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In vivo confocal microscopy of trachoma in relation to normal tarsal conjunctiva.

ABSTRACT: To describe the in vivo confocal microscopy (IVCM) appearances of the tarsal conjunctiva in trachoma compared with the appearance of healthy conjunctiva and to develop grading systems for IVCM examination of the tarsal conjunctiva for use in future studies on trachoma and other conjunctival diseases.Prospective observational study.In vivo confocal microscopy examination was performed on 302 clinically normal adults, 16 clinically normal children, 750 adults with trachomatous conjunctival scarring, and 25 children with active trachoma.Clinical evaluation was performed with ×2.5 loupes, and 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).In vivo confocal microscopy images were analyzed for cellular and tissue changes associated with trachomatous inflammation and scarring compared with healthy subjects.Trachomatous subjects with follicular and papillary inflammation had an increased inflammatory cellular infiltrate, including dendritiform cells, discrete follicular and papillary structures, and cystic lacunae suggestive of tissue edema. Trachomatous conjunctival scarring was seen with IVCM as organization of the subepithelial connective tissue into bands/sheets. Grading systems for inflammatory changes and scarring were developed, with the system for scarring showing good interobserver agreement with an intraclass coefficient of 0.88.In vivo confocal microscopy provides a powerful tool for examining the ocular surface. Numerous cellular and tissue changes were observed in subjects with trachoma, the first time IVCM has been applied to this disease. These changes both complement and add to previous histologic analyses. In vivo confocal microscopy promises to provide new insights into the pathogenesis of trachoma and other conjunctival diseases.

SUBMITTER: Hu VH

PROVIDER: S-EPMC3267042 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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In vivo confocal microscopy of trachoma in relation to normal tarsal conjunctiva.

Hu Victor H VH Massae Patrick P Weiss Helen A HA Cree Ian A IA Courtright Paul P Mabey David C W DC Bailey Robin L RL Burton Matthew J MJ

Ophthalmology 20101105 4

<h4>Objective</h4>To describe the in vivo confocal microscopy (IVCM) appearances of the tarsal conjunctiva in trachoma compared with the appearance of healthy conjunctiva and to develop grading systems for IVCM examination of the tarsal conjunctiva for use in future studies on trachoma and other conjunctival diseases.<h4>Design</h4>Prospective observational study.<h4>Participants</h4>In vivo confocal microscopy examination was performed on 302 clinically normal adults, 16 clinically normal child ...[more]

PMID: 21055819

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Project description:ObjectiveTo characterize the tissue and cellular changes found in trachomatous scarring (TS) and inflammation using in vivo confocal microscopy (IVCM).DesignTwo complimentary case-control studies.ParticipantsThe 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.MethodsAll 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 measuresThe 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.ResultsSubjects 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 ?m from the surface. The presence of tissue edema was strongly associated with the level of clinical inflammation.ConclusionsIn 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.

Project description:PurposeToxic keratopathy (TK) involves complex clinical manifestations and is difficult to differentiate from other ocular surface diseases by conventional slit-lamp examination. The challenge faced by clinicians in confidently diagnosing TK cannot be underestimated. This study aimed to explore the microstructural characteristics and diagnostic parameters by in vivo confocal microscopy (IVCM) in TK.MethodsIn this prospective, cross-sectional, comparative study, slit-lamp and IVCM examinations were performed on 20 normal eyes and 54 eyes with TK. Based on slit-lamp imaging, TK subjects were divided into four groups: superficial punctate keratitis (n = 10 eyes), pseudodendritic keratitis (n = 14 eyes), ulcerative keratitis (UK; n = 16 eyes), and ring keratitis (RK; n = 14 eyes). The microstructural characteristics of TK were described according to the following IVCM parameters: basal cell (BC) density, dendritiform cell (DC) density, DC size, corneal nerve fiber (CNF) length, nerve tortuosity, and keratocyte reflectivity. A receiver operating characteristic (ROC) curve model was also formulated to compare the predictive power of BC density, DC density, and CNF length.ResultsTK eyes showed significantly higher values for DC density (45.8 cells/mm2; range, 25.0-100.0) compared with normal eyes (24.0 cells/mm2; range, 20.8-32.3; P = 0.013; DC size (111.0 µm2; range, 92.0-137.8) compared with normal eyes (63.7 µm2; range, 47.7-70.3; P < 0.001); nerve tortuosity (0.08; range, 0.05-0.09) compared with normal eyes (0.04; range, 0.02-0.04; P < 0.001); and keratocyte reflectivity. BC density and CNF length values were found to be significantly less than those for normal controls (both P < 0.001). In all subgroups, CNF length appeared to be significantly lower than that of controls (all P < 0.001), and DC density was only statistically significantly higher in the UK (P = 0.003) and RK (P < 0.001) groups. Corneal fluorescein staining had no correlation with the analyzed IVCM parameters (all P ˃ 0.05). However, the increase in DC density and DC size showed negative correlations to CNF length (density: r = -0.325, P < 0.005; size: r = -0.493, P < 0.005), as well as positive correlations to duration and frequency of topical eye drops and DC size (density: r = 0.361, P < 0.05; size: r = 0.581, P < 0.05). A ROC curve showed that CNF length had the strongest predictive power, with the estimated area under the curve being 0.992 ± 0.008.ConclusionsLower BC density and CNF length, greater DC density and DC size, and greater keratocyte reflectivity were the microstructural characteristics of TK. The role of subbasal nerve, inflammatory response, and limbal stem cells in the progression of TK and the appropriate treatment of different TK stages are future research directions.Translational relevanceThe evaluation of basal cells, subbasal nerve, and dendritiform cells is helpful to our understanding of the pathological process of TK.

Dataset Information

In vivo confocal microscopy of trachoma in relation to normal tarsal conjunctiva.

Publications

In vivo confocal microscopy of trachoma in relation to normal tarsal conjunctiva.

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