Sirolimus as Therapeutic Approach to Uveitis

Uveitis is a condition in which certain parts of your eye become inflamed. The inflammation
is usually recurrent. If the inflammation is not treated adequately, permanent damage to the
eye and to the vision may occur. The inflammation can be caused by infectious or non
infectious causes. The current research is being done to determine the safety and the
usefulness of treatment of non-infectious uveitis using a drug called sirolimus.

Current treatment options for uveitis include oral corticosteroids and drugs that weaken the
immune system of the body (i.e., immunosuppressant drugs). Treatment using oral
corticosteroids, especially for long periods, may cause many undesirable side effects and
complications such as high blood sugar, high blood pressure, bone weakness, obesity, stomach
ulcers, abnormal hair growth, and increased risks of infection. In addition to that, in some
cases, the disease cannot be controlled even with the highest dose of steroids.

Injection of steroids around and inside the eye can be used to control uveitis. However, the
inflammation does not always respond to such kind of treatment. The eyes may develop high
pressure and cataract with injections of steroids into the eyes or around the eyes.

On the other hand, despite their potential effectiveness, treatment with drugs that weaken
the immune system may cause severe side effects. Increased risk of infection is a common side
effect of all the immunosuppressant drugs. The immune system protects the body from
infections. When the immune system is suppressed, infections are more likely to happen. Some
of these infections are potentially dangerous. Because the immune system protects the body
against some forms of cancer, immunosuppressant drugs are also associated with a slightly
increased risk of cancer. For example, long-term use of immunosuppressant drugs may carry an
increased risk of developing skin cancer as a result of the combination of the drugs and
exposure to sunlight. The immunosuppressive drugs are very powerful and can cause serious
side effects such as high blood pressure, kidney problems, and liver problems. Some side
effects may not show up until years after the medicine is used.

Inclusion Criteria:

1. Males and females greater than or equal to 18 years of age;

2. Able to give informed consent and attend all study visits;

3. Have diagnosis of uveitis determined by the Investigator to be non infectious;

- Have active uveitis, defined as having at least 1+ Vitreous Haze and/or at least
1+ Vitreous Cell Count (SUN scale), and:

- are receiving no other treatment; or,

- are receiving prednisone ≥10 mg/day (or equivalent dose of another
corticosteroid) and/or at least 1 other systemic immunosuppressant; or, b.
Have inactive disease, defined as having 0.5+ Vitreous Haze or less and a
grade of 0.5+ Vitreous Cell Count or less (SUN scale), and:

- are receiving prednisone <10 mg/day (or equivalent dose of another
corticosteroid) and/or at least 1 other systemic immunosuppressant.

4. Have posterior, intermediate, or panuveitis; for panuveitis, if an anterior component
is present, it must be less than the posterior component;

5. Sufficient inflammation to require systemic treatment and, based on the Investigator's
decision, warrants intravitreal or subconjunctival treatment;

6. Best-corrected (ETDRS) visual acuity of 20/40 to 20/400 (approximately 70 to 20
letters) in the study eye;

7. Best- corrected ETDRS visual acuity of 20/400 or better in the fellow eye
(approximately 20 letters).

Exclusion Criteria:

1. Patients with bilateral uveitis who are receiving systemic immunosuppressive therapy
(e.g., methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate
mofetil, tacrolimus, or azathioprine) other than prednisone or other corticosteroids
for the treatment of the uveitis, and the uveitis in the fellow eyes, in the opinion
of the investigator, cannot be controlled with standard local therapies alone;

2. Any significant ocular disease that could compromise vision in the study eye. These
include, but are not limited to:

- Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or
non-proliferative diabetic retinopathy (NPDR) that compromise the vision.

- Age-related macular degeneration;

- Myopic degeneration with active subfoveal choroidal neovascularization.

3. Any of the following treatments within 90 days prior to Day 0 or anticipated use of
any of the following treatments to the study eye:

- Intravitreal injections (including but not limited to steroids or anti-vascular
endothelial growth factors);

- Posterior subtenon's steroids.

4. Intraocular surgery within 90 days prior to Day 0 in the study eye;

5. Capsulotomy within 30 days prior to Day 0 in the study eye;

6. If the patient has had glaucoma surgery (trabeculectomy or aqueous shunt device),
there must be adequate conjunctiva

7. History of vitreoretinal surgery or scleral buckling

8. Any ocular surgery (including cataract extraction or capsulotomy) of the study eye
anticipated within the first 180 days following Day 0;

9. Intraocular pressure ≥25 mmHg in the study eye (glaucoma patients maintained on no
more than 2 topical medications with intraocular pressure (IOP) <25 mmHg are allowed
to participate);

10. Pupillary dilation inadequate for quality stereoscopic fundus photography in the study
eye;

11. Media opacity that would limit clinical visualization;

12. Presence of any form of ocular malignancy in the study eye, including choroidal
melanoma;

13. History of herpetic infection in the study eye or adnexa;

14. Presence of known active or inactive toxoplasmosis in either eye;

15. Ocular or periocular infection in either eye;

16. Participation in other investigational drug or device clinical trials within 30 days
prior to Day 0, or planning to participate in other investigational drug or device
clinical trials within 180 days following Day 0. This includes both ocular and
non-ocular clinical trials.