Eosinophilic esophagitis (EoE) is a prevalent allergic response to food that causes eosinophilic infiltration in the esophagus. EoE can lead to esophageal remodeling, scarring, muscle hypertrophy, and stricture, decreasing quality of life and increasing risk of food impaction. Diagnosis of EoE is made by finding epithelial esophageal eosinophilia in biopsies acquired during upper endoscopy. Patients are treated with topical corticosteroids or dietary exclusion, both of which are chronic therapies that require repeated endoscopic follow up. Reliance on serial endoscopic biopsy for evaluating EoE patients has significantly hindered progress in this field. It is estimated that EoE costs over 1 billion dollars in the US, much of which is due to sedation/anesthesia requirements of endoscopy. Endoscopic exams are quite burdensome for patients, many of whom are children. Also, because biopsies only sample the epithelium, remodeling of deeper tissue cannot be evaluated, leaving gaps in knowledge, diagnosis, and treatment endpoints. For these reasons, there is a major push to find a less invasive diagnostic tool that comprehensively evaluates both esophageal eosinophils and subepithelial remodeling in EoE patients. Our lab has developed a technique called tethered capsule endomicroscopy (TCE) that involves swallowing a tethered pill that conducts 10-µm-resolution optical coherence tomography (OCT) microscopy as it traverses the GI tract. The procedure can be done in unsedated patients, is rapid, and is overwhelmingly preferred over endoscopy. In this grant, we will advance TCE so that it is capable of assessing both inflammation and remodeling in EoE patients. Distinguishing features will include a significant increase in resolution to 1- µm (µOCT) so that individual eosinophils can be identified and counted. Another advance will be implementation of polarization sensitivity (PS) that will provide quantitative data on collagen and muscle content deep within the esophagus. PS-µOCT will then be used in a clinical study that will improve our understanding of esophageal inflammation and remodeling at baseline and after steroid treatment (Aim 2). We will also conduct a clinical study to optimize food re-introduction intervals during dietary exclusion protocols (Aim 3).