Retinitis Pigmentosa

What is Retinitis Pigmentosa?

Retinitis pigmentosa (RP) is a disease condition that was first identified and named by Dr. Donders in 1857. Retinitis pigmentosa is a group of related conditions that are inherited, progressive and clinically distinctive and share a similar feature of dystrophy or damage to the photoreceptors of the retina and of the pigment epithelium underneath the photoreceptors.

Normal retina and Retinitis pigmentosa

The normal retina is a layer or membrane that lies at the back of the eyeball. It is a photosensitive layer with millions of photo receptors that are stimulated when light rays fall on them. These photo receptors or rods and cones transmit the information of the light patterns to the brain via nerves that converge to form the optic nerve. This results in normal visual perception.

Pathophysiology and symptoms of Retinitis pigmentosa

In Retinitis pigmentosa there are initial vision problems especially in dim light. This manifests as a loss of vision around the peripheries. This is known as tunnel vision. Central vision is spared until the later stages of the disease.

Retinitis pigmentosa is the leading cause of inherited retinal degeneration-associated blindness. The disease process begins with changes in pigment and damage to the small arteries and blood vessels that supply the retina. There may be atrophy or damage to the optic nerve as well. The damage to the pigment epithelium occurs due to pigmentation that begins and settles within the layers of the neural retina.

As the disease progresses there is a thinning of the retinal blood vessels. Gradually the light-sensitive cells of the retina deteriorate. Both rod and cone photoreceptors are affected and the type of genetic defect determines which cells are more affected. Rod photoreceptor malfunction is the most commonly encountered problem in RP.

Retinitis pigmentosa and genetics

To date, more than 50 different genetic defects have been identified to be linked with Retinitis pigmentosa. Around 30-40% are autosomal dominant, 50 to 60% are autosomal recessive and 5 to 15% are X chromosome linked (passed from mother to son and carried by daughters to their sons). 

The autosomal dominant forms tend to have milder symptoms with onset usually seen at around fifth or sixth decades of life. The X-linked form is the most severe with loss of central vision seen as early as in the third decade of life itself.

Retinitis pigmentosa statistics

Retinitis pigmentosa is the leading cause of inherited retinal degeneration-associated blindness. The prevalence is 1 in 4,000 among all age groups and 1 in 3,195 persons in population aged between 45 and 64. X linked variety affects men more than women and other types have no sex or ethic preferences.

Diagnosis and treatment of Retinitis pigmentosa

Diagnosis is usually made on the basis of examination of the retina using slit lamp biomicrosopy.

There is no cure for Retinitis pigmentosa and no treatment is known to stop the progressive vision loss in the condition. There are a number of research areas including gene therapy and antioxidant therapies that are being explored in the treatment of the condition.

Retinitis Pigmentosa Symptoms

Retinitis pigmentosa is a group of related conditions associated with progressive degeneration of the light sensitive retina that lies at the back of the eye ball. This layer of photo sensitive cells with photoreceptors called rods and cones is normally associated with vision.

The rod photoreceptors normally provide black and white vision whole the cone photo receptors are associated with color vision. Rods are mostly affected but sometimes the genetic disorder affects the cones as well.

With the course of the disease there is degeneration of the retina and its capability to transmit images of meaningful vision reduces leading to complete loss of vision. Cells from the pigmented layer of the retina enter the layer containing nerve cells leading to typical pattern of black or brown star shape pigmentations in the retina that gives the diseases their name.

