In a presentation at the American Academy of Optometry 2021 Annual Meeting in Boston, Micaela Gobeille, OD, MS, FAAO, discussed the keys to successful management of retinitis pigmentosa.
Reviewed by Micaela Gobeille, OD, MS, FAAO
Retinitis pigmentosa (RP), a progressive rod-cone dystrophy, is the most common inherited retinal dystrophy and is characterized by progressive vision loss throughout the patient’s life from diagnosis to adulthood.
Vision management in these patients is paramount due to the wide variety of disease severity over the lifespan, according to Micaela Gobeille, OD, MS, FAAO, who practices at Solinsky EyeCare in West Hartford, Connecticut, Holyoke Health Center in Holyoke, Massachusetts and IN-SIGHT Vision Rehabilitation in Warwick, Rhode Island.
Diagnosis and follow-up
The diagnosis of RP can be difficult because its presentation can vary widely. Symptoms include night blindness, photopsies in about a third of patients, and loss of visual field. During her presentation at the American Academy of Optometry 2021 annual meeting in Boston, she noted that central visual acuity is relatively spared until the disease process is complete, she noted.
The presentation can vary considerably from patient to patient. The classic presentation of RP includes a triad of attenuated arterioles, waxy disc paleness, and bone spicules. Additional findings include retinal pigment epithelium (RPE) atrophy, pre-retinal gliosis, drusen discs, and vitreous condensation. Other less classic RP presentations include sine pigmento, albescens, sectorial and inversus, she pointed out.
A diagnosis can be made with a few tools available to clinicians, including visual field tests (VF), electroretinography (ERG), and genetic testing.
The classic appearance seen on VF tests includes peripheral middle ring scotoma, peripheral islets, and preserved central vision. This appearance tends to be symmetrical in both eyes. Generally, the rate of loss of VF is 15% to 17% of the remaining area of VF per year.
Full-field ERGs initially show reduced scotopic and combined rod responses, and later reduced photopic responses. ERG goes off in the terminal phase of the disease. The amplitude of the ERG cone decreases by 10% per year.
Genetic testing in RP has identified several modes of inheritance, in particular, autosomal dominant in 30%, autosomal recessive in 20%, X-linked recessive in 15% and sporadic in 30%, with over 40 different genes involved. . Genetic testing for RP requires multigenic panels; however, the genes included in the test panel vary by laboratory, as does the sensitivity and specificity of the test for each individual gene.
Gobe advises that genetic testing in RP should be ordered when the diagnosis remains uncertain after other tests are completed. It is also important to provide information on the patient’s genetic risk profile in order to facilitate genetic counseling and to determine eligibility for gene therapy trials / treatments if the patient is interested.
Early management after diagnosis may include nutritional supplementation. There is limited evidence that vitamin A can reduce the rate of ERG loss. However, the toxicity of vitamin A can produce serious side effects on the liver and kidneys. In particular, vitamin E supplementation accelerates the loss of function.
Management of low vision is important at every stage of RA and is indicated for all patients with RA. Filters or tinted glasses can reduce problems with lighting transitions and glare sensitivity. Patients can also benefit from orientation and mobility (O&M) training, although visual measurements are relatively good. Patients who admit to having experienced trips, bumps, falls or fear of falling should be referred to this type of training. Patients can be trained in the use of non-visual cues to aid navigation, a long white mobility cane, or perhaps with a guide dog once the patient has acquired basic O&M skills.
In PR, vision is relatively preserved until the late stage, with the rods then the cones affected. When the best-corrected visual acuity decreases, other causes associated with RP should be investigated, such as posterior subcapsular cataract and cystoid macular edema (CME). CME associated with RP is usually treated with carbonic anhydrase inhibitors. Oral acetazolamide is superior to topical dorzolamide in reducing edema and improving vision. However, the topical medication is often used instead to avoid the side effect profile associated with its oral counterpart. The effectiveness of the treatment is also limited by a rebound effect.
According to Gobeille, studies using optical coherence tomography (OCT) in patients with RP have shown that the pattern of photoreceptor loss with eccentricity is consistent with field constriction. OCT is also an important tool to assess the CME associated with RP.
In PR, fundus autofluorescence (FAF) shows peripheral median hyperautofluorescence. Studies have shown that the radius of the hyper-FAF ring correlates with the results of ERG and automated / kinetic VF. In addition, the diameter of the normal FAF correlates with the line of photoreceptor integrity preserved on the OCT.
Additional audio strategies are often important for RP patients with advanced vision loss. Some examples include smartphone applications such as KNFB Reader (Sensotec) which can provide instant access to printing; Voice over or Talkback (integrated voice output capabilities for smartphones); and smarthome technologies (for example, Amazon Alexa), which can allow the patient to listen to the news, search the Internet and even control the lighting in the house. This is often recommended in addition to tinted glasses and the mobility strategies mentioned above.
Additionally, Argus II Retinal Prosthesis (Second Sight Medical Products) provides electrical stimulation of the retina to induce visual perception for patients with bare or worse light perceiving vision and confirmed retinal function. Patients who receive an implant can expect an improvement in their ability to detect lights and movement, which Gobeille says can be significant and of functional importance to a patient who would otherwise be blind.
Success with the Argus, Gobeille explained, depends on realistic patient expectations and adherence to training with the device.
On the horizon
Clinical trials are underway to investigate the use of cortical implants for blind patients, and Second Sight’s Orion device is currently recruiting human subjects.
Gene therapies are another area of interest. Due to the genetic heterogeneity of RP, gene therapy is unlikely to cure RP. Gene therapies also aim to prevent further vision loss and are unable to restore already dead tissue. Voretigene neparvovec (Luxturna, Spark Therapeutics) is the first such treatment approved by the FDA for the RPE65 biallelic mutation.
Cell therapies are another potential area of intervention. Early success has been achieved with RPE derived from stem cells on a scaffold for AMD. Photoreceptor cell therapy is less advanced and faces greater challenges, including cell differentiation, migration, synapse formation, and extension of outer segments to the RPE.
“Clinicians should diagnose based on symptoms, clinical appearance, visual field, electrodiagnostic testing and sometimes genetic testing,” Gobeille concluded. “Monitor progress with multimodal imagery. If visual acuity decreases, rule out other etiologies. Managing low vision is essential at all stages of RP.
Retinal prostheses and other innovations are increasingly available, but are not suitable for some patients with RA. Most importantly, there is always something the clinician can do to help these patients.
Micaela Gobeille, DO, MS, FAAO
This article is adapted from Gobeille’s presentation at the 2021 American Academy of Optometry Annual Meeting in Boston. She has no financial interest in this matter.