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Original research
Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging
  1. Anne M Lynch1,
  2. Alan G Palestine1,
  3. Brandie D Wagner2,
  4. Jennifer L Patnaik1,
  5. Ashley A Frazier-Abel3,
  6. Marc T Mathias1,
  7. Frank S Siringo1,
  8. Vernon Michael Holers4,
  9. Naresh Mandava1
  1. 1Department of Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
  2. 2Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, Colorado, USA
  3. 3Exsera BioLabs, University of Colorado School of Medicine, Aurora, Colorado, USA
  4. 4Departments of Medicine and Immunology, University of Colorado School of Medicine, Aurora, Colorado, USA
  1. Correspondence to Dr Anne M Lynch; anne.lynch{at}ucdenver.edu

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.

  • epidemiology
  • inflammation
  • macula
  • retina
  • immunology
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjophth-2019-000361

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    Footnotes

    • Contributors AML, NM and AGP planned and designed the study. AML was responsible for conduct of the study and collection of data. AML and NM were responsible for the overall coordination of the study. BDW and JLP conducted the data analysis. AAF-A measured the complement factors. MTM, FSS, NM and AGP reviewed the images. VMH and AAF-A provided consultation on the interpretation of the complement data. All authors contributed to the interpretation of the data, drafts of the manuscript and editing of the final paper.

    • Funding Support from a Challenge Grant to the Department of Ophthalmology from Research to Prevent Blindness and the Frederic C. Hamilton Macular Degeneration Center.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval The registry is approved by the Colorado Multiple Institutional Review Board.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available upon request.