Compartment-Specific Associations of GDF15 With Intraocular Cytokines in Patients With Idiopathic Epiretinal Membrane

Purpose: The purpose of this study was to characterize the intraocular cytokine context of growth differentiation factor 15 (GDF15), a stress-response cytokine implicated in tissue injury and immune regulation, in eyes with idiopathic epiretinal membrane (iERM) by evaluating paired aqueous humor (AH) and vitreous humor (VH) samples and their compartment-specific associations with other soluble cytokines. Methods: This cross-sectional study included 38 eyes of 38 patients with iERM and no history of intraocular surgery. Undiluted paired AH and VH samples were collected at the beginning of pars plana vitrectomy (PPV). Twenty-seven cytokines were quantified using a multiplex bead-based immunoassay, and GDF15 concentrations were measured by enzyme-linked immunosorbent assay. Paired AH-VH comparisons and compartmental correlations were analyzed. Results: GDF15 was significantly higher in VH than in AH. Ten other cytokines also differed significantly between compartments: eotaxin, IFN-γ, IL-8, IP-10, MCP-1, and RANTES were higher in VH, whereas IL-1β, IL-6, IL-17A, and TNF-α were higher in AH (all P < 0.01). Significant AH-VH correlations were observed for eotaxin, IL-6, IP-10, MCP-1, MIP-1β, RANTES, and GDF15 (all P < 0.01). When VH GDF15 was used as the reference, significant positive correlations were identified with IL-6, IL-8, IP-10, MCP-1, and MIP-1α (all P < 0.01). No significant negative correlations with GDF15 were observed. Conclusions: In eyes with iERM, intraocular GDF15 showed compartment-weighted associations that were concentrated predominantly on vitreous chemokines, with limited coupling to classical upstream inflammatory cytokines. These findings provide a compartment-specific view of the cytokine context in which intraocular GDF15 is observed.