Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration
Open accessAbstract
Topic: To evaluate whether differences exist in systemic complement activation profiles in patients with early to intermediate nonexudative age-related macular degeneration (AMD) or geographic atrophy (GA) compared with control participants without AMD. Clinical Relevance: Complement inhibition has emerged as a therapeutic strategy for GA, although clinical trials to date have yielded mixed results. Despite these efforts, no clear consensus exists regarding what portions of the complement pathway are dysregulated in AMD or when this dysregulation occurs relative to AMD stage. Although past studies have compared systemic complement activation profiles in patients with AMD versus in control participants without AMD, differences in AMD case definition and differing analytical approaches complicate their interpretation. Methods: We performed a systematic review by identifying articles from database inception through October 11, 2020, that reported systemic complement activation profiles in patients with early or intermediate nonexudative AMD or GA versus control participants without AMD by searching PubMed, Google Scholar, and Embase. Risk of bias was assessed using a modified Newcastle-Ottawa score. Results: The 8 reviewed studies included 2131 independent participants. Most studies report significantly higher systemic levels of products associated with complement activation and significantly lower systemic levels of products associated with complement inhibition in patients with early and advanced nonexudative AMD compared with control participants without AMD. Discussion: Evidence suggests that systemic complement overactivation is a feature of early or intermediate and advanced nonexudative AMD. However, given significant heterogeneity, these findings are not conclusive and warrant further investigation.
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Levels of circulating complement activation products may be associated with the severity of AMD.
“There is evidence suggesting that levels of circulating complement activation products may be associated with the severity of AMD”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [214]
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- Authors
- Lin, J. B., Serghiou, S., Miller, J. W., & Vavvas, D. G.
- Affiliations
- Massachusetts Eye and Ear Infirmary (US)
- Google (United States) (US)
- Corresponding author
- Vavvas, Demetrios G.
- Venue
- Ophthalmology Science
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 2
- Issue
- 2
- Pages
- 100118
- ISSN
- 2666-9145 (ISSN-L)
- PMC
- PMC9126439
- OpenAlex
- W4210751967
- Cited by
- 9
- References
- 36
- Citations by year
- 2025: 3 · 2023: 2 · 2022: 4
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Ophthalmology Science (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Eye Institute (R01 EY030088)
- American Macular Degeneration Foundation
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- non-exudative age-related macular degeneration, geographic atrophy, complement inhibition, complement inhibition therapy
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