Retinitis pigmentosa

Definition

Retinitis pigmentosa (RP) refers to a group of inherited disorders that slowly leads to blindness due to abnormalities of the photoreceptors (primarily the rods) in the retina.

Description

The retina lines the interior surface of the back of the eye. The retina is made up of several layers. One layer contains two types of photoreceptor cells referred to as the rods and cones. The cones are responsible for sharp central vision, distinguishing and recognizing colors, and seeing fine details. The cones are primarily located in a small area of the retina called the fovea.

The area surrounding the fovea and on the perimeter of the retina contains the rods, which are necessary for vision on the sides, as well as vision in dark and dimly lit conditions. The number of rods increases in the periphery.

The rod and cone photoreceptors normally convert light that enters the eye into electrical impulses; these impulses are sent to the brain along the optic nerve at the back of the eye and an image is recognized by the brain. Another layer of the retina is called the retinal pigmented epithelium (RPE).

In RP, the photoreceptors begin to break down and lose their ability to function. The rods are primarily affected, and as a result it becomes difficult to see in dim light and in the peripheral areas. The ability to see color is also lost in some cases. In the late stages of the disease, only a small area of central vision remains and this can also be lost.

There are many forms of retinitis pigmentosa and all of them are genetic. Sometimes the disorder is classified by the age of onset or by the inheritance pattern. RP can also be part of a medical syndrome, in which other medical problems are present. This entry focuses on non-syndromic RP, the type that is not associated with other medical complications.

Genetic profile

RP is an inherited disease associated with different inheritance patterns. It is felt that as many as 100 genes can cause the various types of the condition. The RP may be a familial condition, in which multiple family members are affected. It may also be isolated (or simplex), in which there is only one person with RP in the family. People with isolated RP represent 10–40% of all cases. Some of these may be the result of new gene changes (or mutations). Other isolated cases are those in which the person has a relative with a gene mutation, but that relative has no obvious signs of RP.

RP is most commonly inherited as an autosomal dominant, autosomal recessive, or sex-linked condition in a family. Autosomal dominant RP (ADRP) occurs in about 15–25% of affected individuals. At least 14 different genes have been identified as causing ADRP, with significant ones called the RHO, RP1, RDS, and ROM1 genes. People with ADRP often have an affected parent and other relatives in multiple generations. Someone with ADRP has a 50% chance to have a son or daughter with the same type of RP.

Autosomal recessive RP (ARRP) occurs in about 5–20% of affected individuals. At least 22 genes have been identified that cause this type of RP, including significant ones called RPE65, PDE6A, and PDE6B. In ARRP, each parent of the affected person is a carrier of a gene mutation that causes ARRP. Neither of these parents has symptoms of ARRP, and they have a 25% chance to have an affected son or daughter in every pregnancy together. All of the children of someone with ARRP would be a carrier for the condition.

Five to 15% of people with RP have the sex-linked form of recessive RP, which is most often X-linked recessive RP (XLRP). At least five genes have been identified with XLRP, with the most significant called RP2 and RP3. Males are usually more affected than females with XLRP and females carry an XLRP mutation on their X chromosome . Carrier females may not have signs of XLRP or they may have mild symptoms. In some cases, carriers have serious vision loss associated with XLRP. A female carrier's sons have a 50% chance of being affected, and her daughters have a 50% chance to be carriers. For a male with XLRP, his daughters would all be carriers, but none of his sons would be affected. RP is rarely inherited in an X-linked dominant manner. The risks to family members are very similar to XLRP, but females typically have some symptoms of RP instead. The family history pattern can be very similar to ADRP, and the difference may only be the gene mutation causing the RP in the family.

Rarely, RP is inherited by gene mutations in the MTTS2 gene. This gene is located in the cell's mitochondria, as opposed to the cell's nucleus like all of the other genes. When the MTTS2 gene is involved, only a female's sons and daughters would be at risk for RP. If a male has RP caused by the MTTS2 gene, his children would not be at risk for RP.

Also very rarely, RP is caused by the involvement of both the RDS gene and the ROM1 gene in the same family. An individual with RP may have a mutation in each of these genes. The risks to family members would be similar to those found in ADRP.

Demographics

RP is the most common form of blindness in people between the ages of 20 and 60 years old. It is thought to affect about 1.5 million men and women worldwide and approximately one out of every 4,000 people in the United States and Europe. Haim, et al., reported the lifetime risk for RP in Denmark to be one in 2,500 people. For other parts of the world, there are no published data on exact prevalence, but RP is seen in all ethnic groups.

