Retinitis Pigmentosa Treatment & Management

Updated: Apr 06, 2017
  • Author: David G Telander, MD, PhD; Chief Editor: Donny W Suh, MD, FAAP  more...
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Treatment

Medical Care

The diagnosis of retinitis pigmentosa (RP) can be overwhelming to many patients. While therapies are limited, physicians should emphasize the therapies that are available to help patients. Perhaps, most importantly, it is essential to help patients maximize the vision they do have with refraction and low-vision evaluation. Many devices are available to help patients with night vision difficulties, and most low-vision clinics are aware of these devices.

The authors believe that patients should have annual examinations, including visual field testing and periodic (every 5 y) ERG evaluations. Changes in examination findings can help guide patients in their activities and can help with prognosis. Often, these examinations can provide reassurance that the changes are slow. In addition, regular examinations can ensure patients have appropriate community and legal assistance. Finally, as new therapies emerge, routine evaluation can keep patients informed of clinical trials and new treatments.

Vitamin A/beta-carotene

Antioxidants may be useful in treating patients with RP, but no clear, prospective evidence in favor of vitamin supplementation yet exists.

A recent comprehensive epidemiologic study concluded that very high daily doses of vitamin A palmitate (15,000 U/d) slow the progress of RP by about 2% per year. The effects are modest; therefore, this treatment must be weighed against the uncertain risk of long-term adverse effects from large chronic doses of vitamin A.

Annually check liver enzymes and vitamin A levels. Beta-carotene doses of 25,000 IU have been recommended.

Docosahexaenoic acid (DHA)

DHA is an omega-3 polyunsaturated fatty acid and antioxidant.

Studies have shown a correlation of ERG amplitudes with patients' erythrocyte-DHA concentration. Others studies reported trends of less ERG change in patients with higher levels of DHA. Nutritional intake of omega-3 fatty acids may affect the rate of decline of visual acuity (see Diet), although further clinical trials must be done to determine DHA benefit.

Acetazolamide

Macular edema can reduce vision in the later stages of RP. Of the many therapies tried, oral acetazolamide has shown the most encouraging results with some improvement in visual function. Studies by Fishman et al and Cox et al have demonstrated improvement in Snelling visual acuity with oral acetazolamide for patients who have RP with macular edema. [8]

Topical acetazolamide can be effective but has not been found to be as effective as oral therapy.

Adverse effects, including fatigue, renal stones, loss of appetite, hand tingling, and anemia, may limit its use.

The use of corticosteroids for macular edema may be useful but has not been well studied.

Calcium channel blockers

Calcium channel blockers, such as diltiazem, are medications commonly used in cardiac disease.

Calcium channel blockers have shown some benefit in some animal models of RP, but they have been ineffective in other models.

No current recommendations exist regarding the use of calcium channel blockers in patients with RP.

Lutein/zeaxanthin

Lutein and zeaxanthin are macular pigments that the body cannot make but instead come from dietary sources.

Lutein is thought to protect the macula from oxidative damage, and oral supplementation has been shown to increase the macular pigment.

A National Institutes of Health (NIH) clinical trial, the Age-Related Eye Disease Study II (AREDS II), is beginning to test the effectiveness of lutein and zeaxanthin to slow age-related macular degeneration. Their ability to prevent cone photoreceptor cell death (such as what occurs in RP) has not been shown.

Doses from 6-20 mg per day have been recommended.

Valproic acid

Oral valproic acid has shown benefit in small clinical trials, and larger clinical trials are underway.

Medications with potential adverse effects in RP

Isotretinoin (Accutane): A medication used to treat acne has been reported to worsen night vision, ERG response, and dark adaptation. As its safety in patients with RP is not known, many physicians do not recommend isotretinoin use for their patients.

