Melanoma in the eye

Melanoma in the eye starts when a cell in the eye turns cancerous. A melanoma is a cancer that starts in a specific type of pigmented cell called a melanocyte. These cells make up the skin and other tissues in the body. The term “melanoma” probably brings to mind skin cancer, but in rarer cases, the cancer forms in the eye, which also is made of melanocytes. Intraocular melanoma is one of a few types of eye cancer.

• Eye cancer is very rare. About 3,400 new cases are expected to be diagnosed this year in the United States, according to the American Society of Clinical Oncology (ASCO).
• Treatment options include surgery and clinical trials.

What is melanoma in the eye?

Intraocular melanoma is cancer that forms in cells of the eye that produce melanin, which gives skin its color. It’s also called eye melanoma or ocular melanoma and has two main types: uveal melanoma and conjunctiva melanoma. 

Types of melanoma of the eye

The type of eye melanoma depends on where it develops. That’s why it’s important to know the different parts of the eye and what they do.

The eye has three layers. The outermost layer includes the cornea, a clear outer dome over the colored part of the eye, and sclera, the white, protective part of the eye. A thin, clear membrane that covers the sclera, called the conjunctiva, keeps the eye moist. The innermost layer is the retina, a nerve-packed color and light sensing wall that connects to the optic nerve. A gooey substance fills the inside of the eye and gives it shape. The middle layer of the eye, also called the uveal tract, includes the iris, ciliary body and choroid:

• The iris is the colored part of the eye, which contracts and expands to open and close the pupil, controlling how much light reaches the retina.
• The ciliary body is a circle of muscle tissue that makes the iris contract, changing the shape of the lens to focus light. Other ciliary body cells produce the fluid between the cornea and iris.
• The choroid is a network of blood vessels that nourishes the eye.

Melanocytes are present in the uveal tract and the conjunctiva. Intraocular melanoma may develop in either structure. Intraocular melanoma is quite rare, but it most commonly occurs in the uveal tract.

Uveal melanoma

Uveal melanoma is the most common primary intraocular cancer Depending on which part of the uveal tract it affects, uveal melanoma may either spread slowly and stay small, or be more invasive.

About 90 percent of intraocular melanomas start in the choroid or ciliary body, according to the American Cancer Society. Because these structures are harder to see, cancers that develop here are usually found when they’re larger, more advanced and more likely to spread to other body parts.

Intraocular melanoma that develops in the iris is usually found earlier when it’s smaller and less likely to spread. It may show up as a dark spot in the iris and starts to grow. These cancers make up most of the remaining 10 percent of intraocular melanomas.

Conjunctival melanoma

The small percentage of intraocular melanomas that don’t develop in the uveal tract come from cells in the conjunctiva. Conjunctival melanoma is extremely rare, but it may be aggressive, spreading to other eye structures and through the blood and lymph nodes to other parts of the body.

What puts you at risk for uveal melanoma?

Certain people are at a higher risk for intraocular melanoma. Having one of these factors doesn’t mean someone will get cancer, but it does raise the risk. It’s also possible to get intraocular melanoma without having these risk factors.

High-susceptibility individuals:

• Have fair skin and/or light-colored eyes
• Have freckles
• Are older
• Are white
• Are male (men are slightly more likely to get eye melanoma than women)
• Have an inherited condition, such as dysplastic nevus syndrome (these individuals have many abnormal moles), or abnormal brown spots on the iris, choroid or ciliary body
• Have a specific mutation in the gene BAP1, or a family history of eye melanomas that may indicate a genetic predisposition

The connection between sunlight exposure and intraocular melanoma is unclear and needs more research. So far, studies have found no strong correlation. A 2017 review in the journal Current Eye Research of uveal melanoma studies found that occupational sun exposure and outdoor activity did not significantly increase the risk for intraocular melanoma.

Symptoms of uveal melanoma

Intraocular melanoma may have no symptoms. In this case, a tumor may be found during a regular eye check-up with an ophthalmologist (eye doctor). In other instances, intraocular melanoma may affect vision. Keep in mind that other conditions may cause these symptoms, too, so a thorough examination with an eye care specialist is important to narrow down the root cause of any vision problems.

Intraocular melanoma may cause:

• Dark spot on the iris, especially for iris melanoma
• Blurry vision or trouble seeing
• Flashes of light or spots in field of vision
• Change in pupil size or shape
• Shifts in position or movement of the eye within the socket

How is uveal melanoma diagnosed?

An eye exam with pupil dilation is usually used to diagnose intraocular melanoma. Using medicated drops, doctors are able to look inside the eye, inspect for a tumor and take photos of eye structures.

A magnifying lens and light, a microscope or other special instruments may be used to examine the back, inside and front of the eye.

Additionally, they may assess the patient’s general health and well-being. Family history may also help doctors determine whether cancer is likely.

Other eye exams may also detect and take images of a tumor, including:

• Ultrasound of the eye: Drops are used to numb the eye, and a small probe shoots sound waves, which feed back to the probe and create a picture of the inside of the eye and any tumors. Standard ultrasound or a high-resolution ultrasound, which displays more detail, may be used.
• Transillumination of the iris: A light is placed on the upper or lower eyelid to look at the iris and ciliary body.
• Angiography: This exam visualizes the path the blood takes in the eye. A safe dye, such as indocyanine green or fluorescein, is injected into the bloodstream through the arm. The dye eventually makes its way to the blood vessels lining the eye, or the choroid. As the dye moves through these vessels, a special camera takes images to identify any blockage or leakage from a tumor.
• Ocular coherence tomography: Light waves are used to take images of the retina and choroid.
• Biopsies: These are performed very rarely. In a biopsy, small parts of the tumor are surgically removed and examined in a laboratory. There, the DNA of the tumor may be checked to determine whether it’s cancerous.

