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Erschienen in: Der Ophthalmologe 6/2006

01.06.2006 | Leitthema

Früher antiexsudativer Effekt – OCT-Monitoring nach intravitrealer Bevacizumab-Applikation

verfasst von: M. Völcker, S. Peters, W. Inhoffen, Dr. F. Ziemssen

Erschienen in: Die Ophthalmologie | Ausgabe 6/2006

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Zusammenfassung

In der Induktion einer gesteigerten Gefäßpermeabilität ist VEGF 50.000-mal potenter als Histamin. In isolierten Gefäßen wird bereits in den ersten Minuten eine deutliche Erhöhung der hydraulischen Leitfähigkeit und des Diffusionskoeffizienten beobachtet. Es folgt eine anhaltende Phase, in der die Barrierefunktion der Gefäßwand selektiv aufgehoben ist. Die spezifische Inhibition des angiogenen, vasoaktiven und permeabilitätsfördernden Proteins VEGF ist mit neuen Wirkstoffen möglich geworden, von denen Bevacizumab als erstes für den klinischen („off label“) Einsatz frei verfügbar ist. Ödeme der Netzhaut entstehen nach Austritt von Wasser und niedermolekularen Stoffen in das Interstitium und stellen für unterschiedliche okuläre Pathologien eine wesentliche prognostische Determinate der Funktion dar. Die ersten Erfahrungen mit der antihyperpermeablen Wirkung von Bevacizumab deuten auf eine frühzeitige und potente Abdichtung pathologischer Leckage hin. Zukünftige Untersuchungen müssen allerdings erst noch zeigen, für welche Erkrankungen überhaupt ein dauerhafter Nutzen erreicht werden kann.
Literatur
1.
Zurück zum Zitat Aiello LP, Bursell SE, Clermont A et al. (1997) Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes 46: 1473–1480PubMed Aiello LP, Bursell SE, Clermont A et al. (1997) Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor. Diabetes 46: 1473–1480PubMed
2.
Zurück zum Zitat Antonetti DA, Barber AJ, Hollinger LA et al. (1999) Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechanism for vascular permeability in diabetic retinopathy and tumors. J Biol Chem 274: 23463–23467CrossRefPubMed Antonetti DA, Barber AJ, Hollinger LA et al. (1999) Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occludin and zonula occluden 1. A potential mechanism for vascular permeability in diabetic retinopathy and tumors. J Biol Chem 274: 23463–23467CrossRefPubMed
3.
Zurück zum Zitat Avery RL, Pieramici DJ, Rabena MD et al. (2006) Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 113: 363–372CrossRefPubMed Avery RL, Pieramici DJ, Rabena MD et al. (2006) Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 113: 363–372CrossRefPubMed
4.
Zurück zum Zitat Bates DO (1998) The chronic effect of vascular endothelial growth factor on individually perfused frog mesenteric microvessels. J Physiol 513 (Pt 1): 225–233CrossRefPubMed Bates DO (1998) The chronic effect of vascular endothelial growth factor on individually perfused frog mesenteric microvessels. J Physiol 513 (Pt 1): 225–233CrossRefPubMed
5.
Zurück zum Zitat Bates DO, Curry FE (1996) Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels. Am J Physiol 271(6 Pt 2): H2520–H2528PubMed Bates DO, Curry FE (1996) Vascular endothelial growth factor increases hydraulic conductivity of isolated perfused microvessels. Am J Physiol 271(6 Pt 2): H2520–H2528PubMed
6.
Zurück zum Zitat Becker PM, Waltenberger J, Yachechko R et al. (2005) Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. Circ Res 96(12): 1257–1265CrossRefPubMed Becker PM, Waltenberger J, Yachechko R et al. (2005) Neuropilin-1 regulates vascular endothelial growth factor-mediated endothelial permeability. Circ Res 96(12): 1257–1265CrossRefPubMed
7.
Zurück zum Zitat Behzadian MA, Windsor LJ, Ghaly N et al. (2003) VEGF-induced paracellular permeability in cultured endothelial cells involves urokinase and its receptor. FASEB J 17: 752–754PubMed Behzadian MA, Windsor LJ, Ghaly N et al. (2003) VEGF-induced paracellular permeability in cultured endothelial cells involves urokinase and its receptor. FASEB J 17: 752–754PubMed
8.
