This study will evaluate the effectiveness and side effects of a new formulation of triamcinolone acetonide for treating macular edema (swelling in the back of the eye). Triamcinolone is a steroid drug that decreases inflammation and scarring and is routinely used to treat eye inflammation or swelling. The commercially available form of this drug is associated with potentially harmful side effects thought to be due to preservatives in the preparation. This study will use a formulation that does not contain these potentially harmful preservatives. Preliminary findings from other studies suggest that injection of steroids in the eye can reduce macular edema and improve vision. However, they may also cause side effects ranging from mild discomfort to vision-threatening conditions. The effects of the drug on macular edema are not known.

Patients 18 years of age and older with retinal thickening due to macular edema in the study eye and best corrected visual acuity worse than 20/40 in the study eye may be eligible for this study.

Participants undergo the following tests and procedures:

- Medical history and physical examination

- Eye examination to assess visual acuity (eye chart test) and eye pressure, and to examine pupils, lens, retina and eye movements. The pupils will be dilated with drops for this examination.

- Fluorescein angiography to evaluate the eye's 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 using a 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 blood vessel abnormality.

- Optical coherence tomography to measure retinal thickness. This test shines a light into the eye and produces cross-sectional pictures of the retina. These measurements are repeated during the study to determine if retinal thickening is getting better or worse, or staying the same.

- Stereoscopic color fundus photography to examine the back of the eye. The pupils are dilated with eye drops to allow examination and photography of the back of the eye.

- Triamcinolone acetonide injections to treat the eye. A numbing eye drop and an antibiotic eye drop are put in the eye before triamcinolone acetonide is injected. The drug is given either as a 4 mg or 8 mg intravitreal injection (injected with a needle into the vitreous, the jelly-like substance inside the eye) or a sub-tenon injection (injected with a needle under the thin outer surface of the eye, just below the lower eyelid). After the injection, a cold compress is put on the eye for 5 minutes, and an antibiotic eye drop is used for 2 days following treatment.

Patients return to the clinic for follow-up visits 1 day, 7 days, and 1 month after each treatment. Patients whose condition does not improve after 3 months do not receive any more injections, but return for eye examinations at least once a year for 3 years. Patients whose condition improves with treatment return for follow-up visits 6 and 9 months after the first injection and then every 6 months for 2 more years. At each visit, a determination is made whether another injection is needed.

Treatment or Intervention	Phase
Drug: Triamcinolone Acetonide	Phase I

Further Study Details: 

Expected Total Enrollment:  120

The use of intravitreal injections of corticosteroid (triamcinolone acetonide) appears to be a

promising treatment for a variety of ocular diseases associated with inflammation. To date,

the only drug available, "Kenalog -40 Injection" produced by Bristol Myers Squibb, has not been formulated for intraocular use.

The purpose of this study is to evaluate the long-term safety and potential efficacy of novel

intravitreal injections of a preservative-free formulation of triamcinolone acetonide (TAC-PF)

at two dosage levels (4 mg and 8 mg) compared to anterior sub-tenon injections of TAC-PF at

20 mg.

The study will be a masked, randomized Phase I study that will enroll 120 participants with one

of the following diseases: age-related macular degeneration (AMD), diabetic macular edema

(DME), central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), or any

other retinal disease with associated macular edema. The participants will be randomly assigned to one of the three treatment groups. At least 21 participants will be enrolledin the four designated disease strata: AMD, DME, CRVO, and BRVO. The remaining 36 participants may have one of these diseases or may be enrolled with another retinal disease. Within each disease strata, at least seven participants will be randomized to each dosing group. Depending on a participant's response, injections may be repeated at 3-month intervals. Participants will be followed until the last enrolled participant completes 3 years of follow-up.

The primary outcome will be an assessment of post-injection intraocular toxicity-related events

during the 3-year follow-up, including cataract formation, development of glaucoma, and any

adverse event preventing retreatment. The secondary outcomes will be an improvement in best-corrected visual acuity (BCVA, EVA) and decreases in retinal thickening and area of leakage, from baseline to year 1.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA
-Understand and sign the informed consent.
-Be at least 18 years of age.
-Have definite retinal thickening due to macular edema in the study eye, based on the clinical exam.
-Have retinal thickness greater than or equal to 250 microns in the central subfield on OCT.
-Have BCVA worse than 20/40 in the study eye.
-Have sufficiently clear ocular media to permit good quality retinal photographs and angiography to allow assessment of macular area according to standard clinical practice.
-Be able to comply with the study requirements.
EXCLUSION CRITERIA
-Have intraocular pressure greater than 25 or history suggesting glaucoma (e.g., history of the diagnosis of glaucoma, disc/nerv fiber layer defects suggestive of glaucoma) or glaucomatous visual field defects as documented by Goldmann or Humphrey perimetry taken within 6 months to qualification.
- Be allergic to fluorescein dyes.
-Have medical conditions that make consistent follow-up over the treatment period unlikely (e.g., stroke, severe MI, end-stage cancer, or history of chronic renal failure requiring dialysis or kidney transplant).
-Have blood pressure greater than 180/110.
-Be currently using or be likely to need systemic or ocular medications known to be toxic to the lens, retina, or optic nerve, such as:
a. Deferoxamine
b. Chloroquine/Hydroxychloroquine (Plaquenil)
c. Tamoxifen
d. Phenothiazines
e. Ethambutol
-Have used experimental therapies for the present disease in the past 6 months.
- Have any contraindication to performing the necessary diagnostic procedures.
-Have a history of or current acute ocular or periocular infection (including any history of ocular herpes zoster or simplex).
-Have had any major intraocular surgical procedure within one month of enrollment.
-Have used systemic steroids in excess of an average 20 mg daily dose for the past 3 months.
- Have a known history of untoward complications from corticosteroid therapy, including elevated intraocular pressure in response to topical or periocular corticosteroids.
-Have a history of other antiangiogenic treatment in the last 6 months or concomitant administration of other therapies for the presented disease.

Maryland
      National Eye Institute (NEI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050071; 05-EI-0071
Record last reviewed:  December 16, 2004
Last Updated:  March 5, 2005
Record first received:  January 12, 2005
ClinicalTrials.gov Identifier:  NCT00101764
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08