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      KCI등재 SCI SCIE SCOPUS

      Effect of Intravitreal Bevacizumab on Vascular Endothelial Growth Factor Expression in Patients with Proliferative Diabetic Retinopathy

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      https://www.riss.kr/link?id=A101616741

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      다국어 초록 (Multilingual Abstract)

      Purpose: To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco,CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). Materials and Methods: Fibrovascular membranes from 19 eyes of 18 patients with PDR were studied using immunohistochemistry and analyzed in the following 3 groups; group 1: 4 inactive PDR eyes, group 2: 10 active PDR eyes treated preoperatively with adjunctive intravitreal bevacizumab, group 3: five active PDR eyes not treated preoperatively with bevacizumab. Immunohistochemical staining for VEGF, CD31 and CD68 were done. Results: The immunoreactivity to VEGF and CD 31-positive blood vessels was significantly higher in membranes from group 3 than group 1 (p = 0.007 for VEGF, 0.013 for CD 31-positive vessels). Intravitreal bevacizumab caused a reduction in VEGF expression and vascular densities in 4 out of 10 (40%) excised membranes from eyes with PDR. However, six membranes (60%) in group 2 still demonstrated relatively strong VEGF expression and high vascular density. Infiltration of macrophages was observed in 16 out of the 19 membranes, and the density of macrophages was increased in group 2 compared with group 1 (p = 0.043). Conclusion: Intravitreal bevacizumab injections caused some reduction in VEGF expression and vascular densities in a limited number of active PDR patients. A single intravitreal bevacizumab injection may not be enough to induce complete blockage of VEGF and pathologic neovascularization in active PDR patients. Repeated injections, panretinal photocoagulation and/or PPV may be necessary following intravitreal bevacizumab to reinforce the anti-VEGF effect of the drug.
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      Purpose: To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco,CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR)...

      Purpose: To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco,CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). Materials and Methods: Fibrovascular membranes from 19 eyes of 18 patients with PDR were studied using immunohistochemistry and analyzed in the following 3 groups; group 1: 4 inactive PDR eyes, group 2: 10 active PDR eyes treated preoperatively with adjunctive intravitreal bevacizumab, group 3: five active PDR eyes not treated preoperatively with bevacizumab. Immunohistochemical staining for VEGF, CD31 and CD68 were done. Results: The immunoreactivity to VEGF and CD 31-positive blood vessels was significantly higher in membranes from group 3 than group 1 (p = 0.007 for VEGF, 0.013 for CD 31-positive vessels). Intravitreal bevacizumab caused a reduction in VEGF expression and vascular densities in 4 out of 10 (40%) excised membranes from eyes with PDR. However, six membranes (60%) in group 2 still demonstrated relatively strong VEGF expression and high vascular density. Infiltration of macrophages was observed in 16 out of the 19 membranes, and the density of macrophages was increased in group 2 compared with group 1 (p = 0.043). Conclusion: Intravitreal bevacizumab injections caused some reduction in VEGF expression and vascular densities in a limited number of active PDR patients. A single intravitreal bevacizumab injection may not be enough to induce complete blockage of VEGF and pathologic neovascularization in active PDR patients. Repeated injections, panretinal photocoagulation and/or PPV may be necessary following intravitreal bevacizumab to reinforce the anti-VEGF effect of the drug.

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      참고문헌 (Reference)

      1 Arimura N, "Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy" 116 : 921-926, 2009

      2 Clauss M, "Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration" 172 : 1535-1545, 1990

      3 Ferrara N, "Vascular endothelial growth factor: basic science and clinical progress" 25 : 581-611, 2004

      4 Aiello LP, "Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders" 331 : 1480-1487, 1994

      5 Sawada O, "Vascular endothelial growth factor in aqueous humor before and after intravitreal injection of bevacizumab in eyes with diabetic retinopathy" 125 : 1363-1366, 2007

      6 Kim I, "Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells" 276 : 7614-7620, 2001

      7 Alon T, "Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity" 1 : 1024-1028, 1995

      8 Kamba T, "VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature" 290 : H560-H576, 2006

      9 Boulton M, "VEGF localisation in diabetic retinopathy" 82 : 561-568, 1998

      10 Chen E, "Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy" 26 : 699-700, 2006

      1 Arimura N, "Vitreous mediators after intravitreal bevacizumab or triamcinolone acetonide in eyes with proliferative diabetic retinopathy" 116 : 921-926, 2009

      2 Clauss M, "Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration" 172 : 1535-1545, 1990

      3 Ferrara N, "Vascular endothelial growth factor: basic science and clinical progress" 25 : 581-611, 2004

      4 Aiello LP, "Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders" 331 : 1480-1487, 1994

      5 Sawada O, "Vascular endothelial growth factor in aqueous humor before and after intravitreal injection of bevacizumab in eyes with diabetic retinopathy" 125 : 1363-1366, 2007

      6 Kim I, "Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factor-kappa B activation in endothelial cells" 276 : 7614-7620, 2001

      7 Alon T, "Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity" 1 : 1024-1028, 1995

      8 Kamba T, "VEGF-dependent plasticity of fenestrated capillaries in the normal adult microvasculature" 290 : H560-H576, 2006

      9 Boulton M, "VEGF localisation in diabetic retinopathy" 82 : 561-568, 1998

      10 Chen E, "Use of intravitreal bevacizumab as a preoperative adjunct for tractional retinal detachment repair in severe proliferative diabetic retinopathy" 26 : 699-700, 2006

      11 Tatar O, "Tübingen Bevacizumab Study Group, Adam A, et al. Effect of bevacizumab on inflammation and proliferation in human choroidal neovascularization" 126 : 782-790, 2008

      12 Kubota T, "Trabecular meshwork in neovascular glaucoma eyes after the intravitreal injection of bevacizumab" 93 : 557-558, 2009

      13 Lee WS, "Thy-1, a novel marker for angiogenesis upregulated by inflammatory cytokines" 82 : 845-851, 1998

      14 Adamis AP, "The role of vascular endothelial growth factor in ocular health and disease" 25 : 111-118, 2005

      15 Meleth AD, "Serum inflammatory markers in diabetic retinopathy" 46 : 4295-4301, 2005

      16 Joussen AM, "Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo" 160 : 501-509, 2002

      17 Barleon B, "Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1" 87 : 3336-3343, 1996

      18 Oshima Y, "Microincision vitrectomy surgery and intravitreal bevacizumab as a surgical adjunct to treat diabetic traction retinal detachment" 116 : 927-938, 2009

      19 Shimura M, "Macular ischaemia after intravitreal bevacizumab injection in patients with central retinal vein occlusion and a history of diabetes and vascular disease" 94 : 381-383, 2010

      20 Diez-Roux G, "Macrophages kill capillary cells in G1 phase of the cell cycle during programmed vascular regression" 126 : 2141-2147, 1999

      21 Diez-Roux G, "Macrophages induce apoptosis in normal cells in vivo" 124 : 3633-3638, 1997

      22 Sunderkötter C, "Macrophages and angiogenesis" 55 : 410-422, 1994

      23 Chen YS, "Localisation of vascular endothelial growth factor and its receptors to cells of vascular and avascular epiretinal membranes" 81 : 919-926, 1997

      24 Matsuyama K, "Levels of vascular endothelial growth factor and pigment epithelium-derived factor in eyes before and after intravitreal injection of bevacizumab" 53 : 243-248, 2009

      25 Moradian S, "Intravitreal bevacizumab in active progressive proliferative diabetic retinopathy" 246 : 1699-1705, 2008

      26 Avery RL, "Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy" 113 (113): 1-15, 2006

      27 Minnella AM, "Intravitreal bevacizumab (Avastin) in proliferative diabetic retinopathy" 86 : 683-687, 2008

      28 Arevalo JF, "Intravitreal bevacizumab (Avastin) for proliferative diabetic retinopathy: 6-months follow-up" 23 : 117-123, 2009

      29 Wellen KE, "Inflammation, stress, and diabetes" 115 : 1111-1119, 2005

      30 Adamis AP, "Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy" 118 : 445-450, 1994

      31 Kubota T, "Histology of fibrovascular membranes of proliferative diabetic retinopathy after intravitreal injection of bevacizumab" 30 : 468-472, 2010

      32 Matsuoka M, "Expression of pigment epithelium-derived factor and vascular endothelial growth factor in fibrovascular membranes from patients with proliferative diabetic retinopathy" 50 : 116-120, 2006

      33 Bhavsar AR, "Diabetic retinopathy: the latest in current management" 26 : S71-S79, 2006

      34 Baffert F, "Cellular changes in normal blood capillaries undergoing regression after inhibition of VEGF signaling" 290 : H547-H559, 2006

      35 Lang RA, "Apoptosis in mammalian eye development: lens morphogenesis, vascular regression and immune privilege" 4 : 12-20, 1997

      36 Chen E, "Acute visual acuity loss following intravitreal bevacizumab for diabetic macular edema" 40 : 68-70, 2009

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