Background

The name retinitis pigmentosa (RP) was first applied by Doctor Donders in 1857. It is the phenotypic description of several related, yet distinct, hereditary, progressive dystrophies of the photoreceptors of the retina and of the pigment epithelium (which lies just underneath the photoreceptors).

Patients present with ring scotoma and night vision problems, which progress to a slow loss of all peripheral vision; central vision is spared the longest. It is the leading cause of inherited retinal degeneration-associated blindness.^[1]

Pathology

RP is characterised by changes in pigment and arteriolar attenuation, often with some degree of optic nerve atrophy. Post-mortem examination has shown that the pigmentation is caused by cells from the pigment epithelium budding off and settling within the layers of the neural retina. In the late stages of RP a thinning of the retinal blood vessels is seen, probably resulting from the loss of many retinal cells reducing the need for blood.

The common end-point is a gradual deterioration of the light-sensitive cells of the retina. Both rod and cone photoreceptors can be affected, the predominance of one over the other being determined by the particular genetic defect in that patient. Rod photoreceptor malfunction is the most commonly encountered problem in RP - cone dystrophies are distinct and present with a different set of problems.

There are various inheritance patterns. To date, more than 50 different genetic defects have been identified,^[2] including the following: X-linked (5-15%), autosomal dominant (30-40%) and the remainder assumed autosomal recessive (50-60%). ^[3][4] The autosomal dominant forms tend to have a milder course with a late, slow progression and preserved vision until the fifth or sixth decade.^[5] The X-linked form is the most severe; central vision is usually lost by the third decade. Isolated cases, with no family history, also commonly occur

Epidemiology

• Prevalence in all ages is approximately 1 in 4,000 and, in the age group 45 to 64 years, 1 in 3,195.^[6]
• There are no geographical or sex predilections. However, because of X-linked varieties, men may be affected slightly more than women.

Presentation

Symptoms

• Symptoms often start in childhood with impaired night vision (nyctalopia) or dark adaptation.
• Progressive loss of peripheral vision is common (resulting in a tendency to trip over things), although there may be loss of central vision which tends to occur later. This eventually leads to blindness at a variable rate.
• The symptoms usually become apparent between the ages of 10 and 30, although some changes may become apparent in childhood. In one type of RP, Leber's amaurosis, children may become blind, or almost so, within the first six months of life. Other types of RP may only show symptoms late in life.
• In some cases RP is first diagnosed following a road accident.

Signs

Dispersion and aggregation of retinal pigment produces changes ranging from granules or mottling to distinctive focal aggregates with the appearance of bone spicules. The retina shows black or dark brown, star-shaped concentrations of pigmentation. There may be various patterns of change, including pigmentation limited to one quadrant of the retina, abnormalities which appear to be radiating out from the disc and changes associated with a severe vasculopathy. Associated ocular problems may include:

• Myopia (frequently)
• Subcapsular cataract
• Open-angle glaucoma (3% patients)
• Keratoconus
• Vitreous changes (most commonly a posterior vitreous detachment)

Systemic findings

Retinitis pigmentosa is usually confined to the eye but 20-30% of cases have non-ocular problems as well. At least 30 different associated syndromes have been identified:^[4]

• Patients with Usher's syndrome have hearing loss, which may be profound or partial with a congenital or late onset. This accounts for about half of all cases of combined deaf-blindness.
• RP and hearing loss also are associated with Waardenburg's syndrome, Alström's syndrome, Alport's syndrome, Refsum's syndrome, and other systemic conditions, all of which have their own systemic manifestations.
• Short stature, renal dysfunction, and polydactyly are some signs of Bardet-Biedl syndrome or Laurence-Moon syndrome when associated with pigmentary retinopathy.
• The mucopolysaccharidoses may be associated with RP (eg Hurler's syndrome, Scheie's syndrome, Sanfilippo's syndrome), as well as the mitochondrial disorder, Kearns-Sayre syndrome, which manifests as ptosis, external ophthalmoplegia, and heart block.

