Association between systemic complement levels and choroidal thickness in advanced non-neovascular age-related macular degeneration

To investigate associations between systemic complement activation and choroidal thickness (CT) in advanced non-neovascular age-related macular degeneration (nnAMD). Cross-sectional study of 96 patients (187 eyes) with advanced nnAMD enrolled in the University of Colorado AMD Registry (August 2014-June 2021). Medical histories, multimodal imaging, and plasma samples were collected. Plasma was analyzed via enzyme-linked immunosorbent assay and multiplex Luminex assays for complement factors C1q, monoclonal B-cell lymphocytosis, C2, C4, C4b, C3, C3a, Factor B, Bb, Factor D, Factor H, Factor I, C5 and soluble C5b-9. CT was measured subfoveally and at 1000 μm intervals superiorly, inferiorly, nasally, and temporally using Spectralis OCT. Linear modeling with generalized estimating equations assessed log-transformed OCT and complement factors. The mean age was 82.2 years (± 7.1 SD); 54.2% were female. Average CT was negatively associated with Bb (β=-0.47, SE: 0.12, p = 0.0001) and the Bb/Factor B ratio (β=-0.28, SE: 0.12, p = 0.02), but not other complement markers. Bb levels correlated with alternative pathway components but not with classical or lectin pathway markers. We found a key association between systemic complement activation of Factor B and choroidal thickness in patients with advanced nnAMD, implying the potential involvement of the systemic alternative pathway in nnAMD patients.