juvenile onset glaucoma with a strong family history mostly so that you can check the offspring for their risk.”

He added, though, that these instances represent a tiny fraction of his clinic population.

“Even though I can do genetic testing at no cost to my patients, I rarely do,” he said.

The other type of glaucoma gene, which identifies risk factors instead of a high likelihood that disease will develop, is usually found in genome-wide association studies (GWAS). Many of these genes have already been discovered, and new ones are regularly added to the list. These genes cause a very small, incremental risk of developing disease but do not by themselves cause glaucoma. For now they are of greater interest to glaucoma researchers than to individual patients, Dr. Alward said.

NEXT: Genes continued


The most important of these is LOXL1, which is associated with exfoliation glaucoma and was discovered in a large GWAS conducted in Iceland. Individuals who are homozygous for the highest risk alleles are 700 times more likely to develop exfoliation syndrome than those with the lowest risk alleles. The catch is that 25% of the population is homozygous for the highest risk alleles.

“Most people who have the highest risk alleles will never get exfoliation, and testing for it is not helpful,” Dr. Alward said. “It’s a huge discovery and an important part of a complex puzzle, but I don’t know or really care what my LOXL1 phenotype is.”

The American Academy of Ophthalmology task force on genetic testing recommended in a 2012 report that ophthalmologists avoid routine genetic testing for genetically complex disorders such as late-onset, primary open-angle glaucoma.

“Hopefully that will change when there are useful tests for predicting the course or response to therapies,” Dr. Alward said.

He added that there are major, well-established risk factors for glaucoma, such as IOP, pattern standard deviation, and central corneal thickness. Then there are minor risk factors, associations that may appear in some studies but not others or may be of minor clinical significance.

“These genetic factors so far from the GWAS studies fall into the inconsistent or of minor significance categories for most patients,” Dr. Alward said.

The do-it-yourself tests that are not currently available would usually find sequence variations that are either meaningless or that would provide a tiny incremental risk that would not be clinically significant.



Wallace L.M. Alward, MD

P: 319/356-2228


This article was adapted from Dr. Alward’s presentation during Glaucoma Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Alward did not report any relevant disclosures.


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