Abstract
Purpose: :
To investigate the effect of bevacizumab in the aqueous humor on the trabecular meshwork using an perfused anterior chamber model and analyze the ultrastructural effect on trabecular meshwork tissue. Transient and sustained elevated intraocular pressures can occur after injection with bevacizumab, mainly in patients with primary open angle glaucoma (POAG).
Methods: :
Porcine eyes were prepared as described by Johnson et al. Anterior segments were perfused with DMEM, supplemented with 1.5 mg/mL glucose, 1% (vol/vol) fetal calf serum (FCS) and antibiotics (100 U/mL penicillin, 0.1 mg/mL streptomycin, and 17 g/mL gentamicin; all from Invitrogen, Germany) at a constant flow rate of 4.5 µL/min. The anterior eye segments were maintained in an incubator at 37°C in 7% CO2, while the IOP was continuously monitored using 142PC01G pressure sensors (Honeywell™, USA). Data was secured by the Datalogger AD 128™ (Valitec™, USA).After an adaptation period of 12 hours, bevacizumab was injected directly into the anterior chamber. Reflux was prevented by compressing the injection site with forceps for 20 seconds. The contralateral control received an injection with an equal volume of normal perfusion medium. Development of intraocular pressure was followed for 48 hours under constant perfusion. At the end of the perfusion, 1- to 2-mm wide specimens of the four eye quadrants were excised. Specimens of 10 eye pairs were fixed in 4% PFA for immunohistochemical investigations (TUNEL-stain) and in glutaraldehyde fixative for electron microscopy (model 902 A; Carl Zeiss).
Results: :
During perfusion studies a reduction in intraocular pressure of 30.17 % was reduced at the end of 48 hours. No statistical significant difference between control and eyes treated with bevacizumab was noted (p>0.05). After 72 h TUNEL-stain showed 8.67 % of dead cells in the region of the trabecular meshwork of eyes injected with bevacizumab compared to 13.67 % of cell death in the control. In electron microscopy no ultrastructural change regarding diameter of loop vessels, extracellular matrix and basalmembrane thickness was noted.
Conclusions: :
The results could show no effect of bevacizumab on intraocular pressure influenced by the trabecular meshwork in a porcine model.
Keywords: intraocular pressure • trabecular meshwork • injection