Ocular melanoma

Dr Daleen Geldenhuys unpacks what ocular melanoma is.

Melanoma is a malignancy most commonly associated with moles on the skin, but it can occur in other areas, such as the eye (ocular). It can occur in the skin around the eye, the conjunctiva (white part surrounding the colourful part of the eye) and the uveal tract (iris, ciliary body, and choroid (pigmented area in the eyeball).

Approximately 85% of ocular melanomas arise from the uveal tract and the remainder arise in the conjunctiva or (rarely) the orbit. There are significant clinical and genomic differences between melanomas of the uvea, conjunctiva, skin, and other sites.

Approximately 95% of uveal melanomas arise from the ciliary body and/or choroid, and approximately 5% arise in the iris and will be visible to the patient. Most aren’t visible and will present with visual disturbances such as flashes, floaters, or visual field defects. Many will be discovered on a routine eye examination by an optometrist.

Uveal melanoma

The diagnosis is based upon funduscopic examination by an experienced clinician. Special investigations will be performed initially, such as ultrasound, optical coherence tomography (similar to ultrasound but uses light), and fluorescein angiography (an eye test that uses a special dye and camera to look at blood flow in the retina and choroid).

The most common lesion in the differential diagnosis is a uveal nevus, and the two can’t always be distinguished with certainty on clinical examination due to an overlap in size between small melanomas and large nevi. The differential diagnosis also includes metastasis to the uvea, especially from lung and breast cancers, which can be the first manifestation of an occult primary tumour, but this is also a very rare phenomenon.

Treatment

Local treatment for primary uveal melanoma is effective in preventing local recurrence in over 95% of cases, yet up to 50% of patients are at risk for metastatic disease. The high risk of metastatic disease is thought to be due to a propensity for early micro metastasis followed by a variable latency period prior to the emergence of overt metastatic disease.

Advances in understanding the molecular pathogenesis of uveal melanoma are providing important information regarding prognosis. Additional studies are required such as gene expression profiling and chromosomal markers. These results define groups at high risk for the development of metastases.

The management is guided by many factors. The size and where in the eye it is located, presence of extension of the tumour into the surrounding tissues, visual potential, patient age and preference, and presence or absence of metastases.

For asymptomatic patients with small uveal melanocytic tumours, observation is an option. The size should be <12mm in diameter and <2 to 3mm in height and initial management is often observation for evidence of growth.

When observation is chosen, initial follow-up at two- to four-month intervals is typical. 

Radiation

Radiation therapy (RT) is the most common treatment. Since uveal melanomas are radioresistant, they must be treated with high-dose radiation, usually in the form of plaque brachytherapy or charged-particle RT.

Plaque brachytherapy is the most common form of RT used to treat uveal melanoma worldwide. Local tumour recurrence following primary RT is a risk factor for metastasis.

Charged-particle radiotherapy is the second most common form of RT used to treat uveal melanoma. Charged-particle RT can result in collateral damage to ocular structures (lashes, lacrimal gland, cornea, iris, lens, retina, and optic nerve). 

In most circumstances, plaque brachytherapy and charged-particle RT render very similar local control rates. Associated ocular radiation complications are slightly different, with greater anterior eye complications with charged-particle RT and with greater visual acuity loss and immediate procedural discomfort with plaque brachytherapy. 

Linear-accelerator-adapted stereotactic RT has also been used to treat uveal melanomas. The total dose is typically between 50 and 70Gy, delivered in five daily fractions.

All types of radiotherapy for uveal melanoma can be associated with ocular complications, including dry eye, cataracts, neovascular glaucoma, vitreous haemorrhage, exudative retinal detachment, uveitis, scleral necrosis, radiation retinopathy, and optic neuropathy

Other treatments

Other non-invasive techniques include transpupillary thermotherapy, photodynamic therapy, and laser photocoagulation.

External or internal resection of a uveal melanoma without removing the entire eye is technically challenging and may often result in serious and immediate post-operative complications, such as vitreous haemorrhage and retinal detachment. Additionally, local tumour recurrence in the eye and/or orbit is more common with these techniques than with more conventional forms of treatment.

Modern RT techniques offer a reasonable, if not superior, alternative, therefore enthusiasm for local resection has waned. Surgeons continuing to use external or internal resection of a uveal melanoma will now often use adjuvant plaque brachytherapy or charged-particle RT to reduce the risk of recurrence.

Systemic surveillance imaging for metastasis typically focuses on the liver, the most common site of metastatic disease. While we prefer surveillance with MRI of the liver, other options include abdominal ultrasound for low-risk patients or CT.

Uveal melanomas are managed with great success by ophthalmologists at centres of excellence in South Africa. Symptoms mentioned should be treated with the same urgency by the patient as any other tumour.

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