[Bevacizumab is not toxic to human anterior- and posterior-segment cultured cells].
OBJECTIVE
Intravitreal anti-vascular endothelial growth factor (VEGF) treatment with bevacizumab (Avastin) has emerged as a promising therapy for the treatment of choroidal neovascularisation in age-related macular degeneration. Intravitreal administration of bevacizumab is "off-label," and only very limited data regarding short-term toxicity exist. Therefore, we investigated the safety of different doses of bevacizumab on the anterior- and posterior-segment cells of the human eye.


METHODS
Primary human retinal pigment epithelium (RPE) cells, human optic nerve head astrocytes (ONHA), human trabecular meshwork cells (TMC), and cornea buttons not suitable for transplantation were treated with bevacizumab (25 microg/ml, 250 microg/ml, and 2,500 microg/ml) for 48 h, corresponding to 0.1x, 1x, and 10x the dosage used intravitreally. Bevacizumab-related toxicity was evaluated by a colorimetric test (MTT) measuring inhibition of RPE, ONHA, and TMC cell proliferation. Additionally, cell viability was quantified by live/dead fluorescence assay. Corneal endothelium was quantified by phase-contrast microscopy.


RESULTS
Bevacizumab showed adverse effects on primary RPE cell proliferation as well as on cell viability at a concentration of 2,500 microg/ml. The lower concentrations of 25 microg/ml and 250 microg/ml had no influence on RPE cell proliferation or cell viability. There was no toxicity for any investigated concentration on human ONHA, TMC, or corneal endothelium.


CONCLUSIONS
In this study, a 10-fold concentration (compared with common clinical use) of the VEGF-blocking antibody bevacizumab had toxic effects on primary RPE. There was no toxicity for lower concentrations or toxicity to other cell types of the anterior and posterior segments. Therefore, the clinical use of bevacizumab at concentrations of 1-1.25 mg intravitreally seems to be safe.
Kernt
M
M
Augenklinik der Ludwig-Maximilians-Universität, Mathildenstrasse 8, 80336 München. Marcus.Kernt@med.uni-muenchen.de
Welge-Lüssen
U
U
Yu
A
A
Neubauer
A S
AS
Kampik
A
A
D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000166:cytology* / Q000187:drug effects*; D006801:Humans
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab