To evaluate the efficacy of long-term treatment with 2 mg aflibercept via different intravitreal (IVT) treatment regimens to participants with DME pretreated with 2 mg aflibercept every 8 weeks after 5 initial monthly injections for approximately 1 year or more (according to the EU label for the first year of treatment)

Inclusion Criteria:

The subject's history of aflibercept treatment met all of the following:

• Treatment in the study eye was initiated with five monthly (-1 week /+2 weeks) doses of 2 mg aflibercept and improvements of visual and anatomic outcomes were observed and documented.
• Following the above initiation phase, the intervals between treatments were between 6 weeks and 12 weeks (one exception was allowed).
• The interval between the last 2 pre-study injections was ≥ 8 weeks, and visual and anatomic outcomes had been stable over this interval.
• The subject received the last intravitreal (IVT) injection of aflibercept in the study eye 8 weeks (±10 days) before the first planned treatment /randomization in this study.
• Total prior treatment duration with aflibercept (i.e. from first aflibercept treatment ever to enrollment into this study) was 1 year or longer.

To be met at initiation of pre-study aflibercept treatment:

• Type 1 or 2 diabetes mellitus (DM)
• Diagnosis of diabetic macular edema (DME) secondary to DM involving the center of the macula (defined as the area of the center subfield on optical coherence tomography [OCT]) in the study eye
• Decrease in vision determined to be primarily the result of DME in the study eye
• Best corrected visual acuity (BCVA) in the study eye of Early Treatment Diabetic Retinopathy Study (ETDRS) letter score 73 to 24

Exclusion Criteria:

At initiation of pre-study aflibercept treatment:

- Previous treatment with anti-angiogenic drugs in study eye (e.g., pegaptanib sodium, bevacizumab, ranibizumab, or aflibercept) within the last 12 weeks before initiation of aflibercept pre-study treatment

At initiation of pre-study aflibercept treatment, screening for this study, and baseline for this study:

• Prior treatment of the study eye with long acting steroids, either periocular or intraocular, in the preceding 120 days or Iluvien intravitreal implant at any time
• Active proliferative diabetic retinopathy, current iris neovascularization, vitreous hemorrhage, or tractional retinal detachment in the study eye
• Cataract surgery or any other intraocular surgery within 90 days of aflibercept treatment in the study eye
• Ocular inflammation (including trace or above) or history of uveitis in the study eye
• Structural damage to the center of the macula in the study eye that was likely to preclude improvement in BCVA following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia or organized hard exudates
• Concurrent disease in the study eye, other than DME, that could compromise visual acuity, require medical or surgical intervention during the study period, or could confound interpretation of the results (including advanced glaucoma, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
• Uncontrolled DM as defined by hemoglobin (Hb) A1c > 12.0% at screening and baseline for this study
• Any ocular or periocular infection in the preceding 4 weeks in either eye
• History of either cerebral vascular accident and/or myocardial infarction within 180 days before aflibercept treatment