Zusammenfassung
Ansatz
Es erfolgte eine Bestimmung von Zytokinen aus Glaskörperproben von zuvor unbehandelten Patienten mit diabetischer Retinopathie (DRP), retinalem Venenverschluss (RVV) und altersbedingter Makuladegeneration (AMD) mit subretinaler Blutung.
Methode
Bei 187 Patienten (Median 67,0 Jahre, 101 Männer) wurde eine Kombinationstherapie inklusive einer 23-Gauge-Kernvitrektomie durchgeführt. Interleukin-6 (IL-6) und „monocyte chemoattractant protein-1“ (MCP-1) und „vascular endothelial growth factor“ (VEGF) wurden mittels „cytometric bead array“ (CBA) bestimmt und mit Kontrollproben verglichen.
Ergebnisse
Alle Erkrankungen hatten signifikant erhöhte Zytokinspiegel gegenüber der Kontrollgruppe außer VEGF bei AMD. Bei der DRP zeigten sich höhere VEGF-A- und MCP-1-Spiegel beim diffus zystoiden Makulaödem verglichen mit fokal zystoidem Ödem. Die ischämische DRP hatte höhere VEGF-A-Spiegel als die nichtischämische. Alle gemessenen Zytokine waren bei Zentralvenenverschlüssen höher als bei Venenastverschlüssen.
Zusammenfassung
Unterschiedliche intravitreale Zytokinspiegel konnten zwischen DRP, RVV und feuchter AMD dargestellt werden. Die genauere Kenntnis der spezifischen Ausprägung der Zytokindysregulation könnte eine zielgerichtetere Therapie zukünftig ermöglichen.
Abstract
Purpose
The aim of this study was to determine cytokine levels from vitreous samples of treatment-naive patients with diabetic retinopathy (DRP), retinal vein occlusion (RVO) and exudative age-related macular degeneration (ARMD).
Methods
In this study 187 patients (median age 67 years, 101 males) were treated with a combined drug therapy including a 23-gauge core vitrectomy. Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and intravitreal vascular endothelial growth factor (VEGF-A) levels were determined a using cytometric bead assay (CBA) and compared to those of the control group.
Results
Compared to the control group all diseases had significantly elevated cytokine levels, except VEGF in ARMD. In DRP samples of patients with diffuse diabetic macula edema (DME) higher VEGF-A and MCP-1 levels were found than in patients with focal DME. Ischemic DRP had higher VEGF levels than non-ischemic DRP. All measured cytokines were significantly higher in central retinal vein occlusion (CRVO) than in branch retinal vein occlusion (BRVO).
Conclusions
Differences in intravitreal cytokine levels in DRP, RVO and ARMD could be demonstrated. The knowledge of depicted specific characteristic dysregulation of cytokines could allow more targeted future therapies.
Literatur
Jo N, Wu GS, Rao NA (2003) Upregulation of chemokine expression in the retinal vasculature in ischemia-reperfusion injury. Invest Ophthalmol Vis Sci 44(9):4054–4060
Pe’er J et al (1998) Vascular endothelial growth factor upregulation in human central retinal vein occlusion. Ophthalmology 105(3):412–416
Morgan E et al (2004) Cytometric bead array: a multiplexed assay platform with applications in various areas of biology. Clin Immunol 110(3):252–266
Eickmeier O et al (2010) Sputum biomarker profiles in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) and association between pulmonary function. Cytokine 50(2):152–157
Maier R et al (2006) Application of multiplex cytometric bead array technology for the measurement of angiogenic factors in the vitreous. Mol Vis 12:1143–1147
Funk M et al (2010) Angiogenic and inflammatory markers in the intraocular fluid of eyes with diabetic macular edema and influence of therapy with bevacizumab. Retina 30(9):1412–1419
Yoshimura T et al (2009) Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One 4(12):e8158
Kaneda S et al (2011) Multivariate analyses of inflammatory cytokines in eyes with branch retinal vein occlusion: relationships to bevacizumab treatment. Invest Ophthalmol Vis Sci 52(6):2982–2988
Koss MJ et al (2012) Comparison of cytokine levels from undiluted vitreous of untreated patients with retinal vein occlusion. Acta Ophthalmol 90(2):e98–e103
