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The retinal tolerance to bevacizumab in co-application with a recombinant tissue plasminogen activator
  1. Matthias Lüke1,
  2. Kai Januschowski1,
  3. Max Warga1,
  4. Julia Beutel1,
  5. Martin Leitritz1,
  6. Faik Gelisken1,
  7. Salvatore Grisanti1,
  8. Toni Schneider2,
  9. Christoph Lüke3,
  10. Karl Ulrich Bartz-Schmidt1,
  11. Peter Szurman1,
  12. for the Tuebingen Bevacizumab Study Group
  1. 1University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Tuebingen, Germany
  2. 2Institute for Neurophysiology, University of Cologne, Köln, Germany
  3. 3Center of Ophthalmology, University of Cologne, Köln, Germany
  1. Correspondence to: Dr. M Lüke Department of Ophthalmology, University of Tuebingen, Schleichstr. 12–16, D-72076, Tuebingen, Germany; matthias.lueke{at}med.uni-tuebingen.de

Abstract

Aim: To investigate the retinal toxicity of bevacizumab in co-application with a commercially available recombinant tissue plasminogen activator (rt-PA), and to facilitate a new therapeutic concept in the treatment of massive subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD).

Methods: Isolated bovine retinas were perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Bevacizumab (0.25 mg/ml) and rt-PA (20 μg/ml) were added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 60 min with normal nutrient solution. Similarly, the effects of rt-PA (20 μg/ml, 60 μg/ml and 200 μg/ml) on the a- and b-wave amplitudes were investigated. The percentages of a- and b-wave reduction during application and at washout were calculated.

Results: During application of bevacizumab (0.25 mg/ml) in co-application with 20 μg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 μg/ml and 60 μg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 μg/ml rt-PA did not alter the a-wave amplitude. However, 60 μg/ml rt-PA caused a slight but significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200 μg/ml rt-PA, a significant reduction of the a- and b-wave amplitudes was provoked during the exposure. The reduction of ERG amplitudes remained irreversible during the washout.

Conclusion: The present study suggests that a subretinal injection of 20 µg/ml rt-PA in co-application with bevacizumab (0.25 mg/ml) for the treatment of massive subretinal haemorrhage seems possible. This is a safety study. Therefore, we did not test the clinical effectiveness of this combined treatment.

  • AMD, age-related macular degeneration
  • CNV, choroidal neovascularization
  • ERG, electroretinogram
  • rt-PA, recombinant tissue plasminogen activator
  • VEGF, vascular endothelial growth factor
  • age-related macular degeneration
  • bevacizumab
  • recombinant tissue plasminogen activator
  • electroretinogram
  • retinal toxicity
  • AMD, age-related macular degeneration
  • CNV, choroidal neovascularization
  • ERG, electroretinogram
  • rt-PA, recombinant tissue plasminogen activator
  • VEGF, vascular endothelial growth factor
  • age-related macular degeneration
  • bevacizumab
  • recombinant tissue plasminogen activator
  • electroretinogram
  • retinal toxicity

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Footnotes

  • Published Online First 23 March 2007

  • Competing interests: None declared.

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