Twenty-four–Month Outcomes of the Ranibizumab for Edema of the Macula in Diabetes – Protocol 3 with High Dose (READ-3) Study

• Published in: Ophthalmology (Rochester, Minn.) Vol. 123; no. 12; pp. 2581 - 2587
• Main Authors: Sepah, Yasir J., Sadiq, Mohammad Ali, Boyer, David, Callanan, David, Gallemore, Ron, Bennett, Michael, Marcus, Dennis, Halperin, Lawrence, Hassan, Muhammad, Campochiaro, Peter A., Nguyen, Quan Dong, Do, Diana V., Lit, Eugene, Kruger, Erik, Pollack, John, Halperin, Larry, Zhang, Kang, Symons, Andrew, Abraham, Prema, Callanan, David G., Conway, Brian P., Wilson, David J., Sepah, Yasir Jamal, Hanout, Mostafa, Agarwal, Aniruddha, Afridi, Rubbia, Greer, Lisa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2016
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - physiopathology; Double-Blind Method; Female; Follow-Up Studies; Humans; Intravitreal Injections; Macula Lutea - drug effects; Macular Edema - drug therapy; Macular Edema - physiopathology; Male; Middle Aged; Ophthalmology; Ranibizumab - administration & dosage; Ranibizumab - adverse effects; Retreatment; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Visual Acuity - drug effects; Visual Acuity - physiology; OCT; SD OCT; FDA; READ-3; ETDRS; VEGF; TD-OCT; RBZ; VA; PRN; CFT; BCVA; DME; optical coherence tomography; ranibizumab; pro re nata; Food and Drug Administration; diabetic macular edema; Ranibizumab for Edema of the mAcula in Diabetes – Protocol 3 with High Dose; visual acuity; spectral-domain optical coherence tomography; central foveal thickness; time-domain optical coherence tomography; Early Treatment Diabetic Retinopathy Study; vascular endothelial growth factor; best-corrected visual acuity
• ISSN: 0161-6420; 1549-4713; 1549-4713
• DOI: 10.1016/j.ophtha.2016.08.040

To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. A total of 152 patients (152 eyes) with DME. Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24. The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) (P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively (P = 0.08). The mean change in CFT was −192.53 μm in the 0.5 mg RBZ group and −170.64 μm in the 2.0 mg RBZ group (P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.