Inclusion Criteria:

• Willingness to provide written informed consent and, at U.S. sites, Health Insurance Portability and Accountability Act (HIPAA) authorization and in other countries, as applicable according to national laws
• Age ≥ 18 years
• Diabetes mellitus (Type 1 or 2)
• Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea
• Decrease in vision determined to be primarily the result of DME and not to other causes
• For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study
• Ability (in the opinion of the investigator) and willingness to return for all scheduled visits and assessments

Exclusion Criteria:

• History of vitreoretinal surgery in the study eye
• Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eye within 3 months of screening
• Previous use of intraocular corticosteroids in the study eye (e.g., TA) within 3 months of screening
• Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc.) within 3 months of the Day 0 visit
• PDR in the study eye, with the exception of inactive, regressed PDR
• Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in the study eye Concurrent Ocular Conditions
• Vitreomacular traction or epiretinal membrane in the study eye
• Ocular inflammation (including trace or above) in the study eye
• History of idiopathic or autoimmune uveitis in either eye
• Structural damage to the center of the macula in the study eye that is likely to preclude improvement in VA following the resolution of macular edema, including atrophy of the RPE, subretinal fibrosis, or organized hard-exudate plaque
• Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or CNV of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia)
• Concurrent disease in the study eye that would compromise VA or require medical or surgical intervention during the study period
• Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet (YAG) laser capsulotomy within the past 2 months, or any other intraocular surgery within the 90 days preceding Day 0
• Aphakia or absence of the posterior capsule in the study eye
• Uncontrolled glaucoma or previous filtration surgery in the study eye
• Spherical equivalent of the refractive error in the study eye of more than - 8 diopters myopia
• Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current treatment for serious systemic infection
• Uncontrolled blood pressure
• History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0
• Uncontrolled diabetes mellitus
• Renal failure requiring dialysis or renal transplant
• Participation in an investigational trial within 30 days prior to screening that involved treatment with any drug (excluding vitamins and minerals) or device
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or renders the subject at high risk from treatment complications
• Pregnancy or lactation
• History of allergy to fluorescein
• History of allergy to ranibizumab injection or related molecule