Though genetic testing can identify some types of glaucoma, risk assessment and counseling based on family history is more helpful for most patients than genetic testing, said Wallace L.M. Alward, MD.
Iowa City, IA-Though genetic testing can identify some types of glaucoma, risk assessment and counseling based on family history is more helpful for most patients than genetic testing, said Wallace L.M. Alward, MD.
“There are a lot of genetic risk factors for glaucoma coming out of family studies and genome-wide association studies,” said Dr. Alward, professor and Frederick C. Blodi Chair in Ophthalmology and director, glaucoma service, University of Iowa Carver College of Medicine, Iowa City, IA. “Those associations are very useful for understanding the biology of glaucoma, but only in very rare occasions is it clinically useful to test for any of those mutations. For the vast majority of glaucoma, we don’t know the genetic underpinning of the disease.”
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A positive family history of glaucoma remains the single most important factor when it comes to counseling and, for a very few patients, genetic testing, he noted.
Every physician should be soliciting family history from every patient, Dr. Alward said. In ophthalmology, patients with a positive family history for glaucoma should be counseled that they may be at increased risk for the disease themselves. Children of glaucoma patients may similarly be at increased risk for developing glaucoma.
Risk of first-degree relatives
First-degree relatives of patients with primary open-angle glaucoma (POAG) may be at up to 22% risk for POAG themselves, a 10-fold increase in risk compared with the general population. For dominant diseases-such as juvenile open-angle glaucoma, Axenfeld-Rieger syndrome, and aniridia-first-degree relatives have a nearly 50% risk.
“Ophthalmologists know that a lot is happening in the genetics of glaucoma and a growing number of citations in the literature,” Dr. Alward said. “The most common test is for mutations in the myocilin gene, but even that is not applicable to the average patient.
“Patients can have a mutation to the myocilin gene if they have run-of-the-mill open-angle glaucoma,” he added. “Knowing they have the mutation does not change very much about how you would manage that patient. The time testing can make a significant difference is in patients with dominant juvenile glaucoma.”
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Juvenile glaucoma patients typically present with IOP of 40 mm Hg and higher in their 20s, an age when few ophthalmologists would even consider glaucoma. These patients also tend to have a strong family history of glaucoma. Myocilin testing can make a significant difference in both treatment and counseling for this small group of patients.
Juvenile glaucoma patients who test positive for myocilin mutation are highly likely to be resistant to most medical treatment, Dr. Alward explained. Most of the topical medications used for glaucoma are relatively ineffective in this population. Juvenile-onset patients who test positive for myocilin mutation are likely to have a highly aggressive form of the disease and are likely candidates for early surgical intervention.
Identifying myocilin mutations
Identifying a myocilin mutation also helps target counseling. Because first-degree relatives of patients with juvenile glaucoma are at greatly increased risk of developing the disease, genetic testing of siblings and offspring is a viable strategy. Relatives who show evidence of a myocilin mutation themselves are at extremely high risk of developing glaucoma. Those who test negative are at no higher risk than the general population.
“In practice, myocilin testing in the offspring of juvenile glaucoma patients is most useful for those who test negative,” Dr. Alward said. “They know that they are unlikely to go through what dad or granddad did at a similarly early age. That lets you target your angst and your efforts for the people who are actually at increased risk.”
Genetic mutation markers have also been identified for other, less common forms of glaucoma, including Axenfeld-Rieger syndrome and aniridia. These diseases can usually be identified with a slit lamp examination, Dr. Alward said, but the diagnostic criteria are sometimes vague. In those very few cases where the diagnosis is uncertain, genetic testing can be helpful.
“The confluence of those rare diseases where you really aren’t sure of the diagnosis and the availability of genetic testing is pretty uncommon,” he said. “It’s nice that testing is available, but the clinical need for it is just not that common.”
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Genetic testing is available for more than 3,000 inherited disorders, he continued. Tests can generally be ordered individually or in panels and generally cost between $100 and $1,500 per gene. Myocilin testing costs about $200.
A directory of available genetic tests and laboratories equipped to perform testing can be found at https://www.genetests.org.
“Family history is usually what raises the initial alarm to pay closer attention to this particular patient,” Dr. Alward said. “Genetic testing can occasionally be helpful in some instances of specific disease, but it is rarely indicated. I can do these tests for free and I don’t do them very often.”