This study will try to identify markers of immune activity in uveitis patients that
correlate with the state of disease activity. Uveitis is a group of inflammatory eye
diseases that can cause vision loss. The study will examine whether certain substances in
the blood can predict a reactivation of disease before it occurs, and how therapy may
influence the activity of these substances. Previous studies have found some possible
markers called GITR (glucocorticoid induced TNF related family receptor), SOCS (suppressors
of cytokine secretion), and interleukin-15. Markers such as these may help guide physicians
in safely tapering medicines in uveitis patients.
Patients 18 years of age and older with sight-threatening uveitis may be eligible for this
study. Participants are slowly tapered off their medicines when their disease is stable and
there is no evidence of significant inflammation. If the disease remains inactive during
tapering, all drug therapy is eventually stopped. Patients have eye examinations about every
1 to 3 months when the disease is quiet and every 2 to 4 weeks during flare-ups. Blood
samples are drawn 2 to 3 times a year. In addition, patients may have the following
procedures if needed:
- Eye photography: Eye drops are given to enlarge the pupils for a thorough eye
examination, and a special camera is used to take photographs.
- Fluorescein angiography: This test checks for abnormalities of eye blood vessels. A
yellow dye is injected into an arm vein and travels to the blood vessels in the eyes.
Pictures of the retina are taken with a special camera that flashes a blue light into
the eye. The pictures show if any dye has leaked from the vessels into the retina,
indicating possible abnormalities.
Indicators of disease activity in supposed autoimmune conditions are actively being sought.
We have already described the increased expression of GITR-glucocorticoid induced
TNF-related family receptor during active disease and a decrease in its expression when
disease activity diminishes. We have preliminary observations in uveitis patients to suggest
that suppressors of cytokine activity (SOCS) 1, 3, and 5 may also be active during either a
Th1 or Th2 mediated disease. We wish to see if there is a correlation between these markers
and whether they can serve as an indicator of impending activation of disease before actual
clinical disease, and how therapy may alter their expression. Patients with uveitis will
receive standard evaluation and treatment for inflammatory uveitis under this protocol Blood
will be drawn when specific clinical criteria are reached for correlation of potential
markers with disease activity.
- INCLUSION CRITERIA:
- Patients with bilateral sight threatening uveitis requiring systemic immunotherapy
who are 18 years and older are eligible. Disease can be active or quiescent, but
subjects must be on a minimum prescribed therapy upon enrollment of a dose averaging
at least 20 mg/day (or greater than or equal to 0.25 mg/kg/day) of systemic
prednisone or a more intensive immunosuppression regimen. More intensive regimens may
include from one to three anti-inflammatory treatments for uveitis that include any
one of the following (or related) compounds: corticosteroids (including systemic or
periorbital administration), topical corticosteroids (when used in combination with
other agents), cyclophosphamide, cyclosporine, azathioprine, chlorambucil,
tacrolimus, leflunomide, mycophenolate mofetil, or methotrexate.
- Patients who have non-infectious intermediate, posterior, or panuveitis of at least 3
months duration. Included conditions may include but are not limited to intermediate
uveitis of the pars planitis subtype, sarcoidosis, the Vogt-Koyanagi-Harada (VKH)
syndrome, birdshot retinochoroidopathy, retinal vasculitis and sympathetic
- Patients who are 18 years of age or older.
Subjects will not be able to enroll if they:
- Are unwilling or unable to give blood at the designated times in the protocol.
- Have another disease or condition affecting vision that will interfere with obtaining
- Are pregnant