Probe-Based Confocal Laser Endomicroscopy for the Evaluation of Non-Erosive Reflux Disease: A Pilot Study

Abstract

Introduction: Non-erosive reflux disease (NERD) is difficult to diagnose because of the absence of endoscopic findings. Investigators have described esophageal micro-alterations in NERD patients using endoscope-based confocal endomicroscopy (eCLE), but this device is no longer commercially available. Our aim was to assess whether these micro-alterations were visible with a commercially available probe based confocal laser endomicroscopy (pCLE) system. Methods: Patients with refractory gastroesophageal reflux scheduled for upper endoscopy (EGD) with pH testing were prospectively enrolled. Patients with visible erosions or Barrett's esophagus were excluded. Following visual examination, a 3-minute pCLE recording was obtained at 5 cm proximal to the gastro-esophageal junction, and a 48-hour Bravo pH probe was placed. Patients with a DeMeester score ≥14.72 were classified as NERD, and those with DeMeester score<14.72 served as controls. pCLE sequences were reviewed in a blinded fashion using Cellvizio Viewer 1.6.2 (Image 1). The following variables were assessed: papilla diameter, intra-papillary capillary loop (IPCL) diameter, size of intercellular spaces, and time from appearance of IPCLs to visualization of squamous mucosa using 10% intravenous fluorescein as the contrast agent (hypothesized to represent a surrogate measure for epithelial permeability, i.e. barrier function). Receiver operating characteristic (ROC) curves were individually used to assess the accuracy of each of the devised pCLE metrics at predicting NERD, as defined by the DeMeester score. Results: Ten patients were enrolled of whom 6 had NERD. None of the measured variables differed significantly between NERD patients and controls (Table 1). Using the DeMeester score as a reference standard, time from appearance of IPCLs to visualization of squamous mucosa predicted NERD with “fair” accuracy (AUC 0.71), while the other devised metrics either predicted NERD “poorly” or “failed” to predict NERD (Table 2).Table: Table. Demographics, pH testing results and pCLE parametersTable: Table. Observed Areas under Curve (AUCs) for the five devised pCLE metricsConclusion: Micro-alterations described on eCLE in NERD patients were not reproduced using pCLE. A surrogate pCLE measure of epithelial permeability provides “fair” correlation with the DeMeester score. Studies comparing pCLE to validated in vitro measures of permeability in symptomatic and asymptomatic patients may help clarify the utility of pCLE at assessing esophageal barrier function.Figure: A representative pCLE image demonstrating the papilla diameter as measured by the blue double arrow and the intrapapillary capillary loop diameter as measured by the red double arrow.