This study will evaluate the safety and effectiveness of a sustained-release cyclosporin
implant to treat uveitis, a sight-threatening eye inflammation caused by an immune system
abnormality. Previous studies in humans have shown that, taken by mouth, the drug cyclosporin
is effective in treating chronic uveitis.
Uveitis may require long-term treatment with potent immune-suppressing drugs, such as
cyclosporin, cyclophosphamide, methotrexate, azathioprine or steroids. Taken systemically (by
mouth or injection), however, these drugs can do serious damage to the kidneys, liver or
lungs, and can raise blood pressure and lower blood cell counts. Because of this, some
patients cannot or will not use these medicines.
This small pilot study will evaluate the safety, and to some extent effectiveness, of
cyclosporin delivered directly into the eye, to try to prevent harmful side effects. In
animal studies, sustained-release cyclosporin implants did not cause the severe side effects
seen with systemic use of the drug. Some animals developed opacity of the lens and slowed
retinal responses, both of which reversed when the drug was stopped. Earlier animal studies
of cyclosporin injected directly into the eye reduced inflammation that had been produced
experimentally.
Patients with uveitis who have active inflammation and poor vision are eligible to
participate in this study. Patients will be randomly assigned to one of two treatment groups.
One group will receive a 1-mg implant that releases 0.8 micrograms of drug each day; the
second group will receive a 2-mg implant that delivers 1.4 micrograms of drug a day.
Before surgery, patients will have a medical history, basic physical examination, and
complete eye examination, including special tests called electroretinogram and fluorescein
angiography. An electroretinogram measures the electrical responses generated in the retina
in the back of the eye. Fluorescein angiography uses a special camera to photograph the
retina, showing the condition of the blood vessels in the eye.
The surgical procedure to place the implant takes about 1.5 hours and may be done under
either local or general anesthesia. Patients will stay in the hospital overnight. After
discharge from the hospital, they will return for follow-up visits 1 and 2 weeks after
surgery, then once a month for 6 months, and then every 3 months until the implant is
depleted of drug or removed. During these follow-up visits, eye examinations will be repeated
to evaluate the effects of the implant on the eye. Repeat blood tests will measure the amount
of cyclosporin in the blood and the drug's effect on the kidneys. When the implant runs out
of drug (between 2 and 3 years), it may be removed or left in place.