Choroideremia

Tommy was diagnosed with choroideremia in 2005. The Tommy Salisbury Choroideremia Fund was founded in 2005 by his mother Emma Salisbury and her mother Dot Grindley. Find out more about the fund.

Find out how the choroideremia research we fund will have a huge impact for people like Tommy who are living with the condition.

What is choroideremia?

Choroideremia – sometimes known as choroidal sclerosis, progressive tapetochoroidal dystrophy and TCD - is a rare genetic eye condition that almost always affects males. Symptoms usually start in childhood, with progressive sight loss due to a gradual loss of cells in and around the retina, the specialised light-sensitive layer that lines the back of the eye. This happens as a result of damage to the choroid – the network of blood vessels that supplies the retina with the vital nutrients and oxygen it needs to remain healthy. 

Choroideremia is estimated to affect between 1 in every 50,000 to 100,000 people in the UK. However, the condition is likely to be underdiagnosed as symptoms are similar to several other eye conditions, such as retinitis pigmentosa.

What causes choroideremia?

Scientists have discovered that choroideremia is caused by faults in a single gene known as CHM. This gene provides instructions for making a protein called REP1, which plays an essential role in cells in the retina. Faults in the CHM gene lead to either an absence of REP1 or a version that can’t carry out its normal function. In turn, this leads to the eye tissue damage that’s associated with the condition. 

While males are much more likely to develop choroideremia, females can carry the faulty CHM gene. However, they are often asymptomatic carriers, and when females do get choroideremia symptoms, they are often a lot milder than in males. It is very rare for females to develop severe choroideremia. 

Can choroideremia be inherited?

Yes, the CHM gene can be inherited and passed down through families – and how this happens also explains why the condition is more common in males. 

The CHM gene is located on the X chromosome and choroideremia is passed on in an X-linked recessive pattern. Females have two X chromosomes, while males have one X and one Y chromosome. In affected females, generally only one of the X chromosomes will carry a copy of the faulty CHM gene and the other X chromosome is able to compensate for this. In males, there is no second X chromosome, so having just one copy of the faulty gene is enough to result in symptoms. 

This explains why females carrying the faulty CHM gene can pass it on to their children without experiencing any choroideremia symptoms themselves. For each pregnancy, there is a 50% chance female carriers will pass the faulty gene on to their children. 

Males with the faulty CHM gene can pass it on to their female children, who will become carriers. However, it is not possible for them to pass the gene on to their male children, as males always inherit the Y chromosome from their father. 

When a diagnosis of choroideremia is confirmed, families are usually offered genetic counselling. The role of a genetic counsellor is to provide support and help people understand the genetic factors and likelihood of passing on the condition. Genetic testing for other family members can also be arranged. 

What are the signs and symptoms of choroideremia?

Choroideremia symptoms usually start in childhood in young males, typically at around age five or six, becoming progressively worse over time. The rate at which this happens can vary from person to person – even between affected members of the same family. However, choroideremia eventually leads to severe sight loss and blindness in adulthood, although females, if affected, are much more likely to develop only mild symptoms later in life. 

• Difficulty seeing in the dark, or night blindness, is often one of the earliest symptoms. Children may say they struggle to see things in dark rooms or can’t see stars in the sky.
• ‘Tunnel vision’ due to loss of peripheral vision as the condition progresses. This often starts as an irregular ring that gradually expands both inwards and outwards. 
• Other vision changes such as loss of sharpness, depth and colour perception. 
• Severe sight loss and blindness usually develops in adulthood, typically around 20 to 30 years after symptoms began. 

Females who carry the faulty CHM gene will often not experience any sight loss at all, as having two X chromosomes means they are less likely to develop choroideremia symptoms than males (this is explained more fully in the section above). When they are affected, females will usually only notice more mild symptoms of choroideremia, such as night blindness and sensitivity to glare, starting later in adulthood.

How is choroideremia diagnosed? 

An ophthalmologist (hospital eye doctor) is required to confirm a diagnosis of choroideremia. As well as performing tests to examine a person’s visual field, they’ll be able to take a close look at their retina to look for signs of distinctive changes associated with the condition. Genetic testing to identify faults in the CHM gene can help to confirm the clinical diagnosis, along with a family history that is consistent with an X-linked inheritance pattern. 

An optician might pick up on possible signs during a routine eye test – and going for an eye test is often the first thing people do if they start noticing changes to their vision. However, seeing a hospital ophthalmologist usually requires a referral via your GP. An optician might suggest this, if they notice any cause for concern and think further investigations are required. People who already have a known family history of choroideremia and are concerned about their own sight or their child’s, can also talk to their GP about being referred to a specialist. 

How is choroideremia treated?