Symptoms of retinitis pigmentosa include:-

  • Symptoms of vision loss become apparent between the ages of ten and 30. Earlier onset is seen with more severe forms of the condition while those with milder conditions (e.g. those with autosomal dominant forms) may develop the condition in their fifth or sixth decades of life.
  • Loss of vision may be slow or rapid. Again those with a milder disease have a slow progression of the disorder compared to those with a more aggressive form of the disorder.
  • Often the first symptom is night blindness. This is termed nyctalopia. Some people notice that they take progressively longer to adapt to differences of light when they move from a well lit area into a darker area.
  • A typical form of vision loss narrowing of peripheral vision that leads to tunnel vision. This ring pattern of vision loss is called ring scotoma. This may be missed in initial stages but is noticed when the individual trips over objects and misses objects within the range of his or her vision. This defect may be identified after the individual has a road traffic accident at times or tries to take a test for a Driving licence.
  • In a type of retinitis pigmentosa loss of vision begins in the central area. This is called macular dystrophy. Patients notice that they have difficulty with reading and detailed work that requires focussing on a single object.
  • Many patients complain of seeing flashes of light, often described as small shimmering blinking lights.
  • In around 10 to 30 percent of all patients with retinitis pigmentosa there may be associated hearing loss. This is termed Usher syndrome.
  • In one type of Retinitis pigmentosa called Leber's amaurosis children may become blind, or almost so, within the first six months of life.

Retinitis Pigmentosa Diagnosis

Retinitis pigmentosa is commonly identified by the examination of the appearance of the retina using slit lamp biomicroscopy. Common findings on examination and steps in diagnosis include:-

  • The retina shows black or dark brown, star-shaped concentrations of pigmentation. The pigmentation may be limited to part of the retina or involve the whole retina. Abnormalities may appear to be radiating out from the disc. In association there may be abnormalities of the blood vessels as well. Slit-lamp biomicroscopy is the key initial assessment.
  • Imaging studies of the eyes include Retinal photography, ultrasound of the eye, Fluorescein angiography to check the status of the eye blood vessels and Optical computer tomography.
  • The most critical diagnostic test is the electroretinogram (similar to the ECG or electrocardiogram of the heart or EEG or electroencephalogram of the brain). This looks at the electric activities of the nerves within the retina.
  • Other tests include those for visual acuity (refraction tests), Visual field assessment, assessment of Pupillary reflex, assessment of color blindness and intraocular pressure determination.
  • There may be associated problems in the eyes that may be found using appropriate diagnostic tools. These include:
    • Myopia or short sightedness - this is seen frequently and is identified using refraction tests of the eyes.
    • Subcapsular cataract – this may be identified using slit lamp biomicroscopy and examination of the lens.
    • Open angle glaucoma - this is seen in 3% cases of retinitis pigmentosa and is identified by measuring the intraocular pressure using tonometry devices.
    • Changes in the vitreous humor (commonly posterior vitreous detachment) seen on slit lamp biomicroscopy.
  • There may be associated problems seen on other organs as well. These are part of the retinitis pigmentosa syndrome. These are seen in 20 to 30% cases and are identified while diagnosing the condition. At least 30 different associated syndromes have been identified. Some of these include;
    • Usher’s syndrome – Retinitis pigmentosa along with hearing loss. This accounts for about half of all cases of combined deaf-blindness.
    • Loss of hearing along with vision loss of retinitis pigmentosa is also seen in other syndromes such as Waardenburg's syndrome, Alström's syndrome, Alport's syndrome, Refsum's syndrome etc. These have different manifestations as well.
    • Bardet-Biedl syndrome or Laurence-Moon syndrome is associated with retinitis pigmentosa along with features like short height, kidney dysfunction and polydactyly (extra fingers of toes).
    • Hurler's syndrome, Scheie's syndrome, Sanfilippo's syndrome is associated with mucopolysaccharidoses along with retinitis pigmentosa.
    • Kearns-Sayre syndrome is a mitochondrial disorder where retinitis pigmentosa is found along with ptosis (droopy eyelid), opthalmoplegia (vision problems) and heart block.
  • Diagnoses that mimic retinitis pigmentosa need to be ruled out - these include Friedreich's ataxia, trauma to the eye, oxalosis, glaucoma, End-stage Chloroquine or thioridazine or syphilis related neuroretinitis and cancer related retinopathy.
  • Genetic testing for possible mutation that led to the condition is available for 11 possible genetic mutations. Genetic assessment and counselling may be offered to select patients.

