Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irnotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  PubMed  CAS  Google Scholar 

  2. 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 245:68–73

    Article  PubMed  CAS  Google Scholar 

  3. 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. Michels S (2006) Is intravitreal bevacizumab (Avastin) safe? Br J Ophthalmol 90:1333–1334

    Article  PubMed  CAS  Google Scholar 

  5. Fung AE, Rosenfeld PJ, Reichel E (2006) The international intravitreal bevacizumab safety survey: using the internet to assess drug safety worldwide. Br J Ophthalmol 90:1344–1349

    Article  PubMed  CAS  Google Scholar 

  6. 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 12:2609–2622

    Article  PubMed  CAS  Google Scholar 

  7. 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 18:186–193

    Article  CAS  Google Scholar 

  8. Lanthony P (1986) Evaluation du Panel D15 désaturé. J Fr Ophthalmol 12:853–847

    Google Scholar 

  9. Vingrys AJ, King-Smith PEA (1988) A quantitative scoring technique for panel tests of color vision. Inv Ophthalmol Vis Sci 29:50–63

    CAS  Google Scholar 

  10. McCulley TJ, Golnik KC, Lam BL, Feuer WJ (2006) The effect of decreased visual acuity on clinical color vision testing. Am J Ophthalmol 141:194–196

    Article  PubMed  Google Scholar 

  11. Brown M, Marmor M, Vaegan, Zrenner E, Brigell M, Bach M (2006) ISCEV standard for clinical electro-oculography (EOG) 2006. Doc Ophthalmol 113:205–212

    Article  PubMed  Google Scholar 

  12. Naka KI, Rushton WAH (1966) S-potentials from colour units in the retina of the fish (cyprinidae). J Physiol 185:536–555

    PubMed  CAS  Google Scholar 

  13. 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 25:136–142

    Article  Google Scholar 

  14. Verriest G (1963) Further studies on acquired deficiency of color discrimination. J Opt Soc Am 53:185–193

    Article  PubMed  CAS  Google Scholar 

  15. 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 121:1557–1561

    Article  PubMed  Google Scholar 

  16. Anastai M, Brai M, Lauricella M, Geracitano R (1993) Methodological aspects of the application of the Naka–Rushton equation to clinical electroretinogram. Ophthalmic Res 25:145–156

    Article  Google Scholar 

  17. Hébert M, Lachapelle P, Dumont M (1996) Reproducibility of electroretinogramms with DTL electrodes. Doc Ophthalmol 91:333–342

    Article  Google Scholar 

  18. 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):962–968

    Article  PubMed  CAS  Google Scholar 

  19. Luke M, Warga M, Ziemssen F et al (2006) Effects of bevacizumab on retinal function in isolated vertebrate retina. Br J Ophthalmol 90:1178–1182

    Article  PubMed  CAS  Google Scholar 

  20. Shahar J, Avery RL, Heilweil G et al (2006) Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin). Retina 26:262–269

    Article  PubMed  Google Scholar 

  21. 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

    Google Scholar 

  22. Feiner L, Barr EE, Shui YB, Holekamp NM, Brantley MA Jr (2006) Safety of intravitreal injection of bevacizumab in rabbit eyes. Retina 26:882–888

    Article  PubMed  Google Scholar 

  23. Maturi RK, Bleau LA, Wilson DL (2006) Electrophysiologic findings after bevacizumab (Avastin) treatment. Retina 26:270–274

    Article  PubMed  Google Scholar 

  24. 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 114:37–44

    Article  PubMed  Google Scholar 

  25. 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 29:327–336

    Article  Google Scholar 

  26. Phipps JA, Guymer RH, Vingrys AJ (2003) Loss of cone function in age-related maculopathy. Invest Ophthalmol Vis Sci 44:2277–2283

    Article  PubMed  Google Scholar 

  27. Arden GB, Wolf JE (2004) Colour vision testing as an aid to diagnosis and management of age related maculopathy. Br J Ophthalmol 88:1180–1185

    Article  PubMed  CAS  Google Scholar 

  28. Scholl HPN, Zrenner E (2000) Electrophysiology in the investigation of acquired retinal disorders. Surv Ophthalmol 45:29–47

    Article  PubMed  CAS  Google Scholar 

  29. Spitzer MS, Wallenfels-Thilo B, Sierra A et al (2006) Antiproliferative and cytotoxic properties of bevacizumab on different ocular cells. Br J Ophthalmol 90:1316–1321

    Article  PubMed  CAS  Google Scholar 

  30. 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 26:512–518

    Article  PubMed  Google Scholar 

  31. Heiduschka P, Fietz H, Hofmeister S et al (2007) Penetration of bevacizumab through the retina after intravitreal injection in monkey. Invest Opht Vis Res 48:2814–2823

    Article  Google Scholar 

  32. Gora-Kupilas K, Josko J (2005) The neuroprotective function of vascular endothelial growth factor (VEGF). Folia Neuropathol 43:31–39

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department for Ophthalmology, Eberhard-Karls University Tuebingen, Tuebingen, Germany

    Focke Ziemssen, Matthias Lüke, Andre Messias, Julia Beutel, Olcay Tatar, Eberhart Zrenner & Karl U. Bartz-Schmidt

  2. University Eye Hospital of Tuebingen, Schleichstrasse 12-15, 72076, Tuebingen, Germany

    Focke Ziemssen

Authors
  1. Focke Ziemssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthias Lüke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andre Messias
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Julia Beutel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Olcay Tatar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eberhart Zrenner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karl U. Bartz-Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Tuebingen Bevacizumab Study Group

Corresponding author

Correspondence to Focke Ziemssen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ziemssen, F., Lüke, M., Messias, A. et al. 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. Int Ophthalmol 28, 101–109 (2008). https://doi.org/10.1007/s10792-007-9122-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-007-9122-1

Keywords

Search

Navigation