Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Diabetic Macular Edema (BRDME):The BRDME Study, a Randomized Trial

Purpose: To generate conclusive evidence regarding the noninferiority of intravitreal bevacizumab compared with ranibizumab in patients with diabetic macular edema (DME). Design: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. Participants: Eligible patients were older than 18 years, diagnosed with type 1 or type 2 diabetes mellitus, with glycosylated hemoglobin of less than 12%, central area thickness of more than 325 μm, and visual impairment from DME with a best-corrected visual acuity (BCVA) between 24 letters and 78 letters. Methods: From June 2012 through February 2018, a total of 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n = 86) or 0.5 mg ranibizumab (n = 84). Main Outcome Measures: Primary outcome was change in BCVA from baseline to month 6 compared between the 2 treatment arms. The noninferiority margin was 3.5 letters. Results: The difference in mean BCVA between treatment arms was 1.8 letters in favor of ranibizumab after 6 months of follow-up; BCVA improved by 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group. The lower bound of the 2-sided 90% confidence interval (CI) was –3.626 letters, exceeding the noninferiority margin of 3.5 letters. Central area thickness decreased more with ranibizumab (138.2±114.3 μm) compared with bevacizumab (64.2±104.2 μm). In a post hoc subgroup analysis, participants with a worse BCVA at baseline (≤69 letters) improved by 6.7±7.0 letters with bevacizumab and 10.4±10.0 letters with ranibizumab, and central area thickness decreased significantly more in the ranibizumab arm of this subgroup compared with the bevacizumab arm. Participants with an initially better BCVA at baseline (≥70 letters) did not demonstrate differences in BCVA or OCT outcomes between treatment arms. Conclusions: Based on change in BCVA from baseline to month 6, the noninferiority of 1.25 mg bevacizumab to 0.5 mg ranibizumab was not confirmed. Only the subgroup of patients with a lower BCVA at baseline showed better visual acuity and anatomic outcomes with ranibizumab. Our study confirmed the potential differential efficacy of anti–vascular endothelial growth factor agents in the treatment of DME as well as the difference in response between patient groups with different baseline visual acuities

Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Retinal Vein Occlusion:The Bevacizumab to Ranibizumab in Retinal Vein Occlusions (BRVO) study, a Randomized Trial

PURPOSE: Comparing the efficacy of intravitreal injections of bevacizumab to ranibizumab in the treatment of macular edema (ME) resulting from retinal vein occlusion (RVO). DESIGN: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. The noninferiority margin was 4 letters. PARTICIPANTS: Patients with vision loss resulting from ME secondary to a branch or (hemi) central RVO who might benefit from anti-vascular endothelial growth factor treatment were eligible for participation. METHODS: From June 2012 through February 2018, 277 participants were randomized to receive injections of 1.25 mg bevacizumab (n = 139) or 0.5 mg ranibizumab (n = 138). The follow-up was 6 months with a monthly dosing interval. MAIN OUTCOME MEASURES: The primary outcome was a change in visual acuity from baseline at 6 months. Changes in the central area thickness and safety were studied as secondary outcomes. RESULTS: The mean visual acuity (±standard deviation) improved, with 15.3±13.0 letters for bevacizumab and 15.5±13.3 letters for ranibizumab after 6 months of monthly treatment. The lower limit of the 2-sided 90% confidence interval was -1.724 letters, which is within the noninferiority margin of 4 letters. Even in the branch and (hemi-)central RVO subgroups, minimal differences were found in visual acuity outcomes between treatment arms. Changes in central area thickness on OCT at 6 months did not differ significantly between treatment groups, with a decrease of 287.0±231.3 μm in the bevacizumab group and 300.8±224.8 μm in the ranibizumab group. Severe adverse events (SAEs) were also distributed equally over both treatment groups: 10 participants (7.1%) in the bevacizumab group and 13 participants (9.2%) in the ranibizumab group experienced SAEs. CONCLUSIONS: This study showed, based on the change in visual acuity, that bevacizumab is noninferior to ranibizumab for patients with ME resulting from RVO of either subtype when receiving monthly injections for a period of 6 months. In addition, anatomic and safety outcomes did not differ between treatment groups. Based on our findings, bevacizumab may be an effective alternative to ranibizumab

PREDICTIVE VALUE OF OPTICAL COHERENCE TOMOGRAPHIC FEATURES IN THE BEVACIZUMAB AND RANIBIZUMAB IN PATIENTS WITH DIABETIC MACULAR EDEMA (BRDME) STUDY: 812–819

