Retinal Vasculitis in Woman Linked to Secondary CAD: Case Study

Treatment with infliximab and corticosteroids helped improve her vision

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A person looks through a telescope toward the sky, but the end of the telescope shows a closeup of an eye.

A woman with cold agglutinin disease (CAD) secondary to a cancer also developed bilateral retinal vasculitis — inflammation of the blood vessels found at the back of both eyes — in what researchers claim to be “the first report of retinal vasculitis in a patient with CAD.”

Initial treatment consisted of obinutuzumab, a cancer medication, but response was minimal. A good response was then achieved with infliximab, an anti-inflammatory medication, and corticosteroid methylprednisolone.

“Our report not only describes the unique course of CAD-related retinal vasculitis, but also introduces and underscores a successful therapeutic plan,” the researchers wrote.

The report, “Bilateral retinal vasculitis associated with cold agglutinin disease treated with obinutuzumab and infliximab,” was published in the American Journal of Ophthalmology Case Reports.

CAD occurs when some of the body’s B-cells make a type of autoantibodies called cold agglutinins. These autoantibodies bind to red blood cells at low temperatures, causing them to clump together (agglutinate) and ultimately die.

The disease usually occurs well into adulthood, and is more common in women and the elderly. Its symptoms may vary from person to person, but most often include joint pain, muscle weakness, anemia, tiredness, and abnormally pale skin. Ocular (eye) manifestations are rare.

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Bilateral retinal vasculitis associated with secondary CAD

Now, researchers in the U.S. described the rare case of a 69-year-old woman who developed bilateral retinal vasculitis associated with secondary CAD.

The woman was referred to an eye specialist due to gradually worsening, blurry vision in both eyes, especially in the right eye. She had a past history of epiretinal membrane, which is a tissue-like scar that forms on top of the retina, the light-sensitive layer at the back of the eye that plays a key role in vision.

She also had a one-year history of joint disease in both knees, difficulty breathing, and productive cough, for which she had been taking low doses of prednisone and methotrexate. Prednisone is a corticosteroid and methotrexate is an immunosuppressant medication often used in the treatment of joint disease.

Her visual acuity was 20/40 in the right eye and 20/25 in the left one. A slit-lamp examination revealed nuclear sclerotic cataracts (a type of cloudy patches) in both eyes. A dilated fundus examination, in which special eye drops are used to dilate the eye’s pupil, revealed a hazy vitreous humor (the usually clear gel that fills the inside of the eyeball) and blood vessels narrower than normal.

An angiography, which uses a contrast dye called fluorescein to give a detailed view of the blood vessels at the back of the eye, revealed the presence of leaky blood vessels in both eyes.

Blood testing also revealed she had a decrease in the amount of red blood cells in the blood, or hematocrit, and strong agglutination. She also tested positive for antinuclear antibodies, a type of autoantibodies present in many autoimmune diseases.

She stopped taking methotrexate and began treatment with mycophenolate mofetil, another immunosuppressant medication, in addition to prednisone. However, there was “little to no improvement” in her symptoms.

Further tests revealed the presence of cold agglutinins in her blood. A thermal amplitude test, which measures the temperature at which red blood cells clump together, revealed that agglutination occurred at 30 C (86 F). Based on these findings, a diagnosis of CAD was made.

A bone marrow examination revealed the presence of too many B-cells, a finding that echoed what happens in chronic lymphocytic leukemia — a type of B-cell cancer. Sometimes, CAD occurs in association with cancer or other illnesses, in which case it is called secondary CAD.

To treat the cancer while also addressing ocular vasculitis associated with CAD, the woman underwent eight cycles of obinutuzumab over three months. Obinutuzumab is an anti-CD20 antibody that targets B-cells and is sold as Gazyva in the U.S. and as Gazyvaro in Europe. It was given by infusion into a vein, first weekly and then every 2–3 weeks.

Treatment results

After three months of treatment, her best corrected visual acuity remained stable at 20/30 in her right eye and  20/20 in the left one. There was also less agglutination, but angiography conducted six months after treatment initiation still showed signs of blood leakage.

As an alternative treatment, she was given intravenous (into-the-vein) infliximab in combination with methylprednisolone. Infliximab (sold as Remicade, among other brand names) is an antibody that binds to and blocks tumor necrosis factor-alpha (TNF-alpha), a molecule that triggers inflammation. After two treatment cycles, blood leakage had improved and visual acuity remained stable at 20/25 in both eyes.

“It remains unclear whether CAD was the definitive cause of the retinal vasculitis,” the researchers wrote, adding “future studies will be needed to further understand the potential associations between retinal vasculitis and CAD and to guide clinical management.”

At the time of the report’s writing, the woman remained clinically stable on infliximab, but the team was planning a switch to an oral immunomodulatory treatment.