Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration

• Published in: Immunity & ageing Vol. 13; no. 4
• Main Authors: Lechner, Judith, Chen, Mei, Hogg, Ruth E, Toth, Levente, Silvestri, Giuliana, Chakravarthy, Usha, Xu, Heping
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 16-02-2016; BioMed Central
• Subjects: Aged; Care and treatment; Complications and side effects; Fibrosis; Health aspects; Macular degeneration; Risk factors
• ISSN: 1742-4933; 1742-4933
• DOI: 10.1186/s12979-016-0060-5

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. Keywords: Age-related macular degeneration, Choroidal neovascularisation, Complement, Subretinal fibrosis