Systemic Complement Activation Profiles in Nonexudative Age-Related Macular Degeneration: A Systematic Review

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.