A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema

Abstract

Objective: To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME).

Design: Randomized phase II clinical trial.

Participants: One hundred twenty-one eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32 to 20/320.

Interventions: Random assignment to 1 of 5 groups: (A) focal photocoagulation at baseline (n = 19), (B) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks (n = 22), (C) intravitreal injection of 2.5 mg of bevacizumab at baseline and 6 weeks (n = 24), (D) intravitreal injection of 1.25 mg of bevacizumab at baseline and sham injection at 6 weeks (n = 22), or (E) intravitreal injection of 1.25 mg of bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (n = 22).

Main outcome measures: Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks.

Results: At baseline, median CST was 411 mum and median Snellen VA equivalent was 20/50. Compared with group A, groups B and C had a greater reduction in CST at 3 weeks and about 1 line better median VA over 12 weeks. There were no meaningful differences between groups B and C in CST reduction or VA improvement. A CST reduction > 11% (reliability limit) was present at 3 weeks in 36 of 84 (43%) bevacizumab-treated eyes and 5 of 18 (28%) eyes treated with laser alone, and at 6 weeks in 31 of 84 (37%) and 9 of 18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in 1 eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (n = 2), congestive heart failure (n = 1), elevated blood pressure (n = 3), and worsened renal function (n = 3).

Conclusion: These results demonstrate that intravitreal bevacizumab can reduce DME in some eyes, but the study was not designed to determine whether treatment is beneficial. A phase III trial would be needed for that purpose.

Figure 1. Patient Outcome Visit Follow-Up Flow Chart

*Nine subjects/eyes were excluded due to ineligibility: 1 received laser treatment within 3 months prior to randomization, 5 had baseline central subfield thickness < 275 microns, 1 had a baseline optical coherence tomography image that could not be graded due to low signal strength and therefore was unable to confirm central subfield thickness for eligibility, 2 had choroidal neovascularization first identified by the Reading Center and subsequently confirmed by the enrolling ophthalmologist after randomization. Two subjects with no follow-up visits and 1 subject with endophthalmitis after the initial injection also were excluded. †Dropped includes deaths, withdrawals, lost to follow up occurring since the last visit

Figure 1. Patient Outcome Visit Follow-Up Flow Chart

*Nine subjects/eyes were excluded due to ineligibility: 1 received laser treatment within 3 months prior to randomization, 5 had baseline central subfield thickness < 275 microns, 1 had a baseline optical coherence tomography image that could not be graded due to low signal strength and therefore was unable to confirm central subfield thickness for eligibility, 2 had choroidal neovascularization first identified by the Reading Center and subsequently confirmed by the enrolling ophthalmologist after randomization. Two subjects with no follow-up visits and 1 subject with endophthalmitis after the initial injection also were excluded. †Dropped includes deaths, withdrawals, lost to follow up occurring since the last visit