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Compensatory Growth Factor and Cytokine Response in Tears After Subconjunctival Bevacizumab Injection

Purpose: Recent studies support the use of bevacizumab to treat ocular neovascularization (NV). In this study, we aimed to investigate changes in growth factors and cytokines in human tears after a subconjunctival bevacizumab injection and to evaluate the clinical effects and safety of the drug in ocular surface NV. Methods: Bevacizumab (5 mg/0.2 mL) was injected into the subconjunctival space of 15 patients with corneal NV. Tear samples were collected before and at 1 day, 1 week, and 1 month after the injection. Using a multiarray immunobead assay, we measured vascular endothelial growth factor, epidermal growth factor, basic fibroblast growth factor, interleukin-1β, tumor necrosis factor-α, and matrix metalloproteinase-9 levels. We evaluated the changes in the extent of NV using anterior segment photographs. Results: Ten eyes (67%) showed significant improvement in the NV lesions, and the effect was especially prominent in patients with immune-mediated disease. Six eyes (40%) showed localized complications, but these improved spontaneously. The quantitative analysis showed a decrease in vascular endothelial growth factor and increases in epidermal growth factor, basic fibroblast growth factor, interleukin-1β, and tumor necrosis factor-α in tear samples. Conclusions: These findings suggest that bevacizumab stabilizes angiogenesis at the ocular surface primarily by vascular endothelial growth factor suppression, but that compensatory changes in other growth factors and cytokines may contribute as well. Associated complications seem to be rare and not severe. Bevacizumab therefore may provide an effective and a safe new treatment option for corneal NV.