Ocular Melanoma

Where does ocular melanoma occur?  

The eye is made up of three layers. The outer layer is called the sclera, the inner layer is called the retina, and the middle layer is called the uvea. Most ocular melanomas develop in the uvea. This is referred to as uveal melanoma (UM). 

The uvea is in front of the lens and consists of the:  

• Iris – the coloured part of the eye. 
• Ciliary body – a ring of muscle tissue (that cannot be seen) that changes the shape of the lens.
• Choroid – the tissue layer at the back of the eye, underneath the retina, filled with blood vessels. 

*Image courtesy of Melanoma Institute Australia

Ocular melanoma can also develop from the conjunctiva – the clear tissue that covers the white part of the eye.

Conjunctival melanoma is rare and has more in common with melanoma of the skin than uveal melanoma. Unlike UM, conjunctival melanoma can spread locally in the eye or eyelid, as well as to the lymph nodes, lungs and other organs. 

What are the causes and risk factors of ocular melanoma?  

The underlying cause of ocular melanoma is unclear. However, several risk factors have been identified, including:  

• light-coloured eyes  
• fair skin  
• age (the average age at diagnosis is 55 years old)  
• having certain inherited skin conditions, such as dysplastic nevus syndrome  
• having a mole or freckle on the surface of the eye, the iris or the choroid 

Although research has found an association with these factors, OM can occur in any person, regardless of age, race, gender or eye colour. 

What are the signs and symptoms of ocular melanoma?  

Symptoms may include:  

• vision changes, including flashing, seeing floating spots or wavy lines  
• loss of peripheral vision  
• eye pain or redness  
• visible dark or brown patches on the white (sclera) of the eye  
• a dark spot visible on the iris  
• a change in the shape of the pupil 

How is ocular melanoma diagnosed? 

Ocular melanoma can be detected at a routine eye examination with an optometrist, or you may be referred to a specialist eye doctor (ophthalmologist) by your GP if you are experiencing symptoms (such as vision changes) or notice an abnormality on the eye, such as a new spot.  After an OM diagnosis, your doctor may order imaging, which may include an x-ray, MRI, CT scan and/or PET scan to assess the extent of the melanoma in the eye and to check the body for signs of cancer beyond the eye. Unlike cutaneous (skin) melanoma, a biopsy is not usually required to diagnose OM, but can be done.  

Information describing the terminology used in melanoma diagnosis can be found here. 

Tests 

Ophthalmoscopy (fundoscopy)- allows the doctor to look inside the eye to check for abnormalities. Eye drops that dilate the pupil may be used to aid in the examination. A diagnosis of ocular melanoma can sometimes be made through this examination alone.  

Fundus Photography (colour fundus photography)- photographs are taken of the back of the eye to identify a tumour. Taking photographs before and after treatment can help the doctor to determine if treatment has been effective.  

Ultrasound– sound waves to create an image of the inside of the eye. Anaesthetic eye drops are applied to numb the eye, and an ultrasound probe is placed on the surface of the eye. This can be helpful to determine the size, shape and location of a tumour.  

Transillumination -performed before surgery to show exactly where a tumour is. In a darkened room, a doctor will shine a very bright light into the eye to identify the abnormal areas.  

Angiography -looks at blood vessels and blood flow inside the eye. A fluorescent dye is injected into a blood vessel in the arm. As the dye travels through blood vessels in the eye, a special camera takes pictures of the retina and choroid to detect any blockages or leakages.  

Biopsy- a small sample of tissue is extracted from the suspicious area, usually using a fine needle. The tissue sample is then examined in a laboratory.  

Genetic testing  

Genetic testing on a sample of cancerous tissue from the ocular melanoma or site of spread, looks for certain genetic mutations that are thought to assist in the growth of ocular melanoma. Knowing your ‘mutation status’ may help to inform treatment options. The common genetic mutations are:  

• GNAQ and GNA11- is the most common mutations in uveal melanoma, found in around 80% of cases.  
• BAP1 – is found in about half of all uveal melanomas and is associated with a high-risk of cancer spread.  
• BRAF- is not seen in uveal melanoma but occurs in around 30% of conjunctival melanoma. 

