Combined aPproach to Treatment Using Ranibizumab and Efalizumab for Diabetic Macular Edema Study: The CAPTURE DME Study

Inclusion Criteria: * Signed informed consent and authorization of use and disclosure of protected health information * 18 years of Age * Diagnosis of diabetes mellitus (type 1 or type 2) * Serum HbA1c 5.5% within 12 months of randomization * Retinal thickening (diabetic macular edema) involving the center of the fovea * Diagnosis must be confirmed by fluorescein angiography and OCT images over 250 * Best corrected visual acuity score in the study eye of 20/40 to 20/320 * If a female of childbearing potential, a negative pregnancy test and commitment to the use of at least two forms of effective contraception. * If a non-sterile male, commitment to the use of two forms of effective contraception. * Demonstrate understanding of and ability to perform weekly self sub-cutaneous injections. Exclusion Criteria: * Panretinal or macular photocoagulation within 3 months of study entry in the study eye * Use of intraocular or periocular injection of steroids in the study eye within 3 months of study entry * Previous participation in a study and receipt of anti-angiogenic drugs (pegaptanib sodium, ranibizumab, bevacizumab, anecortave acetate, protein kinase C inhibitor, etc.) within 2 months of study entry * Current or history of prior treatment of psoriasis with subcutaneous efalizumab within 6 months of study entry * Proliferative diabetic retinopathy in the study eye, with the exceptions of * inactive, fibrotic proliferative diabetic retinopathy that has regressed following pan-retinal laser photocoagulation OR * tufts of neovascularization elsewhere (NVE) less than one disc area with no vitreous hemorrhage * Vitreomacular traction or epiretinal membrane in the study eye * Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema. * Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the first 6-months. * Cataract surgery in the study eye within 3 months of study entry; (YAG) laser capsulotomy within 1 month of study entry; or any other intraocular surgery within 3 months preceding Day 0. * History of vitreoretinal surgery in the study eye within 3 months of study entry * Uncontrolled glaucoma . * Blood pressure exceeding 180/100 (sitting) during the screening period * Uncontrolled diabetes mellitus, as evidenced by glycosylated hemoglobin \> or = 13%(HbA1c) value * Renal failure requiring dialysis or renal transplant * Premenopausal women unwilling to commit to adequate contraception * History of other diseases or 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 render the subject at high risk from treatment complications * International Normalized Ratio (INR) \> or = 3.0 (e.g. due to current treatment with warfarin). * History of cerebral vascular accident, myocardial infarction, transient ischemic attacks within 6 months of study enrollment. * Have a history of hypersensitivity to efalizumab * Have a history of ongoing uncontrolled serious bacterial, viral, fungal, or atypical mycobacterial infection. Have a history of opportunistic infections. * Have the presence or history of malignancy, including lymphoproliferative disorders. * Have a history of thrombocytopenia, clinically significant hemolytic anemia, or unexplained anemia * Have a platelet count \< 100,000 cells/microliter (uL) * Inability to comply * Patients receiving immunosuppressive agents * All acellular, live and live-attenuated vaccines are excluded from 14 days prior to the first dose of efalizumab until a minimum of 4 weeks after the last dose of efalizumab * Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated. * Participation in another simultaneous medical investigation or trial