Abstract
Background: This study aimed to change the current concept of diabetic macular edema (DME) management through (1) early categorization of our DME patients into either responders or non-responders after the first intravitreal Ranibizumab (IVR) injection, and (2) finding a suitable clinical-biochemical diagnostic panel to identify the possible cause(s) of non-response in each non-responder and changing the treatment plan in each particular patient accordingly. Patients and methods: Our study included 64 eyes of 40 patients with DME (Group A, DME patients) and 40 eyes of 40 healthy individuals matched for age and sex (Group B, controls). Blood and aqueous samples were collected from the study participants before and one month after IVR injection. The DME patients were further subdivided into responders and non-responders according to their response to the first IVR injection. Lymphocyte activation markers, NETosis markers, angiogenic factors, astrocytes, innate immunity, and inflammasome markers were assessed in both groups. Results: Multivariate regression analysis revealed that macular ischemia, aqueous levels of hexokinase 1, SELL CD62L, ELANE, MPO, VEGFA, and SEMA4D were the most significant factors affecting the response to IVR (p < 0.05). Conclusions: defining our DME patients as responders and non-responders after the first IVR injection, combined with potential utilization of a clinical-biochemical panel (macular ischemia- PCR array of combined Hexokinase 1, MPO, and SEMA4D) in each non-responder, may represent a good starting point for changing the current DME management strategy.