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Erschienen in: International Ophthalmology 2/2008

01.04.2008 | Original Paper

Safety monitoring in bevacizumab (Avastin) treatment: retinal function assessed by psychophysical (visual fields, colour vision) and electrophysiological (ERG/EOG) tests in two subgroups of patients

verfasst von: Focke Ziemssen, Matthias Lüke, Andre Messias, Julia Beutel, Olcay Tatar, Eberhart Zrenner, Karl U. Bartz-Schmidt, Tuebingen Bevacizumab Study Group

Erschienen in: International Ophthalmology | Ausgabe 2/2008

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Abstract

Background

Bevacizumab (Avastin™) has been used as off-label treatment for the specific inhibition of the vascular endothelial growth factor (VEGF). Although only intravenous administration of the drug is approved in combination therapy of colorectal carcinoma, promising short-term results have been reported about its intravitreal administration. However, VEGF is also known to exhibit neurotrophic capabilities. Therefore, blockage of all VEGF isoforms by bevacizumab could induce toxic effects. Missing randomized controlled studies and unclear long-term risks require further evaluation.

Methods

Intensified monitoring of bevacizumab treatment was performed in consecutive patients. In ten patients, the functional field score was calculated after obtaining Goldmann visual fields at baseline and 1 year after injection. The other subgroup was examined by means of EOG, ERG and colour testing at baseline and 4 months following treatment. Naka–Rushton plots were calculated to enable statements about retinal function. Lanthony desaturated D15 test was used for repeated colour testing.

Results

Baseline parameters already disclosed predominant cone dysfunction. Drug-related effects caused a significant improvement of visual acuity. There was no sign of clinically relevant retinal toxicity following the bevacizumab injection. No progression of visual field defects was seen within the follow-up of 1 year. Performance in EOG testing was affected by restricted fixation stability, but no parameter indicated deterioration within the 4-monthperiod.

