Probe-based confocal laser endomicroscopy: progress, challenges, and emerging applications

Abstract

Background & Aims: Probe-based confocal laser endomicroscopy (pCLE) provides real-time, cellular-level “optical biopsy” during endoscopy. This review synthesizes the technology, diagnostic performance, clinical use, safety, costs, and future directions of pCLE across gastrointestinal indications. Methods: Targeted narrative review of randomized trials, meta-analyses, and observational studies on pCLE in Barrett’s esophagus, gastric intestinal metaplasia (GIM), colorectal neoplasia, inflammatory bowel disease (IBD), and indeterminate biliary strictures. Outcomes included sensitivity/specificity, impact on biopsy yield and management, adverse events, and cost effectiveness. Results: pCLE combines a fiber-optic probe and IV fluorescein with 488-nm excitation to generate optical sections (~ 1 µm lateral resolution; depth ~ 55–70 µm). In Barrett’s esophagus, adding pCLE to high-definition endoscopy nearly doubled neoplasia detection sensitivity versus standard protocols. For GIM, pooled sensitivity and specificity reached 97% and 94%. For colorectal lesions, sensitivity 81–91% and specificity 75–91% allowed in vivo characterization and fewer unnecessary resections. In IBD surveillance, pCLE identified more neoplasia with fewer biopsies (up to ~ 4.7-fold increase) and pooled sensitivity/specificity of 87–100%/90–94%. In indeterminate biliary strictures, pCLE integrated with ERCP/EUS improved accuracy and achieved negative predictive values up to 100%. Safety is favorable; risks relate mainly to fluorescein. Limitations include superficial penetration, narrow field of view, operator dependence, image-interpretation variability, procedure time, and high capital and per-case costs. Current guidelines view pCLE as an adjunct rather than routine standard. Emerging AI-assisted interpretation and molecular/ multispectral probes may standardize reads, expand indications, and improve yield. Conclusions: pCLE strengthens endoscopic decision-making by enabling immediate, near-histologic assessment, targeted sampling, and earlier therapy. Broader adoption hinges on standardized training, validated image criteria, multicenter randomized trials with health-economic endpoints, and integration of AI and molecular imaging to reduce variability and cost.