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Choroidal melanoma – Written by Dr. Lily Rolfe, BSc, MD and Dr. Roderick O’Day, LLB (Hons), BSc, MBBS (Hons), FRANZCO.

What is choroidal melanoma?

Choroidal melanoma is a rare type of cancer that develops within the eye.

Melanomas may occur at many sites of the body, including the uveal tract of the eye (Figure 1). The uveal tract of the eye includes the iris, ciliary body, and choroid (Figure 2).

The choroid is the most common site for a melanoma in the eye [1]. The choroid is a layer of the eye which contains blood vessels that supply nutrients to the light-sensitive layer of the eye called the retina.

Choroidal melanomas are different to other types of melanomas in both their risk factors and treatment.

This overview will cover the global problem of choroidal melanoma, its risk factors, its common signs and symptoms, how it is diagnosed, and some insights into its management and treatment.

The global problem of choroidal melanoma

While the uveal tract is the second most common site for a melanoma to develop (after the skin), uveal melanomas are rare in general. For example, it is estimated there are only 1500-2000 new cases of uveal melanoma diagnosed in the United States (US) each year [2-4]. Uveal melanomas are more common in Caucasian populations and become more common with age [1, 5, 6].  Males are slightly more likely to be affected by uveal melanoma [1].

Risk factors for choroidal melanoma

The following predisposing factors have been identified which increase the risk of developing uveal melanoma [7, 8]:

• Fair skin colour [1, 5]
• Light eye colour (blue or grey coloured eyes) [8]
• Tendency to get sunburn [9]
• Atypical moles (dysplastic naevi) – unusual-looking moles with irregular microscopic features[10, 11]
• Common skin moles (naevi) and freckles [10]
• Moles in the eye [10, 12]
• Family member with skin melanoma [13-15]
• Family members with uveal melanoma [13-15]
• Oculodermal melanocytosis – a condition present from birth which causes abnormal pigmentation across different areas of the body including the eyes and the skin around the eyes [16, 17]
• Genetic syndromes and mutations
  • FAM-M Syndrome [18]
  • BAP1 Cancer Predisposition Syndrome [19-21]
  • Germline BRCA1/BRCA2 mutations [22-25]

Exposure to sunlight is not a risk factor for uveal melanoma as in the case of skin melanoma [26, 27].

What are the common signs and symptoms of choroidal melanoma?

Choroidal melanomas may or may not be symptomatic depending on their location, size, and activity. In approximately 30% of cases, they are asymptomatic and detected incidentally during an eye examination. When symptoms are present, they may include:

• Blurred vision
• Flashes of light (photopsia)
• Floaters
• Visual field loss
• Pain
• Distorted vision (metamorphopsia) [28]

If you experience any of these signs and symptoms, schedule an appointment with an eye health professional to get your eyes checked. It is also important to note that the development of eye conditions may even start before symptoms appear, which makes going for regular and timely eye checks that much more essential.

How does choroidal melanoma progress?

As choroidal melanomas grow larger, they can cause other problems within the eye. For example, as the tumour grows, it may lift the overlying retina and cause a retinal detachment, which may lead to vision loss.

Other complications include bleeding (haemorrhage) and spreading outside of the eye to other parts of the body (metastasis). The most common site for choroidal melanoma to metastasise is the liver, followed by the lungs [29, 30].

Categories of choroidal melanoma

Choroidal melanomas are commonly classified by their size, which subsequently determines the treatment as the likelihood of metastasis increases with size. Small choroidal melanomas are considered to be less than 3mm in height and/or 10mm in diameter. Medium choroidal melanomas are between 3-8mm in height, and/or less than 16mm in diameter. Large choroidal melanomas are over 8mm in height or 15mm in diameter. As tumour height increases, so too does the mortality rate [31].

How is choroidal melanoma diagnosed?

Choroidal melanomas are diagnosed based on their appearance during a comprehensive eye examination using imaging tools. Choroidal melanomas are distinguished from other lesions in the eye by evaluating its clinical features. The features that confer a higher likelihood of the lesion being a melanoma (as well as an increased risk of growth and metastasis) include:

• Tumour thickness greater than 2mm and diameter greater than 5mm
• Subretinal fluid (i.e. fluid underneath the retina, leaking from the tumour)
• If the lesion is causing reduced vision
• Orange pigment over the surface of the lesion (Figure 3)
• Hollowness on ultrasound imaging [31-33]

While some cancers are diagnosed by taking a tissue sample (biopsy), this is not routinely performed for choroidal melanomas. However, where there is diagnostic uncertainty, a fine-needle aspirate (FNA) biopsy may sometimes be performed. FNA biopsy may be helpful to diagnose suspicious lesions without typical melanoma features, to determine the origin of a cancer (e.g. from the eye itself, or spread from elsewhere in the body) or when visibility is obscured (e.g. by haemorrhage in the eye) and the lesion is unable to be assessed [34, 35].