Retinitis Pigmentosa Genetics

Retinitis pigmentosa is one of the commonest forms of inherited retina degenerative blindness worldwide. With the advent of molecular technologies it has become easier to identify the genetic defects associated with this condition.

Over a 100 genetic mutations have been found to affect the inheritance of this condition. Inheritance patterns are responsible for the different types of retinitis pigmentosa.

Inheritance patterns in retinitis pigmentosa

Inheritance may be:

  • Autosomal dominant
  • Autosomal recessive
  • X linked

Autosomal dominant has the maximum possibility of a parent-to-child transmission. Autosomal recessive classification is based on established inheritance between different family groups following principles of Mendelian genetics.

X linked inheritance is of further two types – Simplex and Multiplex. Simplex reflects isolated cases with one affected member. Multiplex is when at least two family members are affected.

Type 1 and Type 2 Retinitis pigmentosa

There are two types of retinitis pigmentosa depending on relative involvement of rods and cones photoreceptors. Patients with Type 1 RP display early and preferential loss of rod sensitivity and early signs such as diminished night vision. This condition also progresses lowly and leads to a region specific vision loss.

Patients with Type 2 RP have a progressive and combined loss of rod and cone sensitivity with onset in adulthood and later onset of diminished night vision.

Other organs

Retinitis pigmentosa may of two types - nonsyndromic, or "simple" when other organs are not affected or syndromic where other organs are involved (e.g. Usher syndrome). Nonsyndromic retinitis pigmentosa can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.

Digenic inheritance

There may be a rare digenic inheritance as well. Digenic inheritance is seen in persons with both a ROM1 mutation and an RDS gene mutation. Those with simplex cases result from autosomal dominant or X-linked mutation or autosomal recessive inheritance.

Table 1. Causes of Isolated Retinitis Pigmentosa by Mode of Inheritance

Mode of Inheritance

Proportion of All RP

Autosomal dominant RP (adRP)


Autosomal recessive RP (arRP)


X-linked RP (xlRP)


Unknown: Simplex


Digenic RP

Very rare

Genes and proteins in retinitis pigmentosa

Genes associated with retinitis pigmentosa code for proteins that are involved in the visual cycle where the photo reactive pigments are produced and recycled for effective vision. These genes also code for proteins that form photoreceptor structure and photoreceptor cell transcription factors.

Common mutations

Common mutations include those in the RHO gene. This gene codes for the rods and mutations may lead to autosomal dominant RP, autosomal dominant congenital stationary night blindness, or, rarely, autosomal recessive RP.

Similarly mutations of the RDS are also seen. This gene normally codes for peripherin and mutations lead to autosomal dominant RP, autosomal dominant macular degeneration, or digenic RP.

Some common genetic mutations and their associated retinitis pigmentosa types include:-

  • Autosomal Dominant retinitis pigmentosa - three gene mutations are responsible for autosomal dominant retinitis pigmentosa:-
    • RHO 25 to 30%
    • RP1 5 to 10%
    • RDS 5 to 10%

There are more than 100 RHO mutations and P23H is commonly found in 10% of Americans with autosomal dominant retinitis pigmentosa. RDS mutations may lead to macular degeneration to complex maculopathies. Arg677stop and 2280del5 are the much studied RP1 mutations.

  • Autosomal Recessive retinitis pigmentosa – these are rarer genetic mutations. RPE65 (expressed in the RPE), and PDE6A and PDE6B cause 2-5% of cases and mutations in USH2A may account for up to 5% of autosomal recessive cases.
  • X-Linked retinitis pigmentosa – in this type common mutations are seen in RPGR (also called RP3) and RP2 genes. They account for 70-90% and 10-20%, respectively of all X linked cases.
  • Mitochondrial Genes Causing Nonsyndromic retinitis pigmentosa include mutations in the MT-TS2.
  • Digenic retinitis pigmentosa – this is caused by combined presence of a mutation in the RDS gene and a mutation in the ROM1 gene. The RDS mutation is commonly L185P.