Genetic testing was science fiction only a few years ago, but now it is an expanding field with major implications for every healthcare space, including eyecare. Like many emerging technologies, however, despite the interest and attention it drives, many practitioners know little about it.
In 2019, we surveyed 427 optometrists on their knowledge of and opinions on genetic testing in eyecare. We asked whether they offered this service to patients, their opinions on cost and utility, and how these tests have affected their practice.
Those responses are collected in this free report—but there’s even more to come. We’ve collected three reflections from optometrists and practice owners just like you on the current state of genetic testing. Keep reading for our breakdown of what’s contained in the report, or skip ahead to Dr. Melody Huang’s review of the current debates on genetic testing, Dr. Sathi Maiti’s overview of the state of genetic testing today, or Dr. Collin Robillard’s guide to introducing genetic testing in your practice.
The answers to our September 2019 survey revealed a huge disconnect: while many optometrists expected genetic testing to have a strong future in eyecare, only 6% of the ODs we surveyed offered these tests in their practices now, and on a scale of 1 to 10, ODs on average rated their knowledge of diagnostic testing at a 4.79. This suggests that while it might be a hot topic in the eyecare industry, genetic testing is neither well understood nor commonly utilized by optometrists.
What place does genetic testing have in eyecare?
For those optometrists who do offer this service, the vast majority did so to test for retinal conditions in order to guide their treatment protocol. In eyecare, there are two main foci of genetic testing: retinal genetic testing, which is more often used to build risk profiles of how likely a patient is to develop glaucoma or AMD, and corneal genetic testing, which looks for very specific genetic markers that would be a contraindication for laser eye surgery.
Genetic tests for corneal disorders are especially useful for doctors referring their patients for particular kinds of ophthalmic surgeries. Since corneal dystrophies can cause major postoperative complications, knowing whether your patient has any of the variants of TGFBI corneal dystrophy can be an immense help in deciding whether they’re a candidate for laser eye surgery. If a patient with an undiagnosed corneal dystrophy undergoes a procedure where the cornea is cut or altered, a mass deposit of proteins will set in and cloud their vision—and once that process starts, there’s no way to stop it.
Avellino is the first company in the US to offer genetic testing for corneal dystrophies. According to Eric Bernabei, Chief Sales & Marketing Officer at Avellino, “We focused on this very specific group of corneal dystrophies and collagen conditions because they were connected to what doctors were seeing in corneas that they couldn’t really explain. Physicians were looking for a drug to combat it, but the reality in 2008 was that personalized gene therapies were still science fiction. They knew they could do it one day, but it wasn’t reality yet.”
The original test Avellino developed could identify patients with a single point mutation for this particular dystrophy. “And over the next six years,” explains Bernabei, “we were able to find eleven of these different dystrophies associated with TGFBI. When we switched to next-gen sequencing, we were able to identify over 70 mutations.”
Now, emerging tests in the field of corneal genetic testing are casting an even wider net for the kinds of dystrophies that can be picked up by such a test. These offer doctors the opportunity to build the kind of risk profiles that could offer early intervention and management for keratoconus, for instance, which is often attributed to environmental factors when there are in fact genetic predispositions involved.
Because genetic testing is fundamentally proactive instead of reactive, it requires many physicians to adjust their diagnostic and treatment paradigms. “What we try to emphasize,” says Bernabei, “is that this is not meant to replace the doctor, or any of the testing that’s currently being used—rather, it’s meant to allow you to get your patients in earlier than you may have been able to with scanning technologies, so that you can get ahead of the curve.”
Meanwhile, genetic testing for retinal disease is also getting more sophisticated. These tests measure predisposition, which is one main reason why the debate over their utility is so heated.
Is genetic testing expensive?
While the majority of doctors who responded to our survey used these retinal genetic tests to guide their treatment protocol, most felt that the current price of genetic testing was about twice as high as it should be.
