Intravitreal Injections of Bevacizumab Plus Methotrexate versus Bevacizumab Alone for the Treatment of Diabetic Macular Edema: A Randomized, Sham‑Controlled Trial

To evaluate the efficacy of intravitreal bevacizumab (IVB) combined with intravitreal methotrexate (IVM) in the treatment of diabetic macular edema (DME).

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 µg; 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).

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).

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.