miRNA Levels as a Biomarker for Anti-VEGF Response in Patients with Diabetic Macular Edema.

BACKGROUND: The aim of this study was to investigate whether miRNA levels in the circulation could serve as a predictive biomarker for responsiveness to anti-vascular endothelial growth factor (VEGF) therapy in patients with diabetic macular edema. METHODS: Whole blood samples were collected at baseline from 135 patients who were included in the BRDME study, a randomized controlled comparative trial of monthly bevacizumab or ranibizumab treatment for 6 months in patients with diabetic macular edema (Trialregister.nl, NTR3247). Best corrected visual acuity letter score (BCVA) and retinal central area thickness (CAT) were measured monthly during the 6-month follow-up. Levels of selected miRNAs were quantified. RESULTS: Following linear regression analysis, the levels of four miRNAs were negatively associated with baseline CAT. Multivariable regression analysis confirmed this association for miR-181a. No associations with changes in CAT after 3 or 6 months of anti-VEGF treatment were found. In addition, no associations with miRNA levels with baseline BCVA or change in BCVA after 3 or 6 months of anti-VEGF treatment were found. CONCLUSIONS: Circulating miR-181a levels were negatively associated with CAT at baseline. However, no associations between miRNA levels and the response to anti-VEGF therapy were found.

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.

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.