Sildenafil (Viagra): A medication to treat erectile dysfunction has been shown to cause reversible ERG and vision changes. Sildenafil is an inhibitor of PDE5 and less so PDE6. Mutations of the PDE6 gene are known to cause autosomal recessive RP. Therefore, physicians have suggested that this medication may not be safe for patients with RP, including carriers of the PDE6B gene mutation. Some users of sildenafil have experienced blue photopsias, suggesting that the drug is active in the retina at a physiological level.

Vitamin E: Reports have suggested that high doses of vitamin E (400 U/d) may be modestly deleterious in patients with RP. While doses as high as 800 IU/d have been recommended by some authors, the authors of this article recommend avoiding additional supplementation with vitamin E until further studies are conducted.

Other medications

Although doses of 1000 mg/d ascorbic acid have been recommended, no evidence exists that ascorbic acid is helpful.

Although bilberry is recommended by some practitioners of alternative medicine in doses of 80 mg, no controlled studies exist that document its safety or efficacy in treating patients with RP.

In patients who present with antiretinal antibodies, immunosuppressive agents (including steroids) have been used with anecdotal success.

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Surgical Care

Cataract extraction

Cataract surgery can often be beneficial in the later stages of RP. Bastek et al studied 30 patients with RP; 83% of them improved by 2 lines on the Snellen visual acuity chart with cataract surgery. [9]

Perioperative use of corticosteroids is recommended to prevent postoperative cystoid macular edema.

Educating patients about reasonable expectations of cataract surgery is essential.

Growth factors

Ciliary neurotrophic factor (CNTF) has been shown to slow retinal degeneration in a number of animal models.

Phase II clinical trials have been conducted using an encapsulated form of RPE cells producing CNTF (Neurotech) for patients with Usher syndrome and RP. These encapsulated cells must be surgically placed into the eye.

In May 2009, Neurotech released results from this study, showing evidence of retinal thickening after 1 year of treatment. [10] Visual improvement was not seen at this time point, but researchers believe more time may be needed to show preservation of function as compared to the untreated eye. [10] Interestingly, patients with atrophic age-related macular degeneration treated with the same growth factor did have a measurable visual improvement after 1 year. [10]

Transplantation

Cell transplantation to treat retinal disease (including cells derived from stem cells) is being actively investigated as a potential way to replace damaged RPE or photoreceptor cells. Both adult bone marrow–derived stem cells and embryonic stem cells are being used in clinical trials in patients with RP.

In 2011, Advanced Cell Technology (ACT) launched a human trial of a stem-cell–derived therapy for people with age-related macular degeneration and Stargardt disease. In this study, the cells derived from stem cells are differentiated into cells with an RPE phenotype and then injected under the retina during vitrectomy surgery. Initial results demonstrated safety and a trend toward visual improvement in 18 patients over 3-12 months. [11] Hopefully, this technology will also prove to be effective and helpful in patients with RP.

RPE cell transplants (not derived from stem cells) have been placed into the subretinal space to rescue photoreceptors in animal models of RP. One approach that may prove useful is ex vivo modification of these cells to provide trophic factors.

Transplantation of adult retinal tissue has also been studied in clinical trials without successfully or reproducibly improving patients’ vision. Small patches of retinal or RPE tissue have been transplanted, and this technique could be helpful in the following RP forms: when RP is based on an RPE defect, when RP with primary defects exists in the outer segments, if the disease is driven by an overload of the phagocytic activity of the RPE, or if the RPE cannot provide sufficient nutritional support to the outer segments.