Differential Diagnosis^[7]

Secondary pigmentary retinal degeneration occurs in a number of metabolic and neurodegenerative diseases, various syndromes and other eye diseases. In addition to those mentioned above, these include:

• Friedreich's ataxia
• Mucopolysaccharidosis
• Muscular dystrophy (myotonic dystrophy)
• Usher's syndrome
• Batten's syndrome
• Bassen-Kornzweig syndrome
• Homocystinuria
• Oxalosis
• Trauma
• Glaucoma with retinal pigment epithelial changes
• End-stage chloroquine retinopathy
• End-stage thioridazine retinopathy
• End-stage syphilitic neuroretinitis
• Cancer-related retinopathy

Investigations

Slit-lamp biomicroscopy is the key initial assessment. Further tests are to determine the functional integrity of the retina and optic nerve:

• Visual acuity
• Visual field assessment
• Pupillary reflex response
• Colour defectiveness determination
• Refraction

Intraocular pressure will also need to be measured. To find out more about these tests, see separate record on Examination of the Eye. Imaging includes:

• Retinal photography
• Ultrasound of the eye
• Fluorescein angiography
• Optical computer tomography (OCT)

All of these can be performed in a general clinic. The most critical diagnostic test is the electroretinogram (similar to the EEG of the brain or ECG of the heart). It should be carried out in centres with the appropriate facilities (so, patients will need to be referred on if there is not one in your local hospital - this will be done by the ophthalmology team). It provides an objective measure of rod and cone function across the retina. It will typically show a marked reduction of both rod and cone signals, although rod loss generally predominates.

Management

There is currently no definite treatment for this condition although a number of drugs have been proposed for the management. The evidence supporting their effectiveness is variable and generally limited.

• Referral to a low vision specialist is very helpful.
• Patients should make regular visits to an eye care specialist to screen for and treat any ocular complications such as cataracts, glaucoma and cystoid macular oedema.^[5]
• The use of sunglasses to protect the retina from ultraviolet light may help preserve vision. Bright light can provoke the formation of free radicals which are damaging to the epithelium.
• Genetic counselling is important and family members (siblings and offspring) should be examined for evidence of RP.^[5]
• General counselling by experienced staff is vital.^[7] It is worth noting that most children will have enough sight to complete their education in normal schools.^[5]
• The DVLA will need to be informed (by the patient) and there will be a requirement to do a specialised (Estermann) visual field test which is carried out by DVLA-approved optometrists; this is a legal requirement.^[7]
• Eventually, blind or partial sight registration - see separate record on Blindness and Partial Sight.

Drug

• Vitamin A/beta-carotene:^[2][8] antioxidants may be useful in treating patients with RP but no robust evidence currently exists. A recent comprehensive epidemiological 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 long-term doses of vitamin A. Check liver enzymes annually and vitamin A levels. Beta-carotene doses of 25,000 IU have been recommended.
• Acetazolamide: in a small percentage of patients with RP, cystoid oedema may respond to oral carbonic anhydrase inhibitors, such as acetazolamide, with some subjective improvement in visual function.^[9][10]
• Diltiazem: a recent study in Nature Medicine showed decreased degeneration of the retina in mice.^[11] No current recommendations exist regarding the use of diltiazem in patients with RP.
• Lutein: this may slow retinal degeneration experimentally but the benefits of this substance in human diseases are uncertain.^[12]
• Bilberry: has been recommended by some practitioners of alternative medicine in doses of 80 mg, although no controlled studies exist that document its safety or efficacy in treating patients with RP.
• Immunosuppressive agents: (including steroids): have been used, with anecdotal success, in patients who present with antiretinal antibodies.

Patients with some of the rare syndromic forms of RP may benefit from specific diets:

• Abetalipoproteinaemia (Bassen-Kornzweig syndrome): patients also have fat malabsorption. High levels of vitamin A may restore retinal function in early stages (vitamin E may also help).^[4]
• Refsum's disease: dietary reduction of phytanic acid can slow or halt retinitis in this condition.
• Familial isolated vitamin E deficiency (alpha-tocopherol transport protein deficiency): treatment with vitamin E can halt disease progression.^[4]

Surgical

Retinal pigment epithelium transplants and prostheses are in the experimental phase.^[13][14] Where cataracts have occurred or significant keratoconus has developed, surgery for these conditions will also help.

Prognosis

The disorder will continue to progress, although slowly. Complete blindness is uncommon.

Prevention

Some assessment of the risk of having an affected child may be made by genetic counselling. There may be a future role for gene therapy.^[7]