Retinitis Pigmentosa

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

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 sight impairment.[1]

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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, including the following: X-linked (5-15%), autosomal dominant (30-40%) and the remainder assumed autosomal recessive (50-60%). [2] The autosomal dominant forms tend to have a milder course with a late, slow progression and preserved vision until the fifth or sixth decade. 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

  • Prevalence in all ages is approximately 1 in 4,000 and, in the age group 45 to 64 years, 1 in 3,195.[2] 
  • There are no geographical or sex predilections. However, because of X-linked varieties, men may be affected slightly more than women.

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 impaired sight 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 severely sight impaired 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% of patients)
  • Keratoconus
  • Vitreous changes (most commonly a posterior vitreous detachment)

Systemic findings

RP is usually confined to the eye but may also be part of a syndrome with non-ocular features.[3] At least 30 different associated syndromes have been identified:[2]

  • 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 deafblindness.
  • 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.

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:

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 the separate article on Examination of the Eye. Imaging includes:[4] 

  • 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.

There is currently no approved therapy able to stop the evolution of RP or restore vision, so the current management aims to slow down the degenerative process, to provide low vision aids and to provide psychological support.[5] 

A number of drugs have been proposed for the management but 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.
  • 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.
  • General counselling by experienced staff is vital. It is worth noting that most children will have enough sight to complete their education in normal schools.
  • 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.
  • Eventually, registration for severe sight impairment or for sight impairment - see the separate article on Blindness and Partial Sight.

Drug

  • Vitamin A/beta-carotene:
    • Antioxidants may be useful in treating patients with RP but no robust evidence currently exists.[5] 
    • Some studies have shown that a diet high in long-chain omega-3 fatty acids can slow the rate of visual acuity loss among patients with RP receiving vitamin A palmitate.[6][7] 
  • 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.
  • Diltiazem: 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.
  • 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 anti-retinal 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).[2]
  • 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.[2]

Surgical

  • Retinal pigment epithelium transplants and prostheses are in the experimental phase.[8][9]
  • Where cataracts have occurred or significant keratoconus has developed, surgery for these conditions will also help.

The disorder will continue to progress, although slowly. Complete loss of vision is uncommon.

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.[10] 

Further reading & references

  1. Shintani K, Shechtman DL, Gurwood AS; Review and update: current treatment trends for patients with retinitis pigmentosa. Optometry. 2009 Jul;80(7):384-401.
  2. Hartong DT, Berson EL, Dryja TP; Retinitis pigmentosa. Lancet. 2006 Nov 18;368(9549):1795-809.
  3. Ferrari S, Di Iorio E, Barbaro V, et al; Retinitis pigmentosa: genes and disease mechanisms. Curr Genomics. 2011 Jun;12(4):238-49. doi: 10.2174/138920211795860107.
  4. Mitamura Y, Mitamura-Aizawa S, Nagasawa T, et al; Diagnostic imaging in patients with retinitis pigmentosa. J Med Invest. 2012;59(1-2):1-11.
  5. Sahni JN, Angi M, Irigoyen C, et al; Therapeutic challenges to retinitis pigmentosa: from neuroprotection to gene therapy. Curr Genomics. 2011 Jun;12(4):276-84. doi: 10.2174/138920211795860062.
  6. Berson EL, Rosner B, Sandberg MA, et al; omega-3 intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2012 Jun;130(6):707-11. doi: 10.1001/archophthalmol.2011.2580.
  7. Hodge WG, Barnes D, Schachter HM, et al; The evidence for efficacy of omega-3 fatty acids in preventing or slowing the progression of retinitis pigmentosa: a systematic review. Can J Ophthalmol. 2006 Aug;41(4):481-90.
  8. Radtke ND, Aramant RB, Seiler MJ, et al; Vision change after sheet transplant of fetal retina with retinal pigment epithelium to a patient with retinitis pigmentosa. Arch Ophthalmol. 2004 Aug;122(8):1159-65.
  9. Brelen ME, De Potter P, Gersdorff M, et al; Intraorbital implantation of a stimulating electrode for an optic nerve visual prosthesis. Case report. J Neurosurg. 2006 Apr;104(4):593-7.
  10. Al-Saikhan FI; The gene therapy revolution in ophthalmology. Saudi J Ophthalmol. 2013 Apr;27(2):107-111. Epub 2013 Feb 11.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Hayley Willacy
Current Version:
Peer Reviewer:
Dr Helen Huins
Last Checked:
23/01/2014
Document ID:
1705 (v26)
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