November 14, 2017
7 min read

Genetic testing for AMD first step toward personalized medicine in eye care

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Personalized medicine has become a trend in many facets of health care, from oncology to cardiology, and genetic testing for age-related macular degeneration signals its foray into eye care, according to Steven Ferrucci, OD, FAAO.

“A one-size-does-not-fit-all approach is becoming more evident in the treatment of cancers and hereditary eye diseases as well,” Sherry Bass, OD, FAAO, FCOVD, said in an interview with Primary Care Optometry News.

“It’s common sense that if you can tailor your treatment toward an individual’s profile, you’ll be more successful than using the same treatment for everyone,” Brad Sutton, OD, FAAO, told PCON.

It was only recently, in May 2017, that Medicare and Medicaid issued a positive coverage decision for the Macula Risk PGx and Vita Risk (Arctic) tests once again.

The issue was so important to Sutton, who specializes in ocular disease and surgical comanagement, that he took part in a letter writing campaign before the Medicare ruling.

“We wrote letters as to why genetic testing was valuable,” he said. “We were concerned that the one company left wouldn’t survive. If Medicare took the stance that they wouldn’t be able to cover it, Arctic might go out of business. We had several of our doctors here write letters.”

The Macula Risk test is readily available, easy to implement and now covered by most insurances – a fact that most optometrists are not aware of, Sherrol Reynolds, OD, FAAO, an associate professor at Nova Southeastern University and a clinical attending in the diabetes and macular clinic, said in an interview.

Sherrol Reynolds

Genetic factors play a large role in AMD, with estimates on heritability ranging from 46% to 71%, according to research from Kandasamy.

“In 2013, 19 genomic loci associated with AMD risk were reported, four of which (CFH, CFI, C3 and C2/CFB) play integral roles in complement cascade regulation, leading to proinflammatory states in individuals at risk,” Kandasamy wrote.

“What this study’s heritability estimates basically mean is that the role of genetics in AMD-related vision loss is between 46% and 75% of total risk,” Gerry Belgraver, of Arctic, told PCON. “AMD is a genetic disease with a smaller lifestyle component (age, smoking, body mass index, etc.). That is why AMD is really the first disease outside of monogenic diseases such as Stargardt’s and Best’s to be impacted by personalized medicine.”

The controversy

“Currently, I believe genetic testing is underutilized because practitioners are waiting for everyone to agree on the evidence-based medicine. ... I personally believe the controversy will continue,” said Bass, who has been in private practice more than 36 years along with teaching at the State University of New York.


As AMD is a disease of different phenotypes and different rates of progression, “I, for one, cannot believe everyone is the same and should be followed with the same frequency and treated with the same nutraceutical,” Bass continued.

She said that patients are more educated of the risk of zinc and progression to advanced AMD based on genotype.

“I believe the patient should be informed that a genetic test exists but that the evidence-based studies are mixed as to whether the testing is necessary,” Bass added. “Perhaps it is time for the patient to be brought into the picture and their opinions considered when making a decision.”

Cascella and fellow researchers relied on genetic information, disease family history and smoking habits to develop a model for predicting an individual’s risk profile for AMD.

“We show that the average distribution of risk alleles in the general population and the knowledge of parents’ genotype can be decisive to assess the real disease risk,” they wrote.

Sherry Bass, OD, FAAO, FCOVD, recommends genetic testing for patients who have small macular or paramacular drusen and a family history of AMD.
Source: Sherry Bass, OD, FAAO, FCOVD

Bass stated that most optometrists, general ophthalmologists and retinal specialists are confused about how to handle genetic testing.

“The literature features evidence-based studies that support and do not support genetic testing,” she said. “Independent biostatisticians who are well respected in their fields have analyzed data from the Age-Related Eye Disease Study (AREDS) and have found an association between genotype and the choice of nutraceutical formulation.”

Other studies contradict these findings.

This controversy has continued for almost 5 years and remains unresolved, she added.

Belgraver clarified for PCON that Arctic’s testing indicates a zinc-containing AREDS/AREDS 2 formulation “for some, because that has the best outcomes, and a zinc-free formulation for others, because the zinc-containing one has outcomes that are worse than or equal to placebo. That is what the Medicare approval is based on.”

Reynolds pointed out that the American Academy of Ophthalmology (AAO) currently does not recommend genetic testing for AMD on a routine basis, nor does Arctic, according to Belgraver.