To establish the predictive value of specific optical coherence tomography retinal features on visual outcomes and retinal thickness during anti-vascular endothelial growth factor treatment in patients with diabetic macular edema. Post hoc analysis of compound data of a prospective, 6-month, multicenter, randomized controlled trial of 119 patients with diabetic macular edema receiving either intravitreal bevacizumab or ranibizumab were analyzed to assess the associations between baseline retinal morphologic parameters and change in best-corrected visual acuity and central subfield thickness. Based on the study protocol of the core study, best-corrected visual acuity and central subfield thickness were obtained before each mandatory monthly injection during 6 months. The presence of serous retinal detachment at baseline was associated with significant improvement in best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.001 and P = 0.01, respectively). In addition, the presence of disorganization of retinal inner layers was associated with lower best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.05 and P = 0.01, respectively). This study found that serous retinal detachment and disorganization of retinal inner layers were associated with different treatment responses to anti-vascular endothelial growth factor therapy in patients with diabetic macular edem

Antiplatelet and Anticoagulant Drugs Do Not Affect Visual Outcome in Neovascular Age-Related Macular Degeneration in the BRAMD Trial

PURPOSE: To determine if use of antiplatelet or anticoagulant (AP/AC) medication influences visual acuity in patients with active neovascular age-related macular degeneration (N-AMD). DESIGN: Retrospective analysis of data from a randomized controlled trial. METHODS: Setting: Multicenter. STUDY POPULATION: Total of 330 patients with active N-AMD from the BRAMD study, a comparative trial between bevacizumab and ranibizumab in the Netherlands. OBSERVATION PROCEDURES: Patients underwent an extensive ophthalmic examination. Visual acuity was categorized into functional vision (best-corrected visual acuity [BCVA] ≥ 0.5), visual impairment (BCVA < 0.5), and severe visual impairment (BCVA < 0.3). Fundus photographs were graded for presence of retinal or subretinal hemorrhages. Information on AP/AC medication was obtained through interview. Logistic regression analysis was used to determine associations between AP/AC medication and outcomes. Frequency of hemorrhages in users and non-users stratified for visual acuity categories was analyzed with ANCOVA. MAIN OUTCOME MEASURES: BCVA and presence of hemorrhages. RESULTS: In total, 40.9% of the patients used AP/AC medication, of which 73.3% was aspirin. AP/AC use was not associated with visual impairment (adjusted odds ratio [OR] 0.79; 95% confidence interval [CI] 0.43-1.44) or severe visual impairment (adjusted OR 0.75; 95% CI 0.40-1.43). Patients on AP/AC presented with comparable frequencies of hemorrhages (27% vs 32%, P = .32, respectively). Similar results were found when analyses were restricted to aspirin users only. CONCLUSION: In our study, use of AP/AC medication was associated neither with visual decline nor with the occurrence of hemorrhages in patients with active N-AMD

Comparing the Efficacy of Bevacizumab and Ranibizumab in Patients with Retinal Vein Occlusion: The Bevacizumab to Ranibizumab in Retinal Vein Occlusions (BRVO) study, a Randomized Trial

Purpose: Comparing the efficacy of intravitreal injections of bevacizumab to ranibizumab in the treatment of macular edema (ME) resulting from retinal vein occlusion (RVO). Design: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. The noninferiority margin was 4 letters. Participants: Patients with vision loss resulting from ME secondary to a branch or (hemi) central RVO who might benefit from anti–vascular endothelial growth factor treatment were eligible for participation. Methods: From June 2012 through February 2018, 277 participants were randomized to receive injections of 1.25 mg bevacizumab (n = 139) or 0.5 mg ranibizumab (n = 138). The follow-up was 6 months with a monthly dosing interval. Main Outcome Measures: The primary outcome was a change in visual acuity from baseline at 6 months. Changes in the central area thickness and safety were studied as secondary outcomes. Results: The mean visual acuity (±standard deviation) improved, with 15.3±13.0 letters for bevacizumab and 15.5±13.3 letters for ranibizumab after 6 months of monthly treatment. The lower limit of the 2-sided 90% confidence interval was –1.724 letters, which is within the noninferiority margin of 4 letters. Even in the branch and (hemi-)central RVO subgroups, minimal differences were found in visual acuity outcomes between treatment arms. Changes in central area thickness on OCT at 6 months did not differ significantly between treatment groups, with a decrease of 287.0±231.3 μm in the bevacizumab group and 300.8±224.8 μm in the ranibizumab group. Severe adverse events (SAEs) were also distributed equally over both treatment groups: 10 participants (7.1%) in the bevacizumab group and 13 participants (9.2%) in the ranibizumab group experienced SAEs. Conclusions: This study showed, based on the change in visual acuity, that bevacizumab is noninferior to ranibizumab for patients with ME resulting from RVO of either subtype when receiving monthly injections for a period of 6 months. In addition, anatomic and safety outcomes did not differ between treatment groups. Based on our findings, bevacizumab may be an effective alternative to ranibizumab