A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes Mellitus (RIDE)

Inclusion Criteria:

• Willingness to provide written informed consent and, at U.S. sites, Health InsurancePortability and Accountability Act (HIPAA) authorization, and in other countries, asapplicable according to national laws.

• Age ≥ 18 years.

• Diabetes mellitus (Type 1 or 2) .

• Retinal thickening secondary to diabetes mellitus (DME) involving the center of thefovea with central macular thickness ≥ 275 µm in the center subfield as assessed onoptical coherence tomography (OCT).

• Best corrected visual acuity (BCVA) score in the study eye of 20/40 to 20/320approximate Snellen equivalent using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at an initial testing distance of 4 meters.

• Decrease in vision determined to be primarily the result of DME and not to othercauses.

• For sexually active women of childbearing potential, use of an appropriate form ofcontraception (or abstinence) for the duration of the study.

• Ability (in the opinion of the investigator) and willingness to return for allscheduled visits and assessments.

Exclusion Criteria:

• History of vitreoretinal surgery in the study eye.

• Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eyewithin 3 months of screening.

• Previous use of intraocular corticosteroids in the study eye (eg, triamcinoloneacetonide [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 (firstday of treatment) visit.

• Proliferative diabetic retinopathy (PDR) in the study eye, with the exception ofinactive, regressed PDR.

• Iris neovascularization, vitreous hemorrhage, traction retinal detachment, orpreretinal 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 topreclude improvement in VA following the resolution of macular edema, includingatrophy of the retinal pigment epithelium (RPE), subretinal fibrosis, or organizedhard-exudate plaque.

• Ocular disorders in the study eye that may confound interpretation of study results,including retinal vascular occlusion, retinal detachment, macular hole, or choroidalneovascularization (CNV) of any cause (eg, age-related macular degeneration (AMD),ocular histoplasmosis, or pathologic myopia).

• Concurrent disease in the study eye that would compromise visual acuity or requiremedical or surgical intervention during the study period.

• Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet (YAG) lasercapsulotomy within the past 2 months, or any other intraocular surgery within the 90days 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 dioptersmyopia.

• Evidence at examination of infectious blepharitis, keratitis, scleritis, orconjunctivitis in either eye or current treatment for serious systemic infection.

• Uncontrolled blood pressure.

• History of cerebral vascular accident or myocardial infarction within 3 months priorto Day 0.

• Uncontrolled diabetes mellitus.

• Renal failure requiring dialysis or renal transplant.

• Participation in an investigational trial within 30 days prior to screening thatinvolved treatment with any drug (excluding vitamins and minerals) or device.

• History of other disease, metabolic dysfunction, physical examination finding, orclinical laboratory finding giving reasonable suspicion of a disease or condition thatcontraindicates the use an investigational drug, might affect interpretation of theresults of the study, or renders the subject at high risk from treatmentcomplications.

• Pregnancy or lactation.

• History of allergy to fluorescein.

• History of allergy to ranibizumab injection or related molecule.