Uveal melanoma is a cancer that forms in the pigmented layer of the eye called the uvea. It is the most common eye cancer in adults, though it remains rare overall, with roughly 5 cases diagnosed per million people each year in the United States. The uvea has three parts, and tumors can develop in any of them: about 90% arise in the choroid (the blood-rich layer behind the retina), 6% in the ciliary body (the ring of tissue that controls the lens), and 4% in the iris (the colored part of the eye you see in the mirror).
Symptoms and Early Warning Signs
Many uveal melanomas are found during a routine eye exam before they cause any noticeable symptoms. When symptoms do appear, blurred vision is the most common. You might also notice flashing lights (photopsia), floating spots in your vision, or a dark patch that blocks part of your visual field. Some people experience eye pain, redness, or a sensation of pressure.
Iris melanomas can produce a more visible clue: one eye gradually changes color, becoming darker than the other. This uneven coloring, called heterochromia, sometimes develops alongside increased eye pressure. Because these symptoms overlap with many less serious eye conditions, the cancer itself is easy to dismiss early on.
How It Differs From Skin Melanoma
Despite sharing the name “melanoma,” uveal melanoma is genetically distinct from the melanoma that develops on skin. Skin melanomas are typically driven by mutations in genes called BRAF and NRAS. Those mutations are rare in uveal melanoma. Instead, about 84% of uveal melanomas carry a mutation in one of two signaling genes, GNAQ or GNA11. These mutations are thought to act as the initial trigger that causes pigment cells inside the eye to grow uncontrollably.
This genetic difference matters for treatment. Therapies designed for skin melanoma often don’t work against uveal melanoma, which is why research into eye-specific approaches has been so important.
How It Is Diagnosed
Doctors can usually diagnose uveal melanoma without a biopsy, relying instead on imaging. The primary tool is ultrasound of the eye. On ultrasound, choroidal tumors typically appear dome-shaped (about 75% of cases) or mushroom-shaped (about 20%), the mushroom form occurring when the tumor breaks through a thin membrane behind the retina called Bruch’s membrane. The ultrasound also reveals the tumor’s internal structure and blood supply.
Other imaging may include optical coherence tomography (a detailed scan of retinal layers), fundus photography (a high-resolution image of the back of the eye), fluorescein angiography (which highlights blood vessel patterns using a dye), and MRI when more detail about the tumor’s extent is needed. Together, these tools let the care team measure the tumor precisely and plan treatment.
Staging and Prognosis Testing
Uveal melanoma is staged using the AJCC system, which assigns a T category (T1 through T4) based on the tumor’s thickness and basal diameter. Larger tumors carry a higher risk of spread, but size alone doesn’t tell the whole story.
A gene expression profile test can be performed on a small biopsy sample to classify the tumor into one of three risk categories. Class 1A tumors carry the lowest risk of spreading. Class 1B tumors have a moderate long-term risk. Class 2 tumors carry a high risk of metastasis within three to five years. This classification gives patients and their doctors a much clearer picture of what to expect than tumor size alone.
At the genetic level, one of the strongest predictors of poor outcome is a mutation in a tumor suppressor gene called BAP1, combined with the loss of one copy of chromosome 3. In one study, every tumor carrying a BAP1 mutation also showed this chromosomal loss. Researchers believe these molecular changes are established early in the primary tumor, effectively setting the pattern for whether and where the cancer will eventually spread.
Treatment Options
Treatment depends mainly on the tumor’s size and location. For small tumors (under 18 mm across and under 2.5 mm thick) and medium tumors (under 18 mm across, 2.5 to 10 mm thick), eye plaque brachytherapy is a common option. In this procedure, a small radioactive disc is temporarily sutured to the outside of the eye, directly over the tumor, delivering targeted radiation over several days. The goal is to destroy the tumor while preserving the eye and as much vision as possible.
A landmark trial called the Collaborative Ocular Melanoma Study compared plaque brachytherapy to surgical removal of the eye (enucleation) in patients with medium-sized tumors and found no survival difference between the two approaches. That finding made eye-preserving radiation the preferred choice for most small and medium tumors.
Larger tumors, those exceeding 18 mm in diameter or 10 mm in height, are more likely to require enucleation or treatment with proton beam radiation or stereotactic radiosurgery. Tumors that have extended outside the eye wall are generally not candidates for plaque brachytherapy.
Why Metastasis Targets the Liver
Roughly half of all uveal melanoma patients eventually develop metastatic disease, and the pattern of spread is strikingly consistent. About 90% of metastatic cases involve the liver. This strong preference, sometimes called organotropism, appears to be driven by the tumor’s genetics. Research integrating DNA sequencing of 144 metastases with long-term patient outcomes found that liver metastases were especially enriched for cells carrying BAP1 mutations and chromosome 3 loss, suggesting these genetic features actively steer cancer cells toward liver tissue.
Because of this pattern, surveillance after treatment focuses heavily on liver imaging, typically with ultrasound, MRI, or CT scans at regular intervals.
Treating Metastatic Disease
Once uveal melanoma spreads, it has historically been very difficult to treat. The median survival after a metastatic diagnosis was approximately one year, and standard immunotherapy drugs used for skin melanoma showed limited benefit.
That changed with the approval of tebentafusp, a first-in-class therapy designed specifically for metastatic uveal melanoma in patients who carry a particular immune marker (HLA-A*02:01, present in roughly half of people of European descent). In a phase 3 trial, patients treated with tebentafusp had a median overall survival of 21.6 months, compared to 16.9 months for those receiving the best available alternative therapy. At one year, 73% of tebentafusp patients were alive versus 59% in the control group. While not a cure, it represented the first treatment to meaningfully extend survival in this disease and marked a turning point in how metastatic uveal melanoma is managed.
For patients who do not carry the required immune marker, treatment options remain more limited. Clinical trials investigating new combinations and approaches are actively enrolling, and liver-directed therapies such as hepatic artery infusion and isolated hepatic perfusion are used at specialized centers to target liver metastases directly.