Conclusions

Short-term results underline that intraocular bevacizumab injection promises to be not only a cost-effective, but safe treatment option. Assessed functional parameters as error scores (e.g., Lanthony) corresponded to the impaired retinal function which was presumed to be disease-related. Further long-term results have to confirm the good tolerability in repeated treatment.
Literatur
1.
Zurück zum Zitat Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irnotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRef Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irnotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRef
2.
Zurück zum Zitat Lazic R, Gabric N (2007) Intravitreally administered bevacizumab (Avastin) in minimally classic and occult choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 245:68–73PubMedCrossRef Lazic R, Gabric N (2007) Intravitreally administered bevacizumab (Avastin) in minimally classic and occult choroidal neovascularization secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 245:68–73PubMedCrossRef
3.
Zurück zum Zitat Jorge R, Costa RA, Calucci D, Scott IU (2007) Intravitreal bevacizumab (Avastin) associated with the regression of subretinal neovascularization in idiopathic juxtafoveolar retinal teleangiectasis. Graefes Arch Clin Exp Ophthalmol. E-Pub Jorge R, Costa RA, Calucci D, Scott IU (2007) Intravitreal bevacizumab (Avastin) associated with the regression of subretinal neovascularization in idiopathic juxtafoveolar retinal teleangiectasis. Graefes Arch Clin Exp Ophthalmol. E-Pub
4.
5.
Zurück zum Zitat Fung AE, Rosenfeld PJ, Reichel E (2006) The international intravitreal bevacizumab safety survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 90:1344–1349PubMedCrossRef Fung AE, Rosenfeld PJ, Reichel E (2006) The international intravitreal bevacizumab safety survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 90:1344–1349PubMedCrossRef
6.
Zurück zum Zitat Lazarovici P, Marcinkiewicz C, Lelkes PI (2006) Cross talk between the cardiovascular and nervous system: neurotrophic effects of vascular endothelial growth factor (VEGF) and angiogenic effects of nerve growth factor (NGF). Curr Pharm Des 12:2609–2622PubMedCrossRef Lazarovici P, Marcinkiewicz C, Lelkes PI (2006) Cross talk between the cardiovascular and nervous system: neurotrophic effects of vascular endothelial growth factor (VEGF) and angiogenic effects of nerve growth factor (NGF). Curr Pharm Des 12:2609–2622PubMedCrossRef
7.
Zurück zum Zitat Wang Y, Galvan V, Gorostiza O, Ataie M, Jin K, Greenberg DA (2006) Vascular endothelial growth factor improves recovery of sensimotoric and cognitive deficits after focal cerebral ischemia in rat. Brain Res 18:186–193CrossRef Wang Y, Galvan V, Gorostiza O, Ataie M, Jin K, Greenberg DA (2006) Vascular endothelial growth factor improves recovery of sensimotoric and cognitive deficits after focal cerebral ischemia in rat. Brain Res 18:186–193CrossRef
8.
Zurück zum Zitat Lanthony P (1986) Evaluation du Panel D15 désaturé. J Fr Ophthalmol 12:853–847 Lanthony P (1986) Evaluation du Panel D15 désaturé. J Fr Ophthalmol 12:853–847
9.
Zurück zum Zitat Vingrys AJ, King-Smith PEA (1988) A quantitative scoring technique for panel tests of color vision. Inv Ophthalmol Vis Sci 29:50–63 Vingrys AJ, King-Smith PEA (1988) A quantitative scoring technique for panel tests of color vision. Inv Ophthalmol Vis Sci 29:50–63
10.
Zurück zum Zitat McCulley TJ, Golnik KC, Lam BL, Feuer WJ (2006) The effect of decreased visual acuity on clinical color vision testing. Am J Ophthalmol 141:194–196PubMedCrossRef McCulley TJ, Golnik KC, Lam BL, Feuer WJ (2006) The effect of decreased visual acuity on clinical color vision testing. Am J Ophthalmol 141:194–196PubMedCrossRef
11.
Zurück zum Zitat Brown M, Marmor M, Vaegan, Zrenner E, Brigell M, Bach M (2006) ISCEV standard for clinical electro-oculography (EOG) 2006. Doc Ophthalmol 113:205–212PubMedCrossRef Brown M, Marmor M, Vaegan, Zrenner E, Brigell M, Bach M (2006) ISCEV standard for clinical electro-oculography (EOG) 2006. Doc Ophthalmol 113:205–212PubMedCrossRef
