Search

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.

Purpose: To determine the association between diabetic retinopathy (DR) severity and quantitative retinal vascular features. Design: Retrospective image analysis study. Participants: Eyes with DR and eyes with no posterior segment disease (normal eyes) that had undergone ultra-widefield fluorescein angiography (UWFA) with associated color fundus photography. Exclusion criteria were any previous laser photocoagulation, low image quality, intravitreal or periocular pharmacotherapy within 6 months of imaging, and any other significant retinal disease including posterior uveitis, retinal vein occlusion, and choroidal neovascularization. Methods: The centered early mid-phase UWFA frame that captured the maximum vessel area was selected using automated custom software for each eye. Panretinal and zonal vascular features were extracted using a machine learning algorithm. Eyes with DR were graded for DR severity as mild nonproliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). Parameters of normal eyes were compared with age- and gender-matched patients with DR using the t test. Differences between severity groups were evaluated by the analysis of variance and Kruskal-Wallis tests, generalized linear mixed-effects models, and random forest regression models. Main Outcome Measures: Diabetic retinopathy severity and vascular features (panretinal and zonal vessel area, length and geodesic distance, panretinal area index, tortuosity measures, vascular density measures, and zero vessel density rate). Results: Ninety-seven eyes from 60 patients with DR and 12 normal eyes from 12 patients that underwent UWFA for evaluation of fellow eye pathology had images of sufficient quality to be included in this analysis. The mean age was 60 ± 10 years in DR eyes and 46 ± 17 years in normal eyes. Panretinal vessel area, mean geodesic distance, skewness, and kurtosis of local vessel density was significantly higher in normal eyes compared with the age- and gender-matched eyes with DR (P < 0.05). Zero vessel density rate, skewness of vessel density, and mean mid-peripheral geodesic distance were among the most important features for distinguishing mild NPDR from advanced forms of DR and PDR versus eyes without PDR. Conclusions: Automated analysis of retinal vasculature demonstrated associations with DR severity and visual and subvisual vascular biomarkers. Further studies are needed to evaluate the clinical significance of these parameters for DR prognosis and therapeutic response.