Retinitis Pigmentosa

Genetic tests can identify genes associated with retinitis pigmentosa.

Retinitis pigmentosa (RP) represents a group of hereditary progressive retinal disorders. It affects approximately 1.5 million people worldwide. Retinitis pigmentosa usually affects both eyes symmetrically, although in some cases, it affects one eye more than the other. There are several forms of retinitis pigmentosa with different inheritance patterns, clinical signs, and visual symptoms.

Common to all is progressive retina degeneration, specifically of the light-sensitive (photoreceptor) cells known as the rod and cone photoreceptors. The rods, which are largely responsible for night vision, are involved earlier during the disease. RP later affects cones, which are responsible for color and central vision. Rod-cone dystrophy and progressive pigmentary retinopathy are other names for RP.

Difficulty with night vision, slow adaptation to the dark, and gradual loss of peripheral vision are typically the first symptoms. People usually retain central visual acuity until late in the disease. Doctors commonly diagnose RP during adolescence, though symptoms may begin at any age. One uncommon form of RP called Leber's congenital amaurosis occurs with severe vision loss at birth. Other late-onset forms of RP generally carry a better prognosis.

So far, researchers have located over 100 genes associated with RP. However, about half of RP patients have yet to identify the abnormal genes. What these genes all have in common is they are in some way involved in the proper structure and function of the retinal photoreceptor cells, so any abnormalities in these genes will affect retinal health. The most common genetic abnormalities are related to the formation of rhodopsin, a key component of rod photoreceptor cell function. Various inheritance patterns exist; researchers have identified X-linked, autosomal recessive, and autosomal dominant retinitis pigmentosa types. In many cases, there is no known family history of RP.

While most forms of RP only affect the eyes (non-syndromic RP), several forms of RP occur with systemic conditions. For example, retinitis pigmentosa and neural hearing loss characterize Usher syndrome. Bardet-Biedl syndrome (BBS) affects multiple organs; in addition to RP, patients have obesity, abnormalities of fingers and/or toes, small external genitalia in males, kidney anomalies, impaired sense of smell, dental abnormalities, vertebral abnormalities, and in some cases, behavioral and intellectual disability. Another example of an RP syndrome is abetalipoproteinemia (Bassen-Kornzweig syndrome), characterized by misshapen red blood cells, progressive inability to coordinate movement and malabsorption of fat in the digestive system. Although rare, this condition is essential to recognize early, as specific dietary restrictions can treat it.

Symptoms come on gradually. At first, there is increasing difficulty with night vision (night blindness) or trouble adjusting to dim light after being exposed to bright light. As the rod photoreceptors in the retina continue to degenerate, peripheral vision is affected. Slowly progressive constriction of the visual field ultimately leads to tunnel vision. A small area of central vision in both eyes usually persists for years. The degree of total vision loss is variable, with some patients retaining good visual acuity and others losing substantial vision. People first notice the symptoms between 10-40 years of age, although they can appear earlier or later. Generally, autosomal recessive and X-linked forms appear earlier in life.

Some forms of RP affect parts of the eye other than the photoreceptor cells. For example, fluid may accumulate in the macula, which is the center part of the retina. This condition is called cystoid macular edema (CME). The eyes' lenses may also cloud, becoming cataracts. Both CME and cataracts cause blurred or distorted central vision, and both are treatable.

There are no major outward signs of RP, however, many forms of RP do show signs inside the eyes that an eye doctor can see during a dilated eye exam. These include narrowed retinal arterioles, a waxy appearance of the optic nerve, and characteristic bone-spicule clumping of retinal pigment. However, some forms of RP show little or no signs on exam.

Because there are so many variants of RP with different symptoms and signs, the diagnosis may not be straightforward at first. Certain clues in the patient's history (especially retinitis pigmentosa in family members) and complaints (such as difficulty with adapting to the dark) may make one suspect RP. On dilated eye examination, the ophthalmologist may find characteristic clumping of pigment in the retina (a pattern described as bone spicules). This is due to changes in the retinal pigment epithelium, a layer of cells found under the receptors. Other characteristic findings include narrowed retinal arterioles and a waxy appearance of the optic nerve. Other non-RP eye diseases can show similar patterns in the retina (for example, Kearns-Sayre syndrome and congenital syphilis). Therefore, it may be necessary to perform additional testing to confirm the diagnosis of RP.

Visual field (side-vision) testing is important to make the diagnosis of RP and to document the degree of peripheral vision loss.

The electro-retinal exam (ERG) is a test that measures the electrical signals produced by the retinal cells when responding to light. The classic ERG pattern seen in RP shows a markedly diminished rod photoreceptor light-sensing response. The ERG helps distinguish between diseases that predominantly affect rod cells (like RP) from diseases that affect other cells of the retina. For example, the ERG can help distinguish RP from cone-rod dystrophy (CORD), a group of disorders that, as opposed to RP, typically affects central and daytime vision more than peripheral and night vision.

