How is Ocular Melanoma Treated?

Primary ocular melanoma means that the tumor originated in the eye. The goals of treating the primary tumor are to stop tumor growth, spare the eye, preserve vision and improve patient survival. Treatment most often includes a combination of radiation and surgery but depends on the size and location of the tumor, among other factors.

For most small and medium-sized tumors, radiation is the recommended treatment. Plaque brachytherapy is the most common form of radiation used in the US for choroidal and ciliary body melanomas. Proton beam radiotherapy is also often used in major centers. There is currently no evidence that one form of radiation is better than the other. The different types of radiation therapy include: 

• Plaque Brachytherapy (Radiotherapy) – A thin piece of metal, called a plaque, is sewn onto the outside wall of the eye. The radioactive seeds in the plaque give off radiation, which kills the cancer cells. The treatment usually lasts a few days and the plaque is removed at the end of treatment. This is the most common therapy in the United States for posterior (choroidal and ciliary body) ocular melanoma and is considered the standard of care for most OM patients with small or medium-sized tumors. After this treatment, removal of the eye is not usually necessary, and most patients are able to retain some degree of visual function.
• Proton Beam Radiotherapy – Markers are surgically placed onto the eye around the tumor base and an external beam of radiation is aimed at the tumor, most often through the front of the eye. Treatment is usually finished after 4-5 daily outpatient treatments. Proton therapy is especially useful for tumors close to the optic nerve or very large tumors, for which plaque placement may be less effective.

In some cases, the recommended treatment for ocular melanoma is surgical removal of the tumor. Surgery is often recommended for tumors of large size and for iris melanomas. Surgery may also be recommended after radiation. Types of surgery include: 

• Enucleation – Removal of the eye is sometimes recommended in cases involving very large tumors. Following enucleation, an artificial eye may be placed in the socket and, with the help of an ocularist, made to look like a natural eye. 

• Iridectomy – Removal of part of the iris where the tumor is present. 

• Iridocyclectomy – Removal of part of the iris (iridectomy) as well as the ciliary body (cyclectomy) where the tumor is present.
• Trans-Scleral Local Resection – Removal of the tumor through an opening in the wall, or the white part, of the eye. This is often used when the tumor is large. A radioactive plaque may be placed over the treated area to reduce the risk of recurrence.This procedure is now less commonly performed, as it can carry higher complication risks compared to radiation.

The temperature of the tumor is slowly raised, killing cancer cells and shrinking the tumor. This treatment is most often used for small tumors in the choroid. It is now rarely used alone and may be combined with plaque brachytherapy for selected small tumors.

The temperature of the tumor is lowered since melanocytes are susceptible to freezing. This treatment option is not frequently used in OM.

A focused, single dose of radiation is given to the tumor, sparing healthy tissue in and around the eye. This is used less often today but may be considered for tumors not suitable for plaque or when proton therapy is not available.

Injections in the eye are used to administer medications to treat a variety of ocular conditions. These medications may include steroids for inflammation and or anti-angiogenic agents, which prevent leakage from damaged blood vessels and shrink abnormal blood vessels. Intraocular injections might be used if changes have occurred to the retina and optic nerve due to radiation.

In skin melanoma, adjuvant treatment is treatment used after the primary treatment (most often, surgery), to prevent the spread of disease. It can also refer to treatment used in addition to the primary form of treatment. Currently, in ocular melanoma, all adjuvant treatments are in the clinical trial stage and nothing yet has been proven to show great results. Trials are ongoing to evaluate tebentafusp and targeted therapies as possible adjuvant treatments, but none are yet standard of care. 

If OM has spread beyond the eye, it is considered metastatic. Approximately half of OM patients will develop metastatic disease, although each person’s individual risk is based on factors such as tumor genetics and other clinical characteristics. When OM metastasizes, it first spreads to the liver nearly 90% of the time.

In January 2022, the FDA approved tebentafusp (Kimmtrak), a bispecific gp100 peptide-HLA-directed CD3 T cell engager, for HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma. This remains the only approved systemic therapy as of 2025. Beyond tebentafusp, and for patients who are negative for HLA-A*02:01 clinical trial enrollment is preferred whenever possible. Treatments may involve a variety of mechanisms including: To see the Webinar: First FDA Approval for Uveal Melanoma, click the button below.