The costs of genetic testing are significant—both the tests themselves and their implications, whether that means referrals to genetic counseling, gene therapy, or treatment guidelines that arise. However, one of the biggest questions facing genetic testing in eyecare now is not who benefits, but rather—who pays? While the cost of the test can sometimes be billed to insurance companies, it still often falls on the patients themselves.
However, as more tests come on the market, and more patients become aware of the possibilities of genetic testing, we can expect this service to become much more popular very soon—particularly since many respondents suggested that they would certainly begin to offer these tests as they became more mainstream.
The next step for genetic testing, suggests Dr. Aaron Lech, OD, is a full “soup-to-nuts” genetic test, where a provider can run a test against other profiles, research, and get a bigger picture than what is currently given by the variety of tests in existence. As for what the future holds for gene therapies—only time will tell, but in the meantime, the field of genetic testing is continuing to expand, and ODs are ready to keep up.
Keep reading to learn more about the current debates on the role of genetic testing in eyecare, recent developments in the field, and tips on adding these tests to your practice—or head back up to download the report!
The Role of Genetic Testing in Eye Care
Genetic testing for inherited eye diseases has advanced quite a bit in the past several years. Whether or not you’re a proponent of genetic testing in your practice, it’s important to consider the implications of these tests.
Though there’s still a place for traditional diagnostic methods, we should acknowledge the rapidly changing landscape of genomic medicine. Currently, test panels for a variety of eye diseases are available to eye care practitioners. Some of these inherited diseases include:
- Corneal dystrophies (macular corneal dystrophy, Meesmann corneal dystrophy, Fuchs’ endothelial dystrophy, Avellino corneal dystrophy, etc.)
- Age-related macular degeneration
- Macular and retinal dystrophies (Stargardt disease, Vitelliform macular dystrophy, retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy, etc.)
- Glaucoma (juvenile open-angle glaucoma, Axenfeld-Rieger syndrome, ectopia lentis, nail-patella syndrome, etc.)
This is only a small sampling of ophthalmology panels that clinicians can order. With so many panels available to us, how do we determine when genetic testing is warranted? In recent years, this topic has been hotly debated among leading ophthalmologists.
Genetic testing for age-related macular degeneration (AMD) has been at the center of many debates. Several published papers concluded that routine genetic testing for AMD was not indicated. Additionally, studies funded by the National Institutes of Health (NIH) recommended against genetic testing as a determinant in starting patients on an AREDS supplement.
Proponents of genetic testing for AMD have published papers stating that specific genotypes were more likely to benefit from AREDS supplements. In contrast, other genotypes responded neutrally or unfavorably to the AREDS formula. Based on these findings, the authors concluded that testing for AMD was warranted.
These events prompted the American Academy of Ophthalmology (AAO) and the American Society of Retina Specialists (ASRS) to form independent task forces to evaluate these issues. Both entities recommended that routine genetic testing for AMD should be avoided.
Current recommendations on genetic testing
The AAO Task Force on Genetic Testing offers these guidelines on genetic testing for inherited eye diseases. The key points to know:
- Only offer testing if your clinical findings suggest a Mendelian (single-gene) disorder where the gene has been identified and validated.
- Order the most specific test available and avoid unnecessary parallel testing.
- Discourage direct-to-consumer genetic testing and advise patients to seek formal genetic counseling.
- Avoid routine testing for complex genetic diseases such as age-related macular degeneration and late-onset primary open-angle glaucoma. They recommend holding off until specific management strategies have been shown in one or more published clinical trials to benefit patients with specific disease-associated genotypes.
- Avoid testing asymptomatic minors for untreatable conditions, unless necessary. This situation is tricky because the parent is deciding for their child, whether the minor wants genetic testing or not. Consider advising the parent to wait until the child is an adult and can decide for themselves. If the parent desires testing, refer the family for genetic counseling first. All parental guardians should agree to the test.
Pros of genetic testing
There are undoubtedly many advantages to genetic testing in eyecare. When used appropriately, these tools can help us improve patient care and even provide preventive therapy in some cases. Some pros include:
- Combining genetic testing with traditional diagnostic tests allows for more accurate diagnoses.
