June 14, 2016
9 min read

Experts predict genetic testing will revolutionize optometric care

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“When properly performed, interpreted and acted on, genetic tests can improve the accuracy of diagnoses and prognoses, can improve the accuracy of genetic counseling, can reduce the risk of disease occurrence or recurrence in families at risk, and can facilitate the development and delivery of mechanism-specific care,” Edwin M. Stone, MD, PhD, wrote in a study published in Ophthalmology.

According to Charles M.Wormington, PhD, OD, FAAO, a professor at Salus University, there is an exponential increase in genetic knowledge, and new diagnostic, prognostic and treatment options are on the rise. With this new technology and avenue for science, he said, optometrists have additional responsibilities to their patients. These include improving family history-taking and identifying individuals who may benefit from genetic services.

Optometrists should also recognize the historical and physical features of common genetic conditions and learn the indications for genetic testing and the availability of genetic tests for specific ocular conditions, he said in an interview with Primary Care Optometry News.

The “new genetics”

The Association of Schools and Colleges of Optometry (ASCO) Core Competencies in Genetics explains that a distinguishing element to this revolution in health care is the shift from the “old genetics” to the “new genetics.” Old genetics dealt with rare conditions caused by a mutation in a single gene, and new genetics deals with common multifactorial disorders, the group stated.

“This paradigm shift will result ultimately in a gradual change from genetics care being provided almost solely by genetic professionals to genetics care being provided by primary care providers with the assistance of genetics professionals,” ASCO said. Also, the report said the focus has morphed from “diagnosis and treatment” to “prediction and prevention.”

Leo P. Semes, OD, FAAO, screens the brother of a patient with choroideremia.

Image: Semes LP

On March 25, PCON sister publication, Ocular Surgery News, reported on a bipartisan bill, the Advancing Targeted Therapies for Rare Diseases Act of 2015 (S. 2030), which was referred to the Senate Committee on Health, Education, Labor and Pensions in September 2015. The legislation would “allow the sponsor of an application of the approval of a targeted drug to rely upon data and information with respect to such sponsor’s previously approved targeted drugs.”

The bill would likely have a positive impact on ophthalmic research, particularly for medical retinal diseases, Michael X. Repka, MD, MBA, American Academy of Ophthalmology medical director for governmental affairs, told OSN.

S. 2030 is designed to facilitate targeted drugs to address unmet medical needs in one or more patient subgroups or genetic variant subpopulations and to maximize the use of scientific tools or methods such as surrogate endpoints and other biomarkers, according to the OSN article.

To implement or not?

PCON Editorial Board Member Leo P. Semes, OD, FAAO, a professor at the University of Alabama at Birmingham, sees value in the Macula Risk PGx test, which is commercially available from ArticDx.

“Macula Risk PGx is a combined prognostic and pharmacogenetic DNA test designed to determine a patient’s risk of progression to advanced age-related macular degeneration and aid in the selection of appropriate eye supplement formulations for AMD based on his or her individual genetic risk profile,” according to the company’s website.

Leo P. Semes

The patient’s cheek is swabbed in-office, Semes explained, then the laboratory tests for two specific genetic markers for AMD. Based on the results, a risk profile is generated, with suggested optimized supplementation for patients with AMD, he said.

“Perhaps as important, it suggests which components (supplements) might be harmful,” Semes explained. “So what the results give us is a specificity in prescribing supplements to our patients. While diet is very important, and we should get most of our nutrients from food sources, such as eating fish instead of supplementing with omega-3s, not everyone is a poster child for good dietary health. As I see it, supplementation is an easier route. No one wants to eat a bushel of kale every day. It can be an easier sell for patients.”


Corroborating Semes’ stance, at the FLORetina meeting in December 2015, Carl C. Awh, MD, reviewed study results based on Age-Related Eye Disease Study (AREDS) data.

“We found, again, that patients with low CFH and high ARMS2 had an odds ratio of AMD progression of 0.45, suggesting tremendous benefit from supplementation, while those with high CFH and low ARMS2 had an odds ratio of 2.14, suggesting harm.”

