Zusammenfassung
„Vascular-endothelial-growth-factor“ (VEGF)-Inhibitoren werden bei immer mehr Indikationen eingesetzt. Außerhalb der klassischen Anwendungsgebiete der exsudativen Makuladegeneration und des Makulaödems werden sie mittlerweile auch als Off-label-Therapie zur Unterstützung einer panretinalen Laserkoagulation oder als Vorbereitung eines vitreoretinalen Eingriffs bei ischämischer Retinopathie angewandt. Bei vitreoretinalen Eingriffen erfolgt die Anti-VEGF-Behandlung dabei meist wenige Tage vor der Vitrektomie, um die Operationsbedingungen zu verbessern. Zur Unterstützung einer konventionellen, panretinalen Laserkoagulation kann die Injektion dagegen konsekutiv oder parallel zur Laserung erfolgen. Nach wie vor ist aber auch mit dem Einsatz von VEGF-Inhibition in fast allen Fällen eine thermische Koagulation der peripheren Netzhaut unerlässlich. Die größte Gefahr der Anwendung von VEGF-Inhibitoren bei ischämischer Retinopathie besteht darin, dass eine traktiv wirksame Proliferationsmembran unterschätzt oder übersehen wird und sich nach der Injektion durch Kontraktion der Membran eine Traktionsamotio entwickelt. Der vorliegende Beitrag fasst den aktuellen Wissenstand zur Anwendung von VEGF-Inhibitoren bei vitreoretinalen Eingriffen zusammen, weist aber auch auf die teilweise geringe Evidenz der zur Verfügung stehenden Daten hin und belegt somit die Notwendigkeit für weitere groß angelegte Studien.
Abstract
Vascular endothelial growth factor (VEGF) inhibitors are being used for an increasing number of indications. Beyond the classical use in exudative macular degeneration and macular edema, they are being used, for example off-label as additive treatment together with panretinal laser photocoagulation or in preparation for vitrectomy for ischemic retinopathy. In preparation for vitreoretinal surgery VEGF inhibitors are usually given prior to surgery. When given as an adjunct to laser treatment, VEGF inhibitors can be given either consecutively or parallel to laser photocoagulation. In most cases, however, anti-VEGF treatment does not render laser coagulation dispensable. The greatest danger with anti-VEGF treatment in the context of ischemic retinopathies lies in the fact that proliferative membranes are misjudged or overlooked. In these cases, anti-VEGF treatment can induce contraction of these membranes with induction of consecutive tractional retinal detachment. This review summarizes the current knowledge on VEGF inhibition as an adjunct to vitreoretinal surgery and also points out the gaps in the current knowledge and the need for further research.
Literatur
Campochiaro PA, Bhisitkul RB, Shapiro H, Rubio RG (2013) Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion. Ophthalmology 120:795–802
Michaelides M, Fraser-Bell S, Hamilton R et al (2010) Macular perfusion determined by fundus fluorescein angiography at the 4-month time point in a prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (Bolt Study): report 1. Retina 30:781–786
Kollias AN, Ulbig MW (2010) Diabetic retinopathy: early diagnosis and effective treatment. Dtsch Ärztebl Int 107:75–83 (quiz 84)
Klein R, Klein BE, Moss SE et al (1984) The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 102:520–526
Klein R, Klein BE, Moss SE et al (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 102:527–532
Vander JF, Duker JS, Benson WE et al (1991) Long-term stability and visual outcome after favorable initial response of proliferative diabetic retinopathy to panretinal photocoagulation. Ophthalmology 98:1575–1579
Flynn HW Jr, Chew EY, Simons BD et al (1992) Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study. ETDRS report number 17. The Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 99:1351–1357
Cho WB, Oh SB, Moon JW, Kim HC (2009) Panretinal photocoagulation combined with intravitreal bevacizumab in high-risk proliferative diabetic retinopathy. Retina 29:516–522
Mirshahi A, Roohipoor R, Lashay A, Mohammadi S-F (2008) Bevacizumab-augmented retinal laser photocoagulation in proliferative diabetic retinopathy: a randomized double-masked clinical trial. Eur J Ophthalmol 18:263–269
