Ocular Melanoma

Ocular melanoma is the most common eye cancer in adults and the second most common type of melanoma after skin melanoma, yet it remains largely unknown to the public despite affecting approximately 2,000 adults each year in the United States.

Table of contents

• What is ocular melanoma?
• Where ocular melanoma develops
• Types of ocular melanoma
• How common is ocular melanoma?
• Risk factors
• Symptoms and warning signs
• Diagnosis and testing
• Treatment options
• Prognosis and survival
• Living with ocular melanoma

eye melanoma, intraocular melanoma, uveal melanoma, ocular cancer

What is ocular melanoma?

Ocular melanoma is a cancer that develops in the eye when cells that make melanin (the pigment that gives color to skin, hair, and eyes) begin to grow out of control.^[1] It is the most common primary eye cancer in adults, meaning it starts in the eye rather than spreading from another part of the body.^[3]

Unlike skin melanoma, ocular melanoma is biologically distinct and is not thought to be related to ultraviolet (UV) exposure from the sun.^[4] The disease is most commonly diagnosed around age 55 to 60.^[4]

Most ocular melanomas form in parts of the eye that cannot be seen when looking in a mirror, which makes this type of cancer hard to notice on your own.^[1] Ocular melanoma typically does not cause symptoms at first, and it is often discovered during a routine eye examination.^[1]

• Eye (uveal tract)
• Iris
• Ciliary body
• Choroid
• Conjunctiva

Where ocular melanoma develops

The eye has several layers, and ocular melanoma can develop in different parts. Most ocular melanomas originate in the uvea, which is the middle layer of the eye wall.^[1] The uvea contains three main sections where melanoma can occur.^[4]

The iris is the colored area surrounding your pupil at the front of the eye. The ciliary body is a thin tissue layer behind the iris that produces fluid inside the eye and helps the lens change shape for focusing. The choroid, also called the posterior uvea, is a layer of blood vessels between the retina and the white outer layer of the eye (the sclera). This pigmented tissue full of blood vessels nourishes the retina.^[4]

Most uveal tract melanomas originate in the choroid. The ciliary body is less commonly a site of origin, and the iris is the least common location.^[4] Melanoma of the iris usually grows slowly and rarely spreads to other parts of the body, giving it the best prognosis. In contrast, melanomas of the ciliary body have the worst prognosis.^[4]

Less commonly, melanoma can occur in the conjunctiva, which is the thin lining over the white part of the eye, but this is very rare.^[4]

Types of ocular melanoma

Ocular melanoma is divided into two main categories based on where it develops in the eye.^[3]

Uveal melanoma accounts for about 82.5% of all ocular melanomas and develops within the uveal tract of the eye.^[3] Most uveal melanomas develop slowly from the pigmented cells of the choroid, but they can also arise in the iris or ciliary body.^[4] When uveal melanoma spreads beyond the eye, it most often spreads to the liver through the bloodstream.^[4]

Conjunctival melanoma is much rarer and develops in the thin membrane that covers the outer surface of the eyeball.^[4] It often presents as a raised tumor and may contain little or even no pigment. Unlike uveal melanoma, when conjunctival melanoma spreads, it most often spreads to the lymph nodes and lungs rather than the liver.^[4]

How common is ocular melanoma?

Ocular melanoma is diagnosed annually in approximately 7,000 adults globally and 2,000 adults in the United States.^[4] This translates to about 5 to 6 cases per million people per year, but only 0.2 to 0.3 per million individuals in African and Asian populations.^[4]

For people over 50 years old, the rate increases to around 21 per million per year.^[4] For comparison, skin melanoma occurs in approximately 150 per 1 million Americans each year.^[4]

The average age at diagnosis is around 60 years, with a median of 55 years.^[4] The disease affects both sexes equally or slightly more frequently affects males according to some reports.^[4] It is more common among light-skinned individuals, but it can affect individuals from any ethnicity.^[4]

Unlike skin melanoma, which has increased in incidence over the past few decades, uveal melanoma incidence has remained stable over the last three decades.^[3] Conjunctival melanoma, while rare, has shown an increasing incidence.^[3]