Unfortunately, there is currently no cure for choroideremia – but recent advancements in gene therapy research, initially funded by Fight for Sight, are fuelling the development of potential new treatments, providing hope for the future. 

Gene therapy targets the genes involved in certain conditions, either by replacing faulty genes or adding new ones, in order to cure the condition or help the body fight its effects. 

A large international trial led by Nightstar Therapeutics (now Biogen Inc), a gene therapy spin-out company established by the University of Oxford and Syncona, is underway – which if successful could result in a gene therapy treatment becoming available for people living with choroideremia. 

This follows earlier research at Imperial College London funded by Fight for Sight – including £500,000 raised by The Tommy Salisbury Choroideremia Fund - which led to the world’s first gene therapy trial for choroideremia at the University of Oxford. 

The trial involved injecting cells with a harmless virus used to carry a normal copy of the faulty gene associated with choroideremia. Importantly, the gene therapy was found to be safe – and encouragingly it showed benefits in slowing down or stopping choroideremia sight loss. In some people, it even restored some of the sight they’d already lost. 

Another area of interest is Ataluren, a relatively new drug treatment for cystic fibrosis and Duchenne muscular dystrophy. With the help of Fight for Sight funding, research published in 2016 showed that in some cases, the drug could override the genetic fault that causes choroideremia. 

Depending on the type of CHM gene fault in question, the study found Ataluren was able to get REP1 – the protein that’s essential for keeping cells in the retina healthy and which is either absent or unable to work properly in people with choroideremia – to work again. Although further research is needed, these early findings provide another avenue of hope for choroideremia treatments in the future. 

In the meantime, wearing protective sunglasses outdoors may help to protect vision by reducing exposure to ultraviolet (UV) light, which can theoretically cause further retinal damage. 

Living with choroideremia

Choroideremia is a progressive condition that gets worse over many years. When symptoms first become noticeable, they are usually mild to begin with – children may have more difficulty than others with seeing in the dark or in very dimly-lit spaces. As loss of sharpness, depth and colour perception can also occur, being able to see objects that are a similar colour to the background may become increasingly tricky for them.

Over time, choroideremia sight loss gets gradually worse. Tunnel vision is one of the main ways this happens, which can have a greater impact on people’s lives as it means their peripheral field of vision is gradually lost. Eventually, choroideremia leads to blindness, although this can take a number of decades to happen. 

Tools are available to help people living with choroideremia to maximise their remaining vision, including low vision aids such as telescopic and magnifying lenses. Assistive technologies, such as speech to text software, can also help people in their daily lives. 

Choosing which support to access can be an individual decision. Genetic testing and counselling is often recommended, which can be helpful for people diagnosed with choroideremia as well as their families. 

Further stories on living with choroideremia:

• https://gene.vision/knowledge-base/choroideremia-for-patients/#A%20patient's%20perspective
• https://mft.nhs.uk/royal-eye/waynes-story/ 

What research is underway for choroideremia?

Fight for Sight funded the initial research which led the world’s first gene therapy trial for choroideremia, where a harmless virus is used to carry the correct genetic information into the cell, restoring its function. Importantly, this early clinical trial showed that this gene therapy is safe – and encouragingly, it showed benefits in slowing down or stopping sight loss in patients. In some people, it even restored some of their sight. The Tommy Salisbury Choroideremia Fund raised £500,000, which helped Fight for Sight to fund the early stage research at Imperial College London that led to this breakthrough at the University of Oxford.

Due to its promising results, this has since led onto a much larger international trial involving over 100 patients across nine countries in the EU and in North America. The larger study is now led by Nightstar Therapeutics, a gene therapy spin-out company established by the University of Oxford and Syncona. If successful, the follow-on trial could result in a gene therapy treatment available for patients with choroideremia.

Due to its exciting potential, similar gene therapies are also currently in development for several other eye diseases, including macular degeneration, Stargardt disease and retinitis pigmentosa.

What can I do if I have choroideremia?

Support is available for people living with choroideremia to help maximise their remaining vision. For instance, low vision aids such as telescopic and magnifying lenses may be helpful. And there is a wide range of assistive technologies that may help people in their daily lives, such as speech to text software. 

Genetic testing along with counselling is also recommended for people with choroideremia and their family members. 

Have your eyes tested every two years even if you think your vision is fine. An eye test can spot some eye conditions and, if caught early, treatment may prevent further deterioration. 

We would be delighted to speak with, provide you more information, and help you start your fundraising journey with us. Through setting up a Family Fund you can direct all the funds you raise to the condition most pertinent to you. For more information on setting up a family fund or dedicated group, please contact events@fightforsight.org.uk

Last updated January 2023
Approved by Professor Robert Maclaren, Oxford University.