Diabetic macular edema (DME) is the most important cause of vision loss in patients with diabetes mellitus. Diabetic retinopathy has a remarkable impact on public health and on the quality of life of diabetic patients and thus requires special consideration. The first line of treatment remains the management of systemic risk factors but is often insufficient in controlling DME and currently, laser retinal photocoagulation is considered the standard of care. However, laser treatment reduces the risk of moderate visual loss by approximately 50% without guaranteeing remarkable effects on visual improvement. For these reasons, new strategies in the treatment of DME have been studied, in particular the use of anti-vascular endothelial growth factor (anti-VEGF) drugs. VEGF is a pluripotent growth factor that acts as a vasopermeability factor and an endothelial cell mitogen. For this reason, it represents an interesting candidate as a therapeutic target for the treatment of DME. The aim of this article is to review the evidence behind the use of anti-VEGF drugs in the treatment of DME.

1.
Kempen JH, O’Colmain BJ, Leske MC, et al, Eye Diseases Prevalence Research Group: The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol 2004;122:552–563.
[PubMed]
2.
Klein R: Retinopathy in a population-based study. Trans Am Ophthalmol Soc 1992;90:561–594.
[PubMed]
3.
Wild S, Roglic G, Green A, Sicree R, et al: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047–1053.
[PubMed]
4.
Bandello F, Parodi MB, Lanzetta P, et al: Diabetic macular edema. Dev Ophthalmol 2010;47:73–110.
5.
Neufeld G, Cohen T, Gengrinovitch S, et al: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 1999;13:9–22.
[PubMed]
6.
Grant MB, Afzal A, Spoerri P, et al: The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs 2004;13:1275–1293.
[PubMed]
7.
Plate KH, Breier G, Weich HA, et al: Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992;359:845–848.
[PubMed]
8.
Shweiki D, Itin A, Soffer D, et al: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992;359:843–845.
[PubMed]
9.
Aiello LP, Avery RL, Arrigg PG, et al: Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480–1487.
[PubMed]
10.
Gardner TW, Antonetti DA, Barber AJ, et al: Diabetic retinopathy: more than meets the eye. Surv Ophthalmol 2002;47(suppl 2): S253–S262.
[PubMed]
11.
Massin P, Bandello F, Garweg JG, et al: Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010;33:2399–2405.
[PubMed]
12.
Nguyen QD, Shah SM, Heier JS, et al, READ-2 Study Group: Primary end point (six months) results of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study. Ophthalmology 2009;116:2175–2181.
[PubMed]
13.
Nguyen QD, Shah SM, Khwaja AA, et al, READ-2 Study Group: Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology 2010;117:2146–2151.
14.
Mitchell P, Bandello F, Schmidt-Erfurth U, et al: The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011;118:615–625.
[PubMed]
15.
Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1987;94:761–774.
16.
Elman MJ, Bressler NM, Qin H, et al: Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Diabetic Retinopathy Clinical Research Network. Ophthalmology 2011;118:609–614.
17.
Googe J, Brucker AJ, Bressler NM, et al: Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation. Retina 2011;31:1009–1027.
18.
Bandello F, Cunha-Vaz J, Chong NV, et al: New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel. Eye (Lond) 2012;26:485–493.
19.
Sultan MB, Zhou D, Loftus J, et al: A phase 2/3, multicenter, randomized, double-masked, 2-year trial of pegaptanib sodium for the treatment of diabetic macular edema. Ophthalmology 2011;118:1107–1118.
20.
Cunningham ET Jr, Adamis AP, Altaweel M, et al: Macugen Diabetic Retinopathy Study Group. A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema. Ophthalmology 2005;112:1747–1757.
[PubMed]
21.
Diabetic Retinopathy Clinical Research Network: A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007;114:1860–1867.
[PubMed]
22.
Arevalo JF, Sanchez JG, Wu L, et al, Pan-American Collaborative Retina Study Group: Primary intravitreal bevacizumab for diffuse diabetic macular edema: the Pan-American Collaborative Retina Study Group at 24 months. Ophthalmology 2009;116:1488–1497.
[PubMed]
23.
Soheilian M, Ramezani A, Obudi A, et al: Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmology 2009;116:1142–1150.
[PubMed]
24.
Soheilian M, Ramezani A, Yaseri M, et al: Initial macular thickness and response to treatment in diabetic macular edema. Retina 2011;31:1564–1573.
25.
Lim JW, Lee HK, Shin MC: Comparison of intravitreal bevacizumab alone or combined with triamcinolone versus triamcinolone in diabetic macular edema: a randomized clinical trial. Ophthalmologica 2012;227:100–106.
26.
Goyal S, La Valley M, Subramanian ML: Meta-analysis and review on the effect of bevacizumab in diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2011;249:15–27.
[PubMed]
27.
Economides AN, Carpenter LR, Rudge JS, et al: Cytokine traps: multi-component, high-affinity blockers of cytokine action. Nat Med 2003;9:47–52.
[PubMed]
28.
Holash J, Davis S, Papadopoulos N, et al: VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 2002;99:11393–11398.
[PubMed]
29.
Stewart MW, Rosenfeld PJ: Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol 2008;92:667–668.
[PubMed]
30.
Ohr M, Kaiser PK: Intravitreal aflibercept injection for neovascular (wet) age-related macular degeneration. Expert Opin Pharmacother 2012;13:585–591.
31.
Do DV, Schmidt-Erfurth U, Gonzalez VH, et al: The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology 2011;118:1819–1826.
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