What is Ocular Melanoma?
Melanoma is considered a form of skin cancer because it develops in the melanocytes—the cells in our skin that produce pigment—and because most cases of melanoma occur on the skin. But melanocytes exist in other places in our body, including in our eyes, so melanoma can occur in our eyes, too. Melanoma of the eye is generally called ocular melanoma.
Ocular melanoma is a rare disease—diagnosed in about 2,500 people each year in the U.S.—but it is the most common primary cancer of the eye in adults.
Ocular melanoma most often affects the middle layer of your eye (the uvea), which includes the colored portion (the iris), the muscle fibers around the lens (ciliary body), and the layer of blood vessels that lines the back of the eye (choroid).
Melanoma can also develop in the conjunctiva, the clear tissue that covers the white part of the eye and the inside of the eyelids. Melanoma that develops in the choroid, iris or ciliary body is called uveal melanoma, and melanoma that develops in the conjunctiva is called conjunctival melanoma. Although both develop in the eye, these two diseases are biologically and clinically different from one another, and both are very different from the more common form of melanoma occurring on the skin.
Some cases are diagnosed during a routine eye exam without the patient having any symptoms while other patients develop symptoms that prompt them to get an eye exam. The most common treatments for uveal melanoma are radioactive plaques, proton beam therapy, or removal of the eye. As with conjunctival melanoma, uveal melanoma can recur even with aggressive treatment of the primary uveal melanoma. The risk of the melanoma returning can be estimated by the size of the melanoma as well as other clinical and pathological factors; by looking at changes in the chromosomes of the tumor (i.e., cytogenetic testing); and by looking at an altered pattern of genes that are expressed (i.e., gene expression profiling).
About 50% of people with uveal melanoma will develop metastases. When uveal melanoma does recur, it often does so in the liver. Advanced uveal melanoma is a challenging cancer to treat, and a broad range of treatments has been used, including chemotherapy, immunotherapy, molecularly targeted agents, and a number of liver-directed treatments such as bland embolization, chemoembolization, immunoembolization, radioembolization, and infusion of chemotherapy into the liver. The prognosis for metastatic Uveal Melanoma patients is very poor, with the median overall survival after diagnosis being just one year.
The good news for uveal patients is that in January 2022, the U.S. Food and Drug Administration (FDA) approved Kimmtrak (tebentafusp-tebn) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic Uveal Melanoma. Kimmtrak is the first and only FDA-approved therapy for the treatment of unresectable or metastatic Uveal Melanoma (mUM). FDA approval was based on the results of a phase 3 clinical trial in which Kimmtrak showed statistically and clinically meaningful overall survival benefit for mUM patients. A total of 378 previously untreated patients were randomly assigned to either the Kimmtrak (tebentafusp) group (252 patients) or the control group (126 patients). The control group received single-agent treatment with pembrolizumab (82% of control patients), ipilimumab (13%), or dacarbazine (6%). Overall survival (OS) at one year was 73% in the tebentafusp group and 59% in the control group.
Conjunctival melanoma is more rare than uveal melanoma. It has no clear cause, and it usually appears as a pigmented spot on the outer surface of the eye. Individuals diagnosed with conjunctival melanoma commonly have a resection of the melanoma by an ophthalmologic oncologist and may receive further treatments to the eye such as cryotherapy, topical chemotherapy, or radiation. Despite aggressive treatment, primary conjunctival melanoma may recur. Unlike uveal melanoma, which more often spreads to the liver, conjunctival melanoma often metastasizes to the lung when it spreads. There is no standard recommendation for the treatment of patients with advanced conjunctival melanoma primarily because of the rarity of the disease. Generally, these patients are treated similarly to patients with advanced cutaneous melanoma, using immunotherapy, and targeted therapy, if applicable.
Despite the significant advances made in our understanding of conjunctival and uveal melanoma, these diseases are still challenging to treat. To develop more successful treatments, we must support combined efforts between patients dealing with these diseases, the doctors caring for them, and the laboratory and clinical researchers working to develop new treatments for conjunctival and uveal melanoma. It is through this kind of cooperation that we can increase education and awareness of these rare diseases and ultimately identify new, more effective, and potentially curative treatments.
Ocular Melanoma Risk Factors
- Light-colored eyes (blue or green)
- Older age
- Light-colored skin
- Certain genetic conditions, such as BAP1 tumor predisposition syndrome
- Certain inherited skin conditions that cause abnormal moles, such as dysplastic nevus syndrome
- Abnormal skin pigmentation involving the eyelids or increased pigmentation on the uvea
- A mole in the eye or on the eye’s surface*
- A lump on the eye or eyelid
- Exposure to natural sunlight or artificial sunlight (such as from tanning beds) over long periods of time (more specific to conjunctival)
- Exposure to welding
If you have none of the risk factors listed above, the American Academy of Ophthalmology recommends that you get a baseline eye disease screening at age 40. If you have any of these risk factors, make an appointment with an ophthalmologist for a comprehensive eye exam.
*Note that benign choroidal nevi are very common, and only a minority may become cancerous.
Ocular Melanoma Symptoms
In its early stages, ocular melanoma may not cause any symptoms, but when symptoms do occur, they can include:
- A dark spot on the iris or conjunctiva
- Blurred or distorted vision
- The sensation of flashing or specks in your vision
- A change in the shape of the pupil
- Loss of peripheral vision
See an ophthalmologist immediately if you have any of the symptoms listed above.
The video below about ocular melanoma discusses early results of tebentafusp. Look here for a new video with the latest information on tebentafusp soon.