This is an open-label, Phase I/II study of Intravitreally administered 0.3mg ranibizumab in subjects with persistent Diabetic Macular Edema (DME) after recent and frequent bevacizumab (at least 2 bevacizumab intravitreal injections within 2 months prior to enrollment and at least 6 bevacizumab injections within 9 months of enrollment).

30 eyes will be randomized in a 1:2 ratio (Group A= 10 patients; Group B= 20 patients) Group A: ("monthly group")- Consented patient with enrolled eye will receive 12 monthly required injections of 0.3mg ranibizumab over 1 year OR Group B: ("As needed (PRN) Group")- Consented patient with enrolled eye will receive 6 monthly required injections of 0.3mg ranibizumab for 6 months, followed by as needed (PRN) dosing (required ranibizumab if DME persistent on Optical Coherence Tomography (OCT) and Early Treatment Diabetic Retina Study (ETDRS) Best Corrected Visual Acuity (BCVA) <20/20) for 6 months.

Inclusion Criteria:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study.
• >=18 years
• Type I/II diabetes mellitus
• Central-involved DME in study eye (OCT CSF >=275um on Heidelberg Spectralis spectral domain OCT with evidence of intraretinal or subretinal fluid or cysts)
• Definite retinal thickening due to diabetic macular edema involving the center of the macula.
• Media clarity, pupillary dilation and individual cooperation for adequate fungus photography and fluorescein angiography.
• Visual Acuity score in study eye <=80 and >=20 (approximate Snellen equivalent 20/25 to 20/400).
• History of at least 6 intravitreal bevacizumab injections within the past 9 months and 2 intravitreal bevacizumab injections within the past 2 months.
• No history of an anti-VEGF treatment for DME in the past 3 weeks.
• No other DME treatment for DME, other than bevacizumab, in the study eye at any time in the past 3 months.
• No history of major ocular surgery in the study eye within prior 3 months or anticipated within the next six months following randomization.

Exclusion Criteria:

• Pregnancy or lactation
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
• Participation in another medical investigation or trial within 30 days of randomization
• Known allergy to ranibizumab
• Acute cardiovascular event requiring hospitalization within the past 3 months
• Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization or anticipated use during the study
• Macular edema is considered to be due to a cause other than DME
• An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from the resolution of macular edema
• History of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agent other than bevacizumab within 9 months prior to randomization
• History of panretinal photocoagulation within 3 months prior to randomization or anticipated need for panretinal photocoagulation in the 6 months following randomization
• Yag capsulotomy performed within 1 month prior to randomization
• External ocular infection including conjunctivitis, significant blepharitis, etc.