Phase II Combination Steroid and Anti-VEGF for Persistent DME

Inclusion Criteria: 1. Age ≥ 18 years i) Individuals \<18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable. 2. Diagnosis of diabetes mellitus (type 1 or type 2) 3. Any one of the following will be considered to be sufficient evidence that diabetes is present: 1. Current regular use of insulin for the treatment of diabetes 2. Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes 3. Documented diabetes by ADA (American Diabetes Association) and/or WHO (World Health Organization) criteria 4. At least one eye meets the study eye criteria listed below. 5. Fellow eye (if not a study eye) meets criteria. 6. Able and willing to provide informed consent. Meets all of the following ocular criteria in at least the one eye: 1. At least 3 injections of anti-VEGF drug (ranibizumab, bevacizumab, or aflibercept) within the prior 20 weeks. 2. Visual acuity letter score in study eye ≤ 78 and ≥24 (approximate Snellen equivalent 20/32 to 20/320). 3. On clinical exam, definite retinal thickening due to DME involving the center of the macula. 4. OCT CSF thickness, within 8 days of enrollment: i) On Zeiss Cirrus ≥ 290 microns in women; ≥ 305 in men ii) On Heidelberg Spectralis: ≥ 305 microns in women; ≥ 320 in men 5. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCTs. Exclusion Criteria: An individual is not eligible if any of the following exclusion criteria are present: 1. History of chronic renal failure requiring dialysis or kidney transplant. 2. 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). 3. 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. 4. Participation in an investigational trial within 30 days of enrollment that involved treatment with any drug that has not received regulatory approval for the indication being studied. Note: study participants cannot receive another investigational drug while participating in the study. 5. Known allergy to any component of the study drugs (including povidone iodine prep). 6. Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, the individual can become eligible. 7. Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 1 month prior to enrollment. 8. Systemic steroid, anti-VEGF or pro-VEGF treatment within 4 months prior to enrollment or anticipated use during the study. These drugs cannot be used during the study. 9. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 9 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. 10. 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 9 months. The following exclusions apply to the study eye only (i.e., they may be present for the non-study eye unless otherwise specified): 1. Macular edema is considered to be due to a cause other than DME. 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. 2. 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, non-retinal condition, etc.). 3. 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.). 4. Substantial posterior capsule opacity that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., opacity would be reducing acuity to 20/40 or worse if eye was otherwise normal). 5. History of intravitreal anti-VEGF drug within 21 days prior to enrollment. 6. History of intravitreal or peribulbar corticosteroids within 3 months prior to enrollment. 7. History of macular laser photocoagulation within 4 months prior to enrollment. 8. History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to enrollment or anticipated need for PRP in the 6 months following enrollment into run-in phase. 9. Any history of vitrectomy.