Signs and symptoms

The first symptoms are typically difficulties seeing in dimly lit conditions or night blindness. People may notice that they are uncomfortable with an oncoming car's bright headlights when driving at night, or they may have a hard time finding their seat in a darkened movie theatre. People may begin to notice this as young as in childhood, adolescence, or later on in adulthood. In general, the earlier one notices this the more severe their RP may be over time. XLRP is usually associated with a more severe progression of symptoms than other forms of RP.

Eventually, people with RP experience a loss of peripheral vision and this may first start in childhood or early adolescence. This peripheral visual field loss typically progresses to tunnel vision, akin to seeing the world through two narrow straws. Prior to complete constriction of their visual fields, people with undiagnosed RP may be considered clumsy by those who know them, because they may not see the things that are in the normal visual field.

People with RP usually maintain crisp central vision for a very long time, because the cones are not usually involved until the later stages of the condition. Once the cones become involved, people may have their central vision affected, with difficulty distinguishing colors. Occasionally, the loss of the ability to see color occurs before the loss of peripheral vision. Additionally, RP sometimes significantly affects one's visual acuity; men with XLRP may have a visual acuity less than or equal to that of legal blindness.

Specific changes in the eye are consistent with RP. In the early stages of RP, visual testing indicates abnormal rod functioning, but there may be no physical changes in the retina. People may see occasional flickering or small lights flashing in their eyes. Over time this can progress. There may be narrowing to the blood vessels in the retina, fine dust-like coloring within the retina, and floating in the eye's natural liquid. There is often loss of pigment from the layer of tissue underneath the retina. As the rods break down, clumps of dark-colored melanin cause a bone spicule formation along the retina's periphery. These are very characteristic of RP. Eventually, the optic nerve and retinal blood vessels can become pale in color. Others may have white dots deep in the retina, and other abnormalities of the optic nerve.

Those with RP often develop a specific type of cataracts, known as a posterior subcapsular cataract (PSC). These are different than the cataracts found in the general population. PSCs have a yellowish crystal-like appearance in the eye's lens, and this looks different than typical cataracts seen in those without RP. These cataracts may be removed by an ophthalmologist, but this does not help tunnel vision or night blindness.

People with RP usually have these changes in both of their eyes. However, some only have them in one section or one half of an eye. This is called sector RP. People with this usually have no problems with night blindness, though visual testing can identify abnormal rod and cone functioning. Sector RP usually is inherited in a dominant manner, but is also seen in some female carriers of XLRP.

Diagnosis

A diagnosis of RP is usually made based on analysis of a person's symptoms, visual test results, and family history. Genetic testing is available for some types of RP.

When a person complains of problems with night vision, an ophthalmologist or optometrist usually performs a careful eye examination, including pupil dilation, to determine if there are physical changes to the retina and back of the eye that are suggestive of RP. Other retinal problems can cause night blindness and must be ruled out. However, these may not have the retinal changes that are typical of RP. A careful eye examination can also determine one's visual acuity and color vision.

An electroretinogram (ERG) tests how well the photoreceptors in the retina are functioning. Specifically for RP, this test is very good at identifying how well the rod cells are working. It can also show how well the cone cells are working. A dark adaptation curve (DAC) test can document the exact amount of time one's eyes take to adjust to darkness.

Testing of the visual fields can determine how much is being seen from left to right, and up and down. The full field of vision is studied to identify any blind spots or clarify whether the central vision is affected.

Fluorescein angiography (FA) can be helpful to determine whether blood flow is normal throughout the back of the eye. These detailed photographs of the eye's blood vessels can help identify any circulatory problems at the back of the eye, as well as changes in the retina's structure.

Fundus photographs can be taken to document changes in the eye structure, shape, and color.

A consensus conference documented by Marmor, et al., in 1983 established criteria to establish the diagnosis of RP. They are:

• Rod dysfunction as measured by DAC or ERG
• Progressive loss in photoreceptor function
• Loss of peripheral vision
• Involvement of both eyes

Other eye conditions can mimic RP, but do not have the specific eye changes and visual test results of RP. Gyrate atrophy of the choroid and retina, a recessive disorder, may seem like RP in its symptoms. However, it may be associated with round patches affecting the choroids and retina, which occur in the middle of the retina. Choroideremia , an X-linked recessive disorder, causes progressive blindness. However, it usually causes fine dark lines and patches on the choroids, which progress into pale yellow areas.

Leber congenital amaurosis is a group of recessive retinal abnormalities that cause serious vision problems or blindness that appear at or shortly after birth. Children affected with this condition usually have roving eye movements. Cone-rod dystrophy is a retinal problem in which the rods function well, but the cones progressively worsen. The symptoms may be similar to RP, but occur in the reverse order.