• Immunotherapy – A type of systemic treatment given to activate a person’s immune system so that it will destroy melanoma cells within the body. Several immunotherapies are FDA-approved for cutaneous melanoma and some are being studied in ocular melanoma. To date, single-agent checkpoint inhibitors (such as anti-PD-1) have shown limited benefit in OM, though combinations and novel immune approaches are under study. 
• Targeted therapy – A form of treatment in which drugs are developed with the goal of destroying cancer cells while leaving normal cells intact. These drugs are designed to interfere with the specific molecules, genetic mutations in the tumor itself, that are driving the growth and spread of the tumor. Examples under investigation include PKC inhibitors (such as darovasertib) and MEK inhibitors, often tested in combination strategies. 
• Chemotherapy – Overall, chemotherapy has not been shown to be effective for ocular melanoma. However, it may still be recommended in some cases.

First FDA Approval for Metastatic Uveal Melanoma: What it Means for the OM Community – YouTube

Because uveal melanoma most often spreads to the liver, several treatment options focus on delivering therapy directly to that organ. These are called regional or liver-directed therapies, and most are designed to treat the entire liver rather than specific spots.

Approved Therapy:

• HEPZATO KIT (melphalan/Hepatic Delivery System [HDS]) – is a liver-directed treatment for adult patients with metastatic uveal melanoma (mUM) with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.. Approved by the FDA in August 2023, HEPZATO KIT is the first liver-directed therapy specifically approved for metastatic uveal melanoma. 
• Immunoembolization – This approach combines immune-stimulating drugs (cytokines) with embolization of the hepatic artery, the main blood supply to the liver. Blocking the artery cuts off nutrients to the tumor, while the cytokines trigger an inflammatory and immunse response. Chemoembolization (TACE) – In this procedure, chemotherapy is injected into the hepatic artery, followed by embolization to block the blood flow feeding the tumor. This traps the chemotherapy inside the liver, exposing tumor cells to the higher local drug concentrations. 
• Radioembolization – Small beads, embedded with a radioactive material, are injected into the hepatic arteries. These microspheres emit high doses of radiation to the tumor cells to destroy them. This treatment is sometimes referred to as Y-90 radioembolization, Sirspheres or Theraspheres.
• Hepatic Arterial Chemoinfusion (HAI) – Infusion of chemotherapy into the liver through a specialized infusion system in which a catheter is placed into the hepatic artery to  continuously deliver the chemotherapy to the liver. This direct infusion allows for fewer side effects of chemotherapy and allows high doses to be delivered.
• Isolated Hepatic Perfusion (IHP) –  In IHP, a catheter is placed into the hepatic artery and another is placed into the vein that takes blood away from the liver. This temporarily separates the liver’s blood supply from blood circulating through the rest of the body and allows high doses of chemotherapy to be directed only to the liver. When this is done percutaneously, or through the skin, it is referred to as Percutaneous Hepatic Perfusion (PHP).

These treatments may be used in conjunction with systemic (full body, or through the bloodstream) treatments, so be sure to discuss them with your treatment team. 

• Resection – Surgical removal of the tumor. Resection is mainly used when a single tumor is present. It is often reserved for patients who are several years out from a primary diagnosis and repeated imaging studies show only one tumor. Since resection can sometimes remove some healthy tissue along with the tumor, it is reserved for select cases. 
• Ablation – Ablation involves inserting small probes into tumors and heating (i.e. radio frequency ablation, microwave ablation) or freezing (cryoablation) the tumors to kill them. This can be done through the skin or surgically. Like resection, this is typically not recommended if multiple tumors are present.

Radiation – Targeted radiation can be used to treat metastatic disease in some cases. This includes treatments such as stereotactic radiosurgery (Gamma Knife and Cyber Knife), that can be used to target specific tumors while sparing normal tissue. Radiation can be used to treat many areas of the body including lung, bone, and brain, and can be used to treat isolated metastases or to relieve symptoms caused by a specific tumor.

Because there are limited approved treatments for metastatic ocular melanoma, enrolling in a clinical trial is often recommended. Clinical trials give patients access to new and promising therapies and help doctors learn which treatments work best and in what sequence. Participating in a trial can also contribute to advancing care for future patients with this rare cancer.

 Some studies now test adjuvant therapies (after primary eye treatment) or novel liver-directed and systemic approaches, such as tebentafusp combinations, PKC inhibitors, and new forms of immunotherapy.

• Some questions to ask your doctor about clinical trials:
  • Am I eligible for any clinical trials?
  •  Are there studies available for my specific stage or mutation?
  • What are the potential benefits and risks of joining a trial?

Visit the MRF’s Clinical Trial Finder to find an ocular melanoma trial.