Treatment for CI-DME in Eyes With Very Good VA Study

Inclusion criteria

• Age >= 18 years
• Diagnosis of diabetes mellitus (type 1 or type 2)

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

• Current regular use of insulin for the treatment of diabetes
• Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
• Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria.
• Able and willing to provide informed consent.

Meets all of the following ocular criteria in at least the one eye:

• Best corrected E-ETDRS visual acuity letter score ≥ 79 (approximate Snellen equivalent 20/25 or better) at two consecutive visits within 1 to 28 days.
• On clinical exam, definite retinal thickening due to DME involving the center of the macula.
• Diabetic macular edema confirmed on OCT (equivalent to CSF thickness on OCT ≥250 microns on Zeiss Stratus or gender-specific spectral domain OCT equivalent) at two consecutive visits within 1 to 28 days.

(a) Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality.

• The investigator is comfortable with the eye being randomized to any of the three treatment groups (observation, laser, or anti-VEGF initially).

(a) If focal/grid photocoagulation is contraindicated because all leaking microaneurysms are too close to the fovea or the investigator believes the DME that is present will not benefit from focal/grid photocoagulation, the eye should not be enrolled.

• Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCT and fundus photographs.

Exclusion criteria

• History of chronic renal failure requiring dialysis or kidney transplant.
• A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
• Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months.
• Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied.

(a) Note: study participants cannot receive another investigational drug while participating in the study.

• Known allergy to any component of the study drug.
• Blood pressure >180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.
• Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.

These drugs should not be used during the study.

• For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 24 months.

(a) Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.

• Individual is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 24 months of the study.

Individual has any of the following ocular characteristics:

• Macular edema is considered to be due to a cause other than DME.

a) An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities (e.g., a taut posterior hyaloid or epiretinal membrane) are contributing to the macular edema.

• An ocular condition is present such that, in the opinion of the investigator, any visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition).
• An ocular condition is present (other than DME) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.).
• Cataract is present that, in the opinion of the investigator, may alter visual acuity during the course of the study.
• Any history of prior laser or other surgical, intravitreal, or peribulbar treatment for DME (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, or anti-VEGF).
• History of topical steroid or nonsteroidal anti-inflammatory drugs (NSAID) treatment within 30 days prior to randomization.
• History of intravitreal or peribulbar corticosteroid within 4 months prior to randomization for an ocular condition other than DME.
• Any history of or anticipated need for intravitreal anti-VEGF within the next 6 months for an ocular condition other than DME (e.g. choroidal neovascularization, central retinal vein occlusion, PDR).
• History of PRP within 4 months prior to randomization or anticipated need for PRP in the 6 months following randomization.
• Any history of vitrectomy.
• History of major ocular surgery (cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.
• History of YAG capsulotomy performed within 2 months prior to randomization.
• Aphakia.
• Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.