How is ocular melanoma staged? 

Staging refers to how limited or advanced the melanoma is at the time of diagnosis. The higher the stage, the further the melanoma has spread in your body. The Stage you are diagnosed with will guide your treating team to develop your treatment plan. 

Broadly, early ocular melanoma means that the cancer has not spread beyond the eye. When ocular melanoma spreads beyond the eye to other parts of the body it is called advanced or metastatic ocular melanoma. Ocular melanoma most often spreads to the liver, but it can also spread to the lymph nodes, lungs, bones and other organs.  

Staging in ocular melanoma can be very complex and depends on many factors, including the type of OM you have. If you’re interested in learning more about staging and how it might apply to your OM, ask your doctor to explain it to you in a way you understand. 

Note: It is important to be aware that every patient is treated individually and not all patients with the same stage of ocular melanoma at diagnosis will be treated the same way. There are other factors (such as the presence of genetic mutations, other health conditions) which will result in some patients with the same stage of melanoma being treated differently.   

How is ocular melanoma treated? 

It is important to see a doctor who specialises in treating patients with your specific type of melanoma. Your GP or optometrist/ophthalmologist can refer you to a center that treats OM. It is important to note that you may need to travel for treatment, depending on where you live (speak with your GP, the treatment center, the cancer council or the MPA telehealth nurse service to discuss possible travel and accommodation assistance).   

Treatment options for ocular melanoma will depend on the size, location and spread of the melanoma. Treatment options may include radiotherapy, surgery, systemic therapy, or a combination.  

Radiotherapy– for most small and medium-sized tumours, radiation is the recommended treatment. Radiotherapy uses X-rays targeted at a tumour to kill the cancer cells. There are two main forms of radiation therapy used to treat ocular melanoma – brachytherapy and external beam radiation therapy.  

• Brachytherapy- is the most common form of radiotherapy used for early ocular melanoma. The process requires an operation during which a plaque containing radioactive seeds is positioned in the eye. The plaque remains in place for up to a week and delivers targeted radiotherapy confined to the site of the tumour. You will most likely stay in hospital as you will be radioactive and therefore you will be isolated in a single room. A second surgery will occur to remove the plaque.   
• External Beam Radiation Therapy (EBRT)– uses a machine that delivers a beam of radiation through the front of the eye to the affected area. It is generally used to treat medium to large sized early ocular melanomas, including those that cannot be treated with brachytherapy due to their location or the obstruction caused by the optic nerve. 

Surgery– is often recommended for tumours of large size and for iris melanomas. Surgery may also be recommended after radiation. Types of surgery include: 

• Iridectomy– Removal of part of the iris  
• Trans-Scleral Local Resection- Removal of the tumour through an opening in the wall, or the white part, of the eye. A radioactive plaque may be placed over the treated area to reduce the risk of tumour recurrence 
• Enucleation– Removal of the eye. Following enucleation, an artificial eye may be placed in the socket 

Systemic Treatment- Systemic treatments are those that target the entire body, circulating through the bloodstream to kill cancer cells. Systemic treatment may be offered if your OM has spread to lymph nodes or organs. Systemic treatment can include:  

• Immunotherapy– activate a person’s immune system so that it will destroy melanoma cells within the body.  
• Targeted therapy– attacks specific gene changes (mutations) within melanoma cells that allow melanoma to grow and spread. 
• Chemotherapy– attacks rapidly dividing cells in the body. Overall, chemotherapy has not been shown to be effective for uveal melanoma. However, it may still be recommended in some cases. 

Tebentafusp is a newly approved intravenous systemic therapy that works by drawing immune cells close enough to the ocular melanoma cells to attack them. Tebentafusp is only suitable for patients who have a molecule involved in immune system regulation, called HLA-A2 0201. Approximately one-third of ocular melanoma patients are positive for HLA-A2 0201. If Tebentafusp is a treatment option for you, your treating team will organise the required tests to determine your HLA-A2 0201 status. It is important to note, currently Tebentafusp is approved for first line therapy for advanced disease if HLA 0201 positive patients, meaning it cannot be used after another immunotherapy has been given. 

