CRISP: Corneal Confocal Microscopy Real-Time Image Stitching Pipeline

Morphology of the sub-basal nerve plexus (SNP) reflects peripheral nerve health, and corneal confocal microscopy (CCM) provides an important means for in vivo, real-time, non-invasive observation of the SNP. However, mainstream CCM devices offer a limited field of view per frame, whereas the SNP is spatially non-uniform; discrete image sampling is therefore sensitive to sampling location and frame selection, which limits the reproducibility and clinical adoption of CCM as a quantitative assessment tool. Wide-field stitching can reconstruct larger SNP mosaics by integrating sequentially acquired CCM images, but existing methods largely rely on offline post-processing, additional hardware, or specific acquisition protocols, and lack open-source real-time solutions for conventional CCM video streams. This paper presents CRISP (Corneal confocal microscopy Real-time Image Stitching Pipeline), an open-source real-time SNP wide-field stitching framework for conventional CCM examination video streams. CRISP excludes defocused and discontinuous segments via focus-aware gating, propagates poses through local pairwise registration, and maintains non-redundant spatial coverage with a sparse anchor map; when local temporal continuity is interrupted, the system completes relocalization and subgraph merging through global appearance retrieval followed by geometric verification. The framework prioritizes low-latency coverage feedback during examination while outputting accepted frames, poses, and anchor information to initialize offline fine stitching. To our knowledge, CRISP is the first open-source real-time SNP wide-field stitching framework released for conventional CCM video streams. By lowering the barrier to adoption and reproduction of wide-field stitching, CRISP may help move SNP wide-field imaging from a research tool into routine clinical examination workflows.