Computational Imaging Biomarker Correlation with Intraocular Cytokine Expression in Diabetic Macular Edema: Radiomics Insights from the IMAGINE Study

PURPOSE: Various pathways and cytokines are implicated in pathogenesis of diabetic macular edema (DME). Computational imaging biomarkers (CIBs) of vessel tortuosity from ultra-widefield fluorescein angiography (UWFA) and texture patterns from OCT images have been associated with anti–vascular endothelial growth factor (VEGF) therapy treatment response in DME. This analysis was a radiogenomic assessment of the association between underlying cytokines, UWFA, and OCT-based DME CIBs. DESIGN: Biclustering analysis based on UWFA and OCT CIBs to identify a common imaging phenotype across patients with subsequent assessment of underlying cytokine signatures and treatment response attributes. PARTICIPANTS: The IMAGINE DME study was a post hoc study of cytokine expressions that included 24 eyes with sufficient baseline aqueous humor samples and an in-depth assessment of the imaging studies obtained during the phase I/II DmeAntiVEgf study (DAVE) that measured different cytokine expressions. METHODS: A total of 151 graph or morphologic features quantifying leakage shape, size, density, interobject distance, and architecture of leakage spots and 5 vessel tortuosity features were extracted from the baseline UWFA scans, and 494 texture-based radiomics features were extracted from each of the fluid and retinal tissue compartments of OCT images. Biclustering enables simultaneous clustering of patients and features and was used to aggregate patients in terms of their commonality of phenotypes (based on similar imaging attributes) and to identify commonality in terms of cytokine expression and treatment response to anti-VEGF therapy. MAIN OUTCOME MEASURES: Identification of eyes with similar imaging phenotypes to evaluate commonalities of patterns and underlying cytokine expression. RESULTS: Strong correlations between VEGF and 7 UWFA leakage morphologic features (Pearson correlation coefficient [PCC], 0.45–0.51; P < 0.05), 1 vascular tortuosity-based UWFA feature (PCC, 0.45; P = 0.00016), and 2 OCT-derived intraretinal fluid texture features (PCC, 0.58–0.63; P < 0.05) were identified. Strong correlation between intraretinal fluid features and other cytokines (PCC, 0.41–0.59; P < 0.05) were also observed. CONCLUSIONS: This study identified groups of eyes with similar imaging phenotypes as defined by UWFA and OCT CIBs that demonstrated similar treatment response patterns and cytokine expression, including a strong association between VEGF with UWFA-derived leakage morphologic and vessel tortuosity features.