INFLAMMATORY MEDIATORS IN DIABETIC MACULAR EDEMA: A Prospective, Controlled Study.

Abstract

Inflammatory cytokines are key mediators of diabetic macular edema (DME). Prior assessments are limited by study design and small sample size. We rigorously analyzed the association of 24 inflammatory cytokines with DME in a prospective trial of 328 eyes of 164 adult type II diabetic patients with different stages of diabetic retinopathy severity. Early Treatment Diabetic Retinopathy Study visual acuity, fundus photography, and optical coherence tomography (OCT) of each eye were taken at baseline. Bilateral aqueous sampling was performed. A microparticle bead-based multiplex assay was used to measure aqueous levels of 24 inflammatory cytokines. Diabetic macular edema was defined as central subfield thickness >320 µ m on OCT with the presence of intraretinal fluid. Median and interquartile range of vascular endothelial growth factor A, IL-6, and IL-8 were 148.70 pg/mL (103.93-232.96), 7.67 pg/mL (4.64-18.90), and 11.14 pg/mL (6.48-17.46) in eyes without DME, respectively, and 181.32 pg/mL (141.82-307.81), 16.53 pg/mL (8.15-48.68), and 15.95 (10.67-26.53) in eyes with DME, respectively. Positive odds ratios with 95% confidence intervals were observed for IL-8 (2.73 [1.41-5.29]; P = 0.003), FMS-like tyrosine kinase 3 ligand (FLT-3L) (2.27 [1.22-4.23]; P = 0.01), FGF-2 (1.74 [1.06-2.86]; P = 0.029), IL-6 (2.93 [1.62-5.31]; P < 0.001), and IL-10 (2.79 [1.50-5.21]; P = 0.001). We report that IL-8, FLT-3L, FGF-2, IL-6, and IL-10 were significantly elevated in eyes with DME.