Staging uveal melanoma

After the cancer is diagnosed, additional tests are ordered to determine whether the cancer has spread to other parts of the body.

• Blood may be collected to check for unusual levels of certain proteins or molecules. Abnormal blood chemistry results may indicate improper organ function. For example, certain liver proteins are checked to see whether cancer may have spread to the liver.
• Imaging exams such as ultrasound, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans or positron emission tomography (PET) scans may be used to visualize the inside of the body and look for additional tumors.

This testing is important to determine the cancer’s stage, or degree of severity. Treatment is tailored to the stage of cancer. Staging also gives the patient an idea of the prognosis, or expected outcome, of the disease. Doctors may provide information on the average survival rates and treatment options for patients with the same stage of intraocular melanoma.

• Intraocular melanoma of the choroid and ciliary bodies is given a stage from 1 to 4, with 4 being the most severe or advanced.
• Intraocular melanoma of the iris doesn’t have a staging scale.

Staging takes into account whether the cancer has spread and grown. Intraocular melanomas are classified into three categories of size.

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

As cancer progresses, the tumor may grow into surrounding tissue in the eye socket, or down the optic nerve, called extraocular extension. Additionally, cancerous cells from the tumor may travel to distant parts of the body and start new tumors, known as metastasis (a more advanced stage of cancer).

Treating uveal melanoma

Treatment depends on a variety of factors, including:

• Age and general health
• Tumor size, location and spread
• Presence of certain genes associated with the cancer

The National Cancer Institute outlines five standard treatment approaches for intraocular melanoma. Each has specific side effects and risks, so patients should discuss each option with their care team.

Surgery: This is the most common treatment plan. Surgery aims to remove the cancer. All of the following procedures are performed by skilled medical technicians.

• Resection removes the tumor and a small layer of the tissue around it.
• Enucleation removes the eye. This is performed in instances when vision cannot be restored, cancer has spread to the optic nerve, or the tumor is very large or causes high pressure in the eye. An artificial eye is specially designed to match the color and size of the removed eye.
• Exenteration removes the eye and some of the musculature, eyelids and eye socket. This is an option if cancer has spread into these areas. An artificial eye and facial reconstruction may be performed afterward.

Watchful waiting: The patient and doctor may decide to monitor the tumor, especially if the tumor is small and not growing, or the patient isn't experiencing any symptoms. The tumor is observed over time for changes.

Radiation therapy: Radiation therapy uses intense rays of energy to kill cancer cells. A special instrument targets radiation to the tumor cells and reduces exposure to healthy tissue in the eye. Radiation is delivered in two ways:

• External radiation comes from a machine outside of the body. The energy may be a beam of small, charged particles or gamma rays, a type of radiation.
• Internal radiation is usually a substance that is delivered to the tumor with needles, catheters (small flexible tubes that are inserted into the body) or small pellets (seeds). Special devices or boundaries are used to protect the radioactive substance from affecting healthy tissue around the tumor.

Photocoagulation: For small tumors, a laser may be used to kill the blood vessels supplying it with oxygen and nutrients. Without blood, the tumor starves and dies.

Thermotherapy: To shrink tumors, a heat laser is directed at the tumor, overheating and killing the cancer cells.

Besides the standard treatments, clinical trial therapies offer additional options. Clinical trials are research studies testing new therapies or approaches to treat a specific disease. Patients may enter a clinical trial during any stage of cancer treatment, even if they’ve already started a different treatment plan. Clinical trial medications may be specific to certain gene mutations or tailored to the cancer stage and location.  

Survival rates and statistics

According to a 2016 study in The British Journal of Ophthalmology:

• Intraocular melanoma represents about 3 percent to 5 percent of all melanomas in the United States.
• About 85 percent to 90 percent of intraocular melanomas begin in the choroid.
• Up to 50 percent of patients experience metastasis, meaning their cancer spreads to other parts of the body.

About 73 percent of patients are diagnosed at an early stage, according to ASCO. In comparison, 2 percent to 3 percent of people are diagnosed at a more advanced stage with spread to distant parts of the body.

The ASCO outlines five-year survival rates for intraocular melanoma. This statistic means the percentage of individuals surviving five years after their cancer diagnosis.

• For those whose eye cancers were diagnosed at an early stage, meaning without spread, the five-year survival rate is 85 percent.
• For eye cancers that have spread into surrounding tissue or organs and/or nearby lymph nodes, the rate is 71 percent.
• For eye cancers that have spread to distant parts of the body at the time of diagnosis, the rate is 13 percent.

Survival rates also depend on the type of melanoma.

• For iris melanoma, which doesn’t typically spread, the five-year survival rate is more than 95 percent.
• For choroidal melanoma, the five-year survival rates vary by the size.
  • Small choroidal melanoma: 84 percent
  • Medium choroidal melanoma: 68 percent
  • Large choroidal melanoma: 47 percent

Ciliary body melanoma is rare and typically diagnosed at an advanced stage, so the five-year survival rates are difficult to determine.