DRCR.Net Aflibercept vs. Bevacizumab + Deferred Aflibercept for the Treatment of CI-DME

Participant-level Criteria Inclusion

To be eligible, the following inclusion criteria must be met:

• Age ≥ 18 years • Individuals 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 four months prior to randomization or anticipated use during the study.
• These drugs cannot be used during the study.
• For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 24 months.
• 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 next two years.

Study Eye Criteria The study participant must have at least one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below.

Study participants can have two study eyes only if both eyes are eligible at the time of randomization. For study participants with two eligible eyes, the logistical complexities of the protocol must be considered for each individual prior to randomizing both eyes.

The eligibility criteria for a study eye are as follows:

Inclusion

• Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score < 69 (i.e., 20/50 or worse) and ≥ 24 (i.e., 20/320 or better) within eight days of randomization.
• On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
• Diabetic macular edema present on optical coherence tomography (OCT) within eight days of randomization
• Zeiss Cirrus central subfield: ≥ 290µm in women or ≥ 305µm in men
• Heidelberg Spectralis central subfield: ≥ 305µm in women or ≥ 320µm in men
• Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality
• Media clarity, pupillary dilation, and individual cooperation sufficient for adequate fundus photographs.

Exclusions

The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):

• Macular edema is considered to be due to a cause other than diabetic macular edema.
• 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 the primary cause of the macular edema.
• An ocular condition is present such that, in the opinion of the investigator, 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 diabetes) 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.).
• Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
• History of an anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in the past 12 months or history of any other treatment for DME at any time in the past four months (such as focal/grid macular photocoagulation, intravitreous or peribulbar corticosteroids).
• Enrollment will be limited to a maximum of 25% of the planned sample size with any history of anti-VEGF treatment for DME. Once this number of eyes has been enrolled, any history of anti-VEGF treatment for DME will be an exclusio