ODs have role in gene therapy for inherited retinal dystrophies
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FDA approval of the first gene therapy in December 2017 marked the beginning of a new chapter in medical practice.
This breakthrough changed the future of counseling and management for patients with inherited retinal dystrophies (IRDs) by ushering in the new possibility of halting the progression of vision loss and perhaps even regaining vision. Optometrists serve a vital role by identifying patients with these rare conditions, educating them on new treatment options and referring for appropriate genetic testing so patients may benefit from the current surge of innovative research and therapies.
In addition to the current gene therapy for RPE65 mutation-associated retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), there are at least 24 ongoing clinical trials evaluating multiple gene therapies for many other IRDs. These include X-linked retinitis pigmentosa (XLRP), achromatopsia, Stargardt disease and choroideremia.
For example, there are several companies in the U.S. conducting gene therapy clinical trials for XLRP. One XLRP program, sponsored by AGTC, is currently enrolling patients in a phase 2 expansion trial and will initiate a phase 2/3 trial later this year. It is imperative that we inform patients of these opportunities, especially given that earlier treatment of degenerative conditions correlates with better outcomes.
Genetic testing
Genetic testing has become an important component in the assessment of IRDs. In the past, testing provided limited impact on disease management. Today, identification of the causative mutation has become faster, more affordable, more likely to identify the genetic cause of the IRD and has clinical utility toward providing comprehensive disease management. This includes providing more accurate genotypic diagnoses, improved accuracy of prognoses, earlier management of syndromic conditions and family counseling on inheritance risks.
Genetic testing is vital to determine patient eligibility for gene therapy and clinical trials. For instance, there are more than 60 identified genes associated with nonsyndromic retinitis pigmentosa. The current FDA-approved gene therapy targets only the RPE65 gene, whereas the current clinical trials for XLRP target only the RPGR gene. Therefore, a patient with retinitis pigmentosa would need genetic testing to determine eligibility for either the gene therapy or a clinical trial.
Similarly, the majority of achromatopsia is known to be caused by mutations on either the CNGA3 or CNGB3 gene. Patient eligibility for the current clinical trials depends on confirming the affected gene.
Granted, with the hundreds of genes associated with IRDs, the percentage of patients who currently qualify for gene therapy or clinical trials is relatively small. Nonetheless, the possibility of identifying the patients who will qualify and changing the course of their degenerative eye condition is worth the effort. In addition, the number of patients who stand to benefit will only increase as more therapies continue to advance into clinical development and, hopefully, to the market.
Because of the huge array of genes associated with IRDs, several important factors must be considered when proceeding with genetic testing.
For a genetic test to be as effective as possible, appropriate genetic test panels must be selected based on the differential diagnoses. For instance, not all test panels include analysis of the RPGR gene. Patients with suspected XLRP should be tested with a panel that includes the RPGR gene, and rescreening may be indicated if an inconclusive test in the past did not assess for RPGR mutations.
Variants on one gene can be associated with several different eye conditions. Therefore, genetic testing is most useful in conjunction with the necessary and appropriate clinical testing, such as fundus examination and electrodiagnostic testing. Even after the lab report is complete, the results must be considered within the context of the patient’s clinical findings.
Lastly, the full value of these tests is realized when testing is accompanied by effective genetic counseling that helps patients understand test results within the context of prognosis, inheritance risks, potential interventions and clinical trial options.
Interprofessional collaboration
The growing need for identification and genetic testing of IRDs will require close collaboration among optometrists and our interprofessional community, including pediatricians, primary care physicians, ophthalmologists, low vision occupational therapists and low vision optometrists.
Providers who focus on the IRD patient population, such as low vision and retina specialists, can serve as an essential resource by offering in-office genetic testing, counseling and education on ongoing clinical trials. Further, even after successful gene therapy, some degree of residual visual impairment remains, and patients need continued access to low vision resources. Increased frequency of contact with their eye care providers is also recommended to keep patients up-to-date on their clinical trial options within the rapidly evolving field.
Patient resources
The American Optometric Association’s Find a Doctor of Optometry resource can be filtered to search for low vision specialists.
In addition, the My Retina Tracker Program offers genetic testing and counseling for individuals with a clinical diagnosis of an IRD. For more information, visit FightingBlindness.org.
With promising new treatment opportunities on the horizon, ensuring access to genetic testing, clinical trial information and the latest low vision resources collectively builds toward a brighter future for our patients with IRDs. For more information on clinical trials, visit www.clinicaltrials.gov.
For more information:
Rachelle Lin, OD, MS, FAAO, is a full-time assistant professor at the Southern California College of Optometry at Marshall B. Ketchum University (MBKU). She treats patients in the clinical departments of Low Vision Rehabilitation and Acquired Brain Injury at the University Eye Center at Ketchum Health in Anaheim, Calif. She also conducts genetic testing for inherited eye conditions. At MBKU, she teaches low vision rehabilitation, genetics, clinical methods and nutrition. She has lectured internationally, with special interest in traumatic brain injury, vision rehabilitation, genetic testing and gene therapy.
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