Inflammatory and Imaging Biomarkers in Treatment-Naïve Diabetic Macular Edema: Comparison with Irvine–Gass and Cataract Controls

Purpose: To determine whether aqueous flare reflects intraocular inflammation in treatment-naïve diabetic macular edema (DME) and to examine associations between aqueous cytokines and optical coherence tomography (OCT) biomarkers, using Irvine–Gass syndrome (IGS) and cataract eyes as controls. Methods: Seventy-six eyes were included (40 DME, 19 IGS, 17 cataract controls). All eyes underwent OCT imaging and laser flare photometry. Aqueous levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), interferon-γ–inducible protein-10 (IP-10), and vascular endothelial growth factor (VEGF) were measured. OCT biomarkers included hyperreflective foci (HRF), ellipsoid zone (EZ) disruption, and subretinal fluid. Results: IL-6 levels differed among groups (p = 0.015), being higher in IGS than controls, while MCP-1 showed a borderline difference (p = 0.054) with higher levels in IGS versus DME (p = 0.008). IP-10 did not differ among groups, and VEGF levels were similar between IGS and DME (p = 0.659). Flare values were higher in IGS than controls (p = 0.039) but did not differ between DME and controls. Compared with IGS, DME eyes more frequently exhibited HRF and EZ disruption (all p <0.05). In DME, HRF count correlated with IP-10 on univariate analysis (r = 0.33, p <0.05), but this association did not remain significant after multivariate adjustment (p = 0.075). Conclusion: In treatment-naïve DME eyes, inflammatory profiles likely reflect an early disease state and may differ from those observed in chronic or previously treated DME. HRF may represent an OCT phenotype related to inflammatory signaling, although an independent association with IP-10 was not confirmed, with potential relevance for future studies.