- Identifying specific genes allows for personalized medical care. This genetic information may influence a clinician’s treatment plan. They may also discover the need to test for other diseases associated with the genes or that high-risk family members should be checked.
- Presymptomatic testing allows for preventive therapy in treatable eye diseases.
- The patient can have peace of mind knowing if they are susceptible to eye diseases that run in the family. Or, they can learn if they are a carrier for any conditions that their children may inherit.
- More widespread genetic testing may lead to further medical discoveries.
Cons of genetic testing
Genetic testing may not be suitable in some situations. Here are some cons to consider:
- Diagnostic clinical findings is a more accurate way of assessing a patient’s risk for specific eye diseases, rather than relying on genetic testing.
- Avoid routine testing for diseases that do not have specific treatment and management guidelines.
- Because testing should be ordered based on family history and clinical findings, not everyone can receive genetic testing for specific eye diseases. This also prevents placing unnecessary stress on the patient.
- Consider the emotional toll that positive test findings would place on the patient and their family. The patient should have genetic counseling to prepare for this possibility.
- Patient counseling should not be taken lightly, so consider your professional responsibility when referring a patient for genetic testing. Unless you are well-versed in interpreting and discussing test results with patients, refer them to a genetic counselor.
Genetic testing is playing an increasingly essential role in modern eye care. Even if it’s not quite the norm yet in our practices, we should familiarize ourselves with the testing options available for inherited eye diseases and know when to refer patients based on clinical findings.
New Developments in Genetic Testing in Eyecare
Genetic testing has exploded over the last decade with the rapid development of molecular genetic technology that has made testing faster, easier, and more affordable. There are a number of visually threatening inherited eye diseases from anterior to posterior segment for which genetic testing can be beneficial. These include various corneal dystrophies, aniridia, primary glaucoma, albinism, Stargardt disease, retinitis pigmentosa, leber hereditary optic neuropathy and more.
Genetic testing refers to any molecular, chromosomal, or biochemical test that identifies mutations in genes, chromosomes and proteins that can confirm, rule out, or identify the amount of risk someone has for developing or passing on a specific inherited genetic condition.
Even if there is no treatment available for a specific inherited condition, the primary benefit of genetic testing is confirming diagnoses, as often early diagnosis based purely off clinical examination can be difficult. This is crucial for patients who may need to apply for low vision services and disability accommodations as well as prompt genetic counseling and family planning. In addition, as more treatments like gene therapy become available, early diagnosis can help patients access treatments and/or clinical trials.
Testing has historically been available for certain retinal disorders, and more recently tests have been developed to screen for some corneal dystrophies and even keratoconus.
Genetic testing for retinal disease
There are mutations in over 250 genes known to cause what are collectively known as Inherited Retinal Diseases (IRDs). Companies like Blueprint Genetics, Invitae, Centogene, Molecular Vision Laboratory, and Prevention Genetics provide a number of tests for conditions like rod-cone dystrophy, best disease, retinitis pIgmentosa, and usher syndrome. Genetic testing can also be useful for diagnosis of early-onset glaucoma, as mutations in 6 genes are known, and early diagnosis is essential for these patients to start treatment as soon as possible in order to prevent visual field loss.
In addition to for-profit companies, a number of university based testing sites exist. One of the largest is Harvard’s Ocular Genomics Institute which offers a few different grouped panels: the GEDi-R which tests 267 genes for IRDs and related disorders, the GEDi-O which tests 22 genes for optic nerve disease and early onset glaucoma, the GEDi-S which tests 8 genes for strabismus. Other non-profit laboratories include Massachusetts Eye and Ear and The John and Marcia Carver Nonprofit Genetic Testing Laboratory at the University of Iowa.
When looking for a lab, make sure it is certified under the Clinical Laboratory Improvements Amendment, and that its genetic analysis follows the American College of Medical Genetics and Genomics standards.
