Genetic testing shows promise in predicting AMD progression


New study results show using genetic testing and phenotypic evaluations together in patients with drusen can increase the likelihood of determining who may develop advanced AMD.



New study results show using genetic testing and phenotypic evaluations together in patients with drusen can increase the likelihood of determining who may develop advanced AMD.



By Michelle Dalton, ELS; Reviewed by Lawrence J. Singerman, MD, FACS, FICS

Cleveland-Combining both genetic testing and phenotypic evaluations in patients with drusen can more accurately determine which patients are likely to develop advanced age-related macular degeneration (AMD), said Lawrence J. Singerman, MD, FACS, FICS.

“Most patients are referred to us too late, after their AMD has progressed,” he said. “We know from many years’ experience that over half of patients with AMD are referred to retinal specialists for evaluation when their first eye has vision of 20/70 or worse. We now know that we can preserve much better vision in over 90% of patients when we see them early enough.”

The earlier primary eye care physicians can identify and refer patients at a high risk for developing advanced AMD, the more likely AMD-related vision loss can be minimized, said Dr. Singerman, founder of Retina Associates of Cleveland.

In addition to genetic testing, Dr. Singerman said he evaluates the back of the eye for the phenotype of characteristics for AMD.

“Genetic testing in no way replaces phenotypic examination of the eyes,” he said. “We learned many years ago-in large part based on studies from another NEI-sponsored study, the Macular Photocoagulation Study-that patients with larger drusen, confluent drusen, and pigmentary disturbance have a higher risk of progression from early to late stage AMD.”

Other, more recent studies have identified other variables associated with increased risk, he said, including:

·      Patient age at presentation

·      Smoking history

·      Body mass in addition to genetic risk factors

Changing perspectives

Genetic testing is still somewhat controversial, Dr. Singerman said.

As recently as November 2012, the American Academy of Ophthalmology discouraged genetic testing for AMD.

“There’s still some controversy about genetic testing, but it’s decreasing,” Dr. Singerman said.

With a current treatment burden on both physicians and patients, Dr. Singerman said it is important to decide which patients need to be seen every three months and which patients can be seen once a year.

The current genetic testing is divided into five risk categories. Based on where a patient falls on the five-point scale, “we’re doing a better job of deciding how often to see a patient than we can do with just a phenotypic evaluation alone,” he said.

Also, using a combination will further the emphasis on personalized medicine, Dr. Singerman added.

For instance, others have shown the combination of retinal phenotype and genetics yielded an area under the ROC curve for 5-year and 10-year risk of 0.80 and 0.82, respectively, he said, which indicate the superiority of a combination of clinical and genetic data in risk prediction.1

High progression rate

The genetic component in macular degeneration appears to be much stronger than it is in many other diseases, Dr. Singerman said.

“What we’re just bringing out now is that in macular degeneration, the genetic testing has a good correlation with the outcomes,” he said. “Those with a higher genetic risk develop more advanced disease earlier in life.”

“We know from the Age-Related Eye Disease Study (AREDS) that we can reduce the risk of going from intermediate to late AMD by an average of 25%,” Dr. Singerman added, which thus led to further investigation into genetic components in the AREDS population.

A recent study found specific vitamins and minerals are more likely to reduce the likelihood of progression in people with specific genetic components. Some are more likely to benefit from the complete AREDS formulation, whereas other are more likely to benefit from vitamins alone or zinc alone.2

Those authors estimated that using the genotype-directed therapy that the pharmacogenetic analysis VitaRisk (Arctic Dx) provides, would have more than doubled the reduction in AMD progression rates for a subset of 995 patients who took AREDS formula supplements to help prevent progression to advanced AMD.2

“I believe that the value of genetic testing is greatly supported by this paper, and that, over time, these results are likely to minimize controversy and increase the number of ophthalmologists who will find it helpful for their patients,” Dr. Singerman said. “Genetic testing can help retinal specialists personalize their recommendations for vitamins and minerals so that we’re likely to reduce progression to advanced AMD in a higher percentage of patients than when we offer the AREDS formulation to all patients with intermediate AMD.”



1.         Yu Y, Reynolds R, Rosner B, Daly MJ, Seddon JM. Prospective assessment of genetic effects on progression to different stages of age-related macular degeneration using multistate Markov models. Invest Ophthalmol Vis Sci 2012 Mar 21;53:1548-1556.

2.         Awh CC, Lane AM, Hawken S, Zanke B, Kim IK. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology. 2013 Aug 20. pii: S0161-6420(13)00679-9. doi:10.1016/j.ophtha.2013.07.039. [Epub ahead of print]


Lawrence J. Singerman, MD, FACS, FICS

P: (216) 831-5700.

Dr. Singerman is a member of the advisory board of Arctic Dx and receives honoraria and stock options.

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