BLOG: Genetic testing a promising option for keratoconus decision-making
Click Here to Manage Email Alerts
We know from twin and familial studies that keratoconus has a genetic component. First-degree relatives of people with keratoconus have a 15- to 67-fold greater risk for keratoconus than the general population.
Wouldn’t it be cool if we could tell from a person’s genes whether they will develop keratoconus (KC)? Unfortunately, it isn’t quite so simple.
There are a number of corneal disorders, such as type II granular corneal dystrophy, that are monogenic, or caused by a single gene mutation. Testing for these dystrophies is straightforward: A positive result confirms the dystrophy, while a negative test rules it out. Keratoconus is more complex. Not only is it polygenic, or caused by the interaction of several different genes, but genes can explain only a portion of cases. Environmental and other factors also play a role. Nevertheless, there is now an intriguing new genetic test for KC (AvaGen, Avellino) that we plan to integrate into our diagnostic workup at UC-Irvine.
Rather than a yes/no result, the cheek-swab test provides a risk score (0 to 100, or “very low” to “very high” risk) based on dozens of gene variants known to be highly correlated with KC. This test is still new, so there is much to be learned about how it can best be used in practice. However, I think it holds great promise for clinical decision-making in at least three specific areas.
1. Screening for refractive surgery. Genetic testing can help to identify patients who may not be good candidates for LASIK. Just recently, I had a patient who seemed to be a great candidate based on her preoperative workup. At the end of the consultation, she mentioned that her father had an eye condition, which she initially mispronounced but we eventually determined was KC. There is no guarantee she will also have KC, but a history of KC in a close relative certainly gives me pause. We decided to wait until she could have the genetic test and obtain more data points on her corneal health before considering refractive surgery.
2. Tipping the scales in murky cases. In a young patient with obvious KC progression, there is no doubt that cross-linking is needed. But it is not uncommon to have cases in which the physical findings are mild or equivocal. Watchful waiting is a reasonable choice in these cases — but wait too long and the patient could lose lines of vision. Identifying a genetic predisposition could shift the calculation toward earlier treatment or, at the very least, encourage regular follow-up by the patient.
3. Testing family members of patients with KC. I recently saw a patient of mine who underwent the FDA-approved iLink procedure (Glaukos) about a year ago and is doing great. But I just learned that he has two siblings who have never been evaluated for KC. Even those of us who are passionate about early detection and treatment of KC can forget that patients don’t always realize this disease has a genetic component. Genetic testing could be a first step for siblings and other first-degree relatives to better understand their own risk factors. In a relative with a genetic predisposition but no other signs of corneal thinning or topographical changes, we still have valuable information that we can use to educate that patient about eye rubbing and allergy management, counsel them to avoid corneal refractive surgery and consider more frequent monitoring.
Genetic testing will not replace our other diagnostic tests for KC or probably ever be used as the sole factor leading to treatment, but it can be part of our decision matrix. I look forward to learning more about how to interpret and use the results of genetic tests for KC and hope they will contribute to our ability to identify progressive KC and provide treatment to preserve vision.
- Reference:
- Wang Y, et al. Am J Med Genet. 2000;93(5):403-409.
Collapse