12.
Zurück zum Zitat Naka KI, Rushton WAH (1966) S-potentials from colour units in the retina of the fish (cyprinidae). J Physiol 185:536–555PubMed Naka KI, Rushton WAH (1966) S-potentials from colour units in the retina of the fish (cyprinidae). J Physiol 185:536–555PubMed
13.
Zurück zum Zitat Langellan N, Wouters B, Moll AC, de Boer MR, van Rens GHMB (2005) Intra- and interrater agreement and reliability of the functional field score. Ophthalmic Physiol Opt 25:136–142CrossRef Langellan N, Wouters B, Moll AC, de Boer MR, van Rens GHMB (2005) Intra- and interrater agreement and reliability of the functional field score. Ophthalmic Physiol Opt 25:136–142CrossRef
14.
Zurück zum Zitat Verriest G (1963) Further studies on acquired deficiency of color discrimination. J Opt Soc Am 53:185–193PubMedCrossRef Verriest G (1963) Further studies on acquired deficiency of color discrimination. J Opt Soc Am 53:185–193PubMedCrossRef
15.
Zurück zum Zitat Ladewig M, Kraus H, Foerster MH, Kellner U (2003) Cone dysfunction in patiens with late-onset cone dystrophy and age-related macular degeneration. Arch Ophthalmol 121:1557–1561PubMedCrossRef Ladewig M, Kraus H, Foerster MH, Kellner U (2003) Cone dysfunction in patiens with late-onset cone dystrophy and age-related macular degeneration. Arch Ophthalmol 121:1557–1561PubMedCrossRef
16.
Zurück zum Zitat Anastai M, Brai M, Lauricella M, Geracitano R (1993) Methodological aspects of the application of the Naka–Rushton equation to clinical electroretinogram. Ophthalmic Res 25:145–156CrossRef Anastai M, Brai M, Lauricella M, Geracitano R (1993) Methodological aspects of the application of the Naka–Rushton equation to clinical electroretinogram. Ophthalmic Res 25:145–156CrossRef
17.
Zurück zum Zitat Hébert M, Lachapelle P, Dumont M (1996) Reproducibility of electroretinogramms with DTL electrodes. Doc Ophthalmol 91:333–342CrossRef Hébert M, Lachapelle P, Dumont M (1996) Reproducibility of electroretinogramms with DTL electrodes. Doc Ophthalmol 91:333–342CrossRef
18.
Zurück zum Zitat Walter P, Widder RA, Luke C, Koenigsfeld P, Brunner R (1999) Electrophysiological abnormalities in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 237(12):962–968PubMedCrossRef Walter P, Widder RA, Luke C, Koenigsfeld P, Brunner R (1999) Electrophysiological abnormalities in age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 237(12):962–968PubMedCrossRef
19.
Zurück zum Zitat Luke M, Warga M, Ziemssen F et al (2006) Effects of bevacizumab on retinal function in isolated vertebrate retina. Br J Ophthalmol 90:1178–1182PubMedCrossRef Luke M, Warga M, Ziemssen F et al (2006) Effects of bevacizumab on retinal function in isolated vertebrate retina. Br J Ophthalmol 90:1178–1182PubMedCrossRef
20.
Zurück zum Zitat Shahar J, Avery RL, Heilweil G et al (2006) Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin). Retina 26:262–269PubMedCrossRef Shahar J, Avery RL, Heilweil G et al (2006) Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin). Retina 26:262–269PubMedCrossRef
21.
Zurück zum Zitat Manzano RP, Peyman GA, Khan P, Kivilcim M (2006) Testing intravitreal toxicity of bevacizumab (Avastin). Retina 26:257–261; Graefe's Arch Clin Exp Ophthalmol 237:962–968 Manzano RP, Peyman GA, Khan P, Kivilcim M (2006) Testing intravitreal toxicity of bevacizumab (Avastin). Retina 26:257–261; Graefe's Arch Clin Exp Ophthalmol 237:962–968
22.
Zurück zum Zitat Feiner L, Barr EE, Shui YB, Holekamp NM, Brantley MA Jr (2006) Safety of intravitreal injection of bevacizumab in rabbit eyes. Retina 26:882–888PubMedCrossRef Feiner L, Barr EE, Shui YB, Holekamp NM, Brantley MA Jr (2006) Safety of intravitreal injection of bevacizumab in rabbit eyes. Retina 26:882–888PubMedCrossRef
23.
Zurück zum Zitat Maturi RK, Bleau LA, Wilson DL (2006) Electrophysiologic findings after bevacizumab (Avastin) treatment. Retina 26:270–274PubMedCrossRef Maturi RK, Bleau LA, Wilson DL (2006) Electrophysiologic findings after bevacizumab (Avastin) treatment. Retina 26:270–274PubMedCrossRef
24.
