The first and only commercially available genetic test for corneal dystrophy offers a quick, affordable, and accurate way to make refractive surgery safer—and could pave the way for other genetic tests in ophthalmology.
by Peter Falzon
The phrase “personalized medicine” can call to mind the types of sweeping, whole genome sequencing tests currently being marketed to consumers. Many within medicine—myself included—feel that these tests are not quite ready for prime time since the information they uncover may not be immediately actionable and can end up generating confusion and anxiety rather than clarity. The best genetic screening tools look for specific defects associated with known conditions and yield insights that help physicians make good, fully informed choices about their patients’ medical care and lifestyle.
That is what excites me about personalized medicine—the chance to offer patients a previously inconceivable level of safety and specificity in their care. Where we are now in DNA testing for ophthalmic diseases reminds me of where we were with laser technology 25 years ago, when new applications were being conceived and evaluated at a furious pace, including many that would revolutionize ophthalmic surgery and clinical practice.
Personalized medicine holds that same promise—eyecare practitioners can now test for two forms of corneal dystrophy, and more advances should follow quickly. Genetic testing may one day help doctors select glaucoma therapy for their patients based on genetic characteristics, screen for congenital diseases such as retinitis pigmentosa, and prevent, manage, and predict outcomes for a host of other ophthalmic conditions with a genetic component. On the practice level, incorporating the latest genetic tests stands to differentiate eyecare practices in the marketplace—just as the early adoption of laser technology did and continues to do.
Avellino Corneal Dystrophy
In the US, we are fortunate to have one such genetic test already available for use—the Avellino DNA Test, a cheek swab kit for granular corneal dystrophy types 1 and 2 from my company, Avellino Lab USA (Menlo Park, CA). Granular corneal dystrophy type 2 is also called Avellino Corneal Dystrophy after Avellino, a town in southern Italy to which a cluster of cases was traced in the 1980s. Granular corneal dystrophy 1 and 2 are caused by a highly conserved, autosomal dominant mutation in the transforming growth factor, beta-induced (TGFBI) gene essential to normal corneal healing. In response to corneal surgery or injury, patients with genetic mutations associated with granular corneal dystrophy produce abnormal proteins that are deposited within damaged tissue.1-3
Corneal dystrophies may present in infancy in patients homozygous for the condition or later in life among those with heterozygous expression. Without testing, patients with late-developing disease are basically flying under the radar—they may have little or no corneal involvement and have no reason to suspect that anything is unusual about their eyes. That’s important because, if left in the dark, patients may place themselves at undue risk, failing to protect themselves from events and exposures that could trigger their genetically preprogrammed pathologic response—factors such as high UV light exposure, hard contact lens wear, and elective corneal surgeries such as LASIK or PRK.
The prevalence of the corneal dystrophies is not known. In Korea, one in 870 individuals tested positive for Avellino Corneal Dystrophy.4 Based on testing undertaken by the company, one in roughly 1000 patients set to undergo corneal surgery test positive for granular corneal dystrophy types 1 and 2. No particular geographic or ethnic predilection has been observed. Patients with undiagnosed granular corneal dystrophy who undergo corneal refractive surgery—instead of life-enhancing vision improvement—are at high risk of having white opacifications develop that progressively destroy their vision.
Currently, screening for corneal dystrophy prior to LASIK (and other corneal surgeries) is standard of care in South Korea and Japan. The Avellino DNA Test has been available in the US since 2014; with greater awareness and implementation, we can mirror the Asian success and prevent vision loss in hundreds of Americans each year.
To date, surgery has been averted in more than 475 patients who tested positive for the mutation during their presurgical workup. It is hard to come up with a reason not to implement the test—it was 100% sensitive and specific for granular corneal dystrophy types 1 and 2 in clinical trials; it is noninvasive; and results come back within 24 hours of the specimen being received at the lab.
LASIK is awe-inspiring technology—rarely has a medical breakthrough provided so much value to so many people with such little risk. Presurgical testing for corneal dystrophy can whittle that risk even further. Avellino Lab USA is in the process of expanding genetic presurgical screening capabilities to include three other less common forms of corneal dystrophy. A test for keratoconus risk is also in development. In my view, this is the promise of personalized medicine coming to fruition.
Peter Falzon is Chief Executive Officer of Avellino Lab USA, Menlo Park, CA.
- Aldave AJ, Sonmez B, Forsto L, et al. A clinical and histopathologic examination of the accelerated TGFBIp deposition after LASIK in combined granular-lattice corneal dystrophy. Am J Ophthalmol. 2007;143:416-9.
- Banning CS, Kim WC, Randleman JB, et al. Exacerbation of Avellino corneal dystrophy after LASIK in North America. Cornea. 2006;25:482-84.
- Roh MI, Grossniklaus HE, Chung SH, et al. Avellino corneal dystrophy exacerbated after LASIK: scanning electron microscopic findings. Cornea. 2006;25:306-11.
- Lee JH, Cristol SM, Kim WC, et al. Prevalence of granular corneal dystrophy type 2 (Avellino corneal dystrophy) in the Korean population. Ophthalmic Epidemiology. 2010; 17:160-5.