Jerry Rapp, PhD, a professor at SUNY College of Optometry, said in 1995 he read a paper on a subset of autosomal dominant retinitis pigmentosa caused by mutations in rhodopsin.

Jerry Rapp

“The researchers looked at the part of the molecule in which the mutation occurred – comparing those in the cytoplasmic domain vs. those in the intradiscal domain – and how that affected the symptomatology,” he said. “Patients with mutations in the intradiscal domain had, on average, better visual acuity, larger visual field diameter, better dark-adapted sensitivity and larger electroretinogram amplitude (all standard visual performance measurements) than patients with mutations in the cytoplasmic domain – which makes perfect sense if you understand the basic biochemical reactions that occur when rhodopsin is illuminated.

“We know a lot about how rhodopsin functions normally,” Rapp told PCON. “So then looking at different mutations that cause disease and assessing how the particular mutation is likely to disrupt the normal functioning of the molecule, we can get an idea of how severe the manifestation of the disease is likely to be and include that insight as part of a clinical diagnosis.”

That, for him, was an epiphany in realizing that this kind of approach can play a significant role in dealing with ocular disease.

Next, Rapp began advocating for this sort of approach and wrote several opinion pieces urging organized optometry to get involved. Twenty years ago, Rapp saw this emerging area as an important platform for dealing with ocular disease.

Semes and Rapp feel similarly that the general optometric community has not taken advantage of genetic testing to the extent that they believe the profession should.

Rapp says overcoming this challenge involves convincing the American Optometric Association, ASCO and other organizations to set up programs designed to educate and influence optometrists who deal with ocular disease. He said when he began his career at SUNY in the early 1970s, optometrists in New York State could not use any drug, even in diagnosis. He considers genetic testing another facet of optometric care that will take time to be adopted, accepted and understood.

“It’s just a controversy that is holding people back,” Semes said. “When there are multiple genes but there are only two that are well characterized and identified in a specific easy-to-perform test, it just makes it difficult for folks to get onboard.”

In the not-so-distant future, “dozens of markers will be discovered and will be meaningful [to ocular disease],” Semes added. As more genetic markers are discovered, more companies will enter the arena, he said.

“We are just scratching the surface – there is not a long or wide body of evidence; we don’t have information over, let’s say, 20 years to see what outcomes might be,” Semes continued. “So it’s with limited data on which we’re acting. But when you take a look at the data, it seems compelling to me that this is useful in guiding patient management.”

Charles M. Wormington

Wormington is hopeful for genetics technology in eye care but believes some groups with conflicts of interests are manipulating data and making claims that have not been proven.

“The test won’t tell you if a patient will get AMD,” he said. “The vitamins and supplements have been shown to maybe decrease the probability of going from intermediate to advanced stage AMD by 25%. But there is no good evidence that they prevent the development of AMD or cataracts; however, that is sort of the way they are being sold and talked about.


“In the reported AREDS/AREDS2 genetic studies for AMD, essentially all of the subjects were white, so generalization to other ethnicities is questionable,” Wormington continued. “In addition, even the company that makes the Macula Risk PGx test states [on its website] that the test is ‘most appropriate for patients with signs of disease (drusen and/or early, intermediate or advanced AMD) in at least one eye.’ But for such a patient, there is no current need to do the genetic test. The AREDS and AREDS 2 studies indicate that the AREDS formulations should be prescribed for such patients.”

At this point, he does not see a real need in optometrists partaking in genetic testing for AMD.

“But one of the situations where genetic testing can be important is with patients who have Leber’s congenital amaurosis,” Wormington said. “In patients with mutations in the RPE65 gene, gene therapy that delivers a good copy of the RPE65 gene to the eye has shown positive results in a phase 3 clinical trial. The company, Spark Therapeutics, is planning on applying to the FDA this year for approval to market the gene therapy [according to the company’s website].”

