Eyeworld

74 | EYEWORLD | APRIL 2022 R EFRACTIVE visit for keratoconus suspect evaluations, and I always recommend it to my known keratoconus patients for their siblings or offspring." Dr. Yeu said she offers this test to patients in cases where she thinks the information would be truly additive to the clinical decision-mak- ing process. Currently, the test is paid for out of pocket. Dr. Yeu estimated that patients are charged $350–500. It's important to still use other screening tools to make the keratoconus diagnosis. Dr. Yeu uses pachymetry, topography, and tomog- raphy. Corneal epithelial mapping with OCT and biomechanical testing can further enhance the ectasia screening process. She also noted the importance of looking at family history, eye rubbing, systemic comorbidities, ethnicity, and other risk factors. Dr. Yeu said eye rubbing can be a big cause for concern. She strongly urges her patients with known keratoconus or suspicious corneal astigmatism to avoid this. Contact lens intoler- ance can also point to worsening progression of corneal astigmatism. "I watch the corneal astigmatism closely in these patients, as contact lens intolerance can be from dry eye disease or contact lens conjunctivitis," she said. Availability of tests The first commercially available test for corneal dystrophies was made in Korea by Avellino Pre- cision Medicine in 2008, Dr. Yeu said. This only tested for one TGFBI mutation known to cause Avellino corneal dystrophy (now also known as GCD2). The launch of that test led to more test- ing in South Korea and Japan, and eventually, more mutations were defined. The Avellino test was modified by Avellino Precision Medicine to include five mutations of the TGFBI gene. "Today, 42 labs offer corneal disease genetic testing, according to a search on the Genetic Testing Registry," Dr. Yeu said. "Universities with their own labs are also able to offer this type of testing." In 2019, Avellino launched the AvaGen test, which Dr. Yeu said uses next-generation se- quencing to look for more than 70 mutations of the TGFBI gene for corneal dystrophies, as well as markers across 75 other genes associated with keratoconus and related diseases. The developments in testing and therapy resulted in FDA approval of voretigene nepar- vovec-rzyl (Luxturna, Spark Therapeutics) in 2017, the first gene therapy of its type approved for confirmed biallelic RPE65 mutation-associ- ated retinal dystrophy. "While the prevalence of this genetic disease is considerably less than other eye diseases, the promise that this process of testing and therapy development gives is substantial," Dr. Yeu said. "There are a number of labs today that offer testing for published eye-related genes." These tests, Dr. Yeu said, are meant to pro- vide guidance and additive information for the clinical decision-making process. "This will help me determine if I do laser vision correction or LASIK versus PRK or skip the cornea and choose an ICL; it helps determine if crosslinking is war- ranted or what the follow-up schedule should look like for the patient," she said. Dr. Yeu added that the genetic testing tech- nology has improved so that the sample collec- tion process can be done by a nurse, technician, or trained staff member in the clinic in just a few minutes. "The DNA collection is performed by swabbing the buccal mucosa inside of the cheek, and it's deposited into a small vial that preserves the sample," she said. "The DNA sam- ple is shipped to Avellino, and the reports are accessible to the practice via a web portal." Genetic testing, Dr. Donnenfeld said, is another tool to give the doctor and patient more information. "If someone has obvious kerato- conus, I don't need genetic markers," he said. "What we want to do is look at the patient who looks a little unusual, where the topography isn't completely normal but not at the point where it's an easy diagnosis. This gives me that additional information to allow me to make smart decisions." Dr. Donnenfeld said he will use genetic test- ing frequently for family members of those who have had transplants. They often want to have all their children checked. He also discussed the ability of this test to diagnose other stromal dystrophies and noted that new genetic markers, particularly for glau- coma, may be included in future testing. "I think genetic testing is going to be the future of everything we do in ophthalmology, as well as all of medicine, because finding the patients who are at risk for diseases, diagnosing them earlier, and designing a treatment plan that fits their genetic markers is going to allow us to be smarter practitioners and provide bet- ter care," Dr. Donnenfeld said. Contact Donnenfeld: ericdonnenfeld@gmail.com Yeu: eyeulin@gmail.com continued from page 73

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