Dexamethasone Intravitreal Implant for the Treatment of Persistent Diabetic Macular Edema

Macular edema is a major cause of central vision loss in patients presenting with diabetic
retinopathy. Diabetic macular edema (DME) occurs when fluid leaks into the center of the
macula, the part of the eye where sharp, straight-ahead vision occurs. The fluid makes the
macula swell, blurring vision. Diabetic macular edema (DME) affects between 8% to 10% of 23.6
million diabetic individuals in the United States. The prevalence of diabetic macular edema
after 15 years of known diabetes is approximately 20% in patients with type 1 diabetes, 25%
in patients with type 2 diabetes who are taking insulin, and 14% in patients with type 2
diabetes who do not take insulin. Within two years of diagnosis, nearly half of individuals
with DME will lose 2 or more lines of visual acuity (the smallest line you can read on a
standardized vision chart held 20 feet away).

Diabetic macular edema is typically treated with laser and/or intravitreal injections of
drugs such as anti-VEGF agents. Anti-VEGF agents block a protein that slows the growth of the
abnormal blood vessels. Dexamethasone is a corticosteroid used to treat inflammation.
Dexamethasone implant is a steroid implant injected into the eye to treat swelling that may
occur when there is a blockage of certain blood vessels in your eyes. Both anti-VEGF agents
and dexamethasone implant are approved by the FDA to treat DME.

The purpose of this research study is to compare the effectiveness of using a dexamethasone
steroid implant versus monthly intravitreal anti-VEGF injections for research participants
with persistent diabetic macular edema (DME).

Inclusion Criteria:

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

- Age ≥ 18 years

- Diagnosis of diabetes mellitus (type 1 or 2)

- Any one of the following will be considered to be sufficient evidence that
diabetes is present:

- Current regular use of insulin for treatment of diabetes

- Current regular use of oral anti-hyperglycemia agent for the treatment of
diabetes

- Clinical evidence of retinal thickening due to macular edema involving the center of
the macula associated with diabetic retinopathy.

- Previous history of anti-vegf treatment for diabetic macular edema (DME) with
documented incomplete resolution of central subfield thickening by spectral-domain
optical coherence tomography (SDOCT). At least 4 intravitreal anti-vegf injections
within the past six months prior to the baseline study visit are required for
eligibility.

- Central diabetic macular edema present on clinical examination and SDOCT testing with
central 1 mm subfield thickness greater than 300 microns as measured on SDOCT at the
baseline visit.

- Visual acuity score greater than or equal to 19 letters (20/400) and less than or
equal to 74 letters (20/32) by the ETDRS visual acuity protocol.

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

Exclusion Criteria:

- Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women
not using adequate contraception.

- Participation in another ocular investigation or trial simultaneously

- Blood pressure > 180/110 mmHg (systolic above 180 OR diastolic above 110 mmHg)

- Any condition that, in the opinion of the investigator, would preclude participation
in the study (e.g. chronic alcoholism, drug abuse)

- Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be
contributing to the macular edema

- An eye that, in the investigator's opinion, has no chance of improving in visual
acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or
geographic atrophy)

- Presence of another ocular condition that may affect the visual acuity or macular
edema during the course of the study (e.g. AMD, uveitis, Irvine-Gass)

- Evidence of active neovascularization of the iris or retina

- Evidence of central atrophy or fibrosis in the study eye

- Presence of substantial cataract, one that might decrease the vision by 3 or more
lines of vision at sometime during the study.

- History of vitreous surgery in the study eye

- History of cataract surgery within 3 months of enrollment.

- History of YAG capsulotomy within 2 months of enrollment.

- Visual acuity <20/400 on ETDRS visual acuity charts in the fellow eye

- Uncontrolled glaucoma (pressure > 30 mmHg) despite treatment with glaucoma
medications.

- History of cerebral vascular accident or myocardial infarction within 3 months prior
to Day 0.

- Use of systemic steroids (eg, oral, intravenous, intramuscular, epidural, rectal, or
extensive dermal) within one month prior to the baseline study visit