The effects of intravitreous bevacizumab on retinal neovascular membrane and normal capillaries in rabbits.
OBJECTIVE
To evaluate the effects of intravitreous bevacizumab in a rabbit retinal neovascularization model.


METHODS
Twenty-four rabbits were divided into five groups. Group A included four rabbits; all other groups included five rabbits each. Group A received intravitreous VEGF only, and group E received intravitreous bevacizumab only. In groups B, C, and D, bevacizumab was injected at the same time, at day 2 and at week 1 after VEGF injection, respectively. Follow-up evaluations continued for 3 weeks and included color fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). Enucleated eyes were processed for hematoxylin and eosin (H&E) staining.


RESULTS
Intravitreous VEGF was associated with disc hyperemia, vascular dilatation and tortuosity, and fluorescein leakage at the disc and in the anterior chamber (AC) at day 2 and with formation of retinal neovascular membranes (NVM) by week 1. At weeks 2 and 3, the NVM was replaced by a fibrotic membrane and mild to moderate capillary nonperfusion. In groups B and C, injection of bevacizumab was very effective in preventing or stopping fluorescein leakage but was not able to prevent or reverse vascular dilatation and tortuosity completely. In group D, bevacizumab injection resulted in severe capillary nonperfusion at week 2.


CONCLUSIONS
Intravitreous injection of VEGF in rabbits results in florid retinal neovascularization within the first week, followed by closure of normal capillaries by week 2. Early intravitreous injection of bevacizumab can prevent these effects, whereas late injection may be associated with more significant closure of normal capillaries. A sudden drop in effective VEGF concentration may be responsible for the closure of the normal capillaries.
Ameri
Hossein
H
Doheny Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA. hameri@doheny.org
Chader
Gerald J
GJ
Kim
June-Gone
JG
Sadda
Srinivas R
SR
Rao
Narsing A
NA
Humayun
Mark S
MS
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002196:Capillaries / Q000187:drug effects; D002199:Capillary Permeability; D004195:Disease Models, Animal; D019793:Fluorescein / Q000378:metabolism; D005451:Fluorescein Angiography; D006940:Hyperemia / Q000209:etiology; D007267:Injections; D009898:Optic Disk / Q000098:blood supply; D011817:Rabbits; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D014822:Vitreous Body
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D019793:Fluorescein