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The retinal tolerance to bevacizumab in co-application with a recombinant tissue plasminogen activator
  1. Matthias Lüke (matthias.lueke{at}med.uni-tuebingen.de),
  2. Kai Januschowski (kaijanuschowski{at}web.de),
  3. Max Warga (max.warga{at}med.uni-tuebingen.de),
  4. Julia Beutel (julia.beutel{at}med.uni-tuebingen.de),
  5. Martin Leitritz (martin.leitritz{at}med.uni-tuebingen.de),
  6. Faik Gelisken (faik.gelisken{at}med.uni-tuebingen.de),
  7. Salvatore Grisanti (salvatore.grisanti{at}med.uni-tuebingen.de),
  8. Toni Schneider (toni.schneider{at}uni-koeln.de),
  9. Christoph Lüke (aia18{at}uni-koeln.de),
  10. Karl Ulrich Bartz-Schmidt (karl-ulrich.bartz-schmidt{at}med.uni-tuebingen.de),
  11. Peter Szurman (peter.szurman{at}med.uni-tuebingen.de)
  1. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  2. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  3. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  4. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  5. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  6. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  7. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  8. Institute for Neurophysiology, University of Cologne, Germany
  9. Center of Ophthalmology, University of Cologne, Germany
  10. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany
  11. University Eye Hospital, Centre for Ophthalmology, Eberhard-Karls University of Tuebingen, Germany

    Abstract

    Aim: To investigate the retinal toxicity of bevacizumab in co-application with rt-PA, 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 (0.25mg/ml) and rt-PA (20μ;g/ml) was 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 (20μg/ml, 60μg/ml and 200μg/ml) were investigated on the a- and b-wave amplitude. The percentage of a- and b-wave reduction during the application and at the washout was calculated.

    Results: During the application of bevacizumab (0.25mg/ml) in co-application with 20μg/ml (rt-PA) the ERG-amplitudes remained stable. The concentrations of rt- PA alone (20μg/ml and 60μg/ml) induced no significant reduction of the b-wave amplitude. In addition, 20μg/ml rt-PA did not alter the a-wave amplitude. However, during the exposure with 60μg/ml rt-PA provoked a slight significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200μg/ml rt-PA provoked a significant reduction of the a- and b- wave amplitude during the exposure. The reduction of the ERG-amplitudes remained irreversible during the washout.

    Conclusion: The present study suggests that a subretinal injection of 20μg/ml rt-PA in co-application with bevacizumab (0.25mg/ml) for the treatment of massive subretinal haemorrhage seems possible. Higher concentrations of rt-PA should be not applied.

    • age-related macular degeneration
    • bevacizumab
    • electroretinogram
    • recombinant tissue plasminogen activator
    • retinal toxicity

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