Unusual cases of rare eye cancer puzzling doctors

Doctors are puzzling over dozens of cases — mostly women in their 20s and 30s — of a rare eye cancer in two Southern states. Over the last several years, a group of graduates from Auburn University in Alabama and 18 people in Huntersville, North Carolina say they have been diagnosed with ocular melanoma, usually found in just six out of every million people.

Earlier this year, Ashley McCrary, one of the patients who attended Auburn, started a Facebook group to connect with other people from the university who have been diagnosed with the eye cancer. A separate, similar Facebook community was started a few years ago for people in North Carolina.

While doctors are reluctant to call this a cancer cluster — no cause or common thread has been found — researchers are studying these patients to see if a link, if any, exists between the two groups.

What is ocular melanoma?

Ocular melanoma (OM) — melanoma in or around the eye — is a type of cancer that develops in the cells that produce eye color. Just as you can develop melanoma on your skin from mutated pigment cells, you can also develop it inside your eye, but unlike skin melanoma, sun exposure is not the cause.

Although it is the most common eye cancer in adults, ocular melanoma is very rare — about 2,500 adults are diagnosed every year in the U.S. It can occur in all races, at any age, but the average age of diagnosis is 55 years old.

"Most people think of melanoma — the deadliest form of skin cancer — as ominous black spots on the skin, but it can also develop inside your eye. It's rare, accounting for about 5 percent of all melanoma cases, but the eye is the second most common location for melanoma to grow," said Dr. Sapna Patel, a melanoma oncologist at MD Anderson Cancer Center in Houston.

Most eye melanomas form in the part of the eye you can't see when looking in a mirror so they can be difficult to detect. To make matters worse, they often present without any early signs or symptoms.

"Oftentimes patients are asymptomatic at the time of diagnosis and the cancer is diagnosed on a routine eye exam," said Dr. Sunandana Chandra, melanoma medical oncologist at the Robert H. Lurie Comprehensive Cancer Center Northwestern University in Chicago, Illinois. "That's why it is so important to see your ophthalmologist regularly."

If the spot is big enough it may effect one's vision.

Signs of eye melanoma can include:

  • Blurry vision or sudden loss of vision

  • Floaters (spots or squiggles drifting in the field of vision) or flashes of light.

  • Visual field loss (losing part of your field of sight)

  • A growing dark spot on the colored part of the eye (iris)

What causes ocular melanoma?

It's not clear why eye melanomas develop but people with light colored eyes are at higher risk of getting the cancer. Genetic mutations might put people at higher risk.

"It's impossible at this juncture to tell what causes this," said Dr. Jonathan Zager, surgical oncologist and director of Regional Therapies in the Departments of Cutaneous Oncology and Sarcoma, Moffitt Cancer Center in Tampa, Florida. "Suspected contributors include BAP1 mutations and possibly a small link to sun exposure."

Some eye cancers run in the family but most experts believe that the majority of cases develop from random mutations.

"There is ongoing research to try to identify other risk factors, but it's important to note that people who have had a melanoma of the skin aren't at a higher risk of developing of developing an ocular melanoma," said Dr. Zeynep Eroglu medical oncologist and associate member in the Department of Cutaneous Oncology at Moffitt Cancer Center in Tampa, FL.

How is it treated?

"If diagnosed, your choice for treatment is removal of the eye or radiation. They're both equally effective, but you lose your vision with both. Radiation is not performed for vision preservation, just for cosmetic preservation," said Patel.

Immunotherapy drugs like pembrolizumab (Keytruda) or nivolumab (Opdivo) that work well in patients with much more common skin melanomas are far less effective for patients with ocular melanoma, therefore patients with metastatic eye cancer are candidates for clinical trials with newer agents that may show more promise than the currently available drugs, said Eroglu.

Eroglu and Zager, who are leading research for the treatment of OM that has traveled to the liver — the FOCUS trial — hope that percutaneous hepatic perfusion, a surgical procedure that delivers high dose chemotherapy to the liver, is the key to increasing survival in these patients.

How likely is survival after diagnosis?

When the cancer is confined to the eye, the 5-year survival rate is 80 percent. Survival rates tend to be better if the cancer is found early, but early detection can be difficult since the cancer does not present with symptoms most of the time.

"Half of cases will ultimately metastasize. But it can be a delayed metastasis," said Patel. "Thirty percent of people will have metastasis at year five, 40 percent at year 10, and 45 percent at year 15. The cancer cells go directly into the bloodstream and typically travel to the liver."

Once the cancer spreads it becomes much more difficult to treat.

"We can't use chemo to treat. What works for skin melanoma typically doesn't work for eye melanoma."

Therefore, 5-year survival for metastatic eye cancer is less than 10 percent.

"We don't know what causes this cancer, we don't know the underlying risk factors, so it is challenging to recommend preventive strategies, but in general it's a good idea for people to wear sunglasses with ultraviolet protection," said Patel.