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

Eur J Ophthalmol. 2020 Sep;30(5):1061-1068. doi: 10.1177/1120672119857896. Epub 2019 Jun 17.

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.

Keywords: Advanced age-related macular degeneration; complement; geographic atrophy; neovascular age-related macular degeneration.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Choroidal Neovascularization / blood*
  • Choroidal Neovascularization / diagnosis
  • Complement Activation / physiology*
  • Complement C3a / metabolism*
  • Complement Factor B / metabolism*
  • Complement Membrane Attack Complex / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescein Angiography
  • Geographic Atrophy / blood*
  • Geographic Atrophy / diagnosis
  • Humans
  • Male
  • Odds Ratio
  • Tomography, Optical Coherence
  • Wet Macular Degeneration / blood*
  • Wet Macular Degeneration / diagnosis

Substances

  • Complement Membrane Attack Complex
  • SC5b-9 protein complex
  • Complement C3a
  • Complement Factor B