September 2020


Gene Therapy
Genetic testing for keratoconus

by Ellen Stodola Editorial Co-Director

“As more patients have the tests and there’s more data, we’ll be able to learn more, and the test will be even better.”
—William Trattler, MD


While there are many options being explored in the field of genetic testing and gene therapy, one area of interest is genetic testing for keratoconus and other corneal dystrophies. Avellino has developed such genetic testing, including a new test to identify markers for keratoconus. Elizabeth Yeu, MD, William Trattler, MD, and Mitchell Jackson, MD, discussed this type of testing, how they are currently using it, and ways it might be applicable in the future.
Avellino previously developed a genetic test for granular corneal dystrophy (also known as Avellino dystrophy) and further developed to test for several other mutations of the transforming growth factor beta induced (TGFBI) gene.
The AvaGen test was released in late 2019, and according to Dr. Yeu, it looks for dozens of mutations of the TGFBI gene, as well as markers in other genes that are associated with keratoconus and other corneal dystrophies.
When deciding the best candidates for this genetic testing, both Dr. Yeu and Dr. Jackson said they start with patients who are already diagnosed with the disease.
Dr. Jackson noted that in patients already diagnosed with keratoconus, performing this genetic test can identify specific markers to then pinpoint if family members are also at risk. A positive genetic test in family members who are not already diagnosed with keratoconus can be incredibly helpful to monitor progression and earlier diagnosis of clinical findings.
Before the current pandemic, he had been working on a plan to implement genetic testing for keratoconus in his practice. He noted that he is still working on adopting it and structuring how much it would cost to test family members who might be at risk.
“We plan to do that moving forward to see if family members are at risk for a certain strain or genotype of keratoconus to know if we should crosslink early on instead of waiting to see if it appears in corneal topography or slit lamp,” he said.
Dr. Yeu added that keratoconus tends to progress most rapidly in patients aged 13–30, so it’s advantageous to be able to identify and monitor them as early as possible.
This is a nice technology for keratoconus, Dr. Trattler said, because it’s a simple cheek swab that tests for a variety of genes associated with keratoconus.
“Avellino evaluated patients with keratoconus and compared their genetic profile to controls without keratoconus. They also incorporated known genes associated with keratoconus. The Avellino test evaluates more than 75 genes unique to patients who have keratoconus,” he said. Based on these results, a scoring system was developed. The genes that were more common had a higher score, the genes that were less common had a moderate score, and genes that were even less common had a lower score, Dr. Trattler said, explaining there is not one gene that identifies keratoconus.
The big challenge, he said, is that just because a patient has a gene doesn’t mean that the patient will develop keratoconus. In addition, it’s not known yet whether there are genes that predict for more rapid keratoconus progression. Additionally, someone without genetic evidence could also still develop keratoconus. “There’s no hard rule,” Dr. Trattler said. “But it’s interesting to look at the role genes play in keratoconus, and as more data is collected, more will be learned.”

Screening refractive surgery patients

Dr. Yeu said other potential candidates for this genetic test include those with elevated mean corneal curvatures and astigmatism rates that demonstrate progression over time and patients considering corneal refractive surgery with laser vision correction.
Dr. Jackson noted that he has used Avellino dystrophy genetic testing since the test came out, and it is presented to patients as an added “value and safety” piece. The patient pays for this test at their refractive evaluation, and it is nonrefundable but gets applied as a credit to the overall cost of the laser vision correction procedure.
“If the test comes up positive and you’re at risk, even if you don’t have the procedure, it’s still a value add,” Dr. Jackson said. “The good news is in my population of patients, so far we haven’t seen any positive tests.” He said that a technician will do a saliva cheek swab when the test is administered and results usually come back in 24–48 hours.
Dr. Jackson added that with the company working on a faster turnaround of results for its AvaGen test, though it won’t cover 100% likelihood of keratoconus, it will provide a certain percent chance that a patient’s genotype is at risk for keratoconus, helping inform whether a patient should or should not have LASIK. This could be valuable in the future, Dr. Jackson said.
Dr. Trattler also said this type of genetic testing may be helpful if you have a patient coming in for LASIK screening and their topography maps are suspicious. “You could offer the testing, and if they’re positive, it may influence what you want to do,” he said.
“As more patients have the tests and there’s more data, we’ll be able to learn more, and the test will be even better,” Dr. Trattler said.

At a glance

• Avellino has developed genetic testing to look for genetic markers for keratoconus as well as several other corneal dystrophies.
• Currently the test is not covered by insurance, so patients pay out of pocket or the physician needs to cover the cost.
• Physicians may want to use the test for a variety of patients including family members of patients with keratoconus or potential refractive surgery candidates.

About the doctors

Mitchell Jackson, MD
Lake Villa, Illinois

William Trattler, MD
Center for Excellence
in Eye Care
Miami, Florida

Elizabeth Yeu, MD
Virginia Eye Consultants
Norfolk, Virginia

Relevant disclosures
: Avellino
Trattler: None
Yeu: Avellino


Genetic testing for keratoconus Genetic testing for keratoconus
Ophthalmology News - EyeWorld Magazine
283 110
283 110
True, 9