Research from Emily Y. Chew, MD, and colleagues found no statistically significant interaction between CFH and ARMS2 genotype and treatment with AREDS supplements. The findings do not support the conclusions of Awh and colleagues that recommended altering the composition of AREDS supplements based on a patient’s CFH and ARMS2 genotypes, according to the study.

“At this stage, genetic testing does not seem helpful in improving treatment with AREDS supplements,” Chew wrote.

That said, Wormington believes optometry is undergoing a fundamental, revolutionary transformation. Genetics/genomics will change the way optometrists classify, understand, diagnose, treat and manage diseases, he explained.

Genetics is helping practitioners reject the idea of normality and embrace the idea of variation, he said.

“The changing paradigm of medicine is framed around individual variability rather than the distinct separation of medicine between ‘abnormal’ and ‘normal,’” he said.

The clinician’s challenge now becomes, “understanding the variability of the genetic and environmental factors that lead to disease, developing a prevention plan and, if necessary, a treatment plan based on the patient’s unique variability,” Wormington added.

Providers should no longer look at the human body and visual system as a biological machine where the optometrist acts as a mechanic when the parts break down, he said.

Gene therapy for choroideremia

NightstaRx, a biopharmaceutical company that specializes in developing gene therapies for inherited retinal dystrophies, recently announced clinical results and long-term benefits of gene therapy for choroideremia.

The company is developing a gene therapy approach and the viral vector known as adeno-associated virus 2 (AAV2) to deliver a copy of the gene encoding Rab-escort protein 1 (REP-1) gene, the mutation of which leads to damage of retinal cells of patients with choroideremia, according to a press release.

David Fellows

“We’ve taken the adeno-associated virus, which is nonpathogenic, and inserted into it the CHM gene, which encodes for the missing or mutant protein in these patients, and this viral vector is injected subretinally,” David Fellows, CEO of NightstaRx explained. “To get the virus where it needs to be, the surgeon creates a bleb at the back of the eye and infuses the viral vector into the bleb, and it ultimately infects the tissue and carries the genes into the cells. Those genes begin to express the correct protein required to eliminate toxic waste from the retina.”

If the patient is in a relatively early disease stage, it is hoped that he or she will be able to hold onto their central vision for the rest of their lives, he said, but it depends on what point in the disease progression they receive the viral vector.


Phase 1 and 2 trials are complete, and the company will move to phase 3 and testing it in a larger choroideremia population. It is hoped that these trials will provide a basis for an application to the FDA, Fellows said.

“The primary care OD should at least understand what a choroideremia patient’s macula looks like at baseline, so they can diagnose it and refer them to a retinal specialist,” he said.

Fellows thinks top-down encouragement will be necessary for optometrists to more widely accept genetic testing.

“As ODs have become more medically oriented, they have taken it upon themselves with continuing education,” he continued. “It will take top-down pressure to train people coming into practice to look at all of the available diagnostic technologies available. I think ODs could play a big part, but they will need to reorganize their practices to do that.”

Many older optometrists who were not initially trained to perform medical evaluations may be more comfortable focusing on refractive care, Fellows said.

“They don’t know how to generate income around it,” he added.

He predicts some challenges getting insurers to reimburse for genetic testing.

“Most patients may struggle to get answers out of their insurance carriers on genetic testing, because they haven’t had to deal with this before,” Fellows said. “Both physicians and patients will have to work through the road bumps, but genetic confirmation for each patient will likely be a requirement before insurers approve gene therapy in patients.”

ASCO’s core competencies state: “The ability to apply the tremendous amount of information already generated by the genomics revolution to optometric practice is only beginning to materialize. Currently, there are relatively few examples of clinical application. Eventually, the revolution will affect how optometrists understand, classify, diagnose, treat and manage diseases.” – by Abigail Sutton

Disclosures: Fellows is CEO at NightstaRx. Rapp and Wormington reported no relevant financial disclosures. Semes is on the speakers’ bureau of Alcon and Allergan and he is also an advisor for Allergan, a consultant to Maculogix, a stockholder in HPO and on the speakers’ bureau for Optovue.