Non–Invasive Detection of Multinucleated Giant Cells in the Conjunctiva of Patients With Sarcoidosis by in vivo Confocal Microscopy: A Masked Study

Abstract

Abstract: : Purpose:To explore the use of in–vivo confocal microscopy (IVCM) as a potential non–invasive adjunctive tool for diagnosing sarcoidosis. Methods:Inferior conjunctival fornices were imaged using either the ASL–1000 Scanning Confocal Microscope or the Nidek Confoscan in 10 patients with sarcoidosis (age range 37 to 64 years old, 3 males and 7 females) and 27 control patients (age range 18 to 77 years old, 11 males and 16 females). One unmasked and two masked observers reviewed the in–vivo confocal images of the conjunctiva in patients with and without sarcoidosis. Sensitivity was expressed based on two denominators: either the total number of patients with sarcoidosis or the patients with detectable multinucleated giant cells (MGC) as determined by the unmasked observer since biopsy studies indicate that only a subset of patients have conjunctival MGC. The most striking and obvious feature seen on confocal microscopy was the presence of MGCs, which are not universally present in granulomatous inflammation. The other features of granulomatous inflammation were difficult to discern with IVCM. Observers therefore focused on the detection of MGCs when reviewing the conjunctival in–vivo images. Results:Unmasked observation of the scans revealed MGCs in 6 of the 10 sarcoid patients and no MGCs in the controls. One experienced masked observer found MGCs in 5 of the 10 patients with sarcoidosis and had no false–positive results (Fisher’s Exact test, p=0.001, specificity=1, sensitivity=50% for the diagnosis of sarcoidosis and 83% when compared to the unmasked observer). The second less experienced masked observer detected MGCs in 3 of the 10 patients and 3 of 27 controls (11.1% of the controls) (p=0.186, specificity=0.89, sensitivity=30% of all patients with sarcoidosis and 50% when compared to the unmasked observer). Conclusions:IVCM has specifically been designed to look primarily at the anatomy of normal and diseased cornea. The utilization of this modality to visualize the histology and pathology of the conjunctiva is innovative. Our initial results indicate that trained observers can detect MGCs in granulomatous inflammation (p=0.001). With further modification of IVCM or with the use of other in–vivo anterior segment imaging techniques, the histopathology of conjunctival sarcoidosis and other conjunctival diseases may be adequately detected and may be used as an adjunct to the conventional means of diagnosis.

Keywords: conjunctiva • imaging/image analysis: clinical • uveitis-clinical/animal model