AUTHOR=Tang Ningning , Chen Qi , Meng Yunyu , Lei Daizai , Jiang Li , Qin Yikun , Huang Xiaojia , Tang Fen , Huang Shanshan , Lan Qianqian , Chen Qi , Huang Lijie , Lan Rushi , Pan Xipeng , Wang Huadeng , Xu Fan , He Wenjing 

TITLE=An explainable unsupervised learning approach for anomaly detection on corneal in vivo confocal microscopy images

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2025.1576513

DOI=10.3389/fbioe.2025.1576513

ISSN=2296-4185

ABSTRACT=BackgroundIn vivo confocal microscopy (IVCM) is a crucial imaging modality for assessing corneal diseases, yet distinguishing pathological features from normal variations remains challenging due to the complex multi-layered corneal structure. Existing anomaly detection methods often struggle to generalize across diverse disease manifestations. To address these limitations, we propose a Transformer-based unsupervised anomaly detection method for IVCM images, capable of identifying corneal abnormalities without prior knowledge of specific disease features.MethodsOur method consists of three submodules: an EfficientNet network, a Multi-Scale Feature Fusion Network, and a Transformer Network. A total of 7,063 IVCM images (95 eyes) were included for analysis. The model was trained exclusively on normal IVCM images to capture and differentiate structural variations across four distinct corneal layers: epithelium, sub-basal nerve plexus, stroma, and endothelium. During inference, anomaly scores were computed to distinguish pathological from normal images. The model’s performance was evaluated on both internal and external datasets, and comparative analyses were conducted against existing anomaly detection methods, including generative adversarial networks (AnoGAN), generate to detect anomaly model (G2D), and discriminatively trained reconstruction anomaly embedding model (DRAEM). Additionally, explainable anomaly maps were generated to enhance the interpretability of model decisions.ResultsThe proposed method achieved an the areas under the receiver operating characteristic curve of 0.933 on internal validation and 0.917 on an external test dataset, outperforming AnoGAN, G2D, and DRAEM in both accuracy and generalizability. The model effectively distinguished normal and pathological images, demonstrating statistically significant differences in anomaly scores (p < 0.001). Furthermore, visualization results indicated that the detected anomalous regions corresponded to morphological deviations, highlighting potential imaging biomarkers for corneal diseases.ConclusionThis study presents an efficient and interpretable unsupervised anomaly detection model for IVCM images, effectively identifying corneal abnormalities without requiring labeled pathological samples. The proposed method enhances screening efficiency, reduces annotation costs, and holds great potential for scalable intelligent diagnosis of corneal diseases.