If you experience any of these signs and symptoms, schedule an appointment with an eye health professional to get your eyes checked. It is also important to note that the development of eye conditions may even start before symptoms appear, which makes going for regular and timely eye checks that much more essential.

Treatment options for choroidal melanoma

The treatment options for choroidal melanoma include laser therapies, radiation, or surgical removal of the eye. The treatment of choice depends on the tumour size, pigment, location, and the presence of any complications.

Radiation therapy

Radiotherapy delivered by a radioactive plaque (brachytherapy) is the most common treatment modality for small and medium-sized melanomas (Figure 4). The radioactive plaque delivers a high radiation dose to the tumour, while minimising collateral damage to the nearby healthy tissue. The plaque is sewn onto the surface of the eye in the operating theatre and left in place for several days before being removed. The dose of radiation and length of time it is left in place depends on the size and location of the tumour, as well as the strength of the radiation.

Other radiation options include external beam radiotherapy, which can be photons or protons. Proton beam radiotherapy, allow for precise high-dose radiation delivery and offer a useful alternative to brachytherapy for tumours close to the optic nerve, but is only available in a few, specialised centres around the world. Photon based external beam radiotherapy, such as Gamma knife, similarly delivers high-precision radiation, and is useful for patients with large melanomas who are seeking to avoid removal of the eye (enucleation) and is more commonly available.

All radiation modalities achieve excellent tumour control and offer long-term survival rates similar to removing the eye [36-42]. Radiotherapy can cause both short-term and long-term complications. Inflammation and irritation of the surface of the eye is commonly seen shortly after radiation treatment, however this usually resolves quickly. While radiation therapy allows a patient to keep their eye and potentially some vision, many patients experience complications which may lead to vision loss and require further surgeries or procedures.

Delayed complications can present in the months to years following initial treatment. Radiation may lead to vision loss through several mechanisms, including cataract, damage to the blood vessels in the eye (radiation retinopathy), optic nerve damage (optic neuropathy), or by stimulating the formation of immature, leaky blood vessels (neovascularisation) throughout the eye which can lead to glaucoma. Less commonly, radiation therapies may lead to retinal detachment and melting of the outer layer of the eye (scleral melt) [43-45].

Surgery

Before brachytherapy, enucleation was the mainstay of treatment for all choroidal melanomas. Today, enucleation is primarily for tumours too large for brachytherapy, for tumours that recur following brachytherapy, for eyes that have become blind or painful following complications, or if the patient chooses it [46]. A spherical implant is inserted into the eye socket under the remaining tissues of the eye. A prosthesis is typically made in the weeks to months after surgery to create the appearance of a normal eye.

Another surgical option involves cutting the tumour out of the eye, either accessed externally through an opening created in the outer layer of the eye (exoresection) or via passing a cutter inside the eye (endoresection). This procedure is only performed at some ocular oncology centres, and sometimes only after radiotherapy. Endo- and exoresection are associated with complications such as retinal detachment, bleeding and tumour recurrence [47-50].

In severe cases where the tumour has spread outside of the eye into the eye socket, surgery to removal of the entire contents of the eye socket (exenteration) may be required.

Laser therapy

Laser therapies offer a non-invasive out-of-hospital treatment option for small choroidal melanomas, including photodynamic therapy or transpupillary thermotherapy. Photodynamic therapy involves administering a light-sensitive dye and laser to induce tumour cell destruction, and is most effective in small, non-pigmented (amelanotic) tumours [51-56]. Transpupillary thermotherapy utilises a heating laser which aims to destroy the tumour’s vascular supply, and is most useful for small, pigmented choroidal melanomas [57, 58].

Both photodynamic therapy and transpupillary thermotherapy have been associated with visually significant complications [59-65]. However, the relatively high recurrence rate precludes the use of laser therapies as a standalone treatment – but they may be used in conjunction with radiotherapy to consolidate treatment [52, 55, 56, 66].

Ongoing management of choroidal melanoma

After initial treatment has been undertaken, regular follow-up is required for many years afterwards. The follow-up appointments involve screening for local recurrence of the tumour (in and around the eye) as well as metastatic spread (most commonly to the liver) and managing any complications of treatment.

Local recurrence is assessed by examination of the eye and ultrasound imaging of the eye. Metastatic spread is evaluated by blood tests to evaluate liver function as well as liver imaging. Liver imaging may involve ultrasound, computerised tomography (CT) scans or magnetic resonance imaging (MRI). If metastatic spread has occurred, patients may undergo systemic chemotherapy or surgery to remove liver tumours.

Treatment of metastatic choroidal melanoma is very difficult and the prognosis is, generally, poor. This is an area of active research into therapies that may potentially improve a patient’s survival, with a number of drugs being assessed currently. Involvement of medical oncologists who specialise in this area is preferable if it is available.

Can choroidal melanoma be prevented?

Currently, there is no effective way to prevent a choroidal melanoma from developing. Regular eye examinations are of great importance to identify tumours in their earlier, asymptomatic, and smaller stages, which carry a lower risk of metastasis and require less invasive treatment.

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