Evaluation of ocular and systemic inflammatory biomarkers in diabetic macular edema

Purpose: To determine the serum levels of systemic inflammatory biomarkers in patients with and without diabetic retinopathy (DR) and diabetic macular edema (DME) and to evaluate their correlation with morphological findings on optical coherence tomography (OCT). Material and Methods: The cross-sectional study included 120 eyes of 120 type 2 diabetes mellitus (DM) patients. Patients were divided into 3 groups according to the presence of DR and DME. Group 1 included patients without DR, group 2 included patients with DR without DME and group 3 included patients with DR with DME. Age, gender, duration and treatment of DM, hemoglobin A1c (HbA1c) level, fasting blood glucose (FBG), body mass index (BMI) and DR stage were recorded. All patients underwent a detailed ophthalmological examination and OCT was performed. Central macular thickness and volume (CMT, CMV), edema morphology, presence of intraretinal cysts and the length of the largest intraretinal cyst, disorganisation of inner retinal layers (DRIL), hyperreflective spot (HRN), subretinal fluid (SRF), epiretinal membrane (ERM) and presence and length of defects in outer retinal layers were recorded. Interleukin-6 (IL-6), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) levels in serum samples were measured manually with human micro ELISA kits. Results: There was a statistically significant difference in serum IL-6, IL-1β, TNF- α, ICAM-1 levels between the three groups (p<0.001). Serum VCAM-1 levels were similar in the three groups (p=0,268). In groups 2 and 3, IL-6, IL-1β, TNF- α, ICAM-1 levels were significantly higher in the proliferative diabetic retinopathy (PDR) group than in the nonproliferative diabetic retinopathy (NPDR) group (p<0.001). IL-1β, TNF- α and ICAM-1 were positively correlated with SMC and SMV (p< 0.001, r=0.792, r=0.623, r=0.586, r=0.531, respectively). Serum ICAM-1 levels were significantly higher in cystoid macular edema (CME) compared to other edema types (p= 0.035). There was a positive correlation between the largest intraretinal cyst size and serum IL-6 and TNF- α levels (p< 0.010, p=0.006, r=0.557, r=0.366, respectively). There was a statistically significant correlation between the presence of subretinal fluid and IL-6 levels (p=0.026). There was a statistically significant correlation between the defect length in the outer retinal layers and serum ICAM-1 levels. There was a negative correlation (p=0,049, r= -0,555). Conclusion: A significant correlation was found between serum IL-6, IL-1β, TNF- α, ICAM-1 levels and the presence and severity of DR and DME. Serum levels of cytokines and adhesion molecules may be useful for clinicians in both predictive and prognostic processes and may help in the selection of the appropriate therapeutic agent for the patient. Prospective studies with a larger number of patients are needed for patient-specific, cytokine-targeted single or combined treatment options. Keywords: Adhesion molecule, cytokine, diabetic macular edema, inflammation, optical coherence tomography