Uveal melanoma: Treating rare eye cancer
January 26, 2026
When you think of melanoma, a type of skin cancer, you likely picture reddish-brown, irregular spots on the face, arms, trunk, or feet. The eyes are the last place most people associate with this type of cancer, but uveal melanomas, which develop in cells that create melanin within the eye, account for about 5% of U.S. melanoma cases.
Uveal melanoma is an aggressive cancer that can spread quickly – and the liver is a prime target. As many as 90% of uveal melanomas that spread beyond the eye ultimately metastasize to the liver. This can result in liver failure, often without early symptoms.
UT Southwestern is one of few medical centers in the U.S. with the ocular oncology expertise to provide personalized treatments for patients with uveal melanoma.
What is uveal melanoma?
This rare cancer grows in the uveal tract of the eye, comprising the iris, ciliary body, and choroid, which line the inside of the eye.
Malignant uveal melanoma is the most common type of eye cancer and is a high-stakes disease. Uveal melanoma can cause permanent vision loss and is characterized by a high risk of cancer cells spreading (metastasizing) through the bloodstream to the liver (most common site) or other organs.
What causes uveal melanoma?
In nearly every case, there is no clear cause of uveal melanoma. It is not directly associated with UV light exposure or environmental factors, and there is a slight increased risk in men over women.
Additional factors beyond a patient’s control that influence risk include:
- There is an increased risk of uveal melanoma in people with fair skin color or light-colored eyes (green or blue). In particular, white people of northern European descent are at the highest risk, although people of any ancestry can develop uveal melanoma.
- Uveal melanoma is usually not passed from parents to children, but 2%-3% of cases are caused by an inherited gene mutation, most commonly in the BAP1 gene. Patients with an inherited gene mutation may develop uveal melanoma at a younger age.
Symptoms of uveal melanoma
Some patients with uveal melanoma have no symptoms, and their eye cancer is diagnosed during a routine eye exam. However, there are several symptoms and sign that patients may experience:
- Recent onset of blurry, distorted, decreased, or loss of vision in one eye
- Floaters and flashes
- Curtain or shadow blocking the peripheral vision in one eye
- Change in the shape of the pupil
- Growing dark spot on the iris (colored part of the eye)
Importantly, these symptoms are not specific to uveal melanoma and often are caused by another eye problem. It is very important to see an ophthalmologist right away if you notice any of these signs.
Diagnosis and treatment
While effective treatments have been developed for metastatic skin melanoma, treatment options are more limited for metastatic uveal melanoma. Because of the rarity of the cancer and the specialized multidisciplinary team required to treat uveal melanoma, only a few medical centers in the U.S. have the expertise necessary to perform cutting-edge research and clinical trials in this field.
UT Southwestern is one of them.
Treatment options
The highest priority of treatment is to inactivate the cancer. The second priority is to save the eye and vision when possible. Fortunately, the vast majority of patients do not require eye removal (enucleation) and can have their uveal melanoma successfully treated while keeping their eye.
Once uveal melanoma has been diagnosed, treatment options are discussed in detail with the patient so that they understand the risks and benefits of each. Each treatment option represents a balance between efficiency of eliminating cancer cells and preservation of vision.
Active monitoring
Sometimes it is difficult to distinguish a small uveal melanoma from a benign nevus (mole). For these indeterminate lesions, the initial treatment is often to monitor it with periodic ocular oncology examinations. Lesions that grow are more likely to be malignant and to require definitive treatment.
Photodynamic therapy (PDT)
Some small indeterminate lesions can be treated with PDT, or cold laser treatment, which is a safe procedure that can be performed in the office.
Thermotherapy
This is a warm laser technique that slowly heats up the tumor and eliminates cancer cells.
Plaque radiotherapy or brachytherapy
This is by far the most common treatment for uveal melanoma, in which a focal radiation source called a plaque is surgically secured to the eye and left in place for a few days before it is removed in a second procedure. Radioactive seeds are affixed to the plaque, which is placed on the outside surface of the eye overlying the tumor. The seeds aim the radiation directly at the tumor, thereby minimizing radiation exposure to surrounding tissues and organs, such as the other eye and the brain.
