Intravitreal injections of bevacizumab plus methotrexate versus bevacizumab alone for the treatment of diabetic macular edema: A randomized, sham-controlled trial

Purpose: To evaluate the efficacy of intravitreal bevacizumab (IVB) combined with intravitreal methotrexate (IVM) in the treatment of diabetic macular edema (DME). Methods: In this prospective, interventional contralateral eye study, patients with bilateral DME were randomly allocated to receive three monthly injections of IVB (1.25 mg/0.05 mL) plus IVM (400 mu g; 0.16 cc) or IVB alone. The outcome measure was changes in the best corrected visual acuity (BCVA), central macular thickness (CMT), and central macular volume (CMV). Results: Thirty-six treatment-naive eyes of 18 patients with a mean age of 62.38 +/- 6.2 years were included in the study. BCVA logMAR changed from 0.95 +/- 0.53 at baseline to 0.75 +/- 0.53 in the combination group and from 0.72 +/- 0.57 to 0.49 +/- 0.50 in the IVB alone group at 1 month after the 3rd injection. BCVA improvement in both groups was not statistically significant compared with the baseline value (P > 0.99). Compared with the baseline values, mean CMT and CMV were reduced in both groups; however, these changes did not reach a significant level. The differences of CMT changes between the groups were not statistically significant at month 1 (P = 0.82), month 2 (P = 0.21), and month 3 (P = 0.10). Furthermore, the differences of CMV changes between the groups were not statistically significant at month 1 (P = 0.76), month 2 (P = 0.82), and month 3 (P = 0.11). Conclusions: This pilot study demonstrated no significant therapeutic effects for IVB combined with IVM compared to IVB alone in treatment-naive DME patients over a 3-month course.