Diagnostics

Assessing AMD risk using Genetic Testing

Genetic testing makes its way into ophthalmology with advanced age-related macular degeneration risk assessment

Evelyn X. Fu, MD, University Place, Wash.

Advanced age-related macular degeneration (AMD) with choroidal neovascularization (CNV) accounts for approximately 10% of the patients with AMD but is responsible for 90% of the visual loss associated with this disease.¹ Timely diagnosis and treatment of this form of AMD, called exudative or wet AMD, is critical in preserving patients’ vision and preventing further visual loss.

Why genetic testing matters

AMD results from a combination of genetic, demographic, and environmental factors. Traditionally, ophthalmologists have used the Simplified Severity Scale (SSS) developed by the Age-Related Eye Disease Study (AREDS) to assess patients’ risk for advanced AMD.² However, the SSS is based on phenotype observation only and can be limiting. Patients in a particular phenotypic group have varying risks for disease progression based on their genetic predisposition. For example, while one patient with grade three SSS findings may have between a 70% to 90% CNV conversion rate, another patient with the same grade may have a 30% to 40% conversion rate based on genetic influence.³ Although the SSS provides a preliminary idea of patients’ risk of advanced AMD, more accurate risk-assessment requires consideration of genetic and environmental factors.

Implementing genetic testing

Patient selection in genetic testing is critical. I recommend genetic testing in patients with risky lifestyle behaviors, such as smoking; moderate or severe phenotypic findings (SSS grade 3 or 4); and first-degree relatives affected by advanced AMD.

Patient education

I start by educating patients about the pathogenesis and natural history of AMD. I emphasize the importance of regular surveillance, behavior modification and timely treatment. I discuss with them that the results will have an impact on their follow-up regime and treatment recommendations. I provide extensive reading materials and urge patients to carefully consider the cost and implications of the test (RetnaGene, Nicox). Interested patients contact our practice and schedule testing. A technician completes a test requisition form, collects a buccal swab, labels the tube and test requisition form, and prepares the swab for same-day shipping. Patient follow-up appointments are scheduled two weeks after the sample is submitted, which is when the results are returned. At this time, I discuss testing results, recommend lifestyle changes, and outline a surveillance protocol.

Genetic testing results serve as a motivator for patients who make poor lifestyle choices. It also increases their compliance and improves their surveillance regime. Testing also allows me the opportunity to educate patients about home vision monitoring and the importance of early medical attention should any vision loss occur. These efforts should decrease the number of patients who often attribute visual changes from AMD progression to other unrelated causes, such as cataract.

Recommendations

Genetic testing is not warranted in every AMD patient and the AAO has recommended against its routine use.⁴ Genetic screening is limiting in asymptomatic patients who don’t have known risk factors. However, by administering tests in a subset of AMD patients with the highest risk of visual loss, we can encourage lifestyle changes, increase surveillance compliance, promote early detection, and facilitate early treatment. OP

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Evelyn X. Fu, MD is a viteroretinal surgeon at the Cascade Eye and Skin Center in University Place, Washington.