Zurück zum Zitat Browning AC, Gray T, Amoaku WM (2005) Isolation, culture, and characterisation of human macular inner choroidal microvascular endothelial cells. Br J Ophthalmol 89: 1343–1347CrossRefPubMed Browning AC, Gray T, Amoaku WM (2005) Isolation, culture, and characterisation of human macular inner choroidal microvascular endothelial cells. Br J Ophthalmol 89: 1343–1347CrossRefPubMed
9.
Zurück zum Zitat Chan A, Duker JS, Ko TH et al. (2006) Normal macular thickness measurements in healthy eyes using Stratus optical coherence tomography. Arch Ophthalmol 124: 193–198CrossRefPubMed Chan A, Duker JS, Ko TH et al. (2006) Normal macular thickness measurements in healthy eyes using Stratus optical coherence tomography. Arch Ophthalmol 124: 193–198CrossRefPubMed
10.
Zurück zum Zitat Chang YS, Munn LL, Hillsley MV et al. (2000) Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties. Microvasc Res 59: 265–277CrossRefPubMed Chang YS, Munn LL, Hillsley MV et al. (2000) Effect of vascular endothelial growth factor on cultured endothelial cell monolayer transport properties. Microvasc Res 59: 265–277CrossRefPubMed
11.
Zurück zum Zitat Clark ER, Clark EL (1935) Observations on changes in blood vascular endothelium in the living animal. Am J Anat 57: 385–438CrossRef Clark ER, Clark EL (1935) Observations on changes in blood vascular endothelium in the living animal. Am J Anat 57: 385–438CrossRef
12.
Zurück zum Zitat Dejana E, Corada M, Lampugnani MG (1995) Endothelial cell-to-cell junctions. FASEB J 9: 910–918PubMed Dejana E, Corada M, Lampugnani MG (1995) Endothelial cell-to-cell junctions. FASEB J 9: 910–918PubMed
13.
Zurück zum Zitat Detmar M, Brown LF, Claffey KP et al. (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180: 1141–1146CrossRefPubMed Detmar M, Brown LF, Claffey KP et al. (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180: 1141–1146CrossRefPubMed
14.
Zurück zum Zitat Esser S, Wolburg K, Wolburg Het al. (1998) Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140(4): 947–959CrossRefPubMed Esser S, Wolburg K, Wolburg Het al. (1998) Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140(4): 947–959CrossRefPubMed
15.
Zurück zum Zitat Eter N, Bindewald A, Roth Fet al. (2004) OCT in age-related macular degeneration. Findings, usage in clinical routine, and assessment of treatment outcome. Ophthalmologe 101: 794–803PubMed Eter N, Bindewald A, Roth Fet al. (2004) OCT in age-related macular degeneration. Findings, usage in clinical routine, and assessment of treatment outcome. Ophthalmologe 101: 794–803PubMed
16.
Zurück zum Zitat Feng D, Nagy JA, Hipp J et al. (1996) Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin. J Exp Med 183: 1981–1986CrossRefPubMed Feng D, Nagy JA, Hipp J et al. (1996) Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin. J Exp Med 183: 1981–1986CrossRefPubMed
17.
Zurück zum Zitat Feng Y, Venema VJ, Venema RC et al. (1999) VEGF-induced permeability increase is mediated by caveolae. Invest Ophthalmol Vis Sci 40: 157–167PubMed Feng Y, Venema VJ, Venema RC et al. (1999) VEGF-induced permeability increase is mediated by caveolae. Invest Ophthalmol Vis Sci 40: 157–167PubMed
18.
Zurück zum Zitat Fu BM, Shen S (2003) Structural mechanisms of acute VEGF effect on microvessel permeability. Am J Physiol Heart Circ Physiol 284: H2124–H2135PubMed Fu BM, Shen S (2003) Structural mechanisms of acute VEGF effect on microvessel permeability. Am J Physiol Heart Circ Physiol 284: H2124–H2135PubMed
19.
Zurück zum Zitat Gelisken F, Inhoffen W, Partsch M et al. (2001) Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization. Am J Ophthalmol 131: 518–520CrossRefPubMed Gelisken F, Inhoffen W, Partsch M et al. (2001) Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization. Am J Ophthalmol 131: 518–520CrossRefPubMed
20.
