Complications of Immunosuppressive Therapy for Eye Diseases Cohort (SITE) Study
The Complications of Immunosuppressive Therapy for Eye Diseases Cohort (SITE) Study is a multicenter study of approximately 8,000 patients with inflammatory eye diseases followed retrospectively for up to 25 years for mortality (death), using the National Death Index. The study is funded by the National Eye Institute.
What ARE OCULAR INFLAMMATORY DISEASES and Why is the SITE Study Important?
Uveitis refers to a several ocular disorders characterized by intraocular inflammation that involves one or more of the three parts of the eye that comprise the uvea: the iris (the colored part of the eye), the ciliary body (behind the iris, responsible for manufacturing the fluid inside the eye), and the choroid (the vascular lining tissue underneath the retina. (For a diagram of the eye, click here. Ocular inflammatory diseases are the third leading cause of blindness in the United States. In addition to producing profound and irreversible vision loss, especially when unrecognized or treated improperly, other frequent complications include cataract; glaucoma; retinal detachment; neovascularization of the retina, optic nerve, or iris; and cystoid macular edema, the most common cause of decreased vision from uveitis..
Although uveitis and other ocular inflammatory diseases result from many causes, the most common cause is autoimmunity. The immune system is designed to offer protect against germs and other diseases. However, when the immune system malfunctions, it begins to inappropriately “attack” a part of the body. This is called autoimmunity. To control autoimmune problems, patients are often prescribed immunosuppressive medication.
Many patients with ocular inflammation can be treated with topical, periocular, or oral corticosteroids. However, for some patients, supplementary immunosuppression with antimetabolite, T-cell inhibitor, and/or alkylating agent therapies is required to control inflammation without causing excessive side effects. Studies of patients with severe immunologic or other systemic diseases suggest that such treatments may result in an increased risk of cancer and other diseases. However, it is unknown whether the increased risk is the result of these treatments or the underlying systemic diseases.
The SITE study will evaluate whether immunosuppressive therapy for ocular inflammatory diseases is associated with an excess risk of mortality, cancer, and other major diseases. The study is expected to generate critical information in deciding whether immunosuppressive therapy is justified for such patients, and whether certain such agents should be avoided. The study also will provide a rich database for studies evaluating outcomes of ocular inflammatory diseases.
SITE STUDY DESIGN
The study has a retrospective cohort design. Patients "exposed" to immunosuppressive therapies will be compared to both the general U.S. population and to a comparison group of patients with the same ocular inflammatory diseases but who did not receive immunosuppression. An estimated 7689 patients will be accrued from four centers that pioneered the use of immunosuppressive therapy for eye diseases, beginning 19-29 years ago. The four centers are: The Wilmer Eye Institute (Baltimore, Maryland); the Casey Eye Institute (Portland, Oregon); the National Eye Institute (Bethesda, Maryland) and the Massachusetts Eye Research and Surgery Institute (formerly the Ocular Immunology Service of the Massachusetts Eye and Ear Infirmary) (Boston, Massachusetts).
Patients who received immunosuppressive therapy for eye diseases, and patients with the same ocular inflammatory diagnoses who did not, are identified retrospectively through a review of patient charts at the four centers. Patients who have died are being identified through a search of the National Death Index and other databases. Cause of death is abstracted from death certificates into the National Death Index. Patients still living will be contacted and queried regarding the occurrence of cancer, heart disease, and other diagnoses. Next of kin also will be interviewed for subjects who have died to ascertain whether such diagnoses occurred prior to death. An Outcomes Committee will verify the presence of cancer, heart disease and other diagnoses by reviewing medical records.
The primary outcome measures are mortality, cause-specific mortality, and cancer incidence. Secondary outcome measures are the beneficial effects of immunosuppression and the clinical outcomes of these disease conditions, based on clinical information.
SITE STUDY STATUS
Data collection began in May 2005. To date, the records of approximately 450 patients have been entered into the study.
CPOB’s Role in the SITE Study
John Kempen, MD, PhD., CPOB’s Director of Ocular Epidemiology is the Principal Investigator of the SITE Study.
For more information on the SITE Study, contact Dr. John Kempen.