Elsevier

Ophthalmology

Volume 114, Issue 10, October 2007, Pages 1860-1867.e7
Ophthalmology

Original article
A Phase II Randomized Clinical Trial of Intravitreal Bevacizumab for Diabetic Macular Edema

https://doi.org/10.1016/j.ophtha.2007.05.062Get rights and content

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 μm 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.

Section snippets

Participants and Methods

This phase II randomized multicenter clinical trial was conducted by the Diabetic Retinopathy Clinical Research Network (DRCR.net) at 36 clinical sites in the United States. The protocol and Health Insurance Portability and Accountability Act–compliant informed consent forms were approved by multiple institutional review boards. An investigational new drug application number (100 050) was obtained from the FDA for the protocol. Study oversight was provided by an independent data and safety

Results

Between June 5, 2006 and August 4, 2006, 121 subjects were randomized to the 5 treatment groups (one eye per subject) at 36 clinical sites. Of these 121 subjects, 109 met criteria for inclusion in the analyses (19–24 per group; exclusions detailed in Fig 1 [available at http://aaojournal.org]). Median age was 65 years, and 39% were women. The racial/ethnicity distribution was 76% white, 16% black, 6% Hispanic, 1% Asian, and 1% other. Type 2 diabetes was present in 93% and type 1 diabetes in 7%.

Discussion

To assist in the development of a phase III randomized trial protocol, this study was designed to address 6 questions related to the short-term effect of intravitreal bevacizumab for DME plus provide preliminary ocular and systemic safety data.

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    Manuscript no. 2007-411.

    Supported through a cooperative agreement from the National Eye Institute, Bethesda, Maryland, and National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland (nos. EY14231, EY14269, EY14229), and by a grant from the Juvenile Diabetes Research Foundation International, New York, New York.

    For a listing of financial disclosures for all Network investigators as of date of submission, see the DRCR.net Web site (http://www.drcr.net).

    See “Appendix 2” (available at http://aaojournal.org) for a complete list of the Network’s members participating in the trial.

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