ABSTRACT
Introduction:
Tumor necrosis factor alpha (TNF-α) is an inflammatory
cytokine implicated in pathological changes to the
retinal pigment epithelium that are
similar to changes in
geographic atrophy (GA), an advanced form of
age related macular degeneration (AMD). TNF-α also modulates expression of other
cytokines including
vascular endothelial growth factor (
VEGF), leading to choroidal
atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and
VEGF in
patients with GA and intermediate AMD (iAMD) compared to controls without AMD.
Methods:
We examined
plasma levels of TNF-α and
VEGF in
patients with GA, iAMD, and controls without AMD from the
University of
Colorado AMD
registry (2014 to 2021). Cases and controls were characterized by
multimodal imaging. TNF-α and
VEGF were measured via multiplex
immunoassay and data were analyzed using a non-parametric rank based
linear regression model fit to
plasma biomarkers.
Results:
There were 97 GA, 199 iAMD
patients and 139 controls. TNF-α was significantly increased in GA (Median9.9pg/ml, IQR7.3-11.8) compared to iAMD (Median7.4, IQR5.3-9.1) and in both GA and iAMD compared to controls (Median6.4, IQR5.3-7.8), p<0.01 for all comparisons.
VEGF was significantly increased in iAMD (Median8.9, IQR4.8-14.3) compared to controls (Median7.7, IQR4.6-11.1), p<0.01. There was a significant positive correlation between TNF-α and
VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and
VEGF in any group.
Discussion:
These findings suggest TNF-α and
VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and
VEGF may function as systemic
biomarkers for
disease development.