Our experts agree that the testing for high-risk alleles and for progression risk is simple, involving collection of DNA using a tiny brush along the inside of the cheek. The kits are provided at no cost to the eye care practitioner, and postage is included. The results are available in about 3 weeks.

Belgraver noted that the Medicare positive coverage determination has not yet gone into full force, so, “they haven’t started paying yet.”


Sutton was an early adopter to the technology and believes the individual risk profile, tailored treatment plan and vitamin recommendations make it worthwhile. He offers it to anyone with early to intermediate dry AMD.

Brad Sutton

“We discuss what we feel to be the benefit, and no one ever says ‘no;’ pretty much every time they’ve seen the value in it,” he added.

Sutton said he has never heard of a patient being denied coverage for the test.

For Reynolds, one of her barriers to offering the testing was cost. It was covered by Medicare and other insurance providers, then no longer covered and since May it is covered again.

“The flip-flopping in coverage is not easy to follow,” she said, and the May ruling for Medicare may be news for many optometrists.

“While the AAO doesn’t recommend routine genetic testing, it’s good to give our patient the option for this disease,” Reynolds said. “When you look at treatment and management, personalized medicine is important and something we are moving toward and should be the case for our AMD patients.”

Implementing the test

If a patient has small macular or paramacular drusen and a family history of AMD, Bass recommends genetic testing to obtain a macular risk (MR) score, which helps determine frequency of follow-up.

The genetic testing provides an MR score from 1 to 5, which predicts risk for progression to advanced AMD over a 2-, 5- and 10-year period, based on genotype and risk factors such as body mass index, race and history of smoking.

An MR score of 1 or 2 means a patient is at no greater risk than the general population of progressing to AMD and can be examined every 6 months to 1 year. An MR score of 3 to 5 indicates a risk greater than the general population, and the patient should be examined more frequently depending upon the stage of AMD and risk factors, more like every 3 to 4 months, according to Bass.

“The genetic testing provides additional information to help the eye care practitioner decide how to treat and follow these patients,” Bass added.

If the patient can take zinc, Bass recommends any AREDS formulation, unless the patient smokes or has a history of smoking. She recommends a beta carotene-free supplement for those patients.

In the AREDS2 study, individuals randomized to beta carotene had double the risk of lung cancer, with 91% of the incident lung cancers occurring in former smokers, according to a lecture and subsequent paper by Chew.


For patients whose genotype is associated with a risk of progression if they take zinc, Bass recommends a formulation that contains lutein, zeaxanthin and mesozeaxanthin.

For all patients with AMD, Sutton recommends not smoking, regular UV protection, home Amsler grid monitoring, good dietary habits and supplements appropriate to the individual. For low risk patients, he monitors them yearly, while patients with higher risk profiles are seen every 3 to 6 months.

“Patients in the MR5 category can have up to a 98% chance of converting to advanced AMD, so they are followed particularly closely,” he said.

Sutton noted that the Macula Risk test has not been evaluated outside of a Caucasian population, so Arctic cannot guarantee its validity for other races and ethnicities.

Moving forward

As we now know which genes are primarily responsible for AMD, researchers are exploring treatment on a genetic level, Ferrucci, a professor at Southern California College of Optometry and Marshall B. Ketchum University, told PCON.

Changing and altering one’s genes to avoid disease progression sounds like a premise from a science fiction novel, he said, but it could be the future of disease management with genetic testing.

He echoed Bass’ sentiments.

Steven Ferrucci

“Not one treatment is beneficial for all patients,” he said. “Treatments could be tailored based on a patient’s genetics.

Ferrucci said that risk management in AMD is just the tip of the iceberg for genetics. Long-term goals that include genetic testing to identify who will convert from dry AMD to wet, who is likely to lose their vision and what treatment is best are more influential than which vitamin supplement to use, he said.

“To think that every person should respond the same to treatment is obviously short-sighted, and perhaps genetics will help us figure that out,” Ferrucci added. “It’s likely that genetics hold the key. This is eye care’s first foray into personalized medicine.”

“Our understanding of AMD has really evolved over the years,” Reynolds said, “and, as research grows, and with Macula Risk now covered by insurance, more practitioners may incorporate it into their management of AMD patients.” – by Abigail Sutton

Disclosures: Reynolds and Sutton report no relevant financial disclosures. Bass is an investor in Arctic Dx. Belgraver is employed by Arctic. Ferrucci is a former member of the advisory board of Artic Dx.