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

Abstract

ObjectiveSystemic 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 analysisLevels 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.Results109 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.ConclusionsLevels of several systemic complement pathway factors were found to be altered in intermediate AMD. Systemic levels of complement factors were not related to RPD.

Increased Systemic C-Reactive Protein Is Associated With Choroidal Thinning in Intermediate Age-Related Macular Degeneration

“…Serum samples collected at the time of image acquisition were assayed for CRP. 22 , 25 High-sensitivity CRP assays were performed using the automated BN II System nephelometer (Siemens Healthineers, Malvern, PA).…”

“…The focus of recent research from our department has been the contribution of systemic inflammation to AMD, and the department has had several works published in this area. 22 – 24 In this study, we aimed to examine the relationship between CRP and OCT markers of AMD in a cohort of patients with intermediate AMD (iAMD).…”

Plasma Biomarkers of Reticular Pseudodrusen and the Risk of Progression to Advanced Age-Related Macular Degeneration

“…After adjusting for multiple-comparisons testing, we found significantly altered levels of nine complement factors in the cases versus controls with no AMD. 24 The results of that complement study and this proteomic study suggest that the role of systemic inflammation in intermediate AMD progression requires a more comprehensive investigation to specifically determine if select inflammatory markers may be both a target and a biomarker for potential intervention strategies to prevent transition to the devastating forms of advanced AMD. To this end, we will continue to recruit and follow this valuable cohort of patients with intermediate AMD.…”

“…We conducted this cohort study by using records and samples from an AMD research registry and repository (described in detail elsewhere [21][22][23][24] ) developed by the Department of Ophthalmology at the University of Colorado School of Medicine. For this study, we focused on patients in the registry with the intermediate form of AMD.…”

“…Using our AMD registry and biorepository, 21 we have recently reported several proteins linked with the presence of advanced AMD 22 , 23 and intermediate AMD. 24 In the present study, we build on our biomarker research and focus on a cohort of patients with the intermediate phenotype of AMD. To our knowledge, we are presenting the first large-scale biomarker discovery study to utilize a multiplexed aptamer-based proteomic technology in intermediate AMD.…”