Diagnosis, Clinical Trials and Treatments for Inherited Retinal Diseases

Oct. 14, 2023

Inherited retinal diseases (IRDs) vary widely, but most of them lead to progressive and profound visual symptoms. Timely diagnosis, counseling and resource discussions are imperative to improve quality of life. Depending on the condition, treatment may be available, often through clinical trials, with the goal to slow the disease for vision preservation. Mayo Clinic's approach to IRDs combines comprehensive, multidisciplinary care with the latest research, imaging and treatments available.

Clinical trials

Retinitis pigmentosa (RP) is an inherited degenerative disease, and it is one of the most common IRDs. It often leads to loss of night and peripheral vision. "Most inherited retinal diseases are progressive," says Brittni A. Scruggs, M.D., Ph.D., an ophthalmologist at Mayo Clinic in Rochester, Minnesota. "If you could slow down the freight train, you could really have an impact on the quality of life of the patient."

Mayo Clinic is involved in the NAC (N-acetylcysteine) Attack clinical trial. NAC Attack is a phase 3 multicenter, randomized placebo-controlled study to evaluate the efficacy and safety of oral NAC in people with RP. The NAC Attack study identified Mayo Clinic, along with about 30 other clinics that specialize in inherited retinal degenerations, as a participating clinical site.

Studies have proved that excessive oxidative stress plays a key role in photoreceptor cell death in RP. The effect of NAC treatment on reducing photoreceptor loss has been shown in animal studies. Oral NAC treatment is known to be safe short-term, and this was recently demonstrated in 30 patients with RP who received oral NAC for six months.

This phase 3 clinical trial from centers across the world is necessary to determine the long-term safety of NAC and to determine whether oral NAC can slow photoreceptor loss and delay vision loss in patients with RP. Enrollment for this trial at Mayo Clinic started in October 2023.

Mayo Clinic Ophthalmology also is dedicated to advancing ophthalmic gene therapy research and clinical trials for IRDs. In 2024, Mayo will be a clinical trial site for VISTA, a randomized controlled, masked, multicenter phase 2-3 trial to test the safety and efficacy of gene therapy for patients with X-linked RP.

Mayo Clinic is also part of the Foundation for Fighting Blindness (FFB) Consortium, which facilitates clinical studies in patients with rare inherited retinal disorders to accelerate development of treatments. In collaboration with FFB and the JAEB Center for Health Research, Mayo Clinic investigators will soon recruit patients for the international multicenter Universal Rare Gene Study. This will be the largest natural history study for inherited retinal diseases for the purpose of disease characterization and defining subpopulations for future clinical trials of investigative treatments. Enrollment for this study will start in early 2024.

Genetic counseling

"While aging or risk factors can cause common forms of macular degeneration, macular dystrophies and other IRDs are linked to genetic variants that trigger degradation of retinal cells," says Raymond Iezzi Jr., M.D., an ophthalmologist at Mayo Clinic, in Rochester, Minnesota. "Determining the exact genetic cause of a patient's disease allows our team to accurately make a diagnosis and counsel on prognosis, clinical trial opportunities, family planning and vision rehabilitation strategies."

At Mayo Clinic, highly skilled medical geneticists and certified genetic counselors meet with patients of all ages. Patients can expect the highest quality evaluations, timely and cost-effective genetic testing, and counseling by a caring, compassionate genetic counseling team at the time of their ophthalmology evaluation.

"We've built a beautiful collaboration with Mayo genetic consultants and counselors," says Dr. Scruggs. "They see all patients with presumed IRDs within our ophthalmology clinic where they provide consultations, talk through diagnoses, and work with the patient and their families to make informed decisions."

Resources and strategies

Mayo Clinic Ophthalmology has internationally renowned eye physicians, surgeons and optometrists who provide comprehensive care for people who seek answers about ophthalmological diseases and conditions, including inherited retinal diseases. At Mayo Clinic, patients can meet with vision loss rehabilitation specialists, driving experts, social workers and occupational therapists to enhance their experience and, ultimately, their vision.

The department uses state-of-the-art imaging modalities and has collaborative relationships across Mayo Clinic. "Some patients might not have a clinical trial or treatment as an option," says Dr. Scruggs. "Our priority is to optimize our patient's quality of vision and quality of life with the resources that we have."

For more information

Johns Hopkins University. Oral N-acetylcysteine for Retinitis Pigmentosa (NAC Attack). ClinicalTrials.gov.

Campochiaro PA, et al. The mechanism of cone cell death in retinitis pigmentosa. Progress in Retinal and Eye Research. 2018;62:24.

Campochiaro PA, et al. Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase 1 trial. Journal of Clinical Investigation. 2020;130:1527.

Applied Genetic Technologies Corp. A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations. ClinicalTrials.gov.

JAEB Center for Health Research. Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants (Uni-Rare). ClinicalTrials.gov.

Refer a patient to Mayo Clinic.