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T. Ziemssen, F. Ziemssen, S. Grisanti, P. Szurman, Tuebingen Bevacizumab Study Group; Pharmacodynamic Effect of Intravitreous Bevacizumab on the Flicker–Response in Retinal Arterioles . Invest. Ophthalmol. Vis. Sci. 2006;47(13):495.
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The cooperative role of vascular endothelial growth factor (VEGF) and nitric oxide (NO) has been thought to be responsible for the extensive rise of blood pressure sometimes seen after the intravenous application of 5 mg/kg Bevacizumab (combined with 5–fluorouracil chemotherapy). Inhibition of VEGF–mediated release of NO has been demonstrated in vitro by the drug. We wanted to address potential effects on the dynamic perfusion response after flicker which is known to be mediated by NO.
In a subgroup of patients (33 of 140) receiving 1mg of intravitreous Bevacizumab (AvastinTM) for treatment of maculopathy, dynamic flicker response was tested before and at different time points after the injection using the DVA (Dynamic Vessel AnalyzerTM, Weimar, Germany). Simultaneous control of blood pressure was conducted.
Baseline examination revealed a dilatation of the arterial diameter only of 2.1% (median, range –5.8–13.2) and venous dilatation of 3.0% (median, range 0.6–11.3). Reactions of veins were in 42.2% in normal range, whereas only 24.2% of arterial reactions had usual extent. A high percentage of patients with age–related macular degeneration showed poor internal quality parameters in the measurement, therefore limiting the follow–up examinations or further conclusions due to loss of fixation, opaque media and vessel hyperactivity. In 5 patients with stable baseline signal, the postoperative flicker–response was significant reduced (p<0.05). Updated data will be presented at the meeting.
The loss of pre–existing flicker–response after Bevacizumab injection underlines the potential impact of VEGF on the regulation of retinal blood flow. Possible reasons for inconsistent findings after Bevacizumab injections might be inter–individual differences in the influence on NO–release or VEGF/NO–independent pathways. Further investigations after intravenous application of Bevacizumab could evaluate whether there is a direct relationship between the inhibition of flicker–response and the increase in blood–pressure after intravenous application.
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