PeriOcular and INTravitreal Corticosteroids for Uveitic Macular Edema Trial

Macular edema is the most common structural complication and leading cause of visual loss in
patients with uveitis. Regional injections of corticosteroids are the most frequently used
treatments specifically for uveitic macular edema but there is a lack of high quality
evidence to guide choice of drug (e.g., triamcinolone acetonide, dexamethasone) and route of
administration (e.g. periocular, intravitreal). The question of how to approach regional
treatment of uveitic macular edema is a key question for ophthalmologists treating these
patients. The Periocular and Intravitreal Corticosteroids for Uveitic Macular Edema (POINT)
Trial is a randomized trial designed to compare the relative efficacy of three regional
corticosteroids commonly utilized for the initial regional treatment of uveitic macular
edema, periocular triamcinolone (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ),
intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX), and the
intravitreal dexamethasone implant (Ozurdex®, Allergan, Irvine CA) will be conducted by the
MUST Research Group clinical centers throughout the U.S. and one each in Australia and the
UK. After signing informed consent and undergoing eligibility evaluation, eligible patients
will be randomized to one of the three study treatments to be administered at the first study
visit. Randomization is by participant, if both eyes meet eligibility requirements then both
eyes receive assigned treatment. The design outcome is the percent change in central subfield
macular thickness on OCT from baseline to the 8 week visit. After assessment of the primary
outcome at 8 weeks, second injections and best medical judgment will be used if macular edema
has not improved as follows:

Eye(s) meeting trial eligibility criteria receive initial injection of assigned treatment at
P01 visit.

Second injection of assigned treatment permitted at 8 week visit for periocular triamcinolone
and intravitreal triamcinolone and at 12 week visit for intravitreal dexamethasone if

- Eye does not meet the improvement definition (a 20% decrease in central subfield
thickness of the macula) or

- Eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central
subfield or

- ME is worse after initial improvement

And the following repeat injection criterion are met:

• IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

Eyes demonstrating no improvement or worsening of ME as measured by the central submacular
thickness on OCT (at week 12 for periocular and intravitreal triamcinolone arms and at week
20 for intravitreal dexamethasone arm) are considered primary treatment non-responders.

Inclusion Criteria:

Eye level inclusion criteria - at least one eye must meet all of the following conditions:

- Non-infectious anterior, intermediate, posterior or panuveitis; either active or
inactive uveitis is acceptable;

- Macular edema (ME) defined as the presence of central subfield macular thickness
greater than the normal range for the OCT machine being used, regardless of the
presence of cysts, as assessed by study ophthalmologist;

- Best corrected visual acuity (BCVA) 5/200 or better;

- Baseline intraocular pressure > 5 mm Hg and ≤ 21 mm Hg (current use of 3 or fewer
intraocular pressure-lowering medications and/or prior glaucoma surgery are
acceptable);

- Baseline fluorescein angiogram that is gradable for leakage in the central subfield

- Pupillary dilation sufficient to allow OCT testing.

Exclusion Criteria:

Patient level exclusion criteria:

-History of infectious uveitis, or of scleritis, keratitis, or infectious endophthalmitis
in either eye;

History of central serous retinopathy in either eye;

- For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy
test; unwilling to practice an adequate birth control method (abstinence, combination
barrier and spermicide, or hormonal) for duration of trial;

- Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline;

- Oral prednisone dose > 10 mg per day (or of an alternative corticosteroid at a dose
higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤ 10
mg per day that has not been stable for at least 4 weeks(note that if patient is off
of oral prednisone at baseline (P01 visit), dose stability requirement for past 4
weeks does not apply);

- Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks;

- Known allergy or hypersensitivity to any component of the study drugs;

Eye level exclusion criteria - at least one eye that meets all inclusion criteria cannot
have any of the following conditions:

- History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥ 0.9
or any notching of optic nerve to the rim);

- Media opacity causing inability to assess fundus or perform OCT;

- Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of
study ophthalmologist may be significant enough to limit improvement of ME (i.e.,
causing substantial wrinkling of the retinal surface)81;

- Torn or ruptured posterior lens capsule;

- Presence of silicone oil;

- Periocular or intravitreal corticosteroid injection in past 8 weeks;

- Injection of dexamethasone intravitreal implant in past 12 weeks;

- Placement of fluocinolone acetonide implant (Retisert) in past 3 years;