Retinal prosthesis

Artificial vision for patients without any vision has only recently become a reality after years of research and investment. One effective approach uses a retinal prosthesis or phototransducing chip placed on the retinal surface. A digital camera placed in glasses can then transmit a stimulus to the intraocular chip, which electrically stimulates the retina in a pattern mimicking the image transmitted from the glasses, thereby giving the patient an electrically produced image to the ganglion cell layer of the retina. Preclinical trials in animal models have shown long-term stability. [12]

The US Food and Drug Administration (FDA) has approved the first retinal implant, the Argus II Retinal Prosthesis System, for adults aged 25 years or older with advanced RP. [1]  Although this device will not restore vision to patients, it replaces the function of degenerated cells in the retina and may improve a patient’s performance of basic activities by improving their ability to perceive images and movement. [1]

The implant includes a small video camera, transmitter mounted on a pair of eyeglasses, video processing unit (VPU), and an implanted retinal prosthesis (artificial retina). The VPU transforms images from the video camera into electronic data that are wirelessly transmitted to the retinal prosthesis. About two thirds of patients had no adverse events related to the device or the procedure; however, over one third of patients had a total of 23 serious adverse events, including conjunctival erosion, dehiscence, retinal detachment, inflammation, and hypotony. [1]

Chow et al placed subretinal microphotodiodes (prosthesis) in patients with severe RP. [16] These patients had subjective improvement; however, the improvement was delayed and occurred in retinal areas outside of where the chip was placed. Therefore, the effect was thought to be an indirect benefit to adjacent cells.

Gene therapy

Gene therapy is under investigation, with the hope to replace the defective protein by using DNA vector (eg, adenovirus, lentivirus). [17]

Gene therapy was successful in providing the missing protein to a dog with Leger congenital amaurosis (LCA). Using adeno-associated virus (AAV), the Briard dog with RPE65 mutations after treatment had 20% of its RPE cells express the functional protein, thereby allowing the dog to see. This was also effective in a mouse model of Leber congenital amaurosis.

Leber congenital amaurosis. Leber congenital amaurosis.

Gene therapy is now in human clinical trials for LCA, with promising results. In fact, 8 trials referring to gene therapy and RPE65 mutations are being conducted and listed on the clinicaltrials.gov Web site. Trials have also begun for RP, although currently only for MERTK gene mutation.

Because of the wide heterogeneity of defects in RP, gene therapy must be targeted specifically to each mutation.

Jacobson et al found that gene therapy is acceptably safe and effective in the extrafoveal retina for LCA caused by RPE65 mutations; however, no benefit and some risk was noted in treating the fovea. Age-dependent effects were not evident. [18]

It is not known which, if any, of the RP forms will show reversibility (even with a nondestructive reinsertion of the appropriate gene in the appropriate locus with appropriate regulation).

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Consultations

Clearly, RP is associated with several systemic diseases. Because of the severity of the systemic illness and its early presentation in most patients, the ophthalmologist may act as the consultant to an internist.

Low-vision specialists can provide magnifying devices and field-expanding lenses for patients with RP who have poor central vision.

Audiology consults should be considered for patients with hearing loss or for those patients with known Usher syndrome.

Genetic testing and counseling is becoming increasingly valuable as the understanding of RP increases. Identification of the patient’s genotype offers several advantages. First, it confirms the genetic cause of the condition. In addition, it can occasionally help determine prognosis and may likely prove to be important for future therapy choices. Genetic counseling is very helpful to guide patients on the hereditary nature of their disease and the mode of inheritance. This counseling can help the patients with their future plans, such as pregnancy, job choices, and medical treatments.

Moreoever, psychological counseling should be made available to those patients when appropriate.

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Diet

Many practitioners recommend a well-balanced diet with adequate leafy green vegetables that contain the aforementioned supplements in nontoxic doses.

For patients receiving vitamin A palmitate, a diet rich in omega-3 fatty acids may slow the rate of decline of visual acuity. [19]

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Activity

Light exposure

Stressful light exposure, which generates free radicals and strains the regenerative capacity of the eye, might put dystrophic retinas at a disadvantage. However, little direct or epidemiologic evidence exists that the disease is modified by light.

A specific form of RP, the Pro23His mutation in rhodopsin, has been shown to have increased retinal damage with increased light exposure.

UV-absorbing lenses are recommended, particularly in rhodopsin mutation varieties of RP, and patients with cone degeneration frequently benefit from tinted lenses.

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