Increased levels of cytokines in the aqueous humor correlate with the severity of diabetic retinopathy

Aims: To determine the associations between the levels of certain cytokines in the aqueous humor and the severity of diabetic retinopathy. Methods: A total of 103 patients (one eye per patient) who received intravitreal injection with ranibizumab for diabetic retinopathy were enrolled and divided into 3 groups: nonproliferative diabetic retinopathy (NPDR) with macular edema group (42 eyes), proliferative diabetic retinopathy (PDR) group (40 eyes) and neovascular glaucoma due to PDR (NVG-PDR) group (21 eyes). The concentrations of interleukin (IL)-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-beta), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and monocyte chemoattractant protein-1 (MCP-1) in the aqueous humor were measured. Results: In this study, 42, 40 and 21 patients (one eye per patient) were included in the NPDR. PDR and NVG-PDR groups, respectively. The median concentrations of IL-6, IL-8, IL-10, VEGF, TGF-beta, VCAM-1, ICAM-1 and MCP-1 in the groups were measured. The levels of these 8 cytokines increased with the severity of diabetic retinopathy, especially in the NVG-PDR group. Compared with those in the NPDR group, the aqueous concentrations of these 8 cytokines were higher in the PDR group and were the highest in the NVG-PDR group. There were significant differences in all cytokines among the three groups (P < 0.05). Multivariate analysis showed that in the NPDR and PDR groups, the risk of PDR associated with elevated levels of TGF-beta (P- 0.0004, OR 1.11, 95% CI [1.05-1.181) and ICAM-1 (P- 0.0408, OR 10.75, 95% CI [1.10-104.61]). In the PDR and NVG groups, the risk of NVG associated with elevated levels of IL-10 (P = 0.0486, OR 0.7040, 95% CI [0.4966, 0.99791), VEGF (P = 0.0279, OR 0.9963, 95% CI [0.9931, 0.99961), and VCAM-1 (P = 0.0316, OR 0.9998, 95% CI [0.9996, 0.99998]). In the three groups, the risk of developing NVG associated with elevated levels of TGF-beta (P < 0.001, OR 1.04, 95% CI [1.02, 1.05]). Conclusions: The levels of these eight cytokines in the aqueous humor increased with the severity of diabetic retinopathy, especially in NVG-PDR. This study suggests that TGF-beta, ICAM-1, IL-10, VEGF, and VCAM-1 may play a role in the progression of diabetic retinopathy, especially TGF-beta, which may plays a significant role in NVGPDR. These cytokines potentially may be used as biomarkers to predict the progress of diabetic retinopathy, contribute to the choice of treatment options and/or monitor treatment responses. (C) 2020 Elsevier Inc. All rights reserved.