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Thiago Cabral, Luiz Henrique Lima, Julia Polido, Everton Peroschi Correia, Pedro Duraes Serracarbassa, Caio V Regatieri, Belfort Rubens; Angiogenesis Agents Levels After Bevacizumab Intravitreal Injection in Patients with Neovascular Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3341.
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To evaluate the concentration of nineteen angiogenic biomarkers in the aqueous humor before and after intravitreal injection of bevacizumab in treated eyes with neovascular age-related macular degeneration (AMD).
In this prospective study, 23 eyes of 23 patients with choroidal neovascularization secondary to neovascular AMD were treated with three initial intravitreal injections of bevacizumab, according to PrONTO dosing regimen. Aqueous humor samples were obtained by anterior chamber paracentesis before each intravitreal injection (IVB). Nineteen vasogenic biomarkers [angiopoietin-2, bone morphogenetic protein-9 (BMP-9), epidermal growth factor (EGF), endoglin, endothelin-1, fibroblast growth factor (FGF-1 and FGF-2), follistatin, granulocyte-colony stimulating factor (G-CSF), heparin-binding EGF-like growth factor (HB-EGF), hepatocyte growth factor (HGF), interleucin-8 (IL-8), leptin, placental growth factor (PLGF), vascular endothelial growth factor (VEGF-A, VEGF-C, VEGF-D) and tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2) concentration in the aqueous humor were measured using an ELISA assay.
VEGF-A level was elevated in all patients at baseline before the initiation of IVB injection, and a significant decrease in its level was observed at 1 and 2 months follow-up periods immediately before IVB injections. The mean ± SD aqueous concentration of VEGF-A was 79.91 ± 48.17 pg/mL at baseline, 7.660 ± 3.523 pg/mL at 1 month and 7.622 ± 3.423 pg/mL at 2 months follow-up periods (P < 0.0001). Seven study vasogenic biomarkers (VEGF-C, angiopoietin-2, endothelin-1, follistatin, HB-EGF, HGF, IL-8) had statistically significant increase in their levels after intravitreal injection of bevacizumab. The other eleven study biomarkers levels (VEGF-D, BMP-9, EGF, endoglin, FGF-1, FGF-2, G-CSF, leptin, PLGF, TIMP-1 and TIMP-2) did not show statistically significant difference.
Our investigation suggests a correlative relationship between VEGF-A and seven other study biomarkers in the eye with regard to expression that may have therapeutic significance. Aqueous levels of VEGF-C, angiopoietin-2, endothelin-1, follistatin, HB-EGF, HGF, IL-8 significantly increased with the decrease of VEGF-A, suggesting new pathways for the neovascularization. SUCH UPREGULATED ANGIOGENIC BIOMARKERS MAY BE POTENTIAL NEW TREATMENT TARGETS FOR CNV DUE TO AMD.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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