Genetic Testing for IRDs: The Patient’s Perspective with Michelle Glaze

Despite the benefits of genetic testing, there are limitations and potential drawbacks for patients and eye care providers to weigh as well. Genetic test results could cause anxiety for family members, for example, or the test results may fail to reveal the defective gene. So it can be especially helpful for patients to consult with a retinal doctor or genetic counselor before deciding whether or not to move forward.

Researchers at the University of Oklahoma and the University of Southern California have examined the utility of no-cost genetic testing for patients diagnosed with an IRD. Their findings, published last year in the Journal of VitreoRetinal Diseases, revealed that about half of the patient samples (30 of 59) had a diagnostic yield. But nearly as many (28) were undetermined, and one patient received a negative result with no mutations or variants of uncertain significance identified.

“Open-access, no-charge panel testing offers a reasonable diagnostic yield,” the study authors concluded. “Accurate clinical diagnosis of IRD before testing and acknowledgment of the limitations of panel testing are critical.”

A genetic test that comes back with a negative result does not rule out the possibility that a patient has the disease in question. For instance, Stargardt disease causes central vision loss progressively as a patient grows older, and it is traditionally discovered in children. But some patients have mild forms of the disease that goes unnoticed until later in life. When testing is eventually performed, the results are often inconclusive.

Genetic testing relies on previously identified genetic mutations that are known to cause disease. When a test is performed, it compares a patient’s genetic profile to a list of potentially disease-causing mutations. The problem is that for any given IRD, only a subset of mutations has been identified.

In some cases, a patient may clinically have what appears to be consistent with a known IRD, yet their testing comes back without a positive result. In these instances, the individual may have the disease in question even though the database of known mutations hasn’t caught up. It is an issue that remains common for now, he added, although it is becoming less so over time as more and more mutations are identified.