Zurück zum Zitat Moschos MM, Brouzas D, Apostolopoulos M, Koutsandrea C, Loukianou E, Moschos M (2007) Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary multifocal-ERG and OCT study: multifocal-ERG after use of bevacizumab in ARMD. Doc Ophthalmol 114:37–44PubMedCrossRef Moschos MM, Brouzas D, Apostolopoulos M, Koutsandrea C, Loukianou E, Moschos M (2007) Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary multifocal-ERG and OCT study: multifocal-ERG after use of bevacizumab in ARMD. Doc Ophthalmol 114:37–44PubMedCrossRef
25.
Zurück zum Zitat Feigl B, Brown B, Lovie-Kitchin J, Swann P (2003) Cone-mediated multifocal electroretinogramm in early age-related maculopathy and its relationships with subjective macular function tests. Curr Eye Res 29:327–336CrossRef Feigl B, Brown B, Lovie-Kitchin J, Swann P (2003) Cone-mediated multifocal electroretinogramm in early age-related maculopathy and its relationships with subjective macular function tests. Curr Eye Res 29:327–336CrossRef
26.
Zurück zum Zitat Phipps JA, Guymer RH, Vingrys AJ (2003) Loss of cone function in age-related maculopathy. Invest Ophthalmol Vis Sci 44:2277–2283PubMedCrossRef Phipps JA, Guymer RH, Vingrys AJ (2003) Loss of cone function in age-related maculopathy. Invest Ophthalmol Vis Sci 44:2277–2283PubMedCrossRef
27.
Zurück zum Zitat Arden GB, Wolf JE (2004) Colour vision testing as an aid to diagnosis and management of age related maculopathy. Br J Ophthalmol 88:1180–1185PubMedCrossRef Arden GB, Wolf JE (2004) Colour vision testing as an aid to diagnosis and management of age related maculopathy. Br J Ophthalmol 88:1180–1185PubMedCrossRef
28.
Zurück zum Zitat Scholl HPN, Zrenner E (2000) Electrophysiology in the investigation of acquired retinal disorders. Surv Ophthalmol 45:29–47PubMedCrossRef Scholl HPN, Zrenner E (2000) Electrophysiology in the investigation of acquired retinal disorders. Surv Ophthalmol 45:29–47PubMedCrossRef
29.
Zurück zum Zitat Spitzer MS, Wallenfels-Thilo B, Sierra A et al (2006) Antiproliferative and cytotoxic properties of bevacizumab on different ocular cells. Br J Ophthalmol 90:1316–1321PubMedCrossRef Spitzer MS, Wallenfels-Thilo B, Sierra A et al (2006) Antiproliferative and cytotoxic properties of bevacizumab on different ocular cells. Br J Ophthalmol 90:1316–1321PubMedCrossRef
30.
Zurück zum Zitat Luthra S, Narayanan R, Marques LE et al (2006) Evaluation of in vitro effects of bevacizumab (Avastin) on retinal pigment epithelial, neurosensory retinal, and microvascular endothelial cells. Retina 26:512–518PubMedCrossRef Luthra S, Narayanan R, Marques LE et al (2006) Evaluation of in vitro effects of bevacizumab (Avastin) on retinal pigment epithelial, neurosensory retinal, and microvascular endothelial cells. Retina 26:512–518PubMedCrossRef
31.
Zurück zum Zitat Heiduschka P, Fietz H, Hofmeister S et al (2007) Penetration of bevacizumab through the retina after intravitreal injection in monkey. Invest Opht Vis Res 48:2814–2823CrossRef Heiduschka P, Fietz H, Hofmeister S et al (2007) Penetration of bevacizumab through the retina after intravitreal injection in monkey. Invest Opht Vis Res 48:2814–2823CrossRef
32.
Zurück zum Zitat Gora-Kupilas K, Josko J (2005) The neuroprotective function of vascular endothelial growth factor (VEGF). Folia Neuropathol 43:31–39PubMed Gora-Kupilas K, Josko J (2005) The neuroprotective function of vascular endothelial growth factor (VEGF). Folia Neuropathol 43:31–39PubMed
Metadaten
Titel
Safety monitoring in bevacizumab (Avastin) treatment: retinal function assessed by psychophysical (visual fields, colour vision) and electrophysiological (ERG/EOG) tests in two subgroups of patients
verfasst von
Focke Ziemssen
Matthias Lüke
Andre Messias
Julia Beutel
Olcay Tatar
Eberhart Zrenner
Karl U. Bartz-Schmidt
Tuebingen Bevacizumab Study Group
Publikationsdatum
01.04.2008
Verlag
Springer Netherlands
Erschienen in
International Ophthalmology / Ausgabe 2/2008
Print ISSN: 0165-5701
Elektronische ISSN: 1573-2630
DOI
https://doi.org/10.1007/s10792-007-9122-1

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