Zusammenfassung
Hintergrund: Obwohl Bevacizumab (Avastin®) lediglich für die Behandlung des kolorektalen Karzinoms zugelassen ist, haben zahlreiche Berichte gezeigt, dass seine intravitreale Anwendung bei choroidalen Neovaskularisationen (CNV) zu einer Stabilisierung oder sogar zur Rückbildung von pathologischen Gefäßneubildungen führen kann und sich dementsprechend positiv auf die Entwicklung der Sehschärfe auswirken kann. Patienten und Methoden: Zwischen April 2006 und Juli 2007 wurden die CNV verschiedener Ätiologie bei 300 Patienten (Altersdurchschnitt 75,78 Jahre) mit intravitrealen Injektionen von Bevacizumab (1,25 mg in 0,05 mL) behandelt. Für die Diagnosestellung und für die Kontrollen in zwölfwöchigen Abständen dienten Fluoreszenzangiografien und optische Kohärenztomografien. Die Injektionen fanden in sechswöchigen Abständen statt, bis die Makulabefunde als trocken beurteilt wurden. Die Prüfung der Sehschärfe erfolgte mittels ETDRS-Tafel. Ergebnisse: In allen untersuchten Gruppen konnte der Visus stabilisiert oder verbessert werden (+ 4,44 ETDRS Buchstaben nach 3,04 Injektionen im Schnitt). Während des Follow-up wurden sechs kardiovaskuläre Erkrankungen mit Tod in einem Fall diagnostiziert. Nach 1036 Injektionen konnte keine schwere okuläre Komplikation festgestellt werden. Schlussfolgerungen: Die Resultate zeigen deutlich, dass die intravitrealen Injektionen von Bevacizumab wirksam, sicher und kostengünstig sind. Weitere randomisierte Studien sind notwendig, um die dauerhafte Wirkung und die gute okuläre und systemische Verträglichkeit dieser Substanz zu bestätigen.
Abstract
Background: Although bevacizumab (Avastin®) has only been approved for the treatment of colorectal carcinoma, many reports have shown that its intravitreal administration against choroidal neovascularisations (CNV) leads to a stabilisation or even a regression of the pathological neovessels, and thus to a positive evolution of visual acuity. Patients and Methods: From April 2006 to July 2007, the CNV of different aetiologies were treated with intravitreal injections of bevacizumab (1.25 mg in 0.05 mL) in 300 patients with an average age of 75.78 years. Fluorescein angiography and optical coherence tomography were used for the diagnosis and for the checks which were carried out every twelve weeks. The intravitreal injections were performed every six weeks until the macular findings were considered to be dry. The visual acuity was checked using an ETDRS chart. Results: In all the groups considered the visual acuity was stabilised or improved on an average with + 4.44 ETDRS letters after 3.04 injections. During the follow-up six cardiovascular diseases were diagnosed and in one case a patient died. No ocular complications were reported after 1036 injections. Conclusions: The results clearly show that the intravitreal injections of bevacizumab are effective, safe and cost-effective. However, further randomised studies are needed to confirm the duration of the effect, as well as the good ocular and systemic tolerability of the drug.
Schlüsselwörter
choroidale Neovaskularisation - vaskulärer endothelialer Wachstumsfaktor
Key words
choroidal neovascularisation - vascular endothelial growth factor
References
1
Avery R L, Pieramici D J, Rabena M D. et al .
Intravitreal bevacizumab for neovascular age-related macular degeneration.
Ophthalmology.
2006;
113
363-372
2
Bermig J, Tylla H, Jochmann C. et al .
Angiographic findings in patients with exudative age-related macular degeneration.
Graefes Arch Clin Exp Ophthalmol.
2002;
240
169-175
3
Bressler N M.
Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2.
Arch Ophthalmol.
2001;
119
198-207
4
Brown D M, Kaiser P K, Michels M. et al .
Ranibizumab versus verteporfin for neovascular age-related macular degeneration.
N Engl J Med.
2006;
355
1432-1444
5
Falkenstein I A, Cheng L, Morrison V L. et al .
Standardized visual acuity results associated with primary versus secondary bevacizumab treatment for choroidal neovascularization in age-related macular degeneration.
Retina.
2007;
27
701-706
6
Gragoudas E S, Adamis A P, Cunningham E T.
Pegabtanib for neovascular age-related macular degeneration.
N Engl J Med.
2004;
350
2335-2342
7
Heier J S, Boyer D S, Ciulla T A. FOCUS study group .
Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study.
Arch Ophthalmol.
2006;
124
1532-1542
8
Hahn R, Sacu S, Michels S. et al .
Intravitreal bevacizumab versus verteporfin and intravitreal triamcinolone acetonide in patients with neovascular age-related macula degeneration.
Ophthalmologe.
2007;
104
588-593
9
Hurwitz H, Fehrenbacher L, Novotny W.
