Meta-analysis and review on the effect of bevacizumab in diabetic macular edema

  • Sunali Goyal
  • Michael LaValley
  • Manju L. Subramanian
Retinal Disorders

Abstract

Background

Systematic review and meta-analysis to evaluate the effect of bevacizumab (Avastin) in diabetic macular edema (DME)

Methods

Pertinent publications were identified through systematic searches of PUBMED and Cochrane Central Register of Controlled Trials. Change in central subfield macular thickness (CSMT) in μm and best-corrected visual acuity (BCVA) in log MAR equivalents were extracted at 6, 12 and 24 weeks, and results compared between groups receiving intravitreal bevacizumab (IVB), a combination of IVB and intravitreal triamcinolone acetonide (IVT), and macular laser photocoagulation or sham control groups.

Results

The summary mean difference indicated a statistically significant reduction in CSMT at 6 weeks when treated with bevacizumab compared to control. IVB treatment, however, lost significance at 12 weeks and 24 weeks. The summary mean difference in BCVA for IVB group compared to control reached significance only at 6 and 24 weeks. Combination therapy of IVB and IVT did not result in any significant reduction in CSMT or gain in vision compared to treatment with IVB alone at any point in time.

Conclusions

Current data suggests that IVB is an effective short-term treatment for diabetic macular edema, and that its efficacy wanes after 6 weeks. More trials exploring the therapeutic role of intravitreal bevacizumab in DME need to be conducted to define the role of bevacizumab.

