Association of imaging biomarkers and local activation of complement in aqueous humor of patients with early forms of ag
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Association of imaging biomarkers and local activation of complement in aqueous humor of patients with early forms of age-related macular degeneration Vasilena Sitnilska 1 & Philip Enders 1 & Claus Cursiefen 1 & Sascha Fauser 1,2 & Lebriz Altay 1 Received: 24 April 2020 / Revised: 17 August 2020 / Accepted: 20 August 2020 # The Author(s) 2020
Abstract Purpose To investigate a possible correlation between established imaging biomarkers for age-related macular degeneration and local complement system activation, measured in aqueous humor (AH) of patients with early stages of age-related macular degeneration (AMD) and controls. Methods This analysis included prospectively acquired AH samples of 106 eyes (35 with early/intermediate AMD, 71 controls). The levels of complement protein 3 (C3), 4 (C4), 5 (C5); activation products of complement factor 3a (C3a) and Ba, C3b/iC3b; complement factors B, D, H, I (CFB, CFD, CFH, CFI); and total protein concentration were analyzed. Quantitative levels of complement factors were correlated to the presence of reticular pseudodrusen (RPD), the presence of hyperreflective foci (HRF), and total drusen volume (DV) graded on imaging by spectral-domain optical coherence tomography and using Spearman’s rank correlation test. Results DV correlated with C3b/iC3b (r = 0.285; P = 0.034), C3a (r = 0.200; P = 0.047), Ba (r = 0.262; P = 0.009), and C5 (r = 430; P = 0.005), and showed a tendency towards correlation with C3a (r = 0.198; P = 0.057). HRF correlated significantly with C5 (r = 0.388; P = 0.011) and RPD showed a tendency towards correlation with CFB (r = 0.196; P = 0.050). Conclusion In patients with early AMD, HRF and drusen parameters but not RPD show low to fair levels of correlation with local complement activation in patients’ AH. Better understanding of complement activation could provide some insights into the pathogenesis of AMD. Imaging biomarkers could be useful to identify suitable patients for future clinical trials with complementmodulating therapies. Keywords Complement . Age-related macular degeneration . Imaging biomarkers . Aqueous humor
Introduction Age-related macular degeneration (AMD) is one of the leading causes for blindness worldwide in elderly people [1]. Since the discovery of complement components in drusen—the hallmark of the disease—the role of complement system in AMD is extensively studied [2–7]. Several
Sascha Fauser and Lebriz Altay share senior authorship. * Lebriz Altay [email protected] 1
Department of Ophthalmology, Faculty of Medicine and University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany
2
F. Hoffmann-La Roche AG, Basel, Switzerland
genetic studies showed association of genetic variants encoding for complement system components and regulators with increased risk for AMD and its progression [8–12]. The upregulation of complement activation products in serum and plasma of AMD patients further supports the importance of the complement system in AMD. Lately, an increase in sy
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