Koss MJ, Pfister M, Koch FH (2011) Inflammatory and angiogenic protein detection in the human vitreous: cytometric bead assay. J Ophthalmol 2011:459251
Central Vein Occlusion Study Group (CVOS) (1993) Central vein occlusion study of photocoagulation. Manual of operations. Online J Curr Clin Trials Doc No 92:32,228 words; 678 paragraphs
Branch Vein Occlusion Study Group (BVOS) (1986) Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial. Arch Ophthalmol 104(1):34–41
Ogata N et al (2002) Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy. Am J Ophthalmol 134(3):348–353
Funatsu H et al (2003) Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 110(9):1690–1696
Funatsu H et al (2009) Association of vitreous inflammatory factors with diabetic macular edema. Ophthalmology 116(1):73–79
Patel JI et al (2006) Vitreous and aqueous concentrations of proangiogenic, antiangiogenic factors and other cytokines in diabetic retinopathy patients with macular edema: implications for structural differences in macular profiles. Exp Eye Res 82(5):798–806
Giovannini A et al (2000) Optical coherence tomography findings in diabetic macular edema before and after vitrectomy. Ophthalmic Surg Lasers 31(3):187–191
Antonetti DA et al (1998) Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes 47(12):1953–1959
Schober A, Zernecke A (2007) Chemokines in vascular remodeling. Thromb Haemost 97(5):730–737
Yoshida S et al (2003) Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization. J Leukoc Biol 73(1):137–144
Ishida S et al (2003) VEGF164 is proinflammatory in the diabetic retina. Invest Ophthalmol Vis Sci 44(5):2155–2162
Bresnick GH et al (1984) Abnormalities of the foveal avascular zone in diabetic retinopathy. Arch Ophthalmol 102(9):1286–1293
Conrath J et al (2005) Foveal avascular zone in diabetic retinopathy: quantitative vs qualitative assessment. Eye (Lond) 19(3):322–326
Diabetic Retinopathy Clinical Research Network (2007) A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 114(10):1860–1867
Koss MJ et al (2012) Combination therapy in diabetic macular oedema and retinal vein occlusion – past and present. Acta Ophthalmol 90(6):580–589
Noma H et al (2008) Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye (Lond) 22(1):42–48
Noma H et al (2009) Vitreous levels of interleukin-6 and vascular endothelial growth factor in macular edema with central retinal vein occlusion. Ophthalmology 116(1):87–93
Funk M et al (2009) Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Invest Ophthalmol Vis Sci 50(3):1025–1032
Stefansson E (2008) Treatment of branch retinal vein occlusion. Acta Ophthalmol 86(2):122–123
Prager F et al (2009) Intravitreal bevacizumab (Avastin) for macular oedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial. Br J Ophthalmol 93(4):452–456
Ehrlich R et al (2010) Combined treatment of intravitreal bevacizumab and intravitreal triamcinolone in patients with retinal vein occlusion: 6 months of follow-up. Graefes Arch Clin Exp Ophthalmol 248(3):375–380
Funk M et al (2009) Neovascular age-related macular degeneration: intraocular cytokines and growth factors and the influence of therapy with ranibizumab. Ophthalmology 116(12):2393–2399
Roh MI et al (2010) Concentration of cytokines in age-related macular degeneration after consecutive intravitreal bevacizumab injection. Graefes Arch Clin Exp Ophthalmol 248(5):635–640
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Pfister, M., Koch, F., Cinatl, J. et al. Zytokinbestimmung aus Glaskörperproben bei retinalen Gefäßerkrankungen. Ophthalmologe 110, 746–754 (2013). https://doi.org/10.1007/s00347-012-2719-4
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DOI: https://doi.org/10.1007/s00347-012-2719-4
Schlüsselwörter
- Altersbedingte Makuladegeneration
- Diabetische Retinopathie
- Retinaler Venenverschluss
- Interleukin
- Vascular endothelial growth factor