Keywords

Avastin Angiogenesis Anti-VEGF therapy Bevacizumab Diabetic macular edema 

References

  1. 1.
    Klein R, Klein BE, Moss SE (1984) Visual impairment in diabetes. Ophthalmology 91:1–9PubMedGoogle Scholar
  2. 2.
    Moss SE, Klein R, Klein BE (1994) Ten-year incidence of visual loss in a diabetic population. Ophthalmology 101:1061–1070PubMedGoogle Scholar
  3. 3.
    Bresnick GH (1986) Diabetic macular edema. A review. Ophthalmology 93:989–997PubMedGoogle Scholar
  4. 4.
    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy: III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 102:527–532PubMedGoogle Scholar
  5. 5.
    Klein R, Klein BE, Moss SE, Davis MD, DeMets DL (1984) The Wisconsin epidemiologic study of diabetic retinopathy: IV. Diabetic macular edema. Ophthalmology 91:1464–1474PubMedGoogle Scholar
  6. 6.
    Antcliff RJ, Marshall J (1999) The pathogenesis of edema in diabetic maculopathy. Semin Ophthalmol 14:223–32Google Scholar
  7. 7.
    Aroca PR, Salvat M, Fernández J, Méndez I (2004) Risk factors for diffuse and focal macular edema. J Diabetes Complications 18:211–215CrossRefPubMedGoogle Scholar
  8. 8.
    Early Treatment Diabetic Retinopathy Study Research Group (1985) Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report no 1. Arch Ophthalmol 103:1796–1806Google Scholar
  9. 9.
    Nasrallah FP, Jalkh AE, Van Coppenolle F, Kado M, Trempe CL, McMeel JW, Schepens CL (1988) The role of the vitreous in diabetic macular edema. Ophthalmol 95:1335–1339Google Scholar
  10. 10.
    Jonas JB, Kreissig I, Sofker A, Degenring RF (2003) Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 121:57–61CrossRefPubMedGoogle Scholar
  11. 11.
    Loewenstein A, Goldstein M (2006) Intravitreal triamcinolone acetonide for diabetic macula edema. Isr Med Assoc J 8:426–427PubMedGoogle Scholar
  12. 12.
    Grant MB, Afzal A, Spoerri P, Pan H, Shaw LC, Mames RN (2004) The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs 13:1275–1293CrossRefPubMedGoogle Scholar
  13. 13.
    Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487CrossRefPubMedGoogle Scholar
  14. 14.
    Funatsu H, Yamashita H, Ikeda T, Nakanishi Y, Kitano S, Hori S (2002) Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders. Am J Ophthalmol 133:537–543CrossRefPubMedGoogle Scholar
  15. 15.
    Cunningham ET Jr, Adamis AP, Altaweel M, Aiello LP, Bressler NM, D'Amico DJ, Goldbaum M, Guyer DR, Katz B, Patel M, Schwartz SD, Macugen Diabetic Retinopathy Study Group (2005) A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmol 112:1747–1757CrossRefGoogle Scholar
  16. 16.
    Chun DW, Heier JS, Topping TM, Duker JS, Bankert JM (2006) A pilot study of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic macular edema. Ophthalmol 113:1706–1712CrossRefGoogle Scholar
  17. 17.
    Whisenant J, Bergsland E (2005) Anti-angiogenic strategies in gastrointestinal malignancies. Curr Treat Options Oncol 6:411–421CrossRefPubMedGoogle Scholar
  18. 18.
    Kaiser PK (2006) Antivascular endothelial growth factor agents and their development: therapeutic implications in ocular diseases. Am J Ophthalmol 142:660–668CrossRefPubMedGoogle Scholar
  19. 19.
    Lynch SS, Cheng CM (2007) Bevacizumab for neovascular ocular diseases. Ann Pharmacother 41:614–625CrossRefPubMedGoogle Scholar
  20. 20.
    Fung AE, Rosenfeld PJ, Reichel E (2006) The International Intravitreal Bevacizumab Safety Survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 90:1344–1349CrossRefPubMedGoogle Scholar
  21. 21.
    Soheilian M, Ramezani A, Bijanzadeh B, Yaseri M, Ahmadieh H, Dehghan MH, Azarmina M, Moradian S, Tabatabaei H, Peyman GA (2007) Intravitreal bevacizumab (avastin) injection alone or combined with triamcinolone versus macular photocoagulation as primary treatment of diabetic macular edema. Retina 27:1187–1195CrossRefPubMedGoogle Scholar
  22. 22.
    Diabetic Retinopathy Clinical Research Network (2007) A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 114:1860–1867CrossRefGoogle Scholar
  23. 23.
    Ahmadieh H, Ramezani A, Shoeibi N, Bijanzadeh B, Tabatabaei A, Azarmina M, Soheilian M, Keshavarzi G, Mohebbi MR (2008) Intravitreal bevacizumab with or without triamcinolone for refractory diabetic macular edema; a placebo-controlled, randomized clinical trial. Graefes Arch Clin Exp Ophthalmol 246:483–489CrossRefPubMedGoogle Scholar
  24. 24.
    Faghihi H, Roohipoor R, Mohammadi SF, Hojat-Jalali K, Mirshahi A, Lashay A, Piri N, Faghihi Sh (2008) Intravitreal bevacizumab versus combined bevacizumab-triamcinolone versus macular laser photocoagulation in diabetic macular edema. Eur J Ophthalmol 18:941–948PubMedGoogle Scholar
  25. 25.
    Soheilian M, Ramezani A, Obudi A, Bijanzadeh B, Salehipour M, Yaseri M, Ahmadieh H, Dehghan MH, Azarmina M, Moradian S, Peyman GA (2009) Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmology 116:1142–1150CrossRefPubMedGoogle Scholar
  26. 26.
    Paccola L, Costa RA, Folgosa MS, Barbosa JC, Scott IU, Jorge R (2008) Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol 92:76–80CrossRefPubMedGoogle Scholar
  27. 27.
    Lam DS, Lai TY, Lee VY, Chan CK, Liu DT, Mohamed S, Li CL (2009) Efficacy of 1.25 MG versus 2.5 MG intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial. Retina 29:292–299CrossRefPubMedGoogle Scholar
  28. 28.
    Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, Gandorfer A, Ulbig M, Kampik A (2006) Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 26:999–1005CrossRefPubMedGoogle Scholar
  29. 29.
