Retinitis pigmentosa (multiple)

Overview

Retinitis pigmentosa (RP) describes a collection of inherited eye disorders that result in the progressive degeneration of photoreceptor cells within the retina. These specialised cells, known as rods and cones, are responsible for detecting light and converting it into electrical signals for the brain to interpret as vision. Rod cells primarily handle vision in dim light and peripheral vision, while cone cells are crucial for sharp, central vision and colour perception [PMID:36578052].

Over time, in individuals with RP, these photoreceptor cells gradually break down, leading to a decline in visual function. The condition is progressive, meaning symptoms typically worsen over many years. RP is estimated to affect approximately 1 in 4,000 people globally and represents a leading cause of inherited blindness [PMID:29668393]. Due to its genetic basis, RP can run in families, and understanding the specific genetic cause is an important step in managing the condition and informing family planning.

Symptoms & clinical features

The symptoms of retinitis pigmentosa often begin subtly and progress over several decades. The initial symptoms commonly involve reduced vision in low light or darkness, known as night blindness (nyctalopia). This occurs because rod cells, which are primarily affected first in many forms of RP, are essential for dark adaptation. Individuals may find it increasingly difficult to navigate in dimly lit environments or adjust to changes from bright to dark conditions [PMID:36578052].

As the condition progresses, peripheral (side) vision also starts to decline, creating a sensation of 'tunnel vision'. This can make everyday activities challenging, such as walking without bumping into objects or recognising things outside the direct line of sight. Some people may also experience photopsia, which are flashes of light that are not actually present. In later stages, central vision and colour perception can be affected, leading to difficulties with reading, recognising faces, and performing tasks that require fine visual detail.

The rate and severity of vision loss can vary significantly between individuals, even within the same family. Some people may maintain useful vision well into adulthood, while others experience more rapid progression. The age of onset also differs, with symptoms potentially appearing in childhood, adolescence, or early adulthood, depending on the specific genetic cause.

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Affected organs

Retinitis pigmentosa primarily affects the retina, which is the light-sensitive layer of tissue at the back of the eye. Within the retina, the photoreceptor cells (rods and cones) are the main cells that degenerate. Rod cells are typically affected first, leading to night blindness and loss of peripheral vision. Cone cells, which are concentrated in the macula (the central part of the retina responsible for sharp vision), tend to be affected later, leading to a decline in central vision and colour perception.

While the primary impact is on the retina, some forms of RP can be part of broader syndromes affecting other organs, although isolated RP (non-syndromic) is more common. For example, Usher syndrome, a syndromic form of RP, also involves hearing loss.

Multiple body systems

Systemic involvement

Cellular impact

Mechanism at cellular level

Risks & severity

The severity of retinitis pigmentosa can vary widely. Some individuals experience a slow, gradual decline in vision over many decades, allowing for adaptation, while others may have more rapid progression. The lifetime risk of significant visual impairment, including legal blindness, is high for individuals with RP. However, the exact age at which this occurs is unpredictable and depends on the specific genetic mutation and other modifying factors.

Age of onset is also variable. Symptoms can begin in early childhood, adolescence, or adulthood, with typical onset often occurring in teenage years or young adulthood. The prognosis for vision varies; some people retain reading vision well into older age, while others may lose most of their sight earlier in life. Factors such as the specific gene involved, the type of mutation, and even lifestyle choices may influence the rate of progression, though research is ongoing in this area.

Genetic causes

Retinitis pigmentosa is a genetically heterogeneous condition, meaning it can be caused by pathogenic changes in a large number of different genes. These genes play crucial roles in the development, function, and maintenance of photoreceptor cells within the retina. When these genes do not function correctly, it disrupts the intricate processes required for vision, leading to the degeneration of rods and cones.

Some of the genes commonly associated with RP include RHO, RPGR, and USH2A. The RHO gene provides instructions for making rhodopsin, a protein found in rod photoreceptor cells that is essential for vision in dim light [PMID:29668393]. Pathogenic variants in RHO often lead to autosomal dominant forms of RP. The RPGR gene is involved in the transport of proteins within photoreceptor cells, particularly in the cilium, a critical structure for photoreceptor function. Mutations in RPGR typically cause X-linked RP, which predominantly affects males.

USH2A encodes usherin, a protein important for the structure and function of hair cells in the inner ear and photoreceptor cells in the retina. Pathogenic variants in USH2A are a common cause of autosomal recessive RP, and can also lead to Usher syndrome type 2, which combines RP with hearing loss [PMID:32060155]. Identifying the specific genetic cause of RP is important for prognosis and may become relevant for future gene-specific treatments.

• RHO
  rhodopsin
• RPGR
  retinitis pigmentosa GTPase regulator
• USH2A
  usherin

Inheritance pattern

Retinitis pigmentosa can be inherited in several ways, reflecting the diverse genetic causes. The most common patterns of inheritance are autosomal dominant (AD), autosomal recessive (AR), and X-linked. Understanding the inheritance pattern is crucial for assessing the risk to other family members and for genetic counselling.