The UTSW Ocular Oncology Team includes experts in ocular and radiation oncology and radiation physics to provide state-of-the-art treatment planning using three-dimensional computer modeling and customized plaque design that is unique for each patient.
Enucleation (eye removal)
A small minority (about 10%) of patients require enucleation because they are not a good candidate for plaque brachytherapy or other treatment options, usually due to large tumor size, bleeding in the eye, high eye pressure, or other signs of advanced tumor progression. This surgery is performed by a highly experienced oculoplastic surgeon who is a member of the Ocular Oncology Team.
What to know about plaque brachytherapy
Plaque brachytherapy is highly effective in appropriately selected patients, according to J. William Harbour, M.D., Chair and Professor of Ophthalmology at UT Southwestern whose surgical success rate with this treatment over the past 25 years is among the highest reported in the world. In this video, he reviews what patients need to know.
Reducing the risk of spread
Less than 5% of patients with malignant uveal melanoma will have detectable metastatic disease at the time of initial diagnosis. However, up to 50% of patients are at risk for metastasis despite successful treatment of the eye cancer. As a result of recent scientific advances, many of which were discovered in the laboratory of Dr. Harbour, we can now identify with great accuracy which patients are at low, medium and high risk of metastasis, and we can develop a personalized management plan accordingly.
The most important factors for predicting metastatic risk include the 15-gene expression profile (15-GEP) and expression of PRAME, which are assessed from a single fine-needle biopsy at the time of plaque insertion or enucleation using the Castle Biosciences DecisionDX-UM and DecisionDX-PRAME tests.
In 2024, Dr. Harbour and an international team of experts published the largest multicenter biomarker study ever performed in uveal melanoma, showing that 15-GEP (Class 1 or Class 2) and PRAME status (negative or positive) can be integrated to create a highly accurate test for predicting an individual patient’s risk for developing metastatic disease.
Guided by the 15-GEP/PRAME test results, we follow patients regularly in the medical oncology clinic for imaging surveillance, and we discuss potential adjuvant (preemptive) clinical trials for high-risk patients. Current guidelines call for chest, abdominal, and pelvic scans every 3-12 months, based on 15-GEP/PRAME test results.
In these visits, we use advanced imaging to search for early signs that cancer may have spread.
Managing metastatic disease
If metastatic disease is detected, numerous options are available, depending on the circumstances of each individual patient.
Liver-directed therapy
The liver is the primary concern when uveal melanoma spreads; cancer cells can bypass the lymphatic system and travel directly through the bloodstream to the liver.
In patients who have a relatively small amount of metastatic disease limited to the liver, we work closely with our interventional radiology team to consider highly specialized treatments that locally deliver chemotherapy, immunotherapy, radioactive beads, or other forms of local treatment directly to the liver to spare other parts of the body from unnecessary side effects. In occasional situations, surgical resection of liver metastasis can be considered.
In January 2026 UTSW became the first hospital in Texas and neighboring states to offer Hepzato Kit™, the first and only whole liver-directed therapy approved specifically for metastatic uveal melanoma, through a partnership with its manufacturer, Delcath Systems Inc. This catheter-based therapy delivers high doses of the chemotherapy drug melphalan directly to the liver while minimizing exposure to the rest of the body, reducing systemic toxicity.
Offering this advanced treatment in Dallas expands access to more patients who used to have to travel longer distances for care. While Hepzato Kit is not a cure, it can help control disease and extend progression-free survival in eligible patients:
- The treatment is approved by the Food and Drug Administration (FDA) for hepatic-dominant metastatic uveal melanoma when the liver is less than 50% involved and liver function is still preserved.
- Patients may have limited disease outside the liver, as long as those sites can be managed with surgery or radiation.
- Unlike systemic treatments, Hepzato is available to patients regardless of their HLA genetic subtype.
Systemic treatments
For patients with more extensive metastatic disease, we usually recommend systemic therapies delivered by mouth or by intravenous infusion. Rather than traditional chemotherapy, we more frequently use innovative forms of targeted molecular therapy and immunotherapy, in which the patient’s own immune system is activated against the cancer.
