Gene testing, therapy: 4 considerations for IRDs

April 28, 2021
Inherited retinal diseases (IRDs) cause severe visual impairment, but advances in genetic testing and therapy offer a glimmer of hope—how optometry can get involved.
Genetic testing and gene therapy

Advances in genetic research combined with enhanced availability of multi-gene testing panels have solidified genetic testing as part of the clinical workup for patients with inherited retinal diseases (IRDs). But how can optometry incorporate these latest developments into practice?

Only a decade ago, genetic testing and therapy for patients with IRDs was typically a research exercise, but today, this rapidly advancing field has given eye care providers an unprecedented ability to target some of these rare, sight-threatening diseases and potentially stem patients’ vision loss. Such is the case, patients and caregivers are more knowledgeable about these developments than ever, requiring doctors of optometry to understand the options available.

Triggered by at least one malfunctioning gene, IRDs are a group of rare diseases that cause progressive vision loss or blindness. Genetic testing is often recommended for these patients, especially given that a causative mutation can be identified in up to 80% of patients with IRDs. What’s more, gene therapy is currently available for RPE65 mutation-associated retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) with a couple dozen clinical trials evaluating other IRDs.

Rachelle Lin, O.D., an assistant professor at Southern California College of Optometry at Marshall B. Ketchum University, not only treats patients in the Low Vision Rehabilitation clinical department at the University Eye Center at Ketchum Health but also conducts genetic testing for IRDs. An international lecturer on the subject, Dr. Lin says it’s vital that primary care doctors of optometry know what’s possible given how so much has changed recently.

“The field is growing and evolving so rapidly that potential treatment options are changing dramatically for patients with IRDs,” Dr. Lin says. “It’s important that we, as doctors of optometry, identify these patients and either administer testing or refer them for the appropriate testing, so they know whether or not they qualify for the latest in gene therapy or gene therapy clinical trials.”

Considering genes: 4 points doctors should keep in mind

Toward that end, Dr. Lin shares several points of consideration that doctors and patients with IRDs should consider when weighing the benefits of genetic testing and gene therapy. 

  1. Identify patients who will benefit from genetic testing.
    Genetic testing is now recommended as a component in the diagnosis and management of all types of inherited retinal dystrophies. Dr. Lin emphasizes that patients must have a genetic diagnosis to determine eligibility for gene therapy or clinical trials, so it is highly advisable that patients obtain a conclusive genetic test. This is particularly relevant for conditions that currently have gene therapy, i.e., RP and LCA associated with RPE65 Additionally, there are dozens more ongoing clinical trials evaluating other IRDs. Successful genetic testing can have other benefits as well, such as delivering a more accurate prognosis, contributing to earlier management of syndromic conditions, and providing valuable information about inheritance risks for family members.
  1. Use appropriate test panels and procedures.
    A conclusive genetic test is heavily dependent on selecting an appropriate test panel. There’s a misconception that testing is nothing more than collecting a saliva sample, but in fact, effective genetic testing requires multiple steps, from the clinical examination to genetic counseling. The first part of clinical, genetic testing is determining if there is likely an inherited eye disease, Dr. Lin says, and determining the differential diagnoses. Next, the selected panel should be checked to include the genes known to be associated with the differential diagnoses. For example, patients suspected of X-linked RP (XLRP) should be tested with a panel including the RPGR gene, which is responsible for the majority of XLRP cases. With today’s expanded panels, it may be worth retesting patients who received a negative or inconclusive test in the past. Even after receiving the lab report, given that some genes are associated with more than one condition, genetic testing results are best interpreted in conjunction with the individual patient’s clinical findings. It is also recommended to provide the patient access to genetic counseling services.
  2. Educate patients about genetic testing and treatment options.
    Once a patient with an IRD has been identified, Dr. Lin says patient education is critical. Most patients with IRDs have lived their entire lives being told there is no treatment for their condition. Now with the advent of gene therapy, patients need to be educated on the importance of genetic testing and possible treatment options. The field is rapidly progressing—and as such, genetic testing is no longer as pricy as it once was, especially with several foundations and companies available to help with lab costs. Dr. Lin says it’s important to also manage expectations. Though improved, genetic testing for IRDs is still limited to identifying the causative mutation approximately 60-80% of the time. Results are sometimes negative or inconclusive. Additionally, only a small percentage of patients will currently qualify for gene therapy or interventional clinical trials. In the case of RP, the current gene therapy targets only the RPE65 gene and ongoing clinical trials target other genes, such as RPGR and USH2A. However, there are more than 100 genes associated with types of RP and many still to be identified. Nonetheless, testing to identify patients who will qualify for sight-saving treatment is worth doing.

    Likewise, it’s essential for doctors to stay apprised of the latest advances. With so many ongoing clinical trials, doctors can access to search for trials and conditions.
  3. Refer and engage in interprofessional management.
    Lin acknowledges that not every primary care eye doctor may feel comfortable with genetic testing or counseling for rare IRDs; therefore, the growing need for identification means interprofessional collaboration is necessary—be they low-vision doctors of optometry, retinal specialists, pediatricians or other primary care providers. For doctors who do not regularly manage these conditions, it may be most effective to refer the patients for testing and management. Low-vision optometrists, for example, see patients with IRDs regularly and may be able to facilitate genetic testing and patient education. Because most patients with IRDs currently will not qualify for gene therapy, it is crucial that they have access to low-vision resources. Even after successful gene therapy, patients will likely still have some residual vision impairment and need continued services, Dr. Lin notes.

Earn CE in genetic testing, therapy at Optometry’s Meeting®

Interested in learning more about genetic testing and therapy and how doctors of optometry can be at the forefront of implementing these cutting-edge developments in their patient care? Consider attending one of several educational courses Dr. Lin is providing at Optometry’s Meeting®, June 24-26, in Denver, Colorado. Here is what you need to know:

What: Ethical and Legal Considerations of Genetic Testing and Gene Therapy
Thursday, June 24 (Room 4)
Who: Joint OD/Para, available in person; AOA credit and CPC credit

What: Gene Therapy for Inherited Retinal Dystrophies – The Present & Future
Thursday, June 24 (Room 1)
Who: Joint OD/Para, available both in person and virtually; COPE credit and CPC credit

What: Genetic Testing for IRDs: Step-by-Step Workshop from Diagnosis to Gene Therapy
Friday, June 25
Who: ODs, available in person; AOA credit

Is your curiosity piqued? Then don’t wait any longer—register for Optometry’s Meeting today. To maintain occupancy requirements, only a limited number of seats are available for each course, so register and select your preferred educational courses during registration.

Access low-vision resources, find low-vision doctors

Low vision as a condition exacts an enormous psychosocial and economic toll on patients, their families and society with nearly 3 million Americans, age 40 and older, living with some form of low vision. These patients can easily spiral into depression at their loss of independence, purpose and hope; however, low-vision services offer patients a way to maximize the vision they do have via specialized adaptations or devices.

Optometry plays a leading role in providing low-vision care, often alongside a multidisciplinary care team, yet such services do require a different approach than a routine medical eye exam. Visit the AOA’s doctor locator and select “low vision” specialty to find a colleague in your area who provides low-vision services.

Keep reading for more information about the practice of low vision, clinical considerations and new coding and documentation changes for evaluation and management services taking effect in 2021.

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