Intraocular lymphoma, also known as vitreoretinal lymphoma, is a rare form of non-Hodgkin lymphoma (NHL). Intraocular means “inside the eye” and lymphoma is a type of cancer. The tumors of intraocular lymphoma can result in visual changes and sometimes cognitive or behavioral changes. As a “masquerade syndrome,” intraocular lymphoma can mimic characteristics of common eye conditions such as chronic uveitis (eye inflammation). The similar symptoms have made intraocular lymphoma one of the most difficult types of eye cancer to diagnose and treat.

Intraocular lymphoma is very rare, making up less than 1 percent of total NHL cases. In 2020, about 3,400 adults in the U.S. were diagnosed with ocular cancers, including lymphoma, melanoma, and others. However, there is no central database for intraocular lymphoma, so it is difficult to estimate its exact prevalence.

This article discusses an overview of intraocular lymphoma, including causes, risk factors, symptoms, diagnosis process and procedures, and current treatments.

What Is Intraocular Lymphoma?

Intraocular lymphoma is a type of cancer that arises from an abnormal immune response of lymphoid cells (a type of white blood cells) located inside of the eyeball. Most intraocular lymphomas affect the:

• Retina — The light-sensitive inner layer at the back of the eye
• Vitreous fluid — The fluid inside the eyeball
• Optic nerve head — The start of the optic nerve that sends visual signals from the eye to the brain

Between 80 percent to 90 percent of people will develop intraocular lymphoma in both eyes.

Intraocular lymphoma is a high-grade (fast-growing) cancer. It is also a subtype of primary central nervous system lymphoma (PCNSL). PCNSL is a rare form of diffuse large B-cell lymphoma in the majority of cases, although sometimes T-cell lymphomas can occur. About 90 percent of people who have intraocular lymphoma will develop central nervous system (CNS) lymphoma within approximately two years. Intraocular lymphoma can develop before, after, or at the same time as CNS lymphoma. The CNS includes the brain, spinal cord, and optic nerves.

There are two main types of intraocular lymphoma: primary and secondary. Primary intraocular lymphoma (PIOL) arises from the central nervous system and is more common. PIOL affects the retina, vitreous fluid, and optic nerve head. Secondary intraocular lymphoma (SIOL) is lymphoma that has spread to the eye from another part of the body. SIOL commonly affects the uvea of the eye (the middle layer of the eye), specifically the layer called the choroid.

Signs and Symptoms of Intraocular Lymphoma

A common sign of intraocular lymphoma is uveitis, or eye inflammation, which occurs in 75 percent of cases. Symptoms of intraocular lymphoma may respond to uveitis treatment, which makes it a challenge for clinicians to properly diagnose intraocular lymphoma. Additionally, some people may have vitreitis, an inflammation of the vitreous of the eye that requires an examination to diagnose.

The most common symptoms include:

• Blurred vision
• Floaters
• Decreased vision or vision loss
• Common symptoms of lymphoma, like fatigue, night sweats, and weight loss
• Eye swelling
• Eye redness
• Sensitivity to light (photophobia)
• Eye pain

If intraocular lymphoma occurs with CNS involvement, a person may also experience:

• Behavioral and cognitive changes
• Seizures
• Impaired balance or coordination
• Muscle weakness or paralysis

Intraocular Lymphoma Causes and Risk Factors

The cause of intraocular lymphoma is unknown. However, experts have identified some risk factors. A risk factor is something that can make a person more likely to develop cancer. Having one or several risk factors doesn’t guarantee a person will develop cancer, however, and a person can also develop cancer without having any risk factors.

People who have compromised immune systems and who are over the age of 60 are considered at a higher risk of developing intraocular lymphoma. Other risk factors include:

• HIV/AIDS, rheumatoid arthritis, or other autoimmune disorders
• Epstein-Barr virus infection
• Immunosuppressive drugs

Intraocular lymphoma is commonly found in people ages 50 to 60. The age range of people who develop PIOL is 15 to 85 years of age. Sex and race do not seem to affect the risk of intraocular lymphoma.

Diagnosis of Intraocular Lymphoma

Intraocular lymphoma is difficult to diagnose because it looks or acts like other eye conditions. A delayed diagnosis can cause the intraocular lymphoma to spread to the brain and spinal cord and decrease a person’s survival time. However, recent advancements in the diagnostic tools to detect intraocular lymphoma early offer a promising outlook for many people.

Diagnosing intraocular lymphoma may involve biopsies, imaging tests, and genetic testing.

Biopsy

A vitrectomy, or taking a sample of vitreous tissue, is one of the primary diagnostic tests to diagnose intraocular lymphoma. Intraocular lymphoma cells are typically found within the vitreous of the eye and appear larger compared to normal lymphocytes.

Imaging Tests

There are a few ocular imaging tests that may be performed to diagnose lymphoma or rule out other inflammatory ocular conditions.

• Fluorescein angiography is used to visualize cancer cells, lesions, or tumors in the eye.
• Optical coherence tomography is used to visualize subretinal layers of the eye and check for lesions. It is also used to see if the cancer is getting better or worse.
• Fundus autofluorescence is used to detect vitritis. Yellowish-brown lesions called “leopard spots” indicate the presence of intraocular lymphoma cells.
• A magnetic resonance imaging (MRI) scan of the brain may be performed to check for any lesions (tumors) that may have developed. About 25 percent of people will present with lesions in their CNS.

Genetic Tests

Researchers from the University of California, San Francisco and the Proctor Foundation have recently created a new diagnostic tool for intraocular lymphoma, called metagenomic deep sequenc­ing (MDS). MDS takes a sample of intraocular fluid and detects intraocular lymphoma biomarkers (such as genetic mutations, bacteria, and viruses). This method is a major advance that may replace the need for biopsies for intraocular lymphoma in the future.

Treatments for Intraocular Lymphoma

Intraocular lymphoma is typically treated with chemotherapy or radiation therapy. It is important for your oncologist, ophthalmologist, and pathologist to work together in the treatment plan of your intraocular lymphoma.

Chemotherapy

Chemotherapy can be administered in various ways: through a vein, through the spinal fluid, or directly in the eye. Delivering the chemotherapy to the eye or spinal fluid allows the ophthalmologist to treat the tumor directly and decrease potential side effects. The most commonly prescribed drugs are methotrexate and Rituxan (rituximab).

Orbital Radiation Therapy

Radiation therapy essentially uses high amounts of energy to kill the cancer cells or shrink tumors. Low-dose external beam therapy is a more preferred treatment in people with bilateral intraocular lymphoma. It may also be effective in preventing cancer from spreading to the brain or spinal cord. This treatment can affect vision.

Prognosis for Intraocular Lymphoma

Intraocular lymphoma is often diagnosed late and after cancer has spread to the brain. As a result, the prognosis (outlook) is not very good, with an overall survival rate of about three years. Factors that determine the outlook of disease vary from person to person, however. People with intraocular lymphoma should discuss their disease prognosis with their doctor.

Talk With Others Who Understand

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