Uveal melanoma

What is uveal melanoma?

Sometimes called ocular melanoma or intraocular melanoma, uveal melanoma is a type of eye cancer that develops from the cells that give eyes their colour (called ‘melanocytes’). 

Uveal melanoma refers to melanoma that develops in a part of the eye known as the ‘uvea’. The eye is made up of three different layers of tissue and filled with a clear jelly-like substance (the vitreous); the uvea is the middle layer of the eyeball that includes the coloured part (the iris) as well as the ciliary body and choroid (learn more about the anatomy of the eye).

While uveal melanoma is the most common eye cancer in adults, it is still very rare, affecting approximately 5-6 people per million each year in the UK.

While uveal melanoma can affect anyone, certain factors may increase someone’s risk. It is more common in people with fair or pale skin with an increased tendency to sunburn and those with light-coloured (blue and grey) eyes. Although this type of cancer can occur at any age, it is most commonly diagnosed in people 50–70 years of age.

What causes uveal melanoma?

The exact causes of uveal melanoma are not fully understood, but it develops when these cells (melanocytes) develop certain errors – or ‘spelling mistakes’ - in its DNA.

DNA acts as the cell’s instruction manual, telling it how to behave. When this instruction manual accumulates errors, it can start multiplying without the usual biological ‘control checks’, forming a tumour.

As this tumour grows larger, it can damage surrounding healthy tissue. Over time, cancer cells may break away from the main tumour by invading into blood vessels in the eye, but then spread to other parts of the body – a process known as ‘metastasis’.

Who is most at risk of uveal melanoma? 

While it’s not clear why uveal melanoma develops, several factors may increase the risk of it happening. These include:

• Fair or pale skin – uveal melanoma mostly affects white people and is more common in those with fair skin that burns or freckles easily.
• Light eye colour – people with blue, green (‘hazel’) or grey eyes have a higher risk than those with brown eyes.
• Age – the likelihood of developing uveal melanoma increases with age, with most cases diagnosed in people in their 50-70s.
• Sex – it is slightly more common in men than women.
• Ultraviolet (UV) light – although a link is not firmly established, some evidence suggests that exposure to UV radiation (for example, from sunlight or sunbeds) may increase the risk for iris melanomas.
• Certain inherited skin conditions – such as dysplastic nevus syndrome (which causes numerous unusual moles) or ocular melanocytosis (which involves unusual pigmentation on the eyelids, surrounding tissues, and uvea) may increase the risk.
• Genetics – certain genetic errors that are passed from parents to children have been linked to uveal melanoma, including changes in the BAP1, PALB-2 and MBD4 genes. The BAP1 syndrome is the most common of these inherited syndromes associated with uveal melanoma, and can result in the patients developing other cancers, e.g., in the kidney and pleura (called mesotheliomas).

However, most people who develop uveal melanoma have no known risk factors.

Can uveal melanoma be prevented?

Unfortunately, because the exact causes of uveal melanoma remain unclear, it’s difficult to know how to prevent it. Most of these cancers are thought to occur sporadically, and everyone has some level of risk.

As a precaution, some doctors recommend protecting the eyes from UV exposure by wearing UV-blocking sunglasses and a wide-brimmed hat when outdoors in strong sunlight. While the link between UV radiation and uveal melanoma is not firmly established, these measures may help reduce potential risk and promote overall eye health.

What are the signs and symptoms of uveal melanoma?

In its early stages, uveal melanoma may not cause any noticeable signs or symptoms. It is sometimes diagnosed unintentionally  during a routine eye test. However, as the tumour grows, some people may begin to experience symptoms, including:

• Blurred or distorted vision – this will usually only affect one eye.
• Visual disturbances – such as flashes of light or shadows.
• A loss of side (peripheral) vision – difficulty seeing objects to the side.
• A new dark spot on the iris – a visible change in the coloured part of the eye.
• A change in the pupil – a change in shape or size of the dark circle in the centre of the eye.
• Pain or redness in the eye – discomfort or irritation in the affected eye.
• A bulging of one eye – the eyeball may shift position within its socket. This is generally when the tumour is quite large and possibly spread through the sclera (outer white layer of the eye) into the eye socket.

It’s important to be aware that these symptoms can also be caused by other eye conditions. If you notice any changes affecting your vision or eyes, it’s best to consult with your GP or optician.

How is uveal melanoma diagnosed?

Because uveal melanoma may not cause any symptoms in its early stages, it can be detected during a routine eye test. During this examination, an optician will carefully assess the structures of the eyes to check for any abnormalities. If they notice anything unusual, they may refer you to a specialist hospital eye doctor (ophthalmologist) for further evaluation, usually at one of the four ocular oncology centres in England (Liverpool, London and Sheffield) and Scotland (Glasgow). 

If uveal melanoma is suspected, you may be referred for additional tests to confirm a diagnosis. These may include:

• Ultrasound scan – this test uses high-energy sound waves (ultrasound) to create images of the inside of the eye. After numbing the eye with drops, the doctor will gently place a small probe on the closed eyelid or the front surface of the eye. The sound waves are then converted into an image on a computer screen. The procedure is usually painless and takes a few minutes.
• Fluorescein angiogram – this procedure examines the blood vessels and blood flow inside the eye. A doctor will inject a coloured dye into a vein in the arm, which will travel to the blood vessels in the eye. A special camera captures images of the inside of the eye to identify any areas that are blocked or leaking.

