Ocular melanoma is a rare cancer that develops from pigment-producing cells inside or on the surface of the eye. It affects roughly 5 to 8 people per million each year in the United States and Northern Europe, making it the most common primary eye cancer in adults despite its overall rarity. Most cases begin in the uvea, the middle layer of the eye sandwiched between the white outer wall (sclera) and the inner lining (retina), which is why the disease is often called uveal melanoma.
Where It Starts in the Eye
The uvea contains three structures: the choroid (a blood vessel-rich layer lining the back of the eye), the ciliary body (a ring of tissue behind the iris that focuses the lens), and the iris (the colored part of the eye). Melanoma can arise in any of these, but the choroid is the most common site by a wide margin. Tumors starting in the ciliary body or iris are less frequent and sometimes behave differently, with iris melanomas tending to grow more slowly.
In rare cases, melanoma forms on the conjunctiva, the thin clear membrane covering the white of the eye and the inside of the eyelids. Conjunctival melanoma accounts for fewer than 1 case per million people annually and is more closely linked to sun and UV exposure than the uveal form.
Symptoms and Early Warning Signs
Many ocular melanomas produce no symptoms at all in their early stages and are discovered during routine eye exams. When symptoms do appear, they tend to affect only one eye and can include:
- Floaters or flashes of light: specks, threads, or brief flashes drifting across your vision
- A growing dark spot on the iris: a new or expanding area of pigmentation on the colored part of the eye
- Blurry or worsening vision in one eye
- A change in pupil shape: one pupil may look different from the other
- Loss of side vision: difficulty seeing things at the edges of your visual field
None of these symptoms are unique to melanoma, and most turn out to have benign explanations. But a new, persistent change in one eye, especially a visible dark spot that’s growing, is worth having examined promptly.
Risk Factors and Genetics
Ocular melanoma is far more common in people with lighter skin and eye color. Incidence among white Americans is about 7 per million per year, compared to roughly 1 per million in Asian Americans and 0.6 per million in African Americans. Countries around the Baltic and North Seas, including Denmark, Ireland, and Norway, report the highest rates in the world, exceeding 9 to 11 cases per million.
Unlike skin melanoma, UV exposure plays a limited role in most ocular melanomas. The exception is conjunctival melanoma, where prolonged sun or tanning bed exposure does appear to increase risk. For uveal melanoma, the strongest known genetic risk factor is an inherited mutation in a gene called BAP1. People carrying this mutation face elevated odds of uveal melanoma along with certain kidney cancers, skin tumors, and a cancer of the tissue lining the chest and abdomen. The mutation is rare, but when present, uveal melanoma is the most common cancer it causes.
How It Is Diagnosed
Diagnosis typically starts with a thorough eye exam. Your eye doctor may use a bright headlamp with magnifying lenses (indirect ophthalmoscopy) or a microscope with an intense focused beam (slit-lamp biomicroscopy) to look inside the eye. Enlarged blood vessels on the surface of the eye can sometimes be an early clue.
If something suspicious is found, several imaging tests help confirm the diagnosis. Ultrasound, performed by placing a small probe on the closed eyelid or the front of the eye, measures the tumor’s size and shape. Fundus photography captures detailed color images of the back of the eye and can be repeated over time to track growth. Optical coherence tomography uses light waves to create cross-sectional images of the retina and uvea, revealing subtle structural changes. In angiography, a dye injected into an arm vein travels to the eye’s blood vessels, and a specialized camera photographs how blood flows through and around the tumor.
Unlike many other cancers, a biopsy is not usually needed to make the diagnosis. Imaging alone is often sufficient. When a biopsy is performed, it is typically done during treatment rather than as a separate procedure, and it can provide genetic information about the tumor that helps predict how the cancer will behave.
Treatment for Tumors in the Eye
Treatment depends on the tumor’s size, location, and whether it has spread beyond the eye. For small to medium tumors, the goal is usually to destroy the cancer while preserving the eye and as much vision as possible.
Radiation therapy is the most common approach. In plaque brachytherapy, a small radioactive disc (about the size of a bottle cap) is custom-shaped to match the tumor and surgically stitched onto the outside of the eye directly over the cancer. The disc delivers a concentrated dose of radiation to the tumor over several days, then is removed in a second brief procedure. Because the radiation is so focused, damage to surrounding tissue is minimized, though some vision loss in the treated area is common over time.
External beam radiation, such as proton beam therapy, is another option. Instead of a surgically placed disc, a precisely aimed beam of charged particles targets the tumor from outside the body. This method is particularly useful for tumors in locations that are difficult to reach with a plaque.
Eye removal (enucleation) was once the standard treatment for nearly all ocular melanomas, but it is now reserved for specific situations: large tumors too big for radiation, cancers invading the optic nerve, tumors causing uncontrollable eye pressure, or cases where radiation has failed. After enucleation, a prosthetic eye is fitted and typically looks very natural.
Why Spread to the Liver Is So Common
The most serious concern with uveal melanoma is its tendency to spread, and the liver is the destination in about 90% of metastatic cases. This happens because of the eye’s unusual anatomy. The choroid is packed with blood vessels and lacks the protective barrier that other tissues use to keep abnormal cells contained. Cancer cells can slip directly into the bloodstream without needing to break through a structural wall first, which partly explains why circulating tumor cells are found at high rates in patients with uveal melanoma.
Once in the bloodstream, these cells show a strong preference for settling in the liver. The tumor appears to send molecular signals ahead of itself, conditioning liver tissue to become a hospitable environment for cancer growth. About 25 to 31% of patients develop distant metastases within five years of diagnosis, and that number climbs to roughly 50% over 25 years. This is why long-term monitoring, typically with regular liver imaging, continues for years even after successful treatment of the primary tumor.
Survival Rates and Prognosis
When ocular melanoma is caught before it has spread beyond the eye, the five-year relative survival rate is 88%, based on data from patients diagnosed between 2015 and 2021. That number drops sharply to 19% once the cancer has reached distant organs like the liver. The gap between these two numbers underscores why early detection and ongoing surveillance matter so much.
Several factors influence an individual’s prognosis: tumor size, its genetic profile (certain chromosome changes predict more aggressive behavior), and the cell type seen under a microscope. Genetic testing of tumor tissue, often done at the time of treatment, can help classify tumors into lower-risk and higher-risk categories, guiding how closely a patient needs to be monitored afterward.
Treatment for Metastatic Disease
Metastatic uveal melanoma has historically been very difficult to treat, responding poorly to the immunotherapy drugs that work well against skin melanoma. That changed in 2022 with the approval of a first-of-its-kind treatment for patients whose cancer has spread or cannot be surgically removed. This drug works by acting as a bridge: one end locks onto a specific protein found on uveal melanoma cells, while the other end grabs nearby immune cells and activates them to attack. The result is direct killing of tumor cells by the patient’s own immune system.
There is an important limitation. The treatment only works in patients who carry a specific immune marker called HLA-A*02:01, which is found in roughly 40 to 50% of people of European descent and less frequently in other populations. A blood test confirms eligibility before treatment begins. For patients who qualify, this drug represents the first therapy shown to improve overall survival in metastatic uveal melanoma.