Abstract
We investigated the association between von Willebrand factor (VWF) and exudative age-related macular degeneration (AMD) in 114 Japanese patients. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitor is the most effective therapy for AMD. Therefore, we analyzed changes of VWF antigen (VWF:Ag) and VWF multimers (VWFMs) after intravitreal injection of aflibercept, an anti-VEGF antagonist. The relationship between polymorphisms in complement factor H (p.Y402H and p.I62V) and AMD was previously reported. In our patients, p.I62V, but not p.Y402H, was significantly associated with an increased risk of AMD. Pre-treatment plasma levels of VWF:Ag in patients with AMD were significantly higher than those in controls. Unusually large VWFMs (UL-VWFMs) were detected in the majority of AMD patients with concurrent vitreous or subretinal hemorrhage. After intravitreal injection of aflibercept, plasma levels of VWF:Ag and VEGF-A were significantly decreased. UL-VWFMs disappeared after aflibercept injection in three cases, but persisted even 1 month after injection in the other five cases. In conclusion, plasma VWF:Ag levels were significantly elevated in patients with AMD, and decreased after intravitreal aflibercept injection. VWF may play an important role in the pathophysiology of AMD, and aflibercept might improve AMD by reducing plasma levels of VWF in addition to VEGF-A.
Highlights
We investigated the association between von Willebrand factor (VWF) and exudative age-related macular degeneration (AMD) in 114 Japanese patients
Exudative AMD was classified into three subtypes, including typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)
We showed that pre-treatment plasma levels of VWF:Ag were elevated in patients with AMD compared with controls, and for the first time demonstrated the presence of UL-VWF multimers (VWFMs) in patients with severe vitreous or subretinal hemorrhage
Summary
We investigated the association between von Willebrand factor (VWF) and exudative age-related macular degeneration (AMD) in 114 Japanese patients. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitor is the most effective therapy for AMD. Pre-treatment plasma levels of VWF:Ag in patients with AMD were significantly higher than those in controls. After intravitreal injection of aflibercept, plasma levels of VWF:Ag and VEGF-A were significantly decreased. Plasma VWF:Ag levels were significantly elevated in patients with AMD, and decreased after intravitreal aflibercept injection. Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis[3], was previously shown to be elevated in the eyes of patients with AMD4. Plasma VWF is synthesized in vascular endothelial cells and released into the circulation as unusually large VWF multimers (UL-VWFMs), the most biologically active form of VWF17. Deficiency of ADAMTS13 activity (ADAMTS13:AC) induces the accumulation of UL-VWFMs and leads to platelet hyperaggregation under high shear stress, resulting in thrombotic thrombocytopenic purpura (TTP), a life-threatening blood disease[17]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