Bevacizumab plus irnotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
N Engl J Med.
2004;
350
2335-2342
10
Itturalde D, Spaide R F, Meyerle C B.
Intravitreal bevacizumab treatment of macular edema in central retinal vein occlusion: a short-term study.
Retina.
2006;
26
279-284
11
Jonas J B, Spandau U H, Rensch F. et al .
Infectious and noninfectious endophthalmitis after intravitreal bevacizumab.
J Ocul Pharmacol Ther.
2007;
2
240-242
12
Kahook M Y, Schuman J S, Noecker R J.
Intravitreal bevacizumab in a patient with neovascular glaucoma.
Ophthalmic Surg Laser Imaging.
2006;
37
144-146
13
Kernt M, Welge-Lüssen U, Yu A. et al .
Bevacizumab is not toxic to human anterior- and posterior-segment cultured cells.
Ophthalmologe.
2007;
E-pub (in German)
14
Laud K, Spaide R F, Freund K B.
Treatment of choroidal neovascularization in pathologic myopia with intravitreal bevacizumab.
Retina.
2006;
26
960-963
15
Lynch S S, Cheng C M.
Bevacizumab for neovascular ocular diseases.
Ann Pharmacother.
2007;
41
614-625
16
Mason J O, Albert M A, Mays A. et al .
Regression of neovascular iris vessels by intravitreal injection of bevacizumab.
Retina.
2006;
26
839-841
17
Manzano R P, Peyman G A, Khan P. et al .
Testing intravitreal toxicity of bevacizumab.
Retina.
2006;
26
262-269
18
Maturi R K, Bleau L A, Wilson D L.
Electrophysiologic findings after intravitreal bevacizumab treatment.
Retina.
2006;
26
270-274
19
Michels S, Rosenfeld P J, Puliafito C A. et al .
Systemic bevacizumab therapy for neovascular age-related macular degeneration.
Ophthalmology.
2005;
112
1035-1047
20
Quiroz-Mercado H, Ustariz-Gonzales O, Martinez-Castellanos M A. et al .
Our experience after 1765 intravitreal injections of bevacizumab: the importance of being part of a developing story.
Seminars in Ophthalmology.
2007;
22
109-125
21
Raftery J, Clegg A, Jones J. et al .
Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost effectiveness.
Br J Ophthalmol.
2007;
91
1244-1246
22
Rosenfeld P J, Moshfeghi A A, Puliafito C A.
Optical coherence tomography findings after an intravitreal injection of bevacizumab for neovascular age-related macular degeneration.
Ophthalmic Surg Lasers Imaging.
2005;
36
331-335
23
Rosenfeld P J, Brown D M, Heier J S. et al .
Ranibizumab for neovascular age-related macular degeneration.
N Engl J Med.
2006;
355
1419-1431
24
Sakaguchi H, Ikuno Y, Gomi F.
Intravitreal injection of bevacizumab for choroidal neovascularization associated with pathological myopia.
Br J Ophthalmol.
2007;
91
161-165
25
Silva P J, Jorge R, Alves C R.
Short-term results of intravitreal bevacizumab on anterior segment neovascularization in neovascular glaucoma.
Acta Ophthalmol Scand.
2006;
84
556-557
26
Slakter J S, Bochow T W, D’Amico D J.
Anecortave acetate versus photodynamic therapy for treatment of subfoveal neovascularization in age-related macular degeneration.
Ophthalmology.
2006;
11
3-13
27
Spaide R F, Fisher Y L.
Intravitreal bevacizumab treatment of proliferative diabetic retinopathy complicated by vitreous hemorrhage.
Retina.
2006;
26
275-278
28
Wijngaarden van P, Coster D J, Williams K A.
Inhibitors of ocular neovascularization: promise and potential problems.
JAMA.
2005;
293
1509-1513
29
Wu L, Martinez-Castellanos M A, Quiroz-Mercado H. et al .
Twelve-month safety of intravitreal injections of bevacizumab: results of the pan-american collaborative retina study group.
Graefes Arch Clin Exp Ophthalmol.
2007;
Epub
30
Yamamoto I, Rogers A H, Reichel E.
Intravitreal bevacizumab as treatment for subfoveal choroidal neovascularization secondary to pathologic myopia.
Br J Ophthalmol.
2007;
91
157-160
31
Ziemssen F, Lüke M, Messias A. et al .
Safety monitoring in bevacizumab treatment: retinal function assessed by psychophysical (visual fields, colour vision) and electrophysiological (ERG/EOG) tests in two subgroups of patients.
Int Ophthalmol.
2007;
Epub
PD Dr. med. Christophe Valmaggia
Leitender Arzt Retinologie, Augenklinik, Kantonsspital St. Gallen
Rorschacherstrasse 95
9007 St. Gallen, Switzerland
Phone: ++ 41/71/4 94 17 58
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Email: christophe.valmaggia@kssg.ch