Retinitis Pigmentosa: What’s New in Diagnosis and Treatment?

Retinitis pigmentosa (RP) comprises a group of genetic disorders with heterogeneous clinical presentation that may lead to vision loss. Timely diagnosis and intervention are essential for improving the quality of life of individuals with RP. Ninel Gregori, MD, professor of clinical ophthalmology at Bascom Palmer Eye Institute, and a member of the Department of Ophthalmology at the University of Miami Miller School of Medicine, reviews current diagnosis and treatment recommendations for RP.

What signs and symptoms should prompt clinical suspicion of RP?

Typically, presenting symptoms include difficulty walking in dimly lit environments — night blindness — and narrowing of the visual field. Some individuals may report flashes of light not caused by external light sources and decreased visual acuity. RP usually is diagnosed in young adulthood, although it can affect individuals from infancy to their fifties. It has been associated with more than 150 causative genes and has a wide range of phenotypic presentations.^[1,2] The clinician should inquire about family history of RP or other inherited retinal disorders, but keep in mind that around 50% of cases are due to sporadic genetic mutations. A patient with any combination of these signs and symptoms should be referred to an ophthalmologist or retina specialist for further evaluation, including a comprehensive eye examination and possibly specialized testing, such as visual field testing, retina imaging, and genetic testing. Early detection and intervention can help optimize treatment strategies and preserve remaining vision.

Some of these signs and symptoms may lead clinicians to consider more common infectious or inflammatory conditions. Can you help us disentangle this diagnosis?

Several conditions can mimic RP. Night blindness in children can be associated with congenital stationary night blindness or vitamin A deprivation syndrome. Rubella, syphilis, toxoplasmosis, and herpesvirus can induce pigmentary retinopathies.^[3,4] Blunt or penetrating eye injuries can create a retinal appearance similar to RP. Traumatic retinopathy is usually unilateral, but occasionally RP can also be unilateral.^[5] RP can be secondary to drug toxicity — thioridazine and chloroquine^[6] — or parasitic infections, such as diffuse unilateral subacute neuroretinitis or onchocerciasis. Based on clinical evaluation, imaging, visual testing and electrophysiology, the ophthalmologist can support the diagnosis.^[4] The recommendation is to communicate early with the retina specialist for further evaluation.

What is the role of genetic testing in patient management?

Genetic counseling may help the patient and their family cope with and prepare for progressive visual impairment as well as make reproductive decisions, but genetic test results can be complex to interpret. In this context, phenotype-genotype correlations are important for choosing the best genetic test or panel and interpreting test results accurately. Phenotyping allows clinicians to understand the patient’s specific symptoms, medical history, and overall clinical presentation. Having a well-defined clinical phenotype provides important clues for understanding the significance of identified genetic variants and their potential contribution to the patient’s condition.^[2,7] A very exciting development is gene therapy for various forms of RP; several clinical trials are ongoing, with some showing promising results.^[8] The first-ever ocular gene therapy, voretigene neparvovec-rzyl (Luxturna), is now FDA approved for a specific form of RP caused by mutations in both copies of the RPE65 gene. It is important to assess each patient for the gene causing RP so that they can be offered this therapy or participation in a clinical trial and eventually access to other approved therapies specific for their genotype.

This is very exciting. Should we expect more new developments in RP treatment?

It’s important to note that there is currently no cure for RP. Treatment algorithms for RP currently involve symptom management, including low-vision aids, orientation and mobility training, mental health and psychological support, surgery, and adaptive technologies to assist individuals in daily activities — wearable magnifiers, screen readers, voice-activated devices, and smartphone apps. It is worth highlighting that vitamin A supplementation is not recommended as it is not effective, and vitamin E supplements must be avoided, as vitamin E has been shown to be harmful for patients with RP.^[9-11] Retinal prothesis, or “bionic eyes,” is also being developed as an option for end-stage RP patients.^[12,13] Although the first retinal prosthesis, the Argus II implant, was FDA approved, it had limited clinical benefit and is no longer available. New developments in RP treatment still in experimental stages include stem cell therapy and various pharmacologic approaches using neuroprotective agents, anti-inflammatory drugs, and agents targeting specific molecular pathways involved in retinal degeneration.^[14] Treatment for RP should be individualized based on factors such as the patient’s genotype, disease stage, visual function, and preferences. Close collaboration between ophthalmologists, geneticists, low-vision specialists, psychologists, and other healthcare professionals is essential for providing comprehensive care to individuals with RP.