Zurück zum Zitat Hee MR, Puliafito CA, Wong C et al. (1995) Quantitative assessment of macular edema with optical coherence tomography. Arch Ophthalmol 113: 1019–1029PubMed Hee MR, Puliafito CA, Wong C et al. (1995) Quantitative assessment of macular edema with optical coherence tomography. Arch Ophthalmol 113: 1019–1029PubMed
21.
Zurück zum Zitat Heier J, Focus Study Group (2005) Intravitreal ranibizumab (Lucentis) with verteprofin photodynamic therapyy for neovascular age-related macular degeneration: year one results. ASRS scientific paper presentation, Montreal, Quebec, Canada Heier J, Focus Study Group (2005) Intravitreal ranibizumab (Lucentis) with verteprofin photodynamic therapyy for neovascular age-related macular degeneration: year one results. ASRS scientific paper presentation, Montreal, Quebec, Canada
22.
Zurück zum Zitat Hillman NJ, Whittles CE, Pocock TM, Williams B et al. (2001) Differential effects of vascular endothelial growth factor-C and placental growth factor-1 on the hydraulic conductivity of frog mesenteric capillaries. J Vasc Res 38: 176–186CrossRefPubMed Hillman NJ, Whittles CE, Pocock TM, Williams B et al. (2001) Differential effects of vascular endothelial growth factor-C and placental growth factor-1 on the hydraulic conductivity of frog mesenteric capillaries. J Vasc Res 38: 176–186CrossRefPubMed
23.
Zurück zum Zitat Kaiser P, ANCHOR Study Group (2006) ANCHOR DATA (year one results). Macula 2006, paper presentation, New York, NY, USA Kaiser P, ANCHOR Study Group (2006) ANCHOR DATA (year one results). Macula 2006, paper presentation, New York, NY, USA
24.
Zurück zum Zitat Legro MW (1991) Quality of life and cataracts: a review of patient-centered studies of cataract surgery outcomes. Ophthalmic Surg 22: 431–443PubMed Legro MW (1991) Quality of life and cataracts: a review of patient-centered studies of cataract surgery outcomes. Ophthalmic Surg 22: 431–443PubMed
25.
Zurück zum Zitat Majno G, Shea SM, Leventhal M (1969) Endothelial contraction induced by histamine-type mediators: an electron microscopic study. J Cell Biol 42: 647–672CrossRefPubMed Majno G, Shea SM, Leventhal M (1969) Endothelial contraction induced by histamine-type mediators: an electron microscopic study. J Cell Biol 42: 647–672CrossRefPubMed
26.
Zurück zum Zitat Marmor MF (1999) Mechanisms of fluid accumulation in retinal edema. Doc Ophthalmol 97: 239–249CrossRefPubMed Marmor MF (1999) Mechanisms of fluid accumulation in retinal edema. Doc Ophthalmol 97: 239–249CrossRefPubMed
27.
Zurück zum Zitat Massin P, Vicaut E, Haouchine B et al. (2001) Reproducibility of retinal mapping using optical coherence tomography. Arch Ophthalmol 119: 1135–1142PubMed Massin P, Vicaut E, Haouchine B et al. (2001) Reproducibility of retinal mapping using optical coherence tomography. Arch Ophthalmol 119: 1135–1142PubMed
28.
Zurück zum Zitat Meredith TA, Kenyon KR, Singerman LJ et al. (1976) Perifoveal vascular leakage and macular oedema after intracapsular cataract extraction. Br J Ophthalmol 60: 765–769PubMed Meredith TA, Kenyon KR, Singerman LJ et al. (1976) Perifoveal vascular leakage and macular oedema after intracapsular cataract extraction. Br J Ophthalmol 60: 765–769PubMed
29.
Zurück zum Zitat Neal CR, Michel CC (1997) Transcellular openings through frog microvascular endothelium. Exp Physiol 82: 419–422PubMed Neal CR, Michel CC (1997) Transcellular openings through frog microvascular endothelium. Exp Physiol 82: 419–422PubMed
30.