Risk factors

Several factors may increase a person’s chances of developing ocular melanoma. The risk is highest in people with light-colored irises.^[11] Other risk factors include having fair skin that freckles and burns easily, does not tan, or tans poorly, as well as having blue, green, or other light-colored eyes.^[8]

Being older and being White also increase the risk.^[8] Ocular melanoma shares some risk factors with skin melanoma, such as fair skin color, blue eyes, red or blond hair, and freckling or having many moles on the skin.^[4]

Smoking increases the risk for ocular melanoma, and the condition typically affects people in their 60s.^[10] In rare cases, a genetic condition may increase a person’s chances of developing ocular melanoma, but it does not typically run in families. Children, brothers, sisters, and parents of ocular melanoma patients may be screened, but are almost universally free from the condition.^[10]

Symptoms and warning signs

Ocular melanoma may not cause any symptoms, especially in its early stages.^[1] Unlike other severe eye diseases, ocular melanoma does not show signs or symptoms in the vast majority of patients.^[10] As such, uveal melanoma is most often recognized during routine examinations by an eye care specialist.^[10]

When symptoms do occur, they may include blurred vision or other changes in vision.^[1] Some people experience flashes of light or see what look like specks of dust in their vision, sometimes called floaters.^[1]

Other possible symptoms include a growing dark spot in the colored part of the eye (iris), a change in the shape of the pupil (the dark circle at the center of the eye), poor vision or blurry vision in one eye, and not being able to see when looking to the side (called loss of peripheral vision).^[1] Rarely, the eye may be red or painful.^[10]

If you notice sudden changes in your vision or any of these symptoms, you should make an appointment with a healthcare professional.^[1]

Diagnosis and testing

Eye melanoma diagnosis often starts with an eye exam.^[7] During this examination, a healthcare professional may first examine the outside of the eye, looking for blood vessels that are larger than usual, which might indicate something concerning is happening inside the eye.^[7]

The exam also involves looking inside the eye with the help of special equipment. One method uses lenses and a bright light mounted on the healthcare professional’s forehead, called binocular indirect ophthalmoscopy. Another method uses lenses and a microscope with an intense beam of light, called slit-lamp biomicroscopy.^[7]

In most cases, the diagnosis is established by clinical examination with great accuracy.^[3] Unlike in other cancer specialties, a biopsy (removal of a small tissue sample for laboratory testing) is rarely required to diagnose ocular melanoma.^[10] However, advances in genetic testing can only be utilized with the availability of a tumor tissue sample, and these samples are often gathered at the time of treatment.^[10]

Several imaging tests may be used to confirm the diagnosis and show the size of the cancer. Fundus photography takes color pictures of the inside surface of the eye to show an eye melanoma.^[7] An eye ultrasound uses high-frequency sound waves to make images of the eye.^[7] Eye angiography makes pictures of the blood vessels by injecting a colored dye into a vein in the arm, which then travels to the blood vessels in the eye.^[7]

Diagnostic testing typically includes a complete eye exam with dilation of the fundus, indirect ophthalmoscopy, tumor photography, tumor ultrasound, and vascular studies of the tumor using techniques such as fluorescein angiography, indocyanine green angiography, and spectral-domain OCT angiography, along with laser studies of the macula.^[10]

The tumor is then staged, a process that defines the extent of the tumor based on its length, width, and height.^[10] A biopsy of the melanoma can reveal tumor genetics that give the patient and physician an understanding of the risk of the tumor spreading.^[10]

Treatment options

Treatment for small eye melanomas may not cause vision problems, but treatment for large eye melanomas typically leads to some vision loss.^[1] Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye.^[3]

Treatment options range from observation to various active treatments, depending on the size and location of the tumor.^[10]

Radiation therapy is a common treatment for ocular melanoma. Most patients with ocular melanoma will be treated with a radioactive plaque, a form of radiation therapy also called brachytherapy.^[13] After precise measurements of the eye and cancer are taken, a plate embedded with radioactive seeds is created and then surgically attached to the eye near the cancer. It is left in place for up to a week while it delivers radiation directly to the cancer cells.^[13]

