title: Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration: Complement activation in AMD.
abstract: BACKGROUND
  The aim of this study was to investigate the plasma levels of complement C3a, C4a, and C5a in different types of neovascular age-related macular degeneration (nAMD) and whether the levels were related to patients' responsiveness to anti-VEGF therapy.
  
  
  RESULTS
  Ninety-six nAMD patients (including 61 with choroidal neovascularisation (CNV), 17 with retinal angiomatous proliferation (RAP), 14 with polypoidal choroidal vasculopathy (PCV) and 4 unclassified patients) and 43 controls were recruited to this case-control study. Subretinal fibrosis was observed in 45 nAMD patients and was absent in 51 nAMD patients. In addition, the responsiveness to anti-VEGF (Lucentis) therapy was also evaluated in nAMD patients. Forty-four patients were complete responders, 48 were partially responders, and only 4 patients did not respond to the therapy. The plasma levels of C3a, C4a and C5a were significantly higher in nAMD patients compared to controls. Further analysis of nAMD subgroups showed that the levels of C3a, C4a and C5a were significantly increased in patients with CNV but not RAP and PCV. Significantly increased levels of C3a, C4a and C5a were also observed in nAMD patients with subretinal fibrosis but not in those without subretinal fibrosis. Higher levels of C3a were observed in nAMD patients who responded partially to anti-VEGF therapy.
  
  
  CONCLUSIONS
  Our results suggest increased systemic complement activation in nAMD patients with CNV but not RAP and PCV. Our results also suggest that higher levels of systemic complement activation may increase the risk of subretinal fibrosis in nAMD patients.
authors.affiliation: The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Lechner
authors.affiliation: The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.affiliation: The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Hogg
authors.affiliation: The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK.
authors.forename: Levente
authors.initials: L
authors.lastname: Toth
authors.affiliation: The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Silvestri
authors.affiliation: The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK.
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
authors.affiliation: The Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL UK.
authors.forename: Heping
authors.identifier: 0000-0003-4000-931X
authors.initials: H
authors.lastname: Xu
keywords: Age-related macular degeneration; Choroidal neovascularisation; Complement; Subretinal fibrosis