Uveal Melanoma: Understanding Eye Cancer Treatment
Understanding Uveal Melanoma
The uvea is the middle coat of the eye. It contains three parts: the iris (the colored ring at the front of the eye), the ciliary body (a ring of tissue behind the iris that helps the eye focus), and the choroid (a layer of blood vessels that nourishes the retina). Melanoma can develop in any of these structures, but the choroid is the most common location.
Uveal melanoma begins in melanocytes, the pigment-producing cells found throughout the uvea. When the DNA in these cells develops errors, the cells can multiply without normal control and form a tumor. Researchers have identified several genetic changes linked to this process, including loss of one copy of chromosome 3 (monosomy 3), an extra copy of chromosome 8 (trisomy 8), and mutations in specific genes such as BAP1, SF3B1, and EIF1AX.
BAP1 mutations are especially significant. They appear in roughly 47% of primary uveal melanomas and 84% of tumors that have spread to other parts of the body (PMC, 2017). This strong link with metastatic disease makes BAP1 status an important factor in predicting outcomes.
In the United States, choroidal melanoma affects approximately 2,500 people per year, with an incidence of about 6 per million people (ASRS). Historical data show rates have remained relatively stable, ranging from 5.1 per million between 1993 and 2008 to 5.2 per million between 1973 and 2013 (ASRS). While this makes it a rare cancer overall, it is the most frequent primary cancer originating within the eye in adults.
Who Is Affected and Risk Factors
Uveal melanoma most commonly affects people in their 60s. It occurs more frequently in individuals with fair skin and light-colored eyes, such as blue or green. People of European descent have higher rates compared to other populations.
Several factors are associated with a greater chance of developing uveal melanoma. Some of these relate to inherited traits, while others involve growths that may already be present in the eye.
- Fair skin and inability to tan
- Light eye color, especially blue or green
- Ocular or oculodermal melanocytosis (a condition causing increased pigmentation in and around the eye)
- Pre-existing nevi (moles) on the skin, iris, or choroid
- BAP1 gene mutation, which can run in families
- Smoking
Choroidal nevi are benign pigmented spots on the choroid, similar to freckles. They are common and most remain harmless. However, benign choroidal nevi carry approximately a 1 in 8,800 risk of transforming into melanoma (ASRS). For this reason, a retina specialist or ocular oncologist may recommend routine monitoring with imaging if a nevus is found during an eye exam.
Signs and Symptoms
Unlike many other serious eye diseases, uveal melanoma usually does not cause signs or symptoms in the early stages. Most eye melanomas form in the part of the eye a person cannot see when looking in a mirror. Because of this, the tumor is often found during a routine dilated eye examination rather than because a patient noticed a problem.
When symptoms do appear, they tend to be nonspecific and can overlap with other eye conditions. Possible symptoms include the following.
- Floaters (small spots or shapes drifting across the field of vision)
- Flashes of light
- Blurred vision or loss of vision in the affected eye
- A dark spot on the iris that grows over time
- A change in the shape of the pupil
Redness and pain in the eye are rare with uveal melanoma. Any new or worsening visual symptoms should be evaluated by an eye care professional. If a tumor is suspected, a retina specialist or ocular oncologist should be consulted promptly.
Diagnosis and Testing
The first step in diagnosing uveal melanoma is a comprehensive dilated eye examination. During this exam, the specialist uses special lenses and instruments to view the inside of the eye in detail. Many uveal melanomas are discovered this way, even before symptoms develop. This underscores the importance of regular eye exams, especially for people with known risk factors.
Several imaging techniques help confirm the diagnosis and determine the size and location of a tumor. Ultrasound of the eye (ocular ultrasonography) is one of the most important tools. It measures tumor thickness and helps distinguish melanoma from other conditions. Optical coherence tomography (OCT) can detect fluid or changes in the retina near the tumor. Fundus photography creates detailed images of the back of the eye for documentation and monitoring over time.
