Retinitis Pigmentosa

This is a group of hereditary disorders whose common feature is a gradual deterioration of the light sensitive cells of the retina. The name Retinitis Pigmentosa was first applied by Doctor Donders in 1857. That is the phenotypic description of several related, yet distinct, dystrophies of the photoreceptors and the pigment epithelium. It is characterised by changes in pigment and arteriolar attenuation, often with some degree of optic atrophy.

• Prevalence in all ages is approximately 1 in 4000 and in the age group 45 to 64 years of 1 in 3195.¹
• There are no geographical or sex predilections, however, because of X-linked varieties, men may be affected slightly more than women.
• Retinitis Pigmentosa (RP) can be classified according to its inheritance pattern.
• To date, more than 70 different genetic defects have been identified, including the following: X-linked (5-15%), autosomal dominant (30-40%) and the remainder assumed autosomal recessive (50-60%). ^{2 3}
• The autosomal dominant forms tend to have a milder course; the X-linked form is the most severe.
• Isolated cases, with no family history also commonly occur.

Both rod and cone photoreceptors can be affected, the predominace 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.

Patients with rod-cone dystrophies present with ring scotoma and night vision problems, which progress to a slow loss of all peripheral vision; central vision is spared the longest.

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.

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 - see above. 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.⁴ 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 unusual 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.
Other changes include:

• Subcapsular cataract
• Open angle glaucoma (3% patients)
• Keratoconus
• Myopia (frequently)
• 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 syndromes have been identified.³

• Patients with Usher 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 syndrome, Alstrom syndrome, Alport syndrome, Refsum disease, and other systemic conditions, which all have their own systemic manifestations.
• Short stature, renal dysfunction, and polydactyly are some signs of Bardet-Biedl syndrome or Lawrence-Moon syndrome when associated with pigmentary retinopathy.
• The mucopolysaccharidoses may be associated with RP (e.g. Hurler syndrome, Scheie syndrome, Sanfilippo syndrome), as well as the mitochondrial disorder, Kearns-Sayre syndrome, which manifests as ptosis, external ophthalmoplegia, and heart block.

Secondary pigmentary retinal degeneration occurs in a number of metabolic and neurodegenerative diseases and various syndromes. These include:

• Friedreich's ataxia
• Mucopolysaccharidosis
• Muscular dystrophy (myotonic dystrophy)
• Usher's syndrome
• End-stage chloroquine retinopathy
• End-stage thioridazine retinopathy
• End-stage syphilitic neuroretinitis
• Cancer-related retinopathy

Tests to determine the integrity of the retina:

• Visual acuity and visual field assessment
• Retinal examination by ophthalmoscopy
• Pupillary reflex response
• Slit lamp examination
• Refraction test
• Intraocular pressure determination
• Color defectiveness determination
• Retinal photography
• Fluorescein angiography
• Ultrasound of the eye
• Electroretinogram. This is the most critical diagnostic test for RP because 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.

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 the development of cataracts or retinal swelling. Both of these can be treated.
• 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.

Drug

• Vitamin A/ beta-carotene⁵:
  Antioxidants may be useful in treating patients with RP, but no robust evidence currently exists. Thers is some slight evidence against its use.
  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.^{6 7}
• Diltiazem:
  A recent study in Nature Medicine showed decreased degeneration of the retina in mice.⁸ No current recommendations exist regarding the use of diltiazem in patients with RP.
• Lutein:
  Lutein apparently may slow retinal degeneration, but the benefits of this substance in human diseases are uncertain.⁹ Doses of 20 mg/d have been recommended.
• 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) - patients also have fat malabsorption; and high levels of vitamin A may restore retinal function in early stages (vitamin E may also help).³
• 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.³

Surgical

Retinal pigment epithelium transplants and prostheses are in the experimental phase.^{10 11}Cataract surgery is beneficial.

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

Some assessment of the risk of having an affected child may be made by genetic counselling.