Retinitis Pigmentosa: An Overview

  • Post author:Imran Karim Janmohamed
  • DOIDOI:10.48089/jfo7688089

Imran Karim Janmohamed1

1Foundation Year 2 Doctor, Kings College Hospital NHS Trust


Retinitis Pigmentosa (RP) is a genetic disease that encompasses a spectrum of hereditary conditions caused by shared physiological processes that lead to retinal degeneration (1).

Pathophysiology & Aetiology

In RP, genes that encode proteins responsible for photoreceptor and retinal pigment epithelium function get mutated. More than 100 genetic mutations have been implicated in RP, causing a loss of rod and cone photoreceptors in the retina through apoptosis (1). Initially, rod photoreceptors are predominantly affected, followed later by degeneration of cones (rod-cone dystrophy) (2).

The mode of inheritance is often associated with factors such as rate of disease progression and the age of onset. Generally, autosomal dominant causes carry the best prognosis, whilst the X-linked recessive form is the rarest but most severe (2).

Clinical Features

Visual symptoms usually start in childhood and the most common presenting complaint in RP is night blindness and progressive loss of peripheral vision, which leads to tunnel vision (3). A patient might, for example, describe difficulty driving at night, adapting to a dark room, and bumping into furniture. Eventually, central vision is affected, and the majority of patients lose most of their sight (1).

On examination of the retina, the classic triad of findings include bone-spicule pigmentation, arteriolar attention and a ‘waxy’ disc pallor (4).

There are a number of rare syndromes associated with RP, that are characterised by visual and systemic symptoms. The most common among these are Usher’s syndrome and Bardet-Biedl syndrome (5).

Usher’s syndrome (6)Hearing and vision are affected
Features include a defective inner ear and balance problems; children, for example may be slow to walk
Bardet-Biedl syndrome (7)Growth and intellectual impairment, the severity of which may vary
Features include polydactyly, dilated cardiomyopathy and renal failure


All patients should undergo visual field testing and a full-field electroretinogram (ERG) (2).

Visual field testing may reveal mid-peripheral visual field defects, which is pathognomonic of RP. They can start as islands and eventually coalesce to form a complete ring scotoma, which can enlarge and worsen a patient’s tunnel vision (1,2).

Full-field ERG measures retinal electrical activity in response to light stimulation. It involves placing electrodes in contact with the cornea or a skin electrode below the lower eyelid margin. In RP, findings will be abnormal (1,2).

Further tests might include Optical Coherence Tomography (OCT), which is a non-invasive investigation that constructs a 3-D picture of the retina. It should be considered when central vision is affected, for example as a result of cystoid macular oedema (1,2).

Genetic testing may be performed to identify the particular mutation responsible and may help with genetic counselling and identifying the risk of transmission to children (2).


Unfortunately, there is no cure for RP. However, patients may find benefit from visual aids, such as glasses, magnifiers and telescopes.

A number of therapeutic strategies have been proposed, for example vitamin A supplementation. High doses have been shown to reduce the rate at which retinal function declines through ERG responses, but it is still not broadly recommended8. Some studies have shown that high doses may actually worsen other conditions, for example cone-rod dystrophy, which has been observed in studies in mice (9). Although it is safe in some variants of RP, vitamin A can also cause elevation of liver enzymes and triglycerides and increase the risk of osteoporosis (10).

Supplementation with fish oils (docosahexaenoic acid [DHA]) and lutein (a carotenoid) have also been suggested, although the evidence has been inconclusive (11-13).

Gene replacement therapies have been investigated. Treatment for one form of RP, Leber’s Congenital Amaurosis (LCA), which occurs due to mutations in the RPE65 gene, have successfully shown improvement in vision from the gene therapy Voretigene neparvovec, which is a recombinant virus vector that carries the normal RPE65 gene (14).


RP is a genetic condition caused by mutations in photoreceptor and retinal pigment epithelium genes. Characteristic features can be seen broadly, but rare syndromic forms that affect other body organs also exist. Unfortunately, most patients experience significant visual loss later in life and curative therapies are not available. A number of supplements have been proposed to help slow the progression of RP with conflicting evidence, such as vitamin A and DHA. Gene replacement therapy has demonstrated visual improvement in LCA and is an active area of research.


1.        Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368(9549):1795-1809. doi:10.1016/S0140-6736(06)69740-7

2.        Bowling B. Kanski Clinical Ophthalmology, A Systematic Approach.; 2016.

3.        Pruett RC. Retinitis pigmentosa: Clinical observations and correlations. Trans Am Ophthalmol Soc. 1983.

4.        Li ZY, Possin DE, Milam AH. Histopathology of bone spicule pigmentation in retinitis pigmentosa. Ophthalmology. 1995;102(5):805-816. doi:10.1016/S0161-6420(95)30953-0

5.        Koenig R. Bardet-Biedl syndrome and Usher syndrome. Dev Ophthalmol. 2003;37:126-140. doi:10.1159/000072043

6.        Boughman JA, Vernon M, Shaver KA. Usher syndrome: Definition and estimate of prevalence from two high-risk populations. J Chronic Dis. 1983. doi:10.1016/0021-9681(83)90147-9

7.        Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA. New criteria for improved diagnosis of Bardet-Biedl syndrome: Results of a population survey. J Med Genet. 1999. doi:10.1136/jmg.36.6.437

8.        Berson EL, Rosner B, Sandberg MA, et al. A randomized trial of vitamin A and vitamin E supplementation for retinitis pigmentosa. Arch Ophthalmol (Chicago, Ill  1960). 1993;111(6):761-772. doi:10.1001/ARCHOPHT.1993.01090060049022

9.        Radu RA, Hu J, Peng J, Bok D, Mata NL, Travis GH. Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells. J Biol Chem. 2008;283(28):19730-19738. doi:10.1074/JBC.M801288200

10.      Sibulesky L, Hayes KC, Pronczuk A, Weigel-DiFranco C, Rosner B, Berson EL. Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis pigmentosa. Am J Clin Nutr. 1999. doi:10.1093/ajcn/69.4.656

11.      Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol (Chicago, Ill  1960). 2004;122(9):1297-1305. doi:10.1001/ARCHOPHT.122.9.1297

12.      Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol (Chicago, Ill  1960). 2010;128(4):403-411. doi:10.1001/ARCHOPHTHALMOL.2010.32

13.      Massof RW, Fishman GA. How strong is the evidence that nutritional supplements slow the progression of retinitis pigmentosa? Arch Ophthalmol (Chicago, Ill  1960). 2010;128(4):493-495. doi:10.1001/ARCHOPHTHALMOL.2010.46

14.      Maguire AM, Simonelli F, Pierce EA, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358(21):2240-2248. doi:10.1056/NEJMOA0802315

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