Lucentis for Inflammatory Macular Edema Trial

Uveitis, an inflammation that affects the uvea (iris, ciliary body and choroid), is an
important cause of visual loss. There are 30,000 new cases of legal blindness each year due
to uveitis in the U.S. Sight-threatening complications associated with uveitis include
macular edema, which may persist even when inflammation is controlled. The only current
treatment for cystoid macular edema (CME) in uveitis patients is oral or regional steroid
injections. For patients who don't respond to steroids or who are unable to tolerate steroid
therapy, there are no other medical treatments.

The aim of the proposed research is to determine if ranibizumab is an effective treatment for
those patients with uveitis-induced CME who are unable to be treated with or non-responsive
to steroids. Ranibizumab is a recombinant, humanized monoclonal antibody antigen-binding
fragment (Fab) that neutralizes all active forms of vascular endothelial growth factor
(VEGF). VEGF is suspected to play a role in the loss of vascular integrity in the eye, which
is thought to be involved in the pathogenesis of macular edema in the eyes of patients with
uveitis. Ranibizumab was approved by the FDA for the treatment of neovascular age-related
macular degeneration on June 30, 2006, and a number of published papers have shown efficacy
for other causes of macular edema, including that due to diabetes mellitus.

The F. I. Proctor Foundation at UCSF will be enrolling 10 subjects 18 years of age or older
with uveitis-induced CME to clinically evaluate the safety and effectiveness of ranibizumab
administered monthly for three months followed by PRN monthly dosing (up to 12 months). The
study will measure visual acuity, changes in foveal thickness on optical coherence
tomography, and changes in cystoid macular edema by fluorescein angiography to determine the
efficacy of ranibizumab treatment.

Inclusion Criteria:

- Ability to provide written informed consent and comply with study assessments for the
full duration of the study

- Age ≥ 18 years

- A history of non-infectious uveitis with chronic cystoid macular edema (> 3 months
duration)

- Foveal retinal thickness of ≥ 300 µM by OCT testing

- One prior trial of oral or regional steroid treatment for CME ≥ 30 days prior to study
enrollment with persistent CME (≥ 300 µM foveal retinal thickness on OCT) or inability
to use steroid injections due to a history of increased IOP above 30 mmHg thought to
be due to topical steroid treatment or prior steroid injections

- Anterior chamber and vitreous inflammation at the trace or below level according to
the standardized classification of inflammation

- BCVA at 4 m using the ETDRS chart of 20/40 to 20/400 (Snellen equivalent) in the study
eye

- Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT
testing and retinal photography

Exclusion Criteria:

- Pregnancy (positive pregnancy test) or known to be pregnant, or premenopausal but not
using adequate contraception

- Treatment for CME with oral or steroid injections, Macugen, or Avastin within 6 weeks
prior to enrollment in this study. Study subjects will be allowed to continue their
immunomodulatory treatment for uveitis throughout the study.

- Previous vitrectomy

- Active intraocular inflammation in the study eye (greater than trace anterior chamber
or vitreous cells)

- Current vitreous hemorrhage

- Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either
eye

- Known allergy to any component of the study drug

- Intraocular pressure > 30 mm Hg despite treatment with glaucoma medications

- Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood
pressure is brought below 180/110 by anti-hypertensive treatment, the subject can
become eligible.

- Major surgery planned during the next 6 months

- Any other condition that the investigator believes would pose a significant hazard to
the subject if the investigational therapy were initiated

- Participation in another simultaneous medical investigation or trial

- Unwilling or unable to follow or comply with all study related procedures