Systemic activation of the complement system in patients with advanced age-related macular degeneration

Abstract

Purpose: To examine the role of systemic activation of the complement system (assessed by levels of circulating C3a, Ba, and sC5b-9) in patients (n = 122) with advanced age-related macular degeneration, geographic atrophy, and neovascular age-related macular degeneration, compared with cataract controls (n = 27). Methods: Plasma complement factors were measured using enzyme-linked immunosorbent assays. Statistical analysis included univariate and multivariate logistic regression (p < 0.05). Results: Adjusted for age, the odds ratios of C3a and sC5b-9 for any advanced age-related macular degeneration were 1.78 (95% confidence interval = 1.16–2.73, p < 0.01) and 1.20 (95% confidence interval = 1.04–1.39, p = 0.01), respectively. We found a significantly elevated adjusted odds ratio of C3a (adjusted odds ratio = 1.71, 95% confidence interval = 1.12–2.60, p = 0.01) and sC5b-9 (adjusted odds ratio = 1.22, 95% confidence interval = 1.04–1.43, p = 0.01) for neovascular age-related macular degeneration. Adjusted for age, neither C3a, sC5b-9, nor Ba were associated with geographic atrophy. Conclusion: We suggest a role for elevated plasma levels of C3a and sC5b-9 in patients with neovascular age-related macular degeneration. The study’s results reinforce the need for more investigation to assess the impact of therapeutic interventions targeted at the complement signaling pathways in age-related macular degeneration.