In some cases, a retina specialist or ocular oncologist may perform a fine needle aspiration biopsy. This involves using a very thin needle to remove a small sample of cells from the tumor. The sample can be tested for genetic changes, including BAP1, SF3B1, and EIF1AX mutations, as well as chromosome 3 status. These results play a key role in predicting whether the cancer is likely to spread and in guiding follow-up care.
Because uveal melanoma can spread to other parts of the body, patients are typically evaluated with imaging of the liver, lungs, and other organs. The liver is the most common site of metastasis. Imaging may include CT scans, MRI of the liver, or PET scans. Regular systemic surveillance continues for years after the initial diagnosis.
Treatment Options
Plaque brachytherapy (also called plaque radiotherapy) has been the most common treatment for uveal melanoma for nearly a century. During this procedure, a small radioactive disc (plaque) is surgically placed on the outer wall of the eye directly over the tumor. The plaque delivers focused radiation to the tumor over several days, after which it is removed in a second procedure. This approach aims to destroy the tumor while preserving the eye and as much vision as possible.
For tumors that may not be suitable for plaque brachytherapy, other forms of radiation may be considered. Proton beam therapy uses charged particles to target the tumor with high precision. Stereotactic radiosurgery delivers focused radiation beams from outside the eye. A retina specialist or ocular oncologist will recommend the approach best suited to the tumor size, location, and individual patient factors.
Enucleation is the surgical removal of the entire eye. It may be recommended for very large tumors, tumors causing severe pain, or cases where vision has already been lost. While this is a significant step, it can be a necessary and effective treatment. A prosthetic eye is fitted after healing, and many patients achieve a natural-looking appearance.
Transpupillary thermotherapy (TTT) uses an infrared laser to heat and destroy small tumors. It is sometimes used alone for very small melanomas or in combination with plaque radiotherapy to improve tumor control. Photodynamic therapy and other local treatments may also be considered in select cases. These approaches are generally reserved for smaller tumors.
Approximately 50% of patients with uveal melanoma will develop metastatic disease, with common sites including the liver (89%), lung (29%), and bone (17%) (PMC, 2017). Two FDA-approved treatments now exist specifically for metastatic uveal melanoma.
Tebentafusp (Kimmtrak) was the first FDA-approved drug for metastatic uveal melanoma, receiving approval in January 2022 (FDA, 2022). It is a T-cell receptor bispecific molecule that targets a protein called glycoprotein 100 and CD3 on immune cells. Tebentafusp is approved for adult patients who test positive for a specific tissue type called HLA-A*02:01 and have unresectable or metastatic uveal melanoma. In clinical trials, at a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group compared to 16.9 months in the control group. The estimated percentage of patients surviving at three years was 27% in the tebentafusp group and 18% in the control group (NEJM, 2021).
Percutaneous hepatic perfusion with melphalan (a chemotherapy drug) was approved by the FDA in August 2023 based on results from the FOCUS study. This liver-directed therapy delivers high-dose chemotherapy directly to the liver while limiting exposure to the rest of the body. It is the first FDA-approved liver-directed treatment for this disease and provides an important option for patients with liver metastases.
What to Expect
Recovery after plaque brachytherapy or other eye-preserving treatments varies depending on tumor size and location. Some patients experience gradual vision changes in the treated eye over months or years as the tumor responds to treatment. Radiation can affect nearby retinal tissue, potentially causing radiation retinopathy (damage to the retinal blood vessels) or other complications. A retina specialist will monitor the eye closely with regular follow-up exams and imaging.
Ongoing surveillance is a critical part of uveal melanoma care. Even after successful treatment of the primary tumor in the eye, regular imaging of the body, particularly the liver, is recommended for many years. The risk of metastasis can persist for a decade or longer after initial diagnosis. In a combined estimate from multiple studies, patients have a relative survival of 60% at 15 to 20 years after uveal melanoma diagnosis (Nature, 2022). Genetic testing results from the tumor biopsy help guide how frequently and intensively a patient should be monitored.
A diagnosis of eye cancer can be overwhelming. Patients may face concerns about vision loss, the possibility of metastasis, and changes to their appearance if enucleation is needed. Support from oncology social workers, counselors, and patient advocacy groups can be valuable. Many cancer centers offer resources specifically for people with rare cancers. Open communication with the treatment team about fears, expectations, and goals of care is an important part of the process.
Living With Uveal Melanoma
Many patients retain useful vision in the treated eye, especially when the tumor is small or located away from the center of the retina. If vision in one eye is significantly reduced or lost, the brain can adapt to relying more on the other eye over time. Occupational therapists and low vision specialists can help patients adjust to changes in depth perception and peripheral awareness.
A retina specialist or ocular oncologist will establish a follow-up schedule based on the tumor characteristics and genetic profile. This typically involves eye exams every three to six months in the first few years, along with systemic imaging. Patients should report any new visual symptoms such as increased floaters, flashes, or a shadow over the vision promptly. Between scheduled visits, staying aware of changes in vision is an important part of self-monitoring.
While there is no proven way to prevent uveal melanoma from spreading, maintaining overall health supports the body during and after treatment. Patients who smoke should discuss cessation with their medical team, as smoking is a recognized risk factor for the condition. Wearing UV-protective sunglasses may help reduce general risk to the eyes, although a direct link between UV exposure and uveal melanoma has not been firmly established. Following recommended screening guidelines for other cancers is also important, particularly for individuals with BAP1 mutations who may be at increased risk for additional cancer types.
When to See a Retina Specialist
Certain symptoms require immediate evaluation. A sudden increase in floaters, new flashes of light, a curtain or shadow over part of the vision, or sudden vision loss in one eye are reasons to see a retina specialist or go to the emergency room right away. While these symptoms are not specific to melanoma, they can indicate serious retinal conditions that need prompt attention.
Uveal melanoma is a rare and complex condition. Patients benefit from care at centers with experience in ocular oncology. If a suspicious lesion is found during a routine eye exam, a referral to a retina specialist or ocular oncologist is appropriate. Seeking a second opinion, especially before making treatment decisions, is a reasonable and common step. Genetic counseling may also be recommended for patients with BAP1 mutations or a family history of certain cancers.
Questions and Answers
Yes. Many uveal melanomas are discovered during a routine dilated eye examination before the patient notices any symptoms. Because these tumors often grow in areas of the eye that are not visible to the patient, regular eye exams are especially important for early detection. People with known risk factors, such as light eye color, fair skin, or existing nevi in the eye, should discuss appropriate exam frequency with their eye care provider.
Genetic testing of a tumor sample provides information about the likelihood of the cancer spreading. Tumors with BAP1 mutations or monosomy 3 are associated with a higher risk of metastasis, while tumors with EIF1AX mutations tend to have a more favorable outlook. These results help the treatment team determine the best surveillance plan. They may also guide eligibility for certain clinical trials or systemic therapies if metastasis occurs.
In many cases, yes. Plaque brachytherapy and other radiation-based treatments are designed to treat the tumor while preserving the eye. The ability to save the eye depends on factors such as tumor size, thickness, and location within the eye. Very large tumors or those that have caused significant damage may require enucleation. A retina specialist or ocular oncologist will discuss all available options and help determine the best course of action for each individual case.
Follow-up imaging, particularly of the liver, is typically recommended every three to six months during the first several years after diagnosis. The exact schedule depends on tumor characteristics and genetic test results. Patients with higher-risk features may need more frequent imaging. Because the risk of metastasis can persist for many years, some level of ongoing surveillance may continue for a decade or longer. The treatment team will adjust the schedule based on individual needs and any changes over time.
Research into uveal melanoma treatment is active and ongoing. Clinical trials are studying new immunotherapy combinations, targeted therapies, and improved methods of liver-directed treatment. Patients who are interested in clinical trials should discuss options with their ocular oncologist or medical oncologist. National databases such as ClinicalTrials.gov list current studies, and many academic cancer centers participate in trials focused on this rare disease.