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R. J. Courtney, N. Mandava, S. Oliver, H. Quiroz-Mercado, J. L. Olson; Intravitreal Inhibition of CNV in an Animal Model: A Comparison of Infliximab, Anakinra and LD22-4. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2964.
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To determine and compare the degree of inhibition of choroidal neovascularization (CNV) caused by intravitreal infliximab, anakinra and LD22-4 (a novel inhibitor of fibroblast migration) in an animal model of age related macular degeneration.
Brown Norway rats received peripapillary argon laser lesions of sufficient power to rupture Bruch’s membrane in each eye. Immediately following laser application intravitreal injections were performed with the treatment eye receiving an injection of drug and the fellow eye receiving an injection of vehicle as a control. In the infliximab group, a 5 microliter intravitreal infliximab injection of either 0.15mg/ml, 0.5mg/ml, or 15mg/ml was performed. In the LD22-4 group, a 4 microliter injection of full strength, 1:2 dilution, or 1:4 dilution was administered. For the anakinra group, the treatment dose was increased by increasing the number of injections: Animals received 5 microliter injections of anakinra, 150mg/ml, either once only, once every three weeks, or twice every three weeks. The control eyes received injections of vehicle on a matched schedule. On day 30, two million molecular weight FITC-dextran angiography was performed, the animals were euthanized, RPE-choroid-sclera flat mounts were prepared and the amount of CNV quantified with digital analysis software.
Each agent inhibited CNV growth in the model in a dose-response manner. For infliximab, the 1.5 mg/ml group demonstrated an 11% reduction in CNV growth (p=0.01), and in the 15 mg/ml group, CNV growth was decreased by 68% (p<0.0001). In the anakinra group, the minimum dose group had a 26% reduction in CNV while the maximum dose group demonstrated a 62% reduction (all p<0.0001). Maximally diluted LD22-4 showed a 23% reduction in CNV while full strength LD22-4 resulted in a 49% reduction (all p<0.0001).
Intravitreal inhibitors of angiogenesis show similar efficacy despite varying targets in the angiogenesis cascade in an animal model of CNV. While anti-VEGF therapy has arguably become the current standard of practice, therapeutics targeting inflammatory cytokines and accessory cells such as the fibroblast will likely prove useful adjuncts in the treatment of ocular neovascular disease.
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