Avellino’s genetic eye test helps diagnose keratoconus sooner and improve refractive surgery outcomes.

Keratoconus is more frequently diagnosed today largely because of advanced diagnostic tools. Yet, ironically, ophthalmologists still cannot always rely on imaging to make a confident diagnosis. Results can be subjective and require much consideration before surgical steps are taken. Nazneen Aziz, PhD, chief scientific officer with Avellino Precision Medicine, refers to this as the “pause” that physicians find themselves in when reviewing image results. “There may be a suspicion of something wrong with the patient’s cornea, but you are not quite sure,” says Dr. Aziz.

She is hopeful that these times of pause will lead surgeons to utilize a new genetics-based test design

ed to help providers more accurately quantify the risk for or presence of keratoconus and other corneal genetic disorders.

GENOMICS AND EYE HEALTH

The AvaGen genetic eye test is one of the first such tools for ophthalmologists. A non-invasive buccal swab that is inserted inside the cheek, the test extracts DNA to evaluate patients for the potential of predisposition to keratoconus and the presence of corneal dystrophy. “Genomics has gravitated towards certain diseases and disease states, such as oncology, and rightfully so,” says Dr. Aziz, a molecular geneticist. “We are pleased to bring this innovative test to this field of medicine.”

Elizabeth Yeu, MD, a cornea, cataract and refractive surgeon at Virginia Eye Consultants, and medical director with CVP Physicians, says the test has already proven to be especially valuable for three cohorts:

• Those who require refractive surgery screening
• Younger patients who are seen for potential keratoconus due to increasing myopia or increasing astigmatism
• Family of patients diagnosed with keratoconus, due to their genetic risk.

PREVENTIVE AND PRACTICAL

Polygenic in nature, meaning that multiple genes are involved in the disorder’s causation, keratoconus is more treatable with various new modalities the earlier it is identified and managed. Dr. Aziz stresses the importance of initiating the test for patients when there may be suspicion of cornea issues; however, she says there’s increasing evidence that supports more patients to be tested regardless of health status prior to specific procedures.

“Often, patients may have a healthy cornea when they see the physician, say, for vision-correcting surgery, but injury to the cornea could occur during a procedure if it is unknown that the patient was already at high risk for keratoconus,” Dr. Aziz says.

Further, keratoconus can be misdiagnosed as progressive myopia in young patients, Dr. Aziz notes. “The earlier that this disease is caught and treated, the more likely that prevention is possible.”

Dr. Yeu, who estimates she is utilizing the AvaGen test on at least 20% of her patients who require refractive evaluations, says she leans on a few other indicators to decide on discussing testing as an option among patients.

“I think this test is also important for refractive patients if they have higher levels for astigmatism or their cornea is thin and they are borderline for how much tissue might need to be ablated because of the higher prescription,” she says. “Understanding whether they have a genetic predisposition for a weakening of their cornea is helpful. And those who are younger who have against-the-rule or oblique astigmatism should be evaluated for potential primary ectasia keratoconus to rule out natural effects of puberty and the maturation process of the eye.”

If a predisposition is detected, the clinician will follow the patient closely and provide counseling, she explains.

PROCEDURAL POINTS

Tests are conducted through a daily collection kit sent by the manufacturer and then shipped back at room temperature within 1 week of testing. (The swab remains refrigerated prior to its return.) DNA is extracted and next-generation sequencing is conducted at the lab.

“We analyze 75 genes, which is approximately 750 kilobases of DNA, which requires a lot of bioinformatics and application of polygenic risk scores,” says Dr. Aziz. The results are simplified and entered into a password-protected portal. A single score synthesizes the cumulative effect of the analyzed genes that lead to risk for keratoconus.

“It’s like a heat map that makes it easily visible to see the patient as a minimal, medium or high score of developing keratoconus,” Dr. Aziz explains. “The test also reports out corneal dystrophy, including seven different subtypes. It is important to differentiate between those subtypes because not all dystrophies progress at the same rate.”

COUNSELING COMBINATION

Given the complex nature of the disease and sequencing, Avellino provides genetics counseling as part of the overall service. While no reimbursement option is currently available, Dr. Yeu says the benefits of counseling combined with the general awareness of genetic testing today encourage patients to undergo AvaGen. OM