About half of patients with metastatic uveal melanoma have a particular immune marker called HLA-A*02:01 that may qualify them for tebentafusp (KIMMTRAK®), the only immunotherapy approved by the FDA for metastatic uveal melanoma. Tebentafusp binds to the HLA-A*02:01 marker, which helps the patient’s immune system recognize and eliminate uveal melanoma cells.
Patients also have access to a variety of clinical trials to evaluate other promising therapies.
Why choose UT Southwestern?
Our ocular oncologists are ophthalmic surgeons with extensive training and experience in the diagnosis of uveal melanoma. We provide initial evaluations as well as second and third opinions to patients who are referred by community providers or self-referred. We are also pleased to evaluate patients who connect through the Melanoma Research Alliance patient support community and other patient advocacy groups.
We have created the only embedded, multidisciplinary ocular oncology team with focused expertise in uveal melanoma in North Texas. Our uveal melanoma program combines the expertise of:
- J. William Harbour, M.D., Professor and Chair, Department of Ophthalmology, and authority on patient care and research in uveal melanoma and ocular oncology.
- Michael Dohopolski, M.D., Assistant Professor, Department of Radiation Oncology, specializing in ocular brachytherapy and other ocular radiotherapy approaches.
- Seung Kim, M.D., Professor, Department of Radiology, specializing in liver-directed therapies.
- Sanjay Chandrasekaran, M.D., Assistant Professor, Department of Internal Medicine in the Division of Hematology and Oncology, and medical oncologist specializing in uveal melanoma, skin cancers, and sarcoma.
- Adrienne Shannon, M.D., Assistant Professor, Department of Surgery, specializing in surgical oncology, melanomas, and whole-liver perfusion therapy.
- Sanjeeva Kalva, M.D., interventional radiologist for liver-directed therapies.
- Patrick Sutphin, M.D., Ph.D., Associate Professor of Radiology and Chief of the Division of Vascular and Interventional Radiology, interventional radiologist for liver-directed therapies.
- Additional experts in vitreoretinal and oculoplastic surgery.
Dallas is home to two major airports, increasing access to care for patients across the U.S. and abroad. Our program has received the Eugene P. Frenkel, M.D. Scholar in Clinical Medicine Award, a four-year, $1 million award from UTSW to support our program’s growth and translational research efforts. Our goal is to grow our program and provide patients throughout the country and globally with streamlined access to exceptional, personalized uveal melanoma care.
UT Southwestern offers multiple clinical trials for adult patients, including some involving uveal melanoma.
The future of uveal melanoma research
UTSW and the Harold C. Simmons Comprehensive Cancer Center offer multiple clinical trials for adult patients with uveal melanoma. Clinical studies are crucial in advancing the treatment of uveal melanoma. In these trials, patients get access to promising new therapies before they are widely available to the general public while helping us to further our understanding of the disease.
Our program is focused on rapidly growing our portfolio of clinical trials to advance the development of new therapies and offer patients additional treatment options. Key to this work is our collaborative networking with other uveal cancer specialists throughout the U.S. within the Cooperative Ocular Oncology Group (COOG). Dr. Harbour founded the COOG in 2007, and it has grown into a robust network of medical centers and uveal melanoma experts across the country. Through COOG, we can work together to offer patients exceptional care where, how, and when they need it.
In addition, we have established a multidisciplinary ocular tumor board with a full team of specialists who meet monthly to review tough cases.
Uveal melanoma is a rare, malignant eye cancer requiring a comprehensive team-based approach including ocular oncologists, medical oncologists, radiation oncologists, and others to provide the best possible care. The number of treatment options for high-risk and metastatic uveal melanoma is rapidly increasing, and the UT Southwestern Ocular Oncology Team will keep patients up to date on all of their options.
Dr. Harbour has served as a consultant for Castle Biosciences and Ideaya Biosciences. Darovasertib is under clinical development by Ideaya Biosciences. Dr. Chandrasekaran has served as a consultant for Delcath Systems Inc.
To discuss treatment options for uveal melanoma, call 214-645-2020 or request an appointment online. For nonurgent inquiries about the uveal melanoma program, email us at uvealmelanoma@utsouthwestern.edu.
