Inflammatory Proteins Profiling in Tear Fluid in Polypoidal Choroidal Vasculopathy and Neovascular Age-Related Macular Degeneration

Objective: To analyze the differential expression of inflammatory proteins in the tear fluid of patients with polypoidal choroidal vasculopathy (PCV) or neovascular age-related macular degeneration (nAMD).
Methods: A total of 19 patients with PCV, 17 patients with nAMD, and 18 normal controls (NC) aged ≥50 years were enrolled. Tear samples were collected, and the expression levels of 92 inflammatory proteins were quantified using Olink technology. Differentially expressed proteins (DEPs) among the groups were analyzed, with particular attention to consistency with previous findings from aqueous humor studies.
Results: Olink analysis revealed extensive DEPs among PCV, nAMD, and NC groups. Compared with NC, the PCV group exhibited significant upregulation of VEGFA, Interleukin (IL) -18, IL-1α, IL-8, IL-7, Monocyte chemotactic protein (MCP)-2, and Neurturin (NRTN), along with downregulation of Tumor necrosis factor (TNF) and IL-10. The nAMD group showed a more pronounced pro-inflammatory profile, with upregulation of VEGFA, IL-18, IL-8, IL-1α, IL-7, Fibroblast growth factor (FGF)-19, MCP-1, Matrix metalloproteinase (MMP)-10, NRTN, Stem cell factor (SCF), Osteoprotegerin (OPG), Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), MMP-1, MCP-2, Fms-related tyrosine kinase 3 ligand (Flt3L), Tumor Necrosis Factor – like Weak Inducer of Apoptosis (TWEAK), Caspase (CASP)-8, and Tumor necrosis factor receptor superfamily member 9 (TNFRSF9), and downregulation of IL-10 and IL-12β. Comparison between PCV and nAMD indicated that IL-12β and Hepatocyte growth factor (HGF) were specifically upregulated in PCV, whereas SCF, VEGFA, Flt3L, OPG, MCP-1, T-cell surface glycoprotein CD8α (CD8α), Cystatin D (CST5), MMP-1, TNFRSF9, Transforming growth factor-α (TGF-α), 4E-BP1, and CASP-8 were significantly downregulated in PCV relative to nAMD. Boxplot analysis confirmed that Flt3L, IL-18, IL-1α, IL-7, IL-8, MCP-1, MMP-1, OPG, SCF, and VEGFA were specifically elevated in nAMD compared with both PCV and NC groups, while IL-10 was specifically suppressed in PCV.
Conclusions: Tear fluid analysis represents a feasible and noninvasive approach to investigate the pathogenesis of PCV and nAMD.