• Optical coherence tomography (OCT) scan – this is specialised imaging test that uses light waves to take detailed pictures of the layers of tissue at the back of the eye.
• Fine needle diagnostic biopsy – while not usually needed to diagnose uveal melanoma, a biopsy may be performed in some cases to help differentiate the abnormality from other causes of a ‘mass’ in the uvea. These include non-cancerous masses in the uvea (e.g., inflammation) or spreading of other cancers to the eye (e.g. breast or lung cancer). The procedure involves using a thin needle to remove a tiny sample of cells from the affected area of the eye. The procedure may be done under local or general anaesthetic, and the sample is then sent to a laboratory. A pathologist will examine it under a microscope to check for cancer cells.

If uveal melanoma is confirmed, doctors may recommend further tests to find out more about the size and position of the tumour and check whether the disease has spread to other parts of the body. 

• Genetic prognostication biopsy – as above, a biopsy is usually not needed for diagnosis of uveal melanoma; however, it can be performed to determine the risk of the cancer spreading to the liver. Uveal melanoma is unusual compared to other cancers in that it has very well defined genetic changes that are associated with this spreading (known as ‘metastasis’). If these are present in the tumour cells, then the risk of spreading is higher and can be pulled together with other features of the tumour, to create an individualised ‘metastatic’ risk score. This then determines the liver scanning frequency. In ‘high metastatic risk’ uveal melanoma patients, increased scanning can lead to earlier detection of the cancer spreading. This can allow earlier surgical removal.

Is uveal melanoma serious?

Uveal melanoma is a serious condition that requires prompt medical attention. If left undiagnosed or untreated, it can spread beyond the eye to other parts of the body, most often the liver, but also the lungs, brain, kidney and bones.

Up to one in two people with uveal melanoma will develop metastatic disease, which can be life-threatening.

Early detection and prompt treatment are crucial. In general, people with smaller tumours that remain confined to the eye have a better outlook than those with larger tumours or whose cancer has spread to other organs.

What are the treatments for uveal melanoma?

Several treatment options are available for people with primary uveal melanoma, including radiation therapy, surgery and photodynamic therapy. The main goal of treatment is to eliminate the cancer cells while preserving as much vision as possible.

The most suitable treatment depends on the size and location of the tumour, whether the disease has spread to other parts of the body, as well as the person’s overall health and personal preferences.

The main treatment options for primary uveal melanoma (i.e., tumour in the eye) include:

• Brachytherapy – this is a type of radiotherapy that uses radiation to destroy the cancer cells. A small disc, called a ‘plaque’, containing radioactive material is surgically placed on the outside wall of the eye near the tumour. It is secured with temporary stitches and remains in place for up to a week before removal.
• External radiotherapy – a machine directs high-energy X-ray beams at the tumour. This type of radiation therapy is usually given over several days.
• Proton beam radiotherapy – a highly precise type of external radiotherapy that directs tiny particles, called protons, at the tumour. The goal is to destroy the cancer cells while minimising damage to surrounding healthy tissue.
• Surgery – this may be recommended for small tumours that have not spread. The goal is to remove the tumour and some of the healthy tissue around it. In some cases, such as where the tumour is too large for radiotherapy, or is causing severe symptoms such as blindness or pain, it may be necessary to remove the whole eye (this is called ‘enucleation’). After surgery, a person can be fitted with an artificial eye that matches the size and colour of the other eye.
• Photodynamic therapy (PDT) – used for small pale-coloured tumours, PDT combines a light-sensitive drug (delivered through a vein in the arm) with a laser directed at the tumour. When activated by the light from the laser, the drug kills the cancer cells. The procedure is painless and only takes a few minutes.

After treatment for uveal melanoma, regular follow-up appointments at the hospital are essential to check for any signs that the cancer has returned or spread. These visits may include eye examinations, blood tests and/or scans. 

Treatments for metastatic uveal melanoma (eye cancer that has spread to other parts of the body) vary between centres and countries. They include:

• Liver surgery – removal of secondary tumours, if this is possible.
• Regional (liver-based) chemotherapy and radiotherapy – (see more information on regional chemotherapy).
• Systemic chemotherapy – this includes ‘conventional’ chemotherapy, combined chemotherapy and immunotherapy, immunotherapy alone and more recently, immune-mobilising therapy. The latter is a new therapeutic approach that harnesses the body’s immune system to recognise the uveal melanoma cells as ‘foreign’. It has been very promising in clinical trials in a certain subset of uveal melanoma patients.

What research is there into uveal melanoma?

Research into uveal melanoma aims to better understand how these tumours develop, grow and spread. Scientists are working to identify genetic markers that can predict the risk of metastasis and to develop new targeted treatments that can destroy cancer cells while minimising damage to healthy tissues. The goal is to improve treatment options for this type of cancer, helping more people to survive the disease while preserving as much of their vision as possible.

At Fight for Sight, we fund cutting-edge research to advance our understanding of uveal melanoma. Some of our current and past projects include:

• Dr Jason Parsons at the University of Birmingham is working to optimise proton beam therapy for uveal melanoma. He is investigating whether certain drugs can help boost the effectiveness of this type of radiotherapy at killing cancer cell, allowing for lower doses and reducing damage to surrounding healthy tissue, ultimately helping preserve vision.
• Professor Judy Coulson of the University of Liverpool led a laboratory study to identify vulnerabilities in uveal melanoma cells, particularly those with a faulty BAP1 gene, which could be targeted with new treatments. Her research uncovered a potential new strategy for identifying patients who may benefit from a specific type of treatment. 

See our research projects