The ultimate goal with genetic testing is potential for true treatment with gene therapy. Spark Therapeutics, based out of Philadelphia, PA, has one FDA approved gene therapy treatment, Luxterna, for specific mutations of RPE65 causing certain types of leber congenital amaurosis and retinitis pigmentosa. Some of these phenotypes cannot be differentiated by clinical exam, and knowing the specific mutation involved is critical for determining if gene therapy treatment would be beneficial. Spark Therapeutics is also working on gene therapy treatments for choroideremia, an x-linked IRD causing night blindness and constricted visual fields as well as for stargardt disease, caused by mutation in the ABCA4 gene.
Termed Eye Want 2 Know, Spark Therapeutics has a genetic testing initiative which allows practitioners to order full panel genetic tests that test for mutations in over 250 genes known to cause inherited retinal diseases. These are recommended for patients who are suspected of having conditions like retinitis pIgmentosa or Stargardt disease and have symptoms like peripheral field loss, nyctalopia, or loss of color vision. Through Foundation Fighting Blindness, free genetic testing for those with suspected IRDS is also available.
Genetic testing for corneal dystrophies
Outside the retina, the most common inherited eye conditions are corneal. Avellino is the first company in the US to offer genetic testing for corneal dystrophies. They started with testing for the mutation that caused a specific inherited dystrophy, Avellino Corneal Dystrophy (ACD), also known as Granular Corneal Dystrophy Type II. ACD, initially documented in patients with origins in Avellino, Italy is passed on in an autosomal dominant manner and is caused by a mutation in the TGFBI gene. It causes gray-white granular protein deposits in the corneal stroma. While protein deposits are normal during corneal healing, the mutation that causes ACD makes these deposits opaque. They can spread over time to become larger lattice-like lesions, and can cause permanent loss of visual acuity.
The primary benefit of genetic testing for corneal dystrophies like this is when screening for refractive surgery candidates. Due to the opacities that occur, ACD is a contraindication for any refractive surgery. ACD typically develops very slowly over time, and a patient may present for a LASIK or PRK consultation without any corneal deposits visible upon slit lamp exam. Thus, the ability to screen by genetic test before any clinical signs or symptoms occur is vital.
Avellino has since released their Universal Test for more TGFBI related conditions including Granular Corneal Dystrophy Type I, Reis-Bucklers Corneal Dystrophy, Theil-Behnke Corneal Dystrophy, and Lattice Corneal Dystrophy Type I.
A number of other companies including Blueprint Genetics and Asper Ophthalmics have developed tests for various corneal dystrophies, including testing for non TBFBI related conditions. Asper Ophthalmic’s panel includes testing for the CHST6 gene for macular corneal dystrophy, the COL8A2 and ZEB1 genes for Fuch’s dystrophy, the KRT3 and KRT12 genes for Meesmann corneal dystrophy, and more.
Of most interest to the primary care eye practitioner are the newest tests that screen for risk of developing Keratoconus. Avellino has its AvaGen test, which in addition to testing for the previously mentioned corneal dystrophies also examines over 1000 variants across 75 genes for keratoconus. Asper Ophthalmics’ corneal panel includes testing the VSX1 gene for Keratoconus 1. CTGT Genetic Testing also offers a panel that tests the MIR184, PRDM5, VSX1, and ZNF469 genes for Keratoconus.
Given that we now have treatment options like corneal cross-linking to help prevent progression of keratoconus, early testing can be invaluable to patients, in addition to saving them from the complications that would occur from pursuing refractive surgery.
These testing kits are available via each company’s websites, and can often be done in office via simple buccal swab. For a current comprehensive and detailed list of the inherited conditions both ocular and systemic for which genetic testing is available, visit GeneReviews.
Over time, genetic testing for more and more inherited ocular conditions will become available to us as eyecare practitioners. While we may not need to order tests for suspected IRDs that often, tests for corneal dystrophies—particularly the newer tests for corneal dystrophies and keratoconus—could be the next test in our toolkit when performing pre-surgical examinations for refractive surgery.
It is an exciting time for genetics, and genetic testing may one day become a standard part of our comprehensive eye exams.
