Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment
Department of Medicine, Division of Preventive and Behavioral Medicine
Animals; Antibodies, Monoclonal; Choroidal Neovascularization; Disease Models, Animal; Endothelial Growth Factors; Fluorescein Angiography; Immunoglobulin Fragments; Injections; Laser Coagulation; Lymphokines; Macaca fascicularis; Recombinant Fusion Proteins; Safety; Uveitis, Anterior; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vitreous Body
OBJECTIVE: To evaluate the safety and efficacy of intravitreal injections of an antigen-binding fragment of a recombinant humanized monoclonal antibody directed toward vascular endothelial growth factor (rhuFab VEGF) in a monkey model of choroidal neovascularization (CNV).
METHODS: In phase 1 of the study, each animal received intravitreal injections, 500 microg per eye, of rhuFab VEGF in one eye (prevention eye), while the contralateral eye received rhuFab VEGF vehicle (control eye) at 2-week intervals. On day 21, laser photocoagulation was performed to induce CNV. In phase 2, the vehicle-treated eye was crossed over and both eyes received 500 microg of rhuFab VEGF beginning 21 days following laser-induced injury at days 42 and 56. The eyes were monitored by ophthalmic examinations, color photographs, and fluorescein angiography.
RESULTS: rhuFab VEGF did not cause any ocular hemorrhages. All eyes treated with rhuFab VEGF developed acute anterior chamber inflammation within 24 hours of the first injection that resolved within 1 week, and this inflammation was less severe with subsequent injections. The incidence of CNV, defined angiographically, was significantly lower in the prevention eyes than the control eyes (P<.001). Subsequent treatments were associated with less leakage in eyes with established CNV that were crossed over from the control eyes to the treatment eyes (P =.001).
CONCLUSIONS: Intravitreal rhuFab VEGF injections prevented formation of clinically significant CNV in cynomolgus monkeys and decreased leakage of already formed CNV with no significant toxic effects.
CLINICAL RELEVANCE: This study provides the nonclinical proof of principle for ongoing clinical studies of intravitreally injected rhuFab VEGF in patients with neovascular age-related macular degeneration.
DOI of Published Version
Krzystolik MG, Afshari MA, Adamis AP, Gaudreault J, Gragoudas ES, Michaud NA, Li W, Connolly E, O'Neill CA, Miller JW. Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol. 2002 Mar;120(3):338-46. doi:10.1001/archopht.120.3.338.
Archives of ophthalmology
Krzystolik, Magdalena G.; Afshari, Mehran A.; Adamis, Anthony P.; Gaudreault, Jacques; Gragoudas, Evangelos S.; Michaud, Norman A.; Li, Wenjun; Connolly, Edward; O'Neill, Charles A.; and Miller, Joan W., "Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment" (2002). Preventive and Behavioral Medicine Publications. 311.