Zurück zum Zitat Nussenblatt RB, Kaufman SC, Palestine AG et al. (1987) Macular thickening and visual acuity. Measurement in patients with cystoid macular edema. Ophthalmology 94: 1134–1139PubMed Nussenblatt RB, Kaufman SC, Palestine AG et al. (1987) Macular thickening and visual acuity. Measurement in patients with cystoid macular edema. Ophthalmology 94: 1134–1139PubMed
31.
Zurück zum Zitat Paunescu LA, Schuman JS, Price LL et al. (2004) Reproducibility of nerve fiber thickness, macular thickness, and optic nerve head measurements using StratusOCT. Invest Ophthalmol Vis Sci 45: 1716–1724CrossRefPubMed Paunescu LA, Schuman JS, Price LL et al. (2004) Reproducibility of nerve fiber thickness, macular thickness, and optic nerve head measurements using StratusOCT. Invest Ophthalmol Vis Sci 45: 1716–1724CrossRefPubMed
32.
Zurück zum Zitat Pepper MS (2001) Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21: 1104–1117PubMed Pepper MS (2001) Role of the matrix metalloproteinase and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21: 1104–1117PubMed
33.
Zurück zum Zitat Peters S, Julien S, Ziemssen F et al. (2006) Bevacizumab Significantly Reduces VEGF-Related Permeability in Choroidal Endothelial Cells. Invest Ophthalmol Vis Sci 47: A5343 Peters S, Julien S, Ziemssen F et al. (2006) Bevacizumab Significantly Reduces VEGF-Related Permeability in Choroidal Endothelial Cells. Invest Ophthalmol Vis Sci 47: A5343
34.
Zurück zum Zitat Polito A, Del Borrello M, Polini G et al. (2006) Diurnal variation in clinically significant diabetic macular edema measured by the Stratus OCT. Retina 26: 14–20CrossRefPubMed Polito A, Del Borrello M, Polini G et al. (2006) Diurnal variation in clinically significant diabetic macular edema measured by the Stratus OCT. Retina 26: 14–20CrossRefPubMed
35.
Zurück zum Zitat Puliafito CA, Hee MR, Lin CP et al. (1995) Imaging of macular diseases with optical coherence tomography. Ophthalmology 102: 217–229PubMed Puliafito CA, Hee MR, Lin CP et al. (1995) Imaging of macular diseases with optical coherence tomography. Ophthalmology 102: 217–229PubMed
36.
Zurück zum Zitat Reinthal EK, Volker M, Freudenthaler N et al. (2004) Optical coherence tomography in the diagnosis and follow-up of patients with uveitic macular edema. Ophthalmologe 101: 1181–1188CrossRefPubMed Reinthal EK, Volker M, Freudenthaler N et al. (2004) Optical coherence tomography in the diagnosis and follow-up of patients with uveitic macular edema. Ophthalmologe 101: 1181–1188CrossRefPubMed
37.
Zurück zum Zitat Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108 (Pt 6): 2369–2379PubMed Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108 (Pt 6): 2369–2379PubMed
38.
Zurück zum Zitat Schmidt-Erfurth U, Niemeyer M, Geitzenauer W et al. (2005) Time course and morphology of vascular effects associated with photodynamic therapy. Ophthalmology 112: 2061–2069CrossRefPubMed Schmidt-Erfurth U, Niemeyer M, Geitzenauer W et al. (2005) Time course and morphology of vascular effects associated with photodynamic therapy. Ophthalmology 112: 2061–2069CrossRefPubMed
39.
Zurück zum Zitat Schoefl GI (1963) Studies on Inflammation. III. Growing capillaries: Their structure and permeability. Virchows Arch Pathol Anat Physiol Klin Med 337: 97–141CrossRefPubMed Schoefl GI (1963) Studies on Inflammation. III. Growing capillaries: Their structure and permeability. Virchows Arch Pathol Anat Physiol Klin Med 337: 97–141CrossRefPubMed
40.
Zurück zum Zitat Senger DR, Connolly DT, Van de WL et al. (1990) Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res 50: 1774–1778PubMed Senger DR, Connolly DT, Van de WL et al. (1990) Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res 50: 1774–1778PubMed
41.