The First Step in Genetic Testing for Macular Degeneration
Age-Related Macular Degeneration (AMD) is the leading cause of irreversible central acuity loss worldwide among the elderly.1 This is nothing new, but there are new tools in our armament to combat this progressive retinal disease. Since we know there are demographic, behavioral, and genetic risk factors involved with the progression of early and intermediate stages of AMD,2 we need to ensure that we are maximizing our efforts to address each risk factor to our fullest capacity.
As eye doctors, of course we do not shy away from suggesting UV protection to ensure radiation does not influence expression of AMD among other pathologies associated with UV light exposure. We do not hesitate for a moment to recommend smoking cessation to benefit our patients, but what are we doing to address the genetic risk factors associated with this blinding disease? Although environment and behavior play important roles in the risk of AMD development, genetics plays the largest role.3
Knowing that the progression and development of AMD is heavily dependent on patient genetics—up to a 60% association4—should provide the optometric community a large opportunity to become involved in personalized medicine. This form of medicine is becoming increasingly popular and is a fantastic opportunity for optometry to seize. Personalized medicine not only helps us make better decisions for our patients, but also helps us differentiate our practices and be a leader in technology within our field.
Genetic testing in eye care does not need to be intimidating or take excessive chair time away from your busy practice. I may advocate that the little time and energy it takes for your staff to collect a buccal sample will result in something your patients will be impressed with. They will want to know more about how eye doctors may complement their treatment plans based on genetics and their families and friends will as well.
Getting started with genetic testing for AMD
Genetic testing in optometry for AMD is quite effortless and a great place to start. The first step is to know what these tests can actually provide you and your patients, and how these data may alter your care.
Educate your patients that 60% of vision loss in macular degeneration is due to genetics and the remaining 40% is influenced by environment and behavior. With this is mind, genetic testing for AMD can answer three main questions for your patient:
- Did I inherit my family history of AMD and what’s my risk of development?
- Will I have significant vision loss from AMD within the next 2, 5, or 10 years?
- If I need to take an eye vitamin, what formation is the correct one for me?
By answering these questions, we are tailoring our care directly towards our individual patients as opposed to boilerplate treatments for the masses.
How genetic testing can benefit your practice
So what can genetic testing offer you as a provider? I’ll answer that question with a question: Did you know that some forms of AREDS 2 supplements containing zinc can actually be harmful to your patients5? Consider a study done by Ottawa Hospital Research Institute that shows certain genotypes are more likely to progress with their AMD at a faster rate when exposed to higher levels of zinc supplementation. Genetic testing allows you, the doctor to personalize care, treatment, and determine how frequently to see your patient.
Genetic testing answers these questions:
- Patient AMD Genetics with a percentage of genetic risk
- A 2, 5, and 10year risk analysis of a patient developing a neo net/geographic atrophy.
- Supplement recommendation: AREDS 2, AREDS without zinc, Zinc only, or Placebo.
- Genetic counseling resources for your patient
Genetic tests offered on the market today for AMD utilize molecular tools to demonstrate causative DNA mutations and identify persons at risk for an inherited condition. Currently, there is only one company that gives both a genetic profile and a vitamin supplement recommendation, Macula Risk by ArcticDx Inc.
I advocate that if you can do more for your patient, we should. Consider researching your options for offering genetic testing for your patients. It’s best to be thorough and practice to the fullest scope of our field so that our profession flourishes and your patients can do the same.
- Resnikoff S, Pascolini D, Etya’ale D, et al. Global data on visual impairment in the year 2002. Bull World Health Org. 2004;82:844–51.
- H, Chew E. Nutritional supplementation in age-related macular degeneration. Curr Opin Ophthalmol. 2007;18:220–3.
- AREDS Study Group. A randomized, placebo- controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age- related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119:1417–36
- Klein R, Peto T, Bird A, et al. The epidemiology of age-related macular degeneration. Am J Ophthalmol. 2004;137:486–95.
- Ophthalmology. 2015 Jan;122(1):162-9. doi: 10.1016/j.ophtha.2014.07.049. Epub 2014 Sep 4.