Electrophysiologic and retinal penetration studies following intravitreal injection of bevacizumab (Avastin).
OBJECTIVE
Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab.


METHODS
Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration.


RESULTS
The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks.


CONCLUSIONS
Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.
Shahar
Jonathan
J
Department of Ophthalmology, Tel-Aviv Medical Center, Israel.
Avery
Robert L
RL
Heilweil
Gad
G
Barak
Adiel
A
Zemel
Esther
E
Lewis
Geoffrey P
GP
Johnson
Patrick T
PT
Fisher
Steven K
SK
Perlman
Ido
I
Loewenstein
Anat
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D004353:Drug Evaluation, Preclinical; D004596:Electroretinography / Q000187:drug effects; D005074:Evoked Potentials, Visual / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D007267:Injections; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D014822:Vitreous Body
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab