L Altay1, V Sitnilska1, T Schick1, G Widmer2, G Duchateau-Nguyen2, P Piraino3, A Jayagopal2, F M Drawnel4, S Fauser1,2. 1. Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany. 2. Roche Pharma Research and Early Development, Roche Innovation Center Basel, 124 Grenzacherstrasse, 4070, Basel, Switzerland. 3. P Value Research S.R.L., 29015, Castel San Giovanni (PC), Italy. 4. Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany. faye.drawnel@roche.com.
Abstract
OBJECTIVE: To investigate complement activation in aqueous humour of patients with early, intermediate and neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Aqueous humour of 79 AMD patients (early, intermediate and neovascular) and 77 age-matched controls was prospectively collected. The levels of the complement protein 3 (C3), activation products complement factor 3a (C3a) and Ba, C3b/iC3b, complement factors B, H and I (CFB, CFH and CFI), and total protein concentration were measured. Data were modelled using covariate analysis to assess the impact of age and glaucoma status of patients and total protein concentration of samples on complement protein concentration across groups. RESULTS: C3a concentration was significantly increased in the aqueous humour of early (p = 0.016), intermediate (p = 0.003) and neovascular (p = 0.018) AMD patients, whilst C3 concentration was significantly increased in early AMD patients only (p = 0.019). Levels of CFB and CFH were significantly increased in the aqueous humour of neovascular AMD patients (p = 0.023 and p = 0.018, respectively). CONCLUSIONS: Our findings provide evidence for early local complement dysregulation in AMD patients, suggesting that complement pathway inhibition may be a clinically relevant intervention for early stages of AMD.
OBJECTIVE: To investigate complement activation in aqueous humour of patients with early, intermediate and neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Aqueous humour of 79 AMDpatients (early, intermediate and neovascular) and 77 age-matched controls was prospectively collected. The levels of the complement protein 3 (C3), activation products complement factor 3a (C3a) and Ba, C3b/iC3b, complement factors B, H and I (CFB, CFH and CFI), and total protein concentration were measured. Data were modelled using covariate analysis to assess the impact of age and glaucoma status of patients and total protein concentration of samples on complement protein concentration across groups. RESULTS:C3a concentration was significantly increased in the aqueous humour of early (p = 0.016), intermediate (p = 0.003) and neovascular (p = 0.018) AMDpatients, whilst C3 concentration was significantly increased in early AMDpatients only (p = 0.019). Levels of CFB and CFH were significantly increased in the aqueous humour of neovascular AMDpatients (p = 0.023 and p = 0.018, respectively). CONCLUSIONS: Our findings provide evidence for early local complement dysregulation in AMDpatients, suggesting that complement pathway inhibition may be a clinically relevant intervention for early stages of AMD.
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