AMD GENOTYPING

Genetic risk assessment for agerelated macular degeneration (AMD) should be part of the patient selection process for multifocal IOLs, Steve A Arshinoff MD told delegates at the XXXI Congress of the ESCRS in Amsterdam. Dr Arshinoff also believes the information provided by AMD genetic testing allows him to optimise clinical care of his patients in other ways as it allows him to individualise recommendations on follow-up for AMD and use of vitamin-mineral supplements to prevent AMD progression. Dr Arshinoff is in private practice, Toronto, Ontario, Canada.

The recommendation for testing in patients wanting a multifocal IOL recognises that both multifocal implants and AMD reduce contrast sensitivity. Thus there is concern that patients implanted with a multifocal IOL may experience a synergistic reduction in their quality of vision should they develop even mild AMD in the future. Since the patients most interested in an accommodating IOL tend to be younger, they are unlikely to have developed drusen at their initial presentation to their ophthalmologist. Results from commercially available genetic testing (Macula Risk) can be useful for informing the surgical decision for these patients, in Dr Arshinoff’s view.

“Previously we considered the phenotypic appearance of the eye, macular pigment levels and patient-related non-genetic factors to determine AMD risk. Now, using available genetic testing, we can predict with 90 per cent accuracy an individual’s 10-year risk for progression to advanced AMD.” Dr Arshinoff said he tells his patients that if they develop significant drusen from AMD in the future after being implanted with a multifocal IOL, they will see worse than if they had a monofocal IOL. The only way to assess their risk for that outcome is with genetic testing. The test assesses 15 genetic markers across 12 genes that are known to confer AMD risk and integrates information on findings of AMD from the clinical exam plus non-genetic risk factors (age, smoking history, BMI and education) to calculate risk.

Dr Arshinoff said that in his experience so far, most patients agree to the evaluation, which costs about $300. As a caveat, he observed that his current practices reflect understanding of the limitations of existing IOL technology and the power of genetic testing, and his recommendations may change over time. “In the future, we can anticipate availability of presbyopiacorrecting IOL technology with less or no effect on contrast sensitivity as well as advances in genetic testing that will allow us to be more accurate and specific in providing prognostic information for patients,” he said.

Determination of a patient’s risk for developing advanced AMD not only provides useful information on the decision to choose multifocal IOLs, but it identifies people who should be monitored more carefully for AMD. “Retinal specialists see patients only after they have lost vision from AMD in at least one eye, whereas cataract surgeons see everybody. We have an opportunity to make recommendations that may minimise their risk of progression and achieve early detection of CNV.”

In addition, pharmacogenetic testing that is now available as part of the AMD genetic risk assessment provides guidance for recommendations on the use of ocular multivitamin-mineral supplements by patients with moderate AMD. The latter testing was developed based on a recently published study analysing data from patients enrolled in the Age-Related Eye Disease Study (AREDS) who had category 3 AMD [Awh CC, et al. Ophthalmology. 2013;120(11):2317-23].

When patients were profiled with respect to complement factor H (CFH) and agerelated maculopathy sensitivity 2 (ARMS2) inherited genetic polymorphisms and type of nutritional supplement they received (antioxidants and/or zinc), the results showed that the components of the AREDS formulation could be harmful, beneficial or have no effect on progression risk depending on the individual’s genotype.

The only patients who benefited from the combination of antioxidants and zinc were those with one CFH and one ARMS2 risk allele, and they comprised only 23 per cent of the population. Nearly half of the study population would have been better off if they used antioxidants or zinc alone versus the combination, and the risk of disease progression was actually increased among persons having 1 or 2 CFH risk alleles with no ARMS2 risk alleles if they took zinc.