29th December 2023

Retinitis Pigmentosa

Background 

Retinitis Pigmentosa (RP) encompasses a heterogeneous group of progressive inherited rod-cone dystrophies (i.e. principally affects rod photoreceptor cells) with a variety of inheritance patterns and mutations. Over 40 genes have been associated with RP.

Autosomal dominant forms (20-25%) are the most common and have the best prognosis, and typically involve mutations in the rhodopsin gene. Autosomal recessive cases (15-20%) include mutations in RP1. X-linked cases (10-15%) are the least common and often have the worst prognosis; they are most commonly due to RPGR mutations (70%) and may result in complete blindness by the third or fourth decade of life. A large proportion of RP cases (40-50%) are unsolved and may either be sporadic or related to an as yet undiscovered genetic mutation.

Clinical features

Symptoms of RP include nyctalopia (difficulty seeing at night) and progressive reduction in peripheral visual field. Tunnel vision develops as the condition progresses.

The classic triad includes pigmentary retinopathy, arteriolar attenuation, and optic disc pallor. The characteristic pigmentary changes may appear as hypopigmentation or hyperpigmentation (bony spicule and pigment clumping) and typically occur in the mid-peripheral fundus, where rod cells predominate.

Up to 30% of patients with RP develop cystoid macular oedema. Posterior subcapsular cataracts are also common. RP is also associated with myopia, astigmatism, and optic disc drusen.

Systemic Associations

RP can be classified into isolated or syndromic forms.

The latter occurs in conjunction with systemic disease such as in the case of Usher syndrome (sensorineural deafness), Bardet-Biedl syndrome (truncal obesity, polydactyly, short stature, renal failure), Bassen-Kornzweig syndrome (steatorrhoea, ataxia, progressive external ophthalmoplegia) due to fat-soluble vitamin deficiency, Refsum syndrome (ataxia, ichthyosis, peripheral neuropathy, anosmia) due to accumulation of excessive phytanic acid, and mucopolysaccharidoses. Kearns-Sayre syndrome, a mitochondrial disorder, is sometimes associated with pigmentary retinopathy or atypical retinitis pigmentosa.

Management

Genetic testing:

Genetic testing should be considered to identify the defective gene. This may help confirm or refine the diagnosis, identify appropriate patients for clinical trials and future treatments, provide an estimation of visual prognosis and rate of progression, and help with family planning. Genetic counselling should be offered.

Optimising visual outcome:

The majority of RP cases are treated conservatively.

Carbonic anhydrase inhibitors (topical or systemic) should be considered for patients who develop cystoid macular oedema, as should cataract surgery for symptomatic cataracts. Visual rehabilitation in terms of low vision aids and low vision clinic referral are advised.

Treatment with vitamin A and DHA supplementation have previously been recommended, but there is no conclusive evidence that they are effective in halting disease progression.

Slowing disease progression:

Few treatment options specific to RP are available at present. Advances in gene therapy have been made in recent years, and subretinal injections of Voretigene neparvovec (Luxturna) are now available to treat selected cases of retinitis pigmentosa and Leber’s congenital amaurosis due to the RPE65 mutation.

Patients with rare forms of RP, such as Refsum disease, should have a diet restricted in foods containing phytanic acid, such as milk products and animal fats. Those with Bassen-Kornzweig syndrome should have a low-fat diet and take fat-soluble vitamin supplements (specifically vitamins A, D, E and K).

Source: Wikimedia Commons (2017). Fundus of patient with retinitis pigmentosa, mid stage, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Fundus_of_patient_with_retinitis_pigmentosa,_mid_stage.jpg (Accessed on: 18 June 2022).