PurposeTo compare which imaging and biochemical biomarkers are associated with different stages of diabetic retinopathy (DR) in type 2 diabetes mellitus patients with diabetic macular edema (DME).Patients and MethodsIt was a cross-sectional, observational study that included 100 patients of DME with different stages of DR. Patients were divided into two groups: Group A – DME with non-proliferative diabetic retinopathy (NPDR) and Group B - DME with proliferative diabetic retinopathy (PDR). Group A was further subdivided into three subgroups: A (1) – DME with mild NPDR, A (2) – DME with moderate NPDR, and A (3) – DME with severe NPDR. The primary outcome measure was the association of imaging and biochemical biomarkers with different stages of DR in patients with DME.ResultsOut of 100 patients, Group A (1) had 1, Group A (2) 44, Group A (3) 29, and group: B had 29 patients. As Group A (1) had only one patient, we did not include it in the calculation. The overall mean age of the study population was 54.84+9.87 years, with a male preponderance (76%). The HbA1c levels, serum triglyceride level, serum cholesterol level, and microalbuminuria level showed no significant association with different stages of DR (P>0.05). Still, we found high serum urea levels (p=0.027) in Group B patients. The optical coherence tomography (OCT)-based imaging biomarkers – central subfield thickness (CST), cystoid macular edema (CME), subretinal fluid (SRF), and hyperreflective foci (HRF) – showed no significant association with various stages of DR. The presence of diffuse retinal thickness (DRT) (p=0.04) and the epiretinal membrane (ERM) (p=0.04) showed significant association with Group B patients.ConclusionThe essential biochemical biomarkers such as serum urea levels and DRT and ERM may be considered an important imaging biomarker for the advanced stage of DR.