A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema.
OBJECTIVE
To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME).


METHODS
Randomized phase II clinical trial.


METHODS
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.


METHODS
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).


METHODS
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).


CONCLUSIONS
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.
Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. drcrnet@jaeb.org
Scott
Ingrid U
IU
Edwards
Allison R
AR
Beck
Roy W
RW
Bressler
Neil M
NM
Chan
Clement K
CK
Elman
Michael J
MJ
Friedman
Scott M
SM
Greven
Craig Michael
CM
Maturi
Raj K
RK
Pieramici
Dante J
DJ
Shami
Michel
M
Singerman
Lawrence J
LJ
Stockdale
Cynthia R
CR
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D003131:Combined Modality Therapy; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007267:Injections; D017075:Laser Coagulation; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012160:Retina / Q000187:drug effects / Q000473:pathology; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000187:drug effects; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
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