Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade in Patients with Metastatic Melanoma: A New Cause of Uveitis.
J Immunother. 2004 Nov;27(6):478-479.
Robinson MR, Chan CC, Yang JC, Rubin BI, Gracia GJ, Sen HN, Csaky KG, Rosenberg SA.
From the *National Eye Institute, National Institutes of Health, Bethesda, Maryland; and daggerSurgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) is an important costimultory receptor expressed on activated T cells. CTLA-4 blockade using a monoclonal antibody (mAb) in conjunction with tumor vaccines has improved tumor responses in animal models and enhanced numerous models of T cell-associated autoimmune diseases. Two patients with stage IV metastatic melanoma vaccinated with the gp 100 melanocyte/melanoma differentiation antigen either before or during anti-CTLA-4 mAb therapy developed uveitis. This is the first report of autoimmune disease involving the eye in patients treated with anti-CTLA-4 mAb. This suggests that CTLA-4 is an important regulatory molecule for maintenance of tolerance to melanosomal antigens and prevention of uveitis.
Medline on Uveitis.
Uveitis is an inflammation of the the uvea, the layer between the sclera and the retina, which includes the iris, ciliary body, and the choroid.
Causes, incidence, and risk factors
Uveitis is an inflammation inside the eye, affecting the uvea. The uvea provides most of the blood supply to the retina. Causes of uveitis can include autoimmune disorders, infection, or exposure to toxins. However in many cases, the cause remains unknown.
The most common form of uveitis is anterior uveitis, which involves inflammation in the front part of the eye, which is usually isolated to the iris. This condition is often called iritis. The inflammation may be associated with autoimmune diseases such as rheumatoid arthritis or ankylosing spondylitis, but most cases occur in healthy people and do not indicate an underlying disease. The disorder may affect only one eye and is most common in young and middle-aged people. A history of an autoimmune disease is a risk factor.
Pars planitis is inflammation of the pars plana, a narrow area between the iris and the choroid. Pars planitis usually occurs in young men and is generally not associated with any other disease. (There have been a few case reports of an association with Crohn's disease and some experts suggest a possible association with multiple sclerosis. For this reason, these experts recommend that those over 25 years old diagnosed with pars planitis receive an MRI of their brain and spine.)
Posterior uveitis affects the back portion of the uveal tract and involves primarily the choroid. This is called choroiditis. If the adjacent retina is also involved it is called chorioretinitis. Posterior uveitis may follow a systemic infection or occur in association with an autoimmune disease.
The inflammation causes spotty areas of scarring on the choroid and retina that correspond to areas with vision loss. The degree of vision loss depends on the amount and location of scarring. If the central part of the retina, called the macula is involved, central vision becomes impaired.
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