Understanding Ocular Melanoma

Where ocular melanoma develops, the known risk factors, and how it is diagnosed and treated.

Ocular melanoma is a rare cancer that develops in the pigment-producing cells of the eye. Most cases start in the uvea, the middle layer of the eye. The uvea has 3 parts: the choroid, a layer of blood vessels beneath the retina where most uveal melanomas begin; the ciliary body, which helps the eye focus; and the iris, the colored part of the eye. Melanoma can also arise on the conjunctiva, the thin clear membrane over the white of the eye, though this is much less common.

The underlying cause is unknown. Several factors are linked to a higher risk:

• Light-colored eyes and fair skin
• Older age
• Certain moles in or on the eye, or a condition called oculodermal melanocytosis (nevus of Ota)
• Many atypical moles on the skin (dysplastic nevus syndrome)
• A family history of ocular melanoma, or an inherited change in the BAP1 gene

Genetic Factors

Most uveal melanomas carry a mutation in one of 2 genes, GNAQ or GNA11. Changes in other genes, including BAP1, SF3B1, and EIF1AX, help doctors estimate the chance that the tumor will spread. BRAF and NRAS mutations are common in melanoma of the skin and do occur in conjunctival melanoma, but they are rare in uveal melanoma. These tests are run on tumor tissue.

Diagnosis

An eye doctor can often find ocular melanoma during a dilated eye exam, before it causes symptoms. Tests that help confirm it include:

• Ultrasound of the eye
• Photographs and scans of the back of the eye, such as optical coherence tomography and angiography
• MRI or CT in selected cases

Unlike most cancers, uveal melanoma is usually diagnosed from the eye exam and imaging alone, without a biopsy. Some centers take a fine-needle sample to test the tumor's genes and estimate the risk of spread.

Treatment

Treatment depends on the size and location of the tumor. Radiation is the most common choice. In plaque brachytherapy, a surgeon attaches a small radioactive disc to the wall of the eye over the tumor for several days. Proton beam therapy aims charged particles at the tumor from outside the eye. Both can control the tumor while saving the eye in many patients.

Large tumors may need surgery, including removal of the eye. Laser treatment has a role in selected small tumors.

When uveal melanoma spreads, it goes to the liver most often, so follow-up includes regular liver imaging or blood tests. For adults with metastatic uveal melanoma who carry the HLA-A*02:01 tissue type, the FDA approved tebentafusp in 2022. Other options include treatments directed at the liver, immunotherapy, and clinical trials.