Proton therapy is another form of radiation treatment that may be used.^[9]

Surgery may be necessary for larger tumors. Patients with ocular melanomas measuring greater than 22 millimeters in diameter may undergo surgery to remove the melanoma and a portion of healthy tissue around it. In some cases, the entire eye must be removed in a procedure called enucleation.^[13]

Cryotherapy, which uses extreme cold, may be used in some cases to destroy melanoma cells in the eye.^[9]

Immunotherapy uses medication to help the body’s immune system better recognize and attack abnormal cells. This treatment is used for ocular melanoma that has spread beyond the eye.^[13] One immunotherapy drug, tebentafusp, is currently the only FDA-approved treatment for metastatic ocular melanoma.^[13]

For conjunctival melanoma, the current standard treatment is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy, and topical application of chemotherapeutic agents.^[3]

Prognosis and survival

Although primary treatment may be successful in controlling the tumor in the eye, ocular melanoma eventually results in death in approximately 40% to 50% of those it affects despite complete control of the primary tumor.^[4] More than 50% of uveal melanomas spread, mostly to the liver.^[6]

When eye melanoma has spread to distant parts of the body, the five-year survival rate is about 15%.^[6] However, no evidence of metastatic disease (cancer that has spread) is demonstrable at the time of uveal tumor diagnosis in the vast majority of patients.^[4]

Clinical metastases usually develop years after the diagnosis and treatment of the primary eye tumor.^[4] Researchers estimate that undetectable circulating tumor cells, or “micro” metastasis, may have begun growing 2 to 3 years before treatment of the eye tumor in patients who will go on to develop disseminated disease.^[4]

Despite improvements in local treatment, survival rates have remained unchanged because there has been a lack of effective systemic therapy for metastatic disease.^[3] Metastatic disease remains the leading cause of death among patients with uveal melanoma.^[3] For conjunctival melanoma, prognosis is similarly poor for patients with metastasis due to the lack of effective systemic therapy.^[3]

Recent advances in genetics have enhanced the ability to determine which tumors have high metastatic potential, improving prognostication.^[3] The prognosis depends on tumor size, location, and genetic variations.^[11] Iris melanomas have the best prognosis, whereas melanomas of the ciliary body have the worst.^[4]

A dilated eye exam is the best way to diagnose and catch ocular melanoma in its early stages, which gives patients more options and typically drives better outcomes.^[4] Although primary treatment may be successful, monitoring for metastases to other parts of the body is lifelong, as the cancer can show up even when the cancer in the eye is well treated.^[13]

Living with ocular melanoma

Many patients diagnosed with ocular melanoma go on to live long and healthy lives. Two commonalities among patients who have better outcomes are being a proactive self-advocate and living a healthy lifestyle, which can involve a combination of stress reduction, exercise, and dietary changes.^[20]

Losing vision in one eye or experiencing partial vision loss takes time to adjust to, both physically and emotionally. It is normal to experience a period of grief due to these changes and challenges.^[20] Support services from social workers, therapists, and loved ones may be helpful during the adjustment period.^[20]

Many patients experience radiation retinopathy and associated vision loss following treatment. Some may undergo adjuvant therapies to help manage these effects, but partial or full vision loss may become the new normal.^[20]

Depth perception might be affected in several ways, including judging distances while walking and using stairs, catching objects in the air, judging the heights of steps and widths of entrances, pouring liquids into containers, and judging how close people are as they move in and out of your field of vision.^[20] Double vision may also become a challenge and is a known side effect of radiation therapy.^[20]

Your brain will eventually start to assist you in compensating for the change in vision, and most day-to-day tasks and activities should fall back into place after an adjustment period.^[20] Driving is still possible, but patience is needed as you adjust to your new condition. Take time to use your mirrors, become comfortable with the size of your vehicle and its blind spots, as stopping, turning, and changing lanes may be more challenging than before.^[20]

It is important to be proactive in scheduling regular follow-ups with your ophthalmologist and oncologist. Knowledge is power when dealing with ocular melanoma.^[20]