Deep Learning of Fluorescence Lifetime Imaging Ophthalmoscopy for Type 2 Diabetes Classification

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Abstract

PurposeTo evaluate whether fluorescence lifetime imaging ophthalmoscopy (FLIO) combined with deep learning can detect metabolic signatures for classification of type 2 diabetes mellitus (T2DM). DesignCross-sectional analysis of participants included in the AI-READI dataset (version 3) with FLIO imaging and hemoglobin A1c (HbA1c) measurement. Subjects1,783 participants from the AI-READI dataset (version 3) with HbA1c measurements and FLIO imaging scans (6,912 total): 671 normoglycemic, 726 prediabetic, and 386 diabetic. MethodsMean fluorescence lifetime maps were generated using a center-of-mass approach and used as inputs to AI models. We trained convolutional neural networks (CNNs), ResNet-18, and XGBoost under three-class (normal, prediabetic, diabetic) and two binary (normal vs. impaired; normal vs. diabetic) classification schemes, using nested 5-fold cross-validation with participant-level grouping. Main Outcome MeasuresMacro-averaged area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy, F1 score, and positive predictive value (PPV). ResultsGroup-averaged lifetime maps showed longer lifetimes in prediabetic and diabetic participants than in normoglycemic participants in the SSC (p = 0.001), with no significant difference across groups in the LSC (p = 0.056). The CNN achieved the best overall performance in the 3-class classification (accuracy 0.41 {+/-} 0.03, F1 score 0.39 {+/-} 0.02, AUROC 0.58 {+/-} 0.02), compared to the random classifier for 3-class classification (AUROC = 0.50; accuracy = F1 = 0.33). ResNet-18 and XGBoost showed similar performance (AUROC 0.53-0.58). Confusion matrices revealed substantial overlap between classes, with frequent misclassification toward the prediabetes group. Binary reformulation (normal vs. diabetic) improved performance substantially, with the CNN resulting in AUROC 0.63 {+/-} 0.02 and XGBoost 0.67 {+/-} 0.07. ConclusionsFLIO-derived lifetime maps capture metabolic signals associated with glycemic status but yield modest classification performance with current AI models. These findings highlight both the potential and the challenges of using FLIO for early metabolic screening and monitoring, informing future development of clinically applicable imaging biomarkers.

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