How DNA testing screens for corneal dystrophy

Take-Home

A new genetic test for Avellino corneal dystrophy identifies carriers of this rare autosomal dominant mutation. Its presence can lead to visual deterioration and ultimate blindness following corneal refractive surgeries.

VIDEO

By Lynda Charters; Reviewed by David Whiting, MD

St. Louis Park, MN-A new genetic test for Avellino corneal dystrophy (Avellino Gene Detection System, Avellino Lab USA Inc.) identifies carriers of this rare autosomal dominant mutation, which, if present, can cause vision to deteriorate and ultimate blindness following corneal refractive surgeries.

Also referred to as granular corneal dystrophy, the mutation has two genotypes:

> In homozygous individuals, the corneal manifestations are seen in early childhood and the children usually become blind in adolescence.  

> In heterozygous individuals, gray-white granular protein deposits can appear on the cornea during early adolescence but many affected people do not have symptoms until much later at a time when they might be considering a refractive procedure.

These individuals are the target population for screening, explained David Whiting, MD, in private practice, St. Louis Park, MN.

He performs the DNA testing on his patients who are potential candidates for a refractive surgery, and explained that a procedure such as LASIK can worsen the corneal cloudiness in genetically predisposed patients at almost any time postoperatively.

Unless the corneal spots are visible, the dystrophy cannot be identified by any other means other than genetic testing at this point in time.

“We hope to do the DNA screening on every patient who wants to undergo a vision-correction procedure,” Dr. Whiting said.

Patient with Avellino corneal dystrophy, age 34 years, 6 years after LASIK. (Image courtesy of Avellino Labs, with credit to Prof. E.K. Kim)

How the test is done

Using the DNA kit to test for the presence of the gene mutation is a simple noninvasive procedure that only involves rubbing a sterile cotton swab on the inside of the patient’s cheek.

The sample is then placed into a vial, sealed, and mailed to the Avellino laboratory for processing.

Dr. Whiting generally receives the test results sent via e-mail the following day.

The genetic mutation is rare, and the exact prevalence rate presently is unknown. However, 1 in 1,000 patients is thought to carry the gene mutation.

To date, Dr. Whiting has screened roughly 250 patients and has seen no positive test results.

He anticipates, given the suspected prevalence, that one affected patient will be identified among the first 670 patients screened.  

He also pointed out that the prevalence rates may vary with different locations around the country and world because of variations in ethnicities.

A concern is that there may be a higher incidence in Southeast Asian populations or Korean patients.

Cost considerations

The cost effectiveness of using this screening tool also is still undetermined considering the relative rarity of the disease.

Dr. Whiting put that in perspective by commenting about the effort and money that have been invested in ferreting out other pre-existing conditions in refractive surgery candidates, such as keratoconus and ectasia.

“We know that LASIK worsens those conditions,” Dr. Whiting. “The numbers are also hard to ascertain, but we know that perhaps one in 2,000 individuals have an underlying tendency for corneal thinning.

“Nonetheless, we use expensive instruments to screen all patients,” he said. “Having this information affects the decision to perform or not to perform LASIK. The incidence of ACD could be even higher than that of keratoconus and ectasia.”

To Dr. Whiting’s knowledge, he is the only ophthalmologist in the Minneapolis area who offers this DNA test to his potential refractive surgery patients.

“In my practice, we made the decision to perform the DNA test on all patients before they undergo a refractive procedure, and we do not pass the cost of the test along to our patients,” he said.

“Because of the volume of refractive surgeries in my practice-with half of my clinical time dedicated to performing LASIK-my need to know if a patient is affected by this corneal dystrophy is important compared with a practice with a smaller volume of refractive surgeries,” Dr. Whiting said.

Safety aspect

Performing this DNA test enhances Dr. Whiting’s comfort level and keeps his practice at the cutting edge of technology.

“I am very risk-adverse,” said Dr. Whiting, who has performed more than 95,000 LASIK procedures.

“The cost of the test is secondary to determining if this is a meaningful test for my patients,” Dr. Whiting underscored. “Safety is of the utmost importance and this is an important message to convey to patients.”

David Whiting, MD

E: david.whiting@whitingclinic.com

Dr. Whiting has no financial interest in this technology.

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