Tonello M, Costa RA, Almeida FPP et al (2008) Panretinal photocoagulation versus PRP plus intravitreal bevacizumab for high-risk proliferative diabetic retinopathy (IBeHi study). Acta Ophthalmol 86:385–389
Do DV, Nguyen QD, Boyer D et al (2012) One-year outcomes of the DA VINCI Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology 119:1658–1665
Brown DM, Nguyen QD, Marcus DM et al (2013) Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology, doi:pii: S0161-6420(13)00212-1
Adamis AP, Altaweel M, Bressler NM et al (2006) Changes in retinal neovascularization after pegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology 113:23–28
Zhang Z-H, Liu H-Y, Hernandez-Da Mota SE et al (2013) Vitrectomy with or without preoperative intravitreal bevacizumab for proliferative diabetic retinopathy: a meta-analysis of randomized controlled trials. Am J Ophthalmol 156:106–115.e2
Farahvash M-S, Majidi AR, Roohipoor R, Ghassemi F (2011) Preoperative injection of intravitreal bevacizumab in dense diabetic vitreous hemorrhage. Retina 31:1254–1260
Ahmadieh H, Shoeibi N, Entezari M, Monshizadeh R (2009) Intravitreal bevacizumab for prevention of early postvitrectomy hemorrhage in diabetic patients: a randomized clinical trial. Ophthalmology 116:1943–1948
Diabetic Retinopathy Clinical Research Network (2013) Randomized clinical trial evaluating intravitreal ranibizumab or saline for vitreous hemorrhage from proliferative diabetic retinopathy. JAMA Ophthalmol 131:283–293
CVOS-Group (1997) Natural history and clinical management of central retinal vein occlusion. The Central Vein Occlusion Study Group. Arch Ophthalmol 115:486–491 [comment; erratum appears in Arch Ophthalmol 1997 Oct;115(10):1275. Comment in: Arch Ophthalmol 1998 Feb;116(2):260–261; PMID: 9488292]
Adamis AP, Miller JW, Bernal MT et al (1994) Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 118:445–450
Aiello LP, Pierce EA, Foley ED et al (1995) Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci U S A 92:10457–10461
Nakao S, Arima M, Ishikawa K et al (2012) Intravitreal anti-VEGF therapy blocks inflammatory cell infiltration and re-entry into the circulation in retinal angiogenesis. Invest Ophthalmol Vis Sci 53:4323–4328
Hood JD, Meininger CJ, Ziche M, Granger HJ (1998) VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol 274:H1054–H1058
He H, Venema VJ, Gu X et al (1999) Vascular endothelial growth factor signals endothelial cell production of nitric oxide and prostacyclin through flk-1/KDR activation of c-Src. J Biol Chem 274:25130–25135
El-Sabagh HA, Abdelghaffar W, Labib AM et al (2011) Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: histopathologic findings and clinical implications. Ophthalmology 118:636–641
Nakao S, Ishikawa K, Yoshida S et al (2013) Altered vascular microenvironment by bevacizumab in diabetic fibrovascular membrane. Retina 33:957–963
Krohne TU, Eter N, Holz FG, Meyer CH (2008) Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection in humans. Am J Ophthalmol 146:508–512
Behrens-Baumann W (2011) Prophylaxis and therapy of postoperative endophthalmitis. Criticism of the ESCRS study and the Early Vitrectomy study. Ophthalmologe 108:1062, 1064–1066
Arevalo JF, Maia M, Flynn HW et al (2008) Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol 92:213–216
Jeon S, Lee WK (2012) Intravitreal bevacizumab increases intraocular interleukin-6 levels at 1 day after injection in patients with proliferative diabetic retinopathy. Cytokine 60:535–539
Avery RL, Pearlman J, Pieramici DJ et al (2006) Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology 113:1695 e1–e15
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Interessenkonflikt. A. Stahl: Forschungsförderung: Novartis; Referentenhonorare: Zeiss, Novartis; Beratertätigkeit: Bausch und Lomb, Novartis. N. Feltgen: Forschungsförderung: Novartis, Allergan, Bayer Healthcare; Referentenhonorare: Novartis, Allergan, Bayer Healthcare; Beratertätigkeit: Novartis, Bayer Healthcare. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Feltgen, N., Stahl, A. VEGF-Inhibitoren im Rahmen vitreoretinaler Eingriffe. Ophthalmologe 110, 926–934 (2013). https://doi.org/10.1007/s00347-013-2830-1
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DOI: https://doi.org/10.1007/s00347-013-2830-1