Inflammatory Mediators in Diabetic Macular Edema: A Prospective, Controlled Study

PURPOSE: 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. METHODS: ETDRS visual acuity, fundus photography, and 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. DME was defined as central subfield thickness > 320 µm on OCT with the presence of intraretinal fluid. RESULTS: Median and interquartile range (IQR) of VEGF-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), 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). CONCLUSIONS: We report that IL-8, FLT-3L, FGF-2, IL-6, and IL-10were significantly elevated in eyes with DME.