There are a few syndromes that involve RP. These include Usher syndrome and Bardet-Biedl syndrome . Usher syndrome is a group of recessive conditions that combine RP with deafness of varying degrees. Bardet-Biedl syndrome is a group of recessive conditions that combine RP with extra fingers and toes, mental delays, obesity, genital abnormalities, kidney abnormalities, and other medical complications. Genetic blood testing is available for some forms of Usher and Bardet-Biedl syndromes.

Genetic testing from a blood sample is available for some types of non-syndromic RP on a clinical basis. In these cases, an abnormal result would identify a mutation (or mutations) in the gene causing RP for that individual. Other at-risk family members can sometimes be offered genetic testing once a mutation is identified in a family. In some cases, prenatal testing is available through an amniocentesis procedure. All genetic testing should be accompanied by careful genetic counseling .

Treatment and management

There is no cure for RP, or known way to stop the disease progression altogether. However, some things can help maintain good retinal function and health.

It is felt that a diet rich in leafy green vegetables and fish may be good for the retina. In addition, certain fish contain omega-3 fatty acids, such as docosahexanoic acid (DHA) that is naturally found in the retina in very high concentrations. Eating a diet of fish like salmon, tuna, mackerel, or whitefish twice a week should naturally provide good DHA levels. Otherwise, good fish oil capsules containing DHA and other omega fatty acids can be obtained with a prescription or purchased at specialty health stores.

Multivitamins containing vitamins A, E, and C may be useful. These have antioxidant properties, which may be protective for the eyes. However, large doses of certain vitamins may be toxic, and affected individuals should speak to their doctors before taking supplements.

Protecting the eyes from harmful ultraviolet rays is essential to cone cell health. People with RP should wear good sunglasses outdoors and especially when over water or near snow on a bright, sunny day.

Smoking has been associated with deteriorating retinal health. Even quitting smoking late in life can make a positive impact on eye health.

PSCs do not usually severely impact the vision of those with RP. However, in some cases an ophthalmologist can remove the eye's lens and replace it with an artificial one to remove the cataract.

Low vision aids can be helpful for those in school or at work. Binocular lens and magnifying screens, large-print reading materials, closed-circuit television, special eyeglass lenses, and other tools can be helpful and are often available from organizations supporting those with vision loss.

Living with a chronic vision problem makes a significant impact on a person's life and family. It is often helpful for families to have a social worker connect them to helpful resources. Others may find genetic counseling, psychotherapy, or meeting other individuals with RP through support groups helpful.

Prognosis

Life expectancy is normal in RP. It eventually leads to serious visual impairment or blindness. The more severe forms will lead to blindness sooner than the milder forms, but each person's experience with the condition is unique and impossible to predict. Research and future treatments continue to offer hope for those with RP.

Resources

BOOKS

Newell, Frank W. Ophthalmology: Principles and Concepts, 7th ed. St. Louis, MO: Mosby Year Book, 1992.

WEBSITES

Genetic Alliance. 2005 (March 15, 2005). <http://www.geneticalliance.org>.

OMIM–Online Mendelian Inheritance in Man. National Center for Biotechnology Information. (March 15, 2005.) <http://www.ncbi.nlm.nih.gov/Omim/searchomim.html>.

RetNet–Retinal Information Network. 2005 (March 15, 2005). <http://www.sph.uth.tmc.edu/Retnet/>.

ORGANIZATIONS

American Academy of Ophthalmology. P.O. Box 7424, San Francisco, CA 94120-7424. Phone: (415) 561-8500. <http://www.eyenet.org>.

American Association of the Deaf-Blind. 814 Thayer Ave., Suite 302, Silver Spring, MD 20910. Phone: (301) 495-4403. TTY Phone: (301) 495-4402. Fax: (301) 495-4404. Email: info@aadb.org. <http://www.aadb.org/>.

The Foundation Fighting Blindness. 11435 Cronhill Drive, Owings Mills, MD 21117-2220. Local phone: (410) 568-0150. Local TDD: (410) 363-7139. Toll-free phone: (888) 394-3937. Toll-free TDD: (800) 683-5555. Email: info@blindness.org. <http://www.blindness.org/>.

The Foundation Fighting Blindness–Canada. 60 St. Clair Ave., East Suite 703, Toronto, ON, Canada M4T 1N5. Phone: (416) 360-4200. Toll-free phone: (800) 461-3331. Fax: (416) 360-0060. Email: info@ffb.ca. <http://www.ffb.ca/>.

Retinitis Pigmentosa International. P.O. Box 900, Woodland Hills, CA 91365. Phone: (818) 992-0500. Fax: (818) 992-3265. Email: info@rpinternational.org. <http://www.rpinternational.org>.

Deepti Babu, MS, CGC

Amy Vance, MS

Dorothy Elinor Stonely