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
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
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.
Sight threatening uveitis may require long term use of systemic immunosuppressants. In some
patients, aggressive systemic immunosuppressive therapy fails to control inflammation and
can lead to serious side effects. Oral Cyclosporin A (CsA) has been shown in several human
trials to be effective in treating chronic uveitis. This pilot study will assess the
safety, and to some extent efficacy, of a novel intraocular CsA release implant in patients
with active inflammation and poor visual acuity in one eye despite immunosuppressant
therapy. Patients will be randomly assigned to receive in one eye a 1 or 2 mg CsA implant
releasing at either 0.8 microgram per day or 1.4 microgram per day respectively. The main
purpose of the study is to assess the safety of the CsA implant. Secondary outcomes will
include a change from baseline in the ocular inflammation, visual acuity, and the need for
concomitant anti-inflammatory medications.
Age range: 15 or older.
Active non-infectious intermediate, posterior or panuveitis present for at least 6 months
despite systemic immunosupressive therapy including at least 20 mg of oral prednisone or
use of another immunosuppressive agent.
Visual acuity worse than 20/80 (55 letters) and better than 5/200 (4 letters) in the eye
to receive the CsA implant, and better than 20/80 (54 letters) in the non-study eye.
Bilateral or unilateral uveitis with active inflammation in one eye only (eye to be
implanted). Patients may continue systemic immunosuppressants with the exception of
systemic CsA. Patients may not take greater than 1 drop of topical steroid four times a
day in the eye to be implanted for maintenance of anterior segment inflammation after 1
Recordable electroretinogram (ERG).
Willingness and the ability, with assistance of a care giver, if necessary, to comply with
treatment and follow-up procedures.
The ability to understand and sign an informed consent form which must be obtained prior
Negative serum pregnancy test (females of childbearing potential only).
Normal serum creatinine (males 0.9 - 1.4 mg/dL, females 0.7 - 1.3 mg/dL).
No current or past history of retinal detachment.
Current or past history of retinal detachment.
Pregnant or lactating patients or patients with potential for conception unless using
effective contraception. Fertile males must use effective contraception. Contraception
would no longer be mandatory for participation in this study at three months
postoperatively assuming (1) negligible CsA absorption, (2) patient is not taking any
other medications that may affect a developing fetus or spermatogenesis.
Patients who received therapy within the previous one week with any nephrotoxic drugs.
Patients having a known allergy to CsA.
Patients receiving current therapy with CsA. Patients need to be off of systemic CsA
seven days prior to implant surgery. Patients may continue other immunosuppressive
therapies if needed to control inflammation in contralateral (non-study) eye provided the
inflammation is currently not active.