Other conditions such as toxicity from drugs, inflammatory conditions, infections, ischemia, and other forms of age-related retinal degeneration and inherited retinal dystrophy can affect the retinal pigment epithelium, resulting in pigmentary changes that resemble RP on the exam. Here again, the ERG pattern is useful in distinguishing these other retinopathies from RP.

ERG is a painless test. The electroretinogram (ERG), in conjunction with a visual field exam to detect constriction of the visual fields, will usually make the diagnosis of RP.

Additional specialized tests such as EOG, macular optical coherence tomography (OCT), and fluorescein angiography can help define which portions of the retina are secondarily affected in RP.

Genetic testing may identify the presence of one of the genes associated with RP, and evolving treatment modalities may target these specific gene abnormalities. For example, researchers are developing a promising new gene therapy for congenital amaurosis with the RPE65 gene mutation. Clinical trials are underway to treat some types of Usher syndrome with targeted gene therapy, as well.

There is no specific cure for RP at this time. Vitamin supplementation studies showed that 15,000 IU a day of vitamin A palmitate can slow the course of typical forms of RP in adults. Additional supplementation with 12 mg a day of lutein also slowed the disease in some patients.

Take care to avoid side effects. High doses of vitamin A can be toxic to the liver, may worsen osteoporosis, and may increase lung cancer risk in smokers. Vitamin A supplements may harm a developing fetus, therefore women who may become pregnant should discuss with their doctor reducing their dose and stopping altogether if pregnant. Vitamin A supplementation studies have not been done on children, but many doctors recommend smaller doses based on age and weight.

Studies also suggest that an omega-3-rich diet containing DHA (docosahexaenoic acid) can further slow disease progression. Such a diet includes one to two 3-ounce servings per week of oily fish such as salmon, tuna, herring, mackerel, or sardines. Vitamin E supplements appear to harm the course of RP, therefore, people with RP may want to avoid multivitamins that provide extra vitamin E beyond what would normally be found in their diet.

If cystoid macular edema (CME) develops, it may respond to treatment with drugs called carbonic anhydrase inhibitors (CAI), taken orally or as eyedrops, or steroids in some cases. If cataracts develop, doctors can surgically correct them.

Consider genetic diagnostic testing with an ophthalmic geneticist. First, identifying the disease-causing genes may provide patients with a better idea of the prognosis for their particular type of RP. Second, patients may want to seek help from a genetic counselor when planning a family to better understand the odds of passing the genes to the next generation. Some family members may carry the RP genes but show little or no signs of disease. This is often the case with females who carry X-linked recessive RP genes. Finally, a patient could potentially benefit from gene therapy or enter one of the gene-targeted therapy trials underway.

For patients with advanced late-stage disease, maximization of the patient's visual potential is important. Low-vision services at a low-vision center may help patients select from among various devices including magnifiers, lamps, and video screens. Because of the wide variety of visual disabilities among RP patients, and because of the progressive nature of the disease, the selection of the optimal low-vision aids is very patient-specific.

The prognosis varies widely among RP patients, with some retaining 20/40 or better vision in at least one eye and others eventually losing all useful central vision. In general, autosomal dominant retinitis pigmentosa has the best prognosis and X-linked RP is more severe. However, there is tremendous variability among groups and even among family members who share the same genes. Yearly visual field examination can document the course of RP and provide clues as to the prognosis.

There is a large amount of research currently being performed both in the United States and internationally. Trials are underway looking at the effects of ciliary neurotrophic factor, brimonidine, nerve growth factors, and many others, as well as open-label gene therapy and stem cell trials. Implantable devices (artificial retina) also are promising to provide some vision to those who have already lost vision from RP and other retinal diseases. Information on current clinical trials is posted at www.clinicaltrials.gov.

The American Academy of Ophthalmology

"Retinitis Pigmentosa Diagnosis and Treatment," American Academy of Ophthalmology

NIH/National Eye Institute
Building 31 Rm 6A32
31 Center Dr MSC 2510
Bethesda, MD 20892-2510
Tel: 301-496-5248
Fax: 301-402-1065
Email: [email protected]

"Retinitis Pigmentosa," National Institutes of Health, Office of Rare Diseases Research

Retinitis Pigmentosa International
PO Box 900
Woodland Hills, CA 91365
Tel: 818-992-0500
Fax: 818-992-3265
Tel: 800-344-4877
Email: [email protected]

Foundation Fighting Blindness
11435 Cronhill Drive
Owings Mills, MD 21117-2220
Tel: 410-568-0150
Fax: 410-363-2393
Tel: 800-683-5555
TDD: 800-683-5551
Email: [email protected]blindness.org

American Foundation for the Blind
11 Penn Plaza Suite 300
New York, NY 10001
Tel: 212-502-7600
Fax: 212-502-7777
Tel: 800-232-5463
TDD: 212-502-7662
Email: [email protected]