title: 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).
  
  
  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.
authors: Jaeb Center for Health Research, 15310 Amberly Drive, Suite 350, Tampa, FL 33647, USA. drcrnet@jaeb.org
authors: Ingrid U
authors: IU
authors: Scott
authors: Allison R
authors: AR
authors: Edwards
authors: Roy W
authors: RW
authors: Beck
authors: Neil M
authors: NM
authors: Bressler
authors: Clement K
authors: CK
authors: Chan
authors: Michael J
authors: MJ
authors: Elman
authors: Scott M
authors: SM
authors: Friedman
authors: Craig Michael
authors: CM
authors: Greven
authors: Raj K
authors: RK
authors: Maturi
authors: Dante J
authors: DJ
authors: Pieramici
authors: Michel
authors: M
authors: Shami
authors: Lawrence J
authors: LJ
authors: Singerman
authors: Cynthia R
authors: CR
authors: Stockdale
mesh_terms: 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
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
references: Ophthalmology. 2003 Jun;110(6):1159-63
references: 12799241
references: Ophthalmology. 2007 Aug;114(8):1520-5
references: 17353052
references: Ophthalmology. 2002 May;109(5):920-7
references: 11986098
references: Am J Ophthalmol. 2000 Aug;130(2):178-86
references: 11004291
references: Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4569-78
references: 17003454
references: Ophthalmology. 2007 Apr;114(4):743-50
references: 17398322
references: Ophthalmology. 2006 Dec;113(12):2221-30
references: 16989901
references: Am J Ophthalmol. 2006 Dec;142(6):961-9
references: 17046701
references: Retina. 2006 Nov-Dec;26(9):999-1005
references: 17151486
references: Am J Ophthalmol. 2003 Feb;135(2):194-205
references: 12566024
references: Ophthalmology. 2006 Oct;113(10):1706-12
references: 17011952
references: Arch Ophthalmol. 1985 Dec;103(12):1796-806
references: 2866759
references: Ophthalmology. 1987 Jul;94(7):761-74
references: 3658348
references: Ophthalmology. 1991 May;98(5 Suppl):766-85
references: 2062512
references: N Engl J Med. 1993 Sep 30;329(14):977-86
references: 8366922
references: Arch Ophthalmol. 2004 Nov;122(11):1631-40
references: 15534123
references: Diabetes. 2005 Jul;54(7):2188-97
references: 15983221
references: Ophthalmology. 2005 Oct;112(10):1747-57
references: 16154196
references: Retina. 2006 Mar;26(3):270-4
references: 16508425
references: N Engl J Med. 2006 Oct 5;355(14):1419-31
references: 17021318
references: N Engl J Med. 2006 Oct 5;355(14):1432-44
references: 17021319