The retinal tolerance to bevacizumab in co-application with a recombinant tissue plasminogen activator

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 mg/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 mg/ml, 60 mg/ml and 200 mg/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 mg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 mg/ml and 60 mg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 mg/ml rt-PA did not alter the a-wave amplitude. However, 60 mg/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 mg/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 mg/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.