Zurück zum Zitat Shahidi M, Ogura Y, Blair NP et al. (1991) Retinal thickness analysis for quantitative assessment of diabetic macular edema. Arch Ophthalmol 109: 1115–1119PubMed Shahidi M, Ogura Y, Blair NP et al. (1991) Retinal thickness analysis for quantitative assessment of diabetic macular edema. Arch Ophthalmol 109: 1115–1119PubMed
42.
Zurück zum Zitat Stark WJ Jr, Maumenee AE, Fagadau W et al. (1984) Cystoid macular edema in pseudophakia. Surv Ophthalmol 28 [Suppl]: 442–451CrossRefPubMed Stark WJ Jr, Maumenee AE, Fagadau W et al. (1984) Cystoid macular edema in pseudophakia. Surv Ophthalmol 28 [Suppl]: 442–451CrossRefPubMed
43.
Zurück zum Zitat Suarez S, Ballmer-Hofer K (2001) VEGF transiently disrupts gap junctional communication in endothelial cells. J Cell Sci 114 (Pt 6): 1229–1235PubMed Suarez S, Ballmer-Hofer K (2001) VEGF transiently disrupts gap junctional communication in endothelial cells. J Cell Sci 114 (Pt 6): 1229–1235PubMed
44.
Zurück zum Zitat Sundelin K, Lundstrom M, Stenevi U (2005) Self-assessed visual function for patients with posterior capsule opacification before and after capsulotomy. Acta Ophthalmol Scand 83: 729–733CrossRefPubMed Sundelin K, Lundstrom M, Stenevi U (2005) Self-assessed visual function for patients with posterior capsule opacification before and after capsulotomy. Acta Ophthalmol Scand 83: 729–733CrossRefPubMed
45.
Zurück zum Zitat Wang Y, Fei D, Vanderlaan M et al. (2004) Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 7: 335–345CrossRefPubMed Wang Y, Fei D, Vanderlaan M et al. (2004) Biological activity of bevacizumab, a humanized anti-VEGF antibody in vitro. Angiogenesis 7: 335–345CrossRefPubMed
46.
Zurück zum Zitat Weis SM, Cheresh DA (2005) Pathophysiological consequences of VEGF-induced vascular permeability. Nature 437: 497–504CrossRefPubMed Weis SM, Cheresh DA (2005) Pathophysiological consequences of VEGF-induced vascular permeability. Nature 437: 497–504CrossRefPubMed
47.
Zurück zum Zitat Whittles CE, Pocock TM, Wedge SR et al. (2002) ZM323881, a novel inhibitor of vascular endothelial growth factor-receptor-2 tyrosine kinase activity. Microcirculation 9: 513–522CrossRefPubMed Whittles CE, Pocock TM, Wedge SR et al. (2002) ZM323881, a novel inhibitor of vascular endothelial growth factor-receptor-2 tyrosine kinase activity. Microcirculation 9: 513–522CrossRefPubMed
48.
Zurück zum Zitat Wu HM, Yuan Y, Zawieja DC et al. (1999) Role of phospholipase C, protein kinase C, and calcium in VEGF-induced venular hyperpermeability. Am J Physiol 276 (2 Pt 2): H535–H542PubMed Wu HM, Yuan Y, Zawieja DC et al. (1999) Role of phospholipase C, protein kinase C, and calcium in VEGF-induced venular hyperpermeability. Am J Physiol 276 (2 Pt 2): H535–H542PubMed
49.
Zurück zum Zitat Zhang Y, Matsuo H, Morita E (2005) Vascular endothelial growth factor 121 is the predominant isoform in psoriatic scales. Exp Dermatol 14: 758–764PubMed Zhang Y, Matsuo H, Morita E (2005) Vascular endothelial growth factor 121 is the predominant isoform in psoriatic scales. Exp Dermatol 14: 758–764PubMed
Metadaten
Titel
Früher antiexsudativer Effekt – OCT-Monitoring nach intravitrealer Bevacizumab-Applikation
verfasst von
M. Völcker
S. Peters
W. Inhoffen
Dr. F. Ziemssen
Publikationsdatum
01.06.2006
Verlag
Springer-Verlag
Erschienen in
Die Ophthalmologie / Ausgabe 6/2006
Print ISSN: 2731-720X
Elektronische ISSN: 2731-7218
DOI
https://doi.org/10.1007/s00347-006-1356-1

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