To investigate whether ocular imaging and proteomic biomarkers; and systemic biochemical, metabolomic, and genetic biomarkers predict treatment response to intravitreal aflibercept in a cohort of patients with DME.

This is a prospective observational clinical trial with only the use of a standard care of drug, aflibercept. All study eyes will receive intravitreal aflibercept at the initial injection and x 4 monthly injections including at month 3.

Inclusion Criteria:

Participant

1. Age >=21 years

2. Diagnosis of Diabetes Mellitus (Type 1 or type 2)

   1. Current regular use of insulin or oral hypoglycemic agents for treatment of diabetes
   2. Documented diabetes by ADA and/or WHO criteria.

3. Able and willing to provide informed consent.

Study Eye

1. Best corrected ETDRS visual acuity score <= 78 (ie 20/32 or worse)
2. On Clinical Examination, definite retinal thickening due to diabetic macular edema involving the center of the macula.
3. Diabetic macular edema present on OCT (central subfield thickness on OCT >=300um with spectralis (Heidelberg)
4. Media clarity, pupillary dilation and individual cooperation sufficient for study procedure including fundus photography.

Exclusion Criteria:

Participant

1. End stage renal failure requiring hemodialysis or peritoneal dialysis.
2. Medical 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. Participation in an investigational trial within 30 days of enrolment which involves treatment with unapproved investigational drug
4. Known allergy to any component of the study drug.
5. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110 on repeated measurements). If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.
6. Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
7. Systemic anti-VEGF or pro-VEGF treatment within three months prior to randomization or anticipated use during the study.
8. 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.
9. Patient with non study eye VA: counting finger or worse (i.e. only one seeing eye) will be excluded.

Study Eye

1. 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.
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, nonretinal condition).
3. 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.)
4. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by more than three lines (i.e., cataract would be reducing acuity to worse than 20/40 if eye was otherwise normal).
5. History of an anti-VEGF treatment for DME in the past 3 months or history of any other treatment for DME at any time in the past 3 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids).
6. History of pan-retinal photocoagulation within 3 months prior to randomization or anticipated need for immediate pan-retinal photocoagulation. (eg. Proliferative diabetic retinopathy. Cases with severe non-proliferative diabetic retinopathy will still be eligible)
7. History of ocular anti-VEGF treatment for a disease other than DME in the past 3 months
8. History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior four months or anticipated within the next six months following randomization.
9. History of YAG capsulotomy performed within two months prior to randomization.
10. Aphakia.
11. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.
12. History of intravitreal steroids within the last 6 months.