ranibizumab for persistent diabetic macular edema after bevacizumab

Conditions: Diabetic Macular Edema

Summary: 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.

Eligibility criteria:
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 \ =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.