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Choroideremia: for patients

Overview

Choroideremia is a rare disease affecting 1 in 50,000 to 100,000 people.[1] It is caused by genetic changes to the CHM gene, resulting in the degeneration of the retina and choroid layers of the eye over time. It begins in early childhood with difficulties in night vision, followed by loss of peripheral vision and then loss of central vision from late middle age onwards. Males are mainly affected due to its X-linked recessive inheritance pattern.

The retina has a pale yellow appearance in choroideremia while it looks has a darker orange look in a healthy retina.
Comparison between a retina affected by choroideremia (A) and a normal retina (B)

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The condition

Symptoms

The earliest symptom patients notice is difficulty seeing at night (night blindness) starting from early childhood. It then progresses to loss of peripheral vision, leading to “tunnel vision”. The remaining central vision is eventually lost from late middle age onwards. Some patients may experience issues with their colour vision and contrast vision despite having good central vision. The symptoms can vary in severity between patients, even within the same family.

A person driving a car with normal peripheral vision is able to see the girl in a red dress on the left. If the driver has a loss of peripheral vision, the same girl is not noticeable.
Peripheral vision loss

Cause

Choroideremia is caused by mutations in the CHM gene. This gene instructs cells to produce a protein called Rab escort protein 1 (REP-1). REP-1 helps to transport proteins within cells. When the CHM gene is not working properly, proteins cannot reach their correct destination. This malfunction leads to high levels of oxidative stress, which causes damage in the retina and subsequently cell death. This is what causes loss of vision in choroideremia.

How is it diagnosed?

Choroideremia is suspected based on the symptoms, family history and clinical evaluation of the retina. The diagnosis is confirmed with genetic testing by identifying mutations in the CHM gene.

How is it inherited?

1) X-linked recessive pattern

If a mother has 1 copy of the faulty gene in her X chromosome (a carrier) while the father is unaffected, there is 50% chance that a daughter is a carrier and a 50% chance that a son is affected by the condition.
X-linked recessive inheritance

Affected father and the mother is healthy:

  • None of the sons will be affected
  • All daughters will be carriers

Female carriers and the father is healthy:

  • Each son has a 50% chance of being affected
  • Each daughter has a 50% chance of being a carrier like the mother

These risks apply to every new pregnancy.

As choroideremia is a hereditary condition, it is advisable to see a genetic counsellor to obtain more information and advice on inheritance and family planning options.

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Treatment

Is there any treatment?

There is currently no available treatment for choroideremia but researchers are exploring various approaches, some of which have entered clinical trials. In the meantime, here is some useful advice to help limit additional damage to the retina:

  • A healthy diet consisting of fresh fruit and green leafy vegetables
  • Wear UV protected sunglasses in bright light
  • Use blue light screen protectors on mobile devices or computer screens*
  • Avoid smoking

*Current available evidence shows that blue light emitted from screens do not damage the retina but it can disrupt our sleep cycle. The screen protectors are used as a precautionary measure.

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Current research in choroideremia

1) Gene therapy

Gene therapy aims to halt retinal degeneration by replacing the mutated gene with a normal healthy copy. This enables the affected cells to regain some of their function and produce functioning proteins.

In choroideremia, a normal copy of the CHM gene is “packaged” into a harmless virus which is then injected into the retina. This way, the affected retinal cells will have maximum exposure to the viruses containing the normal CHM gene.

Over the last few years, several gene therapy clinical trials for choroidermia have been conducted. The most advanced was the phase 3 STAR study run by Biogen 2021, USA (NCT03496012). This was based on promising earlier phase 1/2 data, but the investigational treatment (timrepigene emparvovec) failed to meet the primary and secondary endpoints.

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2) Nonsense suppression therapy

Nonsense suppression therapy is a new drug-based treatment targeting conditions caused by nonsense mutations. A nonsense mutation introduces an abnormal “stop” signal into a gene that halts protein production prematurely, resulting in a protein which is too short and not functional. A drug called ataluren (Translarna™) modifies the affected cell to “ignore” these abnormal “stop” signals and produce normal full-length functioning protein. [2]

About 30% [3] of choroideremia patients have nonsense mutations. Ataluren has shown to reduce oxidative stress, prevent retinal cell death and regain function in animal and human cell models of choroideremia. However, it has not been studied in patients yet. If proven to be beneficial in clinical trials, ataluren could potentially offer a non-surgical alternative to gene therapy for choroideremia patients.

Research of nonsense suppression therapy in choroideremia

3) Other potential therapies

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Practical advice

Living with choroideremia

Patients are still able to lead fairly independent lives through maximising their available vision and having access to social support. Here are some ideas:

  • Attending the low vision clinic which provides access to low vision specialists, Eye Clinic Liaison Officers (ECLOs), visual aids and visual rehabilitation services
  • Utilising assistive technologies can improve quality of life
  • Contacting the local council’s social services department for access to rehabilitation services and assessment of your individual needs to help you remain independent
  • Getting in touch with the local education authority for access to qualified teachers for children with visual impairment (QTVI)
  • Registering as sight impaired (SI) or severely sight impaired (SSI) if eligible for access to social support and financial concessions
  • Getting in touch with national or local charities for advice and peer support

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Referral to a specialist centre

If you are based in the UK and would like to be seen in the nearest specialist centre for your eye condition, either to receive a more comprehensive genetic management or just to find out more about current research, you can approach your GP to make a referral or alternatively arrange for a private appointment. 

More information can be found in our “How to see a genetic eye specialist?” page

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Further information and support

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A patient’s perspective

A choroideremia patient talking about his personal experience of the condition

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References

  1.  Orphanet. Choroideremia. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=180. Published 2011. Updated 27 October 2019.
  2.  Richardson R, Smart M, Tracey-White D, Webster AR, Moosajee M. Mechanism and evidence of nonsense suppression therapy for genetic eye disorders. Exp Eye Res. 2017;155:24-37
  3.  Moosajee M, Ramsden SC, Black GC, Seabra MC, Webster AR. Clinical utility gene card for: choroideremia. Eur J Hum Genet. 2014;22(4)

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Updated on September 29, 2023
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