Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging

Anne M Lynch; Alan G Palestine; Brandie D Wagner; Jennifer L Patnaik; Ashley A Frazier-Abel; Marc T Mathias; Frank S Siringo; Vernon Michael Holers; Naresh Mandava

doi:10.1136/bmjophth-2019-000361

Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging

BMJ Open Ophthalmol. 2020 Jan 14;5(1):e000361. doi: 10.1136/bmjophth-2019-000361. eCollection 2020.

Authors

Anne M Lynch¹, Alan G Palestine², Brandie D Wagner³, Jennifer L Patnaik², Ashley A Frazier-Abel⁴, Marc T Mathias², Frank S Siringo², Vernon Michael Holers⁵, Naresh Mandava²

Affiliations

¹ Department of Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA anne.lynch@ucdenver.edu.
² Department of Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA.
³ Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, Colorado, USA.
⁴ Exsera BioLabs, University of Colorado School of Medicine, Aurora, Colorado, USA.
⁵ Departments of Medicine and Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA.

Abstract

Objective: Systemic activation of the complement system in intermediate age-related macular degeneration (AMD) is understudied. Moreover, links between the presence of reticular pseudodrusen (RPD) and systemic complement dysregulation have not been studied. The aim of this study was to determine if there is a difference in plasma complement factor levels in intermediate AMD compared with controls, and if complement levels are related to the presence of RPD.

Methods and analysis: Levels of complement factors C1q (µg/mL), C4 (µg/mL), C2 (µg/mL), Mannose Binding Lectin (ng/mL), C4b (µg/mL), C3 (µg/mL), factor B (µg/mL), factor D (µg/mL), properdin (µg/mL), C3a (ng/mL), iC3b/C3b (ng/mL), Ba (ng/mL), factor H (µg/mL), factor I (µg/mL), C5 (µg/mL), C5a (pg/mL) and SC5b-9 (ng/mL) were measured in plasma.

Results: 109 cases and 65 controls were included in the study. Thirty-nine (36%) cases had RPD. Significantly lower systemic levels of: C1q (OR 0.96, 95% CI 0.94 to 0.98), factor B (OR 0.98, 95% CI 0.96 to 0.99), iC3b/C3b (OR 0.97, 95% CI 0.95 to 0.98), factor H (OR 0.99, 95% CI 0.98 to 0.99), factor I (OR 0.83, 95% CI 0.77 to 0.89) and C5 (OR 0.94, 95% CI 0.90 to 0.98) were found in cases versus controls. Significantly elevated levels of: C2 (OR 1.29, 95% CI 1.07 to 1.59), C3a (OR 1.03, 95% CI 1.01 to 1.05) Ba (OR 1.03, 95% CI 1.01 to 1.05) and C5a (OR 1.04, 95% CI 1.02 to 1.07) were found in cases versus controls. Systemic levels of complement factors measured were not related to the presence of RPD.

Conclusions: Levels of several systemic complement pathway factors were found to be altered in intermediate AMD. Systemic levels of complement factors were not related to RPD.

Keywords: epidemiology; immunology; inflammation; macula; retina.