Intraocular (Uveal) Melanoma Stages & Treatment

Intraocular melanoma is a rare disease in which cancer forms in melanocytes inside the eye. Melanocytes are the cells responsible for producing melanin, the pigment that gives skin and eyes their color. Although it is rare, intraocular melanoma is the most common primary intraocular malignancy in adults.

The cancer develops in the uvea, the middle layer of the wall of the eye. The uvea has three main parts:

Certain factors may increase the risk of developing intraocular melanoma. Known risk factors include:

• Having fair skin that freckles and burns easily, does not tan, or tans poorly
• Having blue, green, or other light-colored eyes
• Being older in age
• Being of northern European descent

Men have a somewhat higher incidence of intraocular melanoma than women. The median age at diagnosis is approximately 62.

Intraocular melanoma may not cause noticeable signs or symptoms in its early stages. In many cases, it is first detected during a routine eye exam when a doctor dilates the pupil and examines the inside of the eye.

When symptoms do occur, they may include:

• Blurred vision or other changes in vision
• Floaters (spots that drift in your field of vision) or flashes of light
• A dark spot on the iris
• A change in the size or shape of the pupil
• A change in the position of the eyeball in the eye socket

These signs and symptoms may be caused by intraocular melanoma or by other conditions. It is important to speak with a doctor if you notice any of these changes.

Several tests and procedures are used to detect and diagnose intraocular melanoma. A thorough physical exam and medical history review are typically the starting point, followed by specialized eye exams and imaging.

The pupil is dilated using medicated eye drops so the doctor can look through the lens and pupil to examine the retina and optic nerve. Several types of dilated eye exams may be used:

• Ophthalmoscopy: An exam of the inside of the back of the eye to check the retina and optic nerve using a small magnifying lens and light.
• Slit-lamp biomicroscopy: An exam of the inside of the eye using a strong beam of light and a microscope to check the retina, optic nerve, and other structures.
• Gonioscopy: An exam of the front part of the eye between the cornea and iris, using a special instrument to evaluate fluid drainage.
• Transillumination of the globe and iris: An exam of the iris, cornea, lens, and ciliary body using a light placed on the upper or lower eyelid.

• Ultrasound exam of the eye: High-energy sound waves are bounced off the internal tissues of the eye to create a picture of its interior. Eye drops are used to numb the eye before a small probe is placed on its surface.
• High-resolution ultrasound biomicroscopy: A more detailed version of the standard ultrasound, used to evaluate the tumor’s size, shape, and thickness, and to look for signs of spread to nearby tissue.
• Fluorescein angiography: An orange fluorescent dye is injected into the bloodstream to highlight blood vessels in the eye. A special camera captures images of the retina and choroid to find areas that are blocked or leaking.
• Indocyanine green angiography: Similar to fluorescein angiography, but uses a green dye to focus specifically on the blood vessels in the choroid layer.
• Ocular coherence tomography (OCT): An imaging test that uses light waves to create cross-section pictures of the retina and sometimes the choroid, to detect swelling or fluid beneath the retina.

A biopsy, which involves removing cells or tissue to examine under a microscope, is rarely needed to diagnose intraocular melanoma. In cases where a biopsy is performed, the tissue may be tested using cytogenetic analysis (looking for chromosome changes) or gene expression profiling (checking for specific types of RNA). It is worth noting that a biopsy carries a small risk of retinal detachment, which can typically be repaired with surgery.

After intraocular melanoma has been diagnosed, the next step is staging, the process used to determine whether and how far the cancer has spread. Knowing the stage is essential to planning the most appropriate treatment.

The following tests and procedures may be used in the staging process:

Intraocular melanoma tumors are described using the following size classifications:

• Small: The tumor is 5 to 16 millimeters in diameter and 1 to 3 millimeters thick.
• Medium: The tumor is 16 millimeters or smaller in diameter and 3.1 to 8 millimeters thick.
• Large: The tumor is more than 8 millimeters thick at any diameter, or at least 2 millimeters thick and more than 16 millimeters in diameter.

Though most intraocular melanoma tumors are raised, some are flat. These diffuse tumors grow widely across the uvea.

Cancer can spread through tissue by growing into nearby areas, through the lymph system via lymph vessels, or through the blood via blood vessels. When cancer reaches a new location through any of these pathways, it is called metastasis. The cells at that new site remain the same type as the original tumor. For example, if intraocular melanoma spreads to the liver, those cells are still intraocular melanoma cells, and the disease is called metastatic intraocular melanoma, not liver cancer.

There are two staging systems for intraocular melanoma. The system used depends on where in the eye the cancer first formed: the iris, or the ciliary body and choroid. If intraocular melanoma has spread to the optic nerve or nearby tissue of the eye socket, it is called extraocular extension.

• Stage I: The tumor is in the iris only and is no more than one-fourth the size of the iris.
• Stage IIA: The tumor is in the iris only and is more than one-fourth the size of the iris; or it has caused glaucoma; or it has spread to the ciliary body, choroid, or both, and has caused glaucoma.
• Stage IIB: The tumor has spread to the ciliary body, choroid, or both, and has also spread into the sclera. Glaucoma is present.
• Stage IIIA: The tumor has spread through the sclera to the outside of the eyeball. The portion outside the eyeball is no more than 5 millimeters thick.
• Stage IIIB: The tumor has spread through the sclera to the outside of the eyeball. The portion outside the eyeball is more than 5 millimeters thick.
• Stage IV: The tumor may be any size and has spread to nearby lymph nodes, or to other parts of the body such as the liver, lung, bone, or areas under the skin.

