gms | German Medical Science

24th Annual Meeting of the German Retina Society

German Retina Society

17.06. - 18.06.2011, Aachen

Compatibility of co-applied rtPA and bevacizumab for neovascular AMD with submacular hemorrhage

Meeting Abstract

  • Jost Hillenkamp - Universitäts-Augenklinik Schleswig-Holstein, Kiel
  • S. Puls - Universitäts-Augenklinik Schleswig-Holstein, Kiel
  • A. Klettner - Universitäts-Augenklinik Schleswig-Holstein, Kiel
  • F. Treumer - Universitäts-Augenklinik Schleswig-Holstein, Kiel
  • J. Roider - Universitäts-Augenklinik Schleswig-Holstein, Kiel

German Retina Society. 24th Annual Conference of the German Retina Society. Aachen, 17.-18.06.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11rg10

doi: 10.3205/11rg10, urn:nbn:de:0183-11rg107

This is the translated version of the article.
The original version can be found at:

Published: June 15, 2011

© 2011 Hillenkamp et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Purpose: To investigate the compatibility of rtPA and bevacizumab in-vitro because intraoperatively rtPA, or rtPA-induced plasmin may cleave and inactivate bevacizumab.

Methods: To simulate the intraoperative range of mixing ratios of rtPA, bevacizumab, and subretinal blood we calculated the volumes of 12 submacular hemorrhages (SMH) with a spherical cap formula using measurements derived from fundus photographs and spectralis OCT images. Bevacizumab was incubated with rtPA or plasmin before gel-electrophoresis with Coomassie Blue and silver staining. The anti-angiogenetic activity of bevacizumab in the presence of rtPA, plasmin, or clotted human blood was quantified by VEGF-Elisa after incubation with the supernatant of primary RPE cell cultures.

Results: The volumes of SMH were 28.6, 24.7, 6.2–94.6 µl (mean, standard deviation, range). In electrophoresis with Coomassie Blue single and double chain fragments of rtPA alone migrated at 69 to 36 kDa, plasmin alone migrated at 46 to 64 kDa, and light and heavy chains of bevacizumab alone migrated at 28 to 147 kDa. Silver staining revealed additional rtPA and bevacizumab fragments between 27 and 34 kDa. All detected fragments remained unchanged in co-application of bevacizumab with either rtPA or plasmin. The anti-angiogenetic activity of bevacizumab quantified by VEGF-Elisa remained unchanged in co-application with plasmin. Corresponding results with rtPA and clotted blood are pending.

Conclusion: We demonstrate the absence of cleavage of bevacizumab by rtPA and plasmin and the absence of inactivation of bevacizumab by plasmin. In clinical practice, rtPA and bevacizumab can be co-applied to simultaneously clear subretinal hemorrhage and reduce choroidal new vessel activity.