Abstract
OBJECTIVE: To analyze the relationship of aqueous interleukin-6 (IL-6) with diabetic retinopathy (DR) severity. DESIGN: Prospective, controlled trial at a tertiary academic medical center. SUBJECTS: Three hundred twenty-eight eyes of 164 adult type II diabetic patients with varying levels of DR. METHODS: A total of 328 eyes of 164 diabetic patients were enrolled based on DR severity: 46 eyes of 23 patients in the no DR group, 236 eyes of 118 patients in the moderate nonproliferative DR (NPDR) group, and 46 eyes of 23 patients in the proliferative DR (PDR) group. ETDRS visual acuity, spectral-domain OCT, and color fundus photographs were taken at baseline. Blood draw and aqueous sampling of each eye was performed. Blood glucose and hemoglobin A1c (HbA1c) were measured. Aqueous IL-6 was measured using a microparticle bead-based multiplex assay. MAIN OUTCOMES MEASURES: Aqueous IL-6 levels, HbA1c, DR severity, Diabetic macular edema (DME). RESULTS: Median HbA1c differed between the 3 DR groups (P = 0.03), but there was no correlation between IL-6 and HbA1c (ρ = 0.08, P = 0.179). Baseline aqueous IL-6 levels were significantly different between DR groups. Median IL-6 and interquartile range was 5.40 pg/mL (2.99-8.77) for eyes in the no DR group, 9.25 pg/mL (5.35-22.35) for eyes in the moderate NPDR group, and 15.71 pg/mL (9.24-48.58) for eyes in the PDR group (P < 0.001). Median central subfield thickness (CST) did not differ significantly between the 3 groups (P = 0.351), but there was a significant positive correlation between IL-6 and CST (ρ = 0.18, P = 0.001). There was also a significant positive correlation between IL-6 and macular volume (ρ = 0.12, P = 0.031). Increased IL-6 was significantly associated with increased odds of having DME (odds ratio = 1.00, P = 0.015). CONCLUSIONS: We report the largest analysis of aqueous IL-6 in diabetic eyes. We observed that IL-6 is significantly associated with DR severity and DME. Our results considerably strengthen the prevailing evidence that IL-6 is a key contributor to the pathogenesis of DR and may represent both a biomarker of disease activity and a novel therapeutic target. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.