The Correlation of Plasma Cytokines with Complement Factor H polymorphism Y402H, Choroidal Thickness and Drusen Load in Dry Age-Related Macular Degeneration

Abstract

Purpose: Several key components of the complement cascade are associated with the pathogenesis of age-related macular degeneration (AMD), including the Y402H variation in the gene encoding complement factor H (CFH), which confers a several-fold increased risk for developing AMD. Earlier studies, including ours, demonstrated an association between drusen, a hallmark of early AMD, and increased inflammatory cytokines in retina of postmortem eye tissues. In this study, we address the correlation between plasma cytokines and drusen load, choroidal thickness and the Y402H polymorphism in CFH gene in patients with dry AMD.

Methods: Forty-four patients with dry AMD were recruited. Drusen area and volume were determined using the spectral-domain optical coherence tomography (SD-OCT) software, and choroidal thickness was measured using enhanced depth imaging (EDI). The subjects’ blood samples were analyzed for multiple cytokines using Bio-Plex suspension assays and genotyped for the CFH Y402H polymorphism. Statistical analyses were conducted using ANCOVA and multiple regression.

Results: We found an inverse correlation between choroidal thickness and drusen load (r = -0.35, p = 0.04). Drusen load also correlated with logMAR visual acuity (r = 0.32, p = 0.04). A correlation between choroidal thickness and logMAR visual acuity was suggested (r = -0.22, p = 0.21). Patients with the high-risk CC variant had higher levels of plasma cytokines than those with TT variant (IL-1β IL-1ra, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-17, G-CSF, IFN-γ, MIP-1α, TNF-α and VEGF) (p ≤ 0.05). Patients with thinner choroids also had increased levels of MIP-1β (β = -0.35, p = 0.05). No correlation was found between the tested cytokines and drusen load.

Conclusions: The CFH Y402H genotype is associated with elevated systemic levels of inflammatory cytokines. These findings provide support for the role of inflammation in the pathogenesis of AMD. The atrophy in RPE-choroid interface may be associated with the elevated systemic inflammatory cytokines. SD-OCT can be used to assess the correlation between drusen load and choroidal thickness, both of which show a relationship with visual acuity. Therefore, the measurement of these outcomes may serve as important outcome parameters in routine clinical care and in clinical trials for dry AMD.

Keywords: 412 age-related macular degeneration • 557 inflammation • 490 cytokines/chemokines