In autosomal dominant RP, a person inherits one altered copy of a gene from one parent, which is sufficient to cause the condition. Each child of an affected parent has a 50% chance of inheriting the altered gene and developing RP. In autosomal recessive RP, a person must inherit two altered copies of the same gene, one from each parent, to develop the condition. Parents who each carry one altered copy of the gene are typically unaffected but are carriers. Each child of two carrier parents has a 25% chance of inheriting both altered copies and developing RP, a 50% chance of being an unaffected carrier, and a 25% chance of inheriting neither altered copy.

X-linked RP is caused by altered genes on the X chromosome. Because males have only one X chromosome, if they inherit an altered gene on it, they will typically develop the condition. Females have two X chromosomes, so if they inherit one altered X chromosome, they are usually carriers and may have milder symptoms or no symptoms at all. Sons of a carrier mother have a 50% chance of inheriting the altered gene and developing RP. Daughters of a carrier mother have a 50% chance of being carriers themselves. Affected fathers pass the X-linked gene to all their daughters, making them carriers, but none of their sons.

Diagnosis & testing

Diagnosing retinitis pigmentosa typically involves a comprehensive eye examination by an ophthalmologist, often with specialist expertise in retinal conditions. The diagnostic process usually includes several tests to assess retinal function and structure. These may include a visual field test to map peripheral vision, an electroretinogram (ERG) to measure the electrical activity of retinal cells in response to light, and optical coherence tomography (OCT) to provide detailed cross-sectional images of the retina.

Confirmation of retinitis pigmentosa and identification of the specific genetic cause is often achieved through genetic testing. Referral to a clinical genetics service is usually made by the ophthalmologist. Genetic testing can involve analysing a panel of genes known to be associated with RP. In the UK, such testing is available through the NHS Genomic Medicine Service (GMS). Relevant R-codes for genetic testing for inherited retinal disorders, such as R86 and R87, may be used to guide testing strategies within the GMS, helping to identify the specific gene and mutation responsible [PMID:32060155]. Genetic counselling is an integral part of this process, providing information about the condition, inheritance patterns, and implications for family members.

Management & lifestyle

Currently, there is no cure for retinitis pigmentosa, but management focuses on slowing progression, treating associated complications, and supporting individuals to maximise their remaining vision. Regular monitoring by an ophthalmologist is essential to track changes in vision and retinal health. This may involve ongoing visual field tests, OCT scans, and ERG assessments.

Supportive therapies can include visual aids, such as magnifiers and telescopic lenses, to assist with reading and other close-up tasks. Occupational therapy can help individuals adapt to vision loss by suggesting modifications to their home or work environment. In some cases, nutritional supplements, such as high doses of Vitamin A, may be considered, though this should only be done under medical supervision due to potential side effects and varying efficacy across different genetic forms of RP. More recently, some specific genetic forms of RP have become eligible for gene therapy, such as voretigene neparvovec for RPE65-mediated retinal dystrophy [PMID:36578052].

Access to care for individuals with RP in the UK typically involves referral through their GP to an ophthalmology department, and subsequently to a clinical genetics service for diagnostic clarification and genetic counselling. Support organisations also play a vital role in providing information, peer support, and advocacy for those affected by RP.

UK care pathway

In the UK, individuals suspected of having an inherited retinal disorder like retinitis pigmentosa would typically be referred by their GP or optometrist to an ophthalmologist. Following an initial diagnosis based on clinical findings and retinal imaging, patients would then often be referred to a regional NHS Genomic Medicine Centre for genetic testing. This is facilitated by the NHS Genomic Medicine Service (GMS), which offers a national testing service for rare diseases.

Genetic tests for inherited retinal disorders fall under specific R-codes, such as R86 (for syndromic retinal dystrophy) and R87 (for non-syndromic retinal dystrophy), enabling comprehensive gene panel testing. Following genetic diagnosis, patients will receive genetic counselling to understand the inheritance pattern, implications for family members, and available support. This integrated pathway ensures access to specialist care, advanced diagnostics, and ongoing support.

Related conditions

Several conditions share clinical features or genetic causes with retinitis pigmentosa. Usher syndrome is a well-known example, characterised by progressive vision loss due to RP combined with hearing impairment. Different types of Usher syndrome are caused by mutations in various genes, including USH2A, which can also cause isolated RP.

Other conditions that can present with similar visual symptoms include Leber congenital amaurosis (LCA), which typically causes severe vision loss at birth or in early childhood, and cone-rod dystrophy, where cone cells are affected earlier and more severely than rods, leading to central vision loss and colour vision abnormalities first. Differentiating between these conditions often requires careful clinical assessment and targeted genetic testing.

• Retinitis pigmentosa (dominant, RHO)
  Ophthalmology
  Shares 1 gene
• X-linked retinitis pigmentosa
  Ophthalmology
  Shares 1 gene

Frequently asked questions