Intraocular melanoma of the ciliary body and choroid is first placed into one of four size categories based on width and thickness before being assigned a stage.

• Category 1: No more than 12 mm wide and no more than 3 mm thick; or no more than 9 mm wide and 3.1 to 6 mm thick.
• Category 2: 12.1 to 18 mm wide and no more than 3 mm thick; or 9.1 to 15 mm wide and 3.1 to 6 mm thick; or no more than 12 mm wide and 6.1 to 9 mm thick.
• Category 3: 15.1 to 18 mm wide and 3.1 to 6 mm thick; or 12.1 to 18 mm wide and 6.1 to 9 mm thick; or 3.1 to 18 mm wide and 9.1 to 12 mm thick; or 9.1 to 15 mm wide and 12.1 to 15 mm thick.
• Category 4: More than 18 mm wide at any thickness; or 15.1 to 18 mm wide and more than 12 mm thick; or 12.1 to 15 mm wide and more than 15 mm thick.

The stages are as follows:

• Stage I: Category 1 tumor in the choroid only.
• Stage IIA: Category 1 tumor that has spread to the ciliary body; or Category 1 tumor with limited spread through the sclera (no more than 5 mm outside); or Category 2 tumor in the choroid only.
• Stage IIB: Category 2 tumor spread to the ciliary body; or Category 3 tumor in the choroid only.
• Stage IIIA: Category 2 tumor with limited extraocular extension; or Category 3 tumor spread to the ciliary body or with limited extraocular extension; or Category 4 tumor in the choroid only.
• Stage IIIB: Category 3 tumor with extraocular extension to the ciliary body; or Category 4 tumor spread to the ciliary body or with limited extraocular extension.
• Stage IIIC: Category 4 tumor with extraocular extension and ciliary body involvement; or any size tumor with more than 5 mm of extraocular extension without ciliary body involvement.
• Stage IV: The tumor may be any size and has spread to nearby lymph nodes, or to other parts of the body such as the liver, lung, bone, or areas under the skin.

Several factors influence the prognosis (chance of recovery) and the treatment options available to a patient:

• How the melanoma cells look under a microscope
• The size and thickness of the tumor
• The part of the eye the tumor is in (the iris, ciliary body, or choroid)
• Whether the tumor has spread within the eye or to other parts of the body
• Whether there are certain gene changes linked to intraocular melanoma
• The patient’s age and general health
• Whether the tumor has recurred after treatment

In general, iris melanoma carries a better prognosis and a lower risk of spreading than choroidal melanoma. Choroidal melanoma has a significantly higher rate of metastasis, particularly to the liver.

Several types of treatment are available for patients with intraocular melanoma. Some are considered standard treatments, while others are being evaluated in clinical trials. A doctor will recommend a treatment plan based on the location and stage of the tumor, the patient’s overall health, and other individual factors.

Surgery is the most common treatment for intraocular melanoma. Three types of surgery may be used, depending on the size and location of the tumor and whether vision can be preserved.

Watchful waiting involves closely monitoring a patient’s condition without administering treatment until signs or symptoms appear or change. This approach is used for patients who have no symptoms and whose tumor is not growing, or when the tumor is located in the patient’s only eye with useful vision. During watchful waiting, photographs are taken periodically to track changes in tumor size and growth rate.

Radiation therapy uses high-energy rays or particles to kill cancer cells or prevent them from growing. For intraocular melanoma, several forms of radiation therapy may be used.

• Localized plaque radiation therapy: A type of internal radiation therapy. Radioactive seeds are attached to a small disk, called a plaque, which is placed directly on the wall of the eye over the tumor. The plaque, often made of gold to protect nearby tissue, delivers radiation directly to the eye.
• Charged-particle external beam radiation therapy: A machine outside the body directs tiny particles, called protons or helium ions, precisely at the cancer cells. This type of radiation is designed to minimize damage to surrounding healthy tissue.
• Gamma Knife therapy: A type of stereotactic radiosurgery that delivers tightly focused gamma rays directly to the tumor in a single treatment session. Despite its name, it does not involve a surgical incision.

Photocoagulation is a procedure that uses laser light to destroy the blood vessels supplying nutrients to the tumor, causing the tumor cells to die. It may be used to treat small tumors and is sometimes called light coagulation.

Thermotherapy uses heat from a laser to destroy cancer cells and reduce the size of the tumor.

New types of treatment are continuously being evaluated in clinical trials. For some patients, participating in a clinical trial may be the best available treatment option. Clinical trials test whether new treatments are safe, effective, and potentially better than current standard treatments. Patients may be eligible to enroll before, during, or after beginning cancer treatment, and participation also helps advance care for future patients. For information about current clinical trials for intraocular melanoma, visit the National Cancer Institute’s website.

After treatment ends, follow-up tests will continue on a scheduled basis. These tests help detect any changes in the patient’s condition and identify whether the cancer has recurred. It is important to keep all follow-up appointments and to report any new or returning symptoms to your radiation oncology care team.