Clinical Trials- Clinical trials are medical research studies that aim to find a better way to manage a particular disease. They are used to test new treatments to see if they are better than the currently available treatments. Clinical trials are part of best practice medicine and are one of many options for treatment. Your doctor may suggest taking part in a clinical trial as treatment for ocular melanoma. You can read more about clinical trials at www.australiancancertrials.gov.au. 

Note: It is important to work closely with a team of medical professionals to develop a personalized treatment plan that considers your individual needs and circumstances. 

Treating liver metastasis- Treatments targeting the liver may be used in combination with systemic treatment. Some treatments directly target cancerous tumours growing in the liver. These include:  

• Surgery– may be used to remove a tumour in the liver when there is only a single tumour present in an area that was safe to remove.  
• Ablation– Conducted through the skin or via surgery, ablation involves inserting small probes into a tumour and heating or freezing it to destroy it. Like surgery, it is typically only used when there is one tumour present in the liver.  
• Radiation– uses a beam of radiation to destroy cancer cells. Targeted radiation therapies can be used to treat tumours in the liver, as well as other areas of the body such as the lungs, bone and brain. 
• Embolization– radioactive beads or chemotherapy is injected into the hepatic arteries (the arteries that supply the liver).  

Conjunctival melanoma 

Biopsy and wide local excision (procedure that identifies, removes and examines the closest lymph nodes to the melanoma that may contain melanoma cells) is the current standard treatment approach for conjunctival melanoma. Excision can be followed by one or more types of treatment (adjuvant therapy) to help prevent the melanoma from spreading around the eye or to other areas of the body (metastasizing). Types of adjuvant therapies could include cryotherapy (using freezing or near-freezing temperatures), topical chemotherapy via eye drops or radiation therapy (brachytherapy or external beam radiation therapy).  

Because conjunctival melanoma usually spreads through the lymph system, sentinel lymph node biopsy (removal of lymph nodes that may contain melanoma) may be considered. Risk factors for metastasis include tumour thickness, ulceration and mitotic rate.  

How did I get ocular melanoma?  

Do I need a biopsy? What will that consist of? When will I know the results? 

Is this related to cutaneous (skin) melanoma? Should you check the rest of my skin?  

Has the melanoma spread?  

What are the stages of ocular melanoma? What is my stage of OM?  

If I need more tests, what will they be?  

Should I get a second opinion or explore another treatment centre with more experience with ocular melanoma?  

How will this diagnosis affect my quality of life?  

What is my prognosis?  

Have you tested my melanoma for genetic mutations? 

What are my treatment options?   

Am I eligible for a clinical trial?  

What are the side effects of the treatment you recommend?  

Will my vision be affected? 

Will I be able to continue my normal daily life?   

What type of follow-up will I need? 

What Supports are available? 

Having a rare melanoma can feel isolating. Additionally, treatment can be disfiguring or impact your quality of life in many ways. Here are some options for support available to you: 

Melanoma Patients Australia (MPA)–  

• Melanoma telehealth nurse service. A free and confidential service offering evidence-based information and support. To book a consult, please click on the link Melanoma Nurse Telehealth Service – Melanoma Patients Australia 
• National Support Line (1300 88 44 50). Available Monday to Friday in business hours offering a listening ear & advice and access into MPA services.  
• Closed Facebook support group Melanoma Patients Australia Support Group | Facebook 
• For more information, visit the MPA website www.melanomapatients.org.au 

The Australasian Ocular Melanoma Alliance (AOMA)- offer information, current research and events  www.aoma.org.au 

Rare Cancers Australia- offer support (such as emotional, practical and financial) as well as advocacy for rare cancers. www.rarecancers.org.au 

Melanoma Institute of Australia (MIA)- offer information sheets on early and advanced ocular melanoma  

Early Ocular Melanoma 

Advanced Ocular Melanoma 

OM closed Facebook Support Group- OcuMel Australia and New Zealand–https://www.facebook.com/groups/OcularMelanomaAustralia  

International websites 

EyeMelanoma.org- www.eyemelanoma.org/organizations 

Melanoma Research Foundation-Cure OM- www.melanoma.org/patients-caregivers/cure-om/ 

AIM at Melanoma Foundation- www.aimatmelanoma.org