    Arevalo JF, Fromow-Guerra J, Quiroz-Mercado H, Pan-American Collaborative Retina Study Group (2007) Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Collaborative Retina Study Group at 6-month follow-up. Ophthalmology 114:743–750CrossRefPubMedGoogle Scholar
  30. 30.
    Yanyali A, Aytug B, Horozoglu F, Nohutcu AF (2007) Bevacizumab (Avastin) for diabetic macular edema in previously vitrectomized eyes. Am J Ophthalmol 144:124–126CrossRefPubMedGoogle Scholar
  31. 31.
    Kumar A, Sinha S (2007) Intravitreal bevacizumab (Avastin) treatment of diffuse diabetic macular edema in an Indian population. Indian J Ophthalmol 55:451–455CrossRefPubMedGoogle Scholar
  32. 32.
    Ornek K, Ornek N (2008) Intravitreal bevacizumab treatment for refractory diabetic macular edema. J Ocul Pharmacol Ther 24:403–407CrossRefPubMedGoogle Scholar
  33. 33.
    Kook D, Wolf A, Kreutzer T, Neubauer A, Strauss R, Ulbig M, Kampik A, Haritoglou C (2008) Long-term effect of intravitreal bevacizumab (avastin) inpatients with chronic diffuse diabetic macular edema. Retina 28:1053–1060CrossRefPubMedGoogle Scholar
  34. 34.
    Roh MI, Byeon SH, Kwon OW (2008) Repeated intravitreal injection of bevacizumab for clinically significant diabetic macular edema. Retina 28:1314–1318CrossRefPubMedGoogle Scholar
  35. 35.
    Fang X, Sakaguchi H, Gomi F, Oshima Y, Sawa M, Tsujikawa M, Ikuno Y, Kamei M, Kusaka S, Tano Y (2008) Efficacy and safety of one intravitreal injection of bevacizumab in diabetic macular oedema. Acta Ophthalmol 86:800–805CrossRefPubMedGoogle Scholar
  36. 36.
    Soliman W, Vinten M, Sander B, Soliman KA, Yehya S, Rahman MS, Larsen M (2008) Optical coherence tomography and vessel diameter changes after intravitreal bevacizumab in diabetic macular oedema. Acta Ophthalmol 86:365–371CrossRefPubMedGoogle Scholar
  37. 37.
    Seo JW, Park IW (2009) Intravitreal bevacizumab for treatment of diabetic macular edema. Korean J Ophthalmol 23:17–22CrossRefPubMedGoogle Scholar
  38. 38.
    Velez-Montoya R, Fromow-Guerra J, Burgos O, Landers MB 3rd, Morales-Catón V, Quiroz-Mercado H (2009) The effect of unilateral intravitreal bevacizumab (avastin), in the treatment of diffuse bilateral diabetic macular edema: a pilot study. Retina 29:20–26CrossRefPubMedGoogle Scholar
  39. 39.
    Arevalo JF, Sanchez JG, Fromow-Guerra J, Pan-American Collaborative Retina Study Group (2009) Comparison of two doses of primary intravitreal bevacizumab (Avastin) for diffuse diabetic macular edema: results from the Pan-American Collaborative Retina Study Group (PACORES) at 12-month follow-up. Graefes Arch Clin Exp Ophthalmol 247:735–43CrossRefPubMedGoogle Scholar
  40. 40.
    Bonini-Filho M, Costa RA, Calucci D, Jorge R, Melo LA Jr, Scott IU (2009) Intravitreal bevacizumab for diabetic macular edema associated with severe capillary loss: one-year results of a pilot study. Am J Ophthalmol 147:1022–1030CrossRefPubMedGoogle Scholar
  41. 41.
    Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F (2000) Methods for Meta-Analysis in Medical Research. John Wiley & Sons, New York, pp 31–33Google Scholar
  42. 42.
    Verhagen AP, de Vet HC, de Bie RA, Kessels AG, Boers M, Bouter LM, Knipschild PG (1998) The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol 51:1235–1241CrossRefPubMedGoogle Scholar
  43. 43.
    Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analysis. BMJ 327:557–560CrossRefPubMedGoogle Scholar
  44. 44.
    Normand S-L (1999) Tutorial in biostatistics: meta-analysis: formulating, evaluating, combining and reporting. Stat Med 18:321–359CrossRefPubMedGoogle Scholar
  45. 45.
    Bakri SJ, Snyder MR, Reid JM, Pulido JS, Singh RJ (2007) Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmology 114:855–859CrossRefPubMedGoogle Scholar
  46. 46.
    Dafer RM, Schneck M, Friberg TR, Jay WM (2007) Intravitreal ranibizumab and bevacizumab: a review of risk. Semin Ophthalmol 22:201–204CrossRefPubMedGoogle Scholar
  47. 47.
    Bhisitkul RB (2006) Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol 90:1542–1547CrossRefPubMedGoogle Scholar
  48. 48.
    Gillies MC (2006) What we don't know about avastin might hurt us. Arch Ophthalmol 124:1478–1479CrossRefPubMedGoogle Scholar
  49. 49.
    Schlichtenbrede FC, Mittmann W, Rensch F, Vom Hagen F, Jonas JB, Euler T (2009) Toxicity assessment of intravitreal triamcinolone and bevacizumab in an retinal explant mouse model using two-photon microscopy. Invest Ophthalmol Vis Sci 50:5880–5887CrossRefPubMedGoogle Scholar
  50. 50.
    Wu L, Martínez-Castellanos MA, Quiroz-Mercado H, Arevalo JF, Berrocal MH, Farah ME, Maia M, Roca JA, Rodriguez FJ, Pan American Collaborative Retina Group (PACORES) (2008) Twelve-month safety of intravitreal injections of bevacizumab(Avastin): results of the Pan-American Collaborative RetinaStudy Group (PACORES). Graefes Arch Clin Exp Ophthalmol 246:81–87CrossRefPubMedGoogle Scholar
  51. 51.
    O'Doherty M, Dooley I, Hickey-Dwyer M (2008) Interventions for diabetic macular oedema: a systemic review of literature. Br J Ophthalmol 92:1581–1590CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Sunali Goyal
    • 1
    • 2
  • Michael LaValley
    • 3
  • Manju L. Subramanian
    • 1
  1. 1.Department of OphthalmologyBoston University School of MedicineBostonUSA
  2. 2.Department of OphthalmologyUniversity of Arkansas Medical SciencesLittle RockUSA
  3. 3.Department of BiostatisticsBoston University School of Public HealthBostonUSA

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