In Vivo Confocal Microscopy in Scarring Trachoma

OBJECTIVE: To characterize the tissue and cellular changes found in trachomatous scarring (TS) and inflammation using in vivo confocal microscopy (IVCM). DESIGN: Two complimentary case-control studies. PARTICIPANTS: The first study included 363 cases with TS (without trichiasis), of whom 328 had IVCM assessment, and 363 control subjects, of whom 319 had IVCM assessment. The second study included 34 cases with trachomatous trichiasis (TT), of whom 28 had IVCM assessment, and 33 control subjects, of whom 26 had IVCM assessment. METHODS: All participants were examined with ×2.5 loupes. The IVCM examination of the upper tarsal conjunctiva was carried out with a Heidelberg Retina Tomograph 3 with the Rostock Cornea Module (Heidelberg Engineering GmbH, Dossenheim, Germany). MAIN OUTCOME MEASURES: The IVCM images were graded in a masked manner using a previously published grading system evaluating the inflammatory infiltrate density; the presence or absence of dendritiform cells (DCs), tissue edema, and papillae; and the level of subepithelial connective tissue organization. RESULTS: Subjects with clinical scarring had a characteristic appearance on IVCM of well-defined bands and sheets of scar tissue visible. Similar changes were also seen in some clinically normal subjects consistent with subclinical scarring. Scarred subjects had more DCs and an elevated inflammatory infiltrate, even after adjusting for other factors, including the level of clinical inflammation. Cellular activity was usually seen only in or just below the epithelium, rarely being seen deeper than 30 μm from the surface. The presence of tissue edema was strongly associated with the level of clinical inflammation. CONCLUSIONS: In vivo confocal microscopy can be quantitatively used to study inflammatory and scarring changes in the conjunctiva. Dendritic cells seem to be closely associated with the scarring process in trachoma and are likely to be an important target in antifibrotic therapies or the development of a chlamydial vaccine. The increased number of inflammatory cells seen in scarred subjects is consistent with the immunopathologic nature of the disease. The localization of cellular activity close to the conjunctival surface supports the view that the epithelium plays a central role in the pathogenesis of trachoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.