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Refractive Surgery | Sep 2015

DNA Test Detects Corneal Dystrophies

A genetic diagnostic assay may identify patients at risk for post-LASIK complications.

“First do no harm,” one of the most important tenets in the Hippocratic Oath, is a principle to which doctors and patients alike ascribe great importance. How does this principle apply to refractive surgery? In laser refractive surgery, physicians routinely achieve visual acuities of 20/20 or better in more than 90% of patients, but the risk of complications remains. Unfortunately, several underlying health issues known to cause complications cannot be accurately detected without the help of a genetic test.

The biggest fear of most LASIK surgeons is postoperative corneal ectasia. The prevalence of this condition is about 1 in 2,000 eyes, comparable with that of keratoconus in the general population.1 Advanced corneal topography systems make it easier for clinicians to identify patients at increased risk of postsurgical ectasia, but the condition can still go undetected preoperatively.

Another potential complication after laser vision correction is the exacerbation of heterozygous granular corneal dystrophy (GCD) type 1 (GCD1) or type 2 (GCD2).2 These conditions are caused by genetic mutations on the transforming growth factor beta (TGF-beta)–induced gene, which is associated with the wound-healing process of the cornea. While homozygous patients start to lose visual acuity at a young age, those with the heterozygous condition may develop visual acuity loss later in life. This loss can be activated and exacerbated by refractive surgery procedures such as LASIK, LASEK, PRK, and small incision lenticule extraction.

At a Glance

• Genetic testing provides surgeons with the opportunity to detect conditions not typically identified through corneal topography or other methods.
• The biggest fear of refractive surgeons is post-LASIK ectasia; however, granular corneal dystrophy can also lead to a devastating postoperative course and eventual blindness.
• Refractive surgery may be contraindicated in patients with GCD, as the procedure can exacerbate the incidence of corneal opacity postoperatively.
• The Avellino DNA Test for LASIK Safety can detect the presence of the genetic mutations that cause GCD and identify whether a person carries the GCD1 or GCD2 gene mutation.

HIGHER PREVALENCE

What many do not know is that the global prevalence of heterozygous GCD appears to be greater than that of keratoconus, and patients undergoing laser vision correction may be at higher risk of developing GCD than corneal ectasia, based on the known prevalence rates of each condition.3,4

When it is present, GCD causes grey-white granular protein deposits to appear at various layers of the cornea and can eventually lead to blindness. In homozygous patients, these protein deposits begin to appear during infancy. However, heterozygous patients may have no symptoms until much later in life. The deposits can be found earlier if a patient carrying the heterozygous gene undergoes LASIK, which can worsen the density of the cloudiness, resulting in diminished vision and eventual blindness caused by upregulation of TGF-beta from activated keratocytes. Because of this, refractive surgery procedures such as LASIK may be contraindicated in patients with GCD, as the procedure can exacerbate the incidence of corneal opacity postoperatively.

There is no cure or treatment for GCD. However, the Avellino DNA Test for LASIK Safety (Avellino) can detect the presence of the genetic mutations that cause GCD, making refractive surgery safer for patients by identifying whether a person carries the GCD1 or GCD2 gene mutation.

During the test, 10 swipes are taken from the inside of each cheek of the patient in order to obtain an adequate sample. The collected sample is then sent to Avellino Lab USA, a molecular diagnostic testing lab certified under the US Clinical Laboratory Improvement Amendments. Within 24 to 48 hours of Avellino’s receipt of the sample, the results are provided to the physician to share with the patient.

GLOBAL INCIDENCE OF GCD

Despite common belief, GCD is not a condition specific to Asian populations, although one study found that 1 of every 870 individuals studied in a Korean population was at risk of carrying the GCD2 genetic mutation.4 Because the test originated in Asia and was developed as a commercial test in Korea and Japan, the majority of documented cases come from those two countries. However, there is evidence documenting cases of GCD mutations in most ethnic groups around the world. A recent study suggested that Europe and the United States have proportionately higher rates of GCD1 compared with GCD2.5

As clinics in Europe and the United States continue to use this DNA test, more information will become available about the global incidence for GCD1 and GCD2. Testing is under way to determine the prevalence rate among US refractive surgery candidates for GCD1.

Since 2008, Avellino Lab reports, nearly 500,000 individuals have been tested with the Avellino DNA Test for LASIK Safety. Of those, 450 have been identified as positive for the genetic mutation that causes GCD and have thus been protected from possible blindness. If a patient tests positive for GCD, it should be recommended that he or she not undergo LASIK. Due to the company’s rapid turnaround of results, there should be little delay in scheduling a laser vision correction procedure quickly after a surgery candidate’s preoperative evaluation.

The test is now available in 50 countries around the world including the United Kingdom, Germany, France, Switzerland, Italy, Netherlands, and most other European countries.

CONCLUSION

Screening for GCD is accepted as a norm in Korea and Japan and also should be considered a norm in Europe and the United States. As the Hippocratic Oath states, it is the surgeon’s responsibility to ensure that he or she does not cause harm to patients. In refractive surgery, genetic testing now helps surgeons to comply with this oath. I would advise all European refractive surgeons to administer the Avellino DNA Test to appropriately selected patients. n

1. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297-319.

2. Davis AS, Syed NA. Granular corneal dystrophy discovered following LASIK: a clinicopathologic correlation of granular corneal dystrophy type 2 and LASIK. September 16, 2011. http://EyeRounds.org/cases/140-post-LASIK-Granular-Corneal-Dystrophy.htm. Accessed July 21, 2015.

3. Wheeler J, Hauser MA, Afshari NA, et al. The genetics of keratoconus: A review. Reprod Syst Sex Discord. 2012;3(Suppl 6).

4. Lee JH, Cristol SM, Kim WC, et al. Prevalence of granular corneal dystrophy type 2 (Avellino corneal dystrophy) in the Korean population. Ophthalmic Epidemiol. 2010;17:160-165.

5. Mashima Y, Yamamoto S, Inoue Y, et al. Association of autosomal dominantly inherited corneal dystrophies with BIGH3 gene mutations in Japan. Am J Ophthalmol. 2000;130(4):516-517.

John Marshall, PhD, FRCPath, FRCOphth(Hon)
• Frost Professor of Ophthalmology and Chairman of the Academic Department of Ophthalmology, Kings College London at Saint Thomas’ Hospital, London
marshall-eye@kcl.ac.uk
• Financial disclosure: Consultant (Avellino)

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