Optical Coherence Tomography-Based Grading of Diabetic Macular Edema Is Associated with Systemic Inflammatory Indices and Imaging Biomarkers

<b><i>Introduction:</i></b> Objectives of the study were to investigate the correlation between optical coherence tomography (OCT)-based grading of diabetic macular edema (DME) and systemic inflammatory indices, imaging biomarkers, and early anti-vascular endothelial growth factor (VEGF) treatment response. <b><i>Methods:</i></b> A total of 111 eyes from 111 patients with DME treated with intravitreous anti-VEGF therapy for 3 consecutive months every month were enrolled in this retrospective study. According to a protocol termed “TCED,” DME was divided into early, advanced, severe, and atrophic stages. The best-corrected visual acuity (BCVA), subretinal fluid (SRF), and the number of hyperreflective foci (HRF) in the whole retinal layers were analyzed at baseline and 3 months after the first injection. Peripheral blood inflammatory indices were calculated, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet (PLT)-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and C-reactive protein (CRP). Statistical analysis was performed to compare the visual and anatomical results and evaluate HRF and SRF in different stages of DME before and after treatment. <b><i>Results:</i></b> There were significant differences in systemic inflammatory indices among the four groups, including NLR, PLR, MLR, SII, and CRP (all <i>p</i> &lt; 0.05). The CRP, NLR, PLR, MLR, and SII were significantly higher in the atrophic stage compared to the advanced stage (all <i>p</i> &lt; 0.05). Conversely, the CRP, NLR, PLR, MLR, and SII were significantly lower in the advanced stage compared to the early stage (all <i>p</i> &lt; 0.05). Except for the atrophic stage, BCVA and central retinal thickness (CRT) were significantly improved after treatment in early, advanced and severe stages (all <i>p</i> &lt; 0.05), especially in the severe stage. The decline in the proportion of SRF and HRF ≥20 was the most significant in the advanced stage after anti-VEGF treatment (<i>p</i> &lt; 0.001, <i>p</i> = 0.016), but not in the early and severe stages (all <i>p</i> &gt; 0.05). <b><i>Conclusion:</i></b> Systemic inflammatory indices and the decline in the proportion of SRF and HRF ≥20 were closely associated with different stages of DME based on “TCED.” Meanwhile, the “TCED” grading system can predict visual and anatomical prognosis of DME after anti-VEGF treatment, which may be a biomarker for identifying risk stratification and management of DME.