Citation: Kheirkhah A, Rahimi Darabad R, Cruzat A, et al. Corneal epithelial immune dendritic cell alterations in subtypes of dry eye disease: a pilot in vivo confocal microscopic study. Invest Ophthalmol Vis Sci. 2015;56:7179-7185. DOI:10.1167/ iovs.15-17433 PURPOSE. To evaluate density and morphology of corneal epithelial immune dendritic cells (DCs) in different subtypes of dry eye disease (DED) using in vivo confocal microscopy (IVCM). METHODS. This retrospective study included 59 eyes of 37 patients with DED and 40 eyes of 20 age-matched healthy controls. Based on clinical tests, eyes with DED were categorized into two subtypes: aqueous-deficient (n ¼ 35) and evaporative (n ¼ 24). For all subjects, images of laser scanning in vivo confocal microscopy (IVCM) of the central cornea were analyzed for DC density and DC morphology (DC size, number of dendrites, and DC field). These DC parameters were compared among all dry eye and control groups. RESULTS. Compared with the controls, patients with DED had significantly higher DC density, larger DC size, higher number of dendrites, and larger DC field (all P < 0.001). Comparison between aqueous-deficient and evaporative subtypes demonstrated that DC density was significantly higher in aqueous-deficient subtype (189.8 6 36.9 vs. 58.9 6 9.4 cells/mm 2 , P ¼ 0.001). However, there were no significant differences in morphologic parameters between DED subtypes. When aqueous-deficient DED with underlying systemic immune disease (Sjögren's syndrome and graft versus host disease) were compared with nonimmune conditions, the immunologic subgroup showed significantly higher DC density, DC size, and number of dendrites (all P < 0.05). CONCLUSIONS. Corneal IVCM demonstrated differential changes in DC density and morphologic DC parameters between subtypes of DED. These changes, which reflect the degree of immune activation and inflammation in DED, can be used for clinical practice and endpoints in clinical trials. Keywords: dry eye disease, in vivo confocal microscopy, inflammation, dendritic cells D ry eye disease (DED) is one of the most commonly encountered ophthalmic disorders. It is a multifactorial disease of the ocular surface and tear film, characterized by symptoms of eye irritation, tear instability, and vision impairment. 1 In addition to evaluating symptoms, a variety of clinical tests are currently being used to diagnose DED, including the Schirmer's wetting test, tear break-up time (TBUT), tear osmolarity, and vital dye staining of the ocular surface by fluorescein, Rose Bengal and Lissamine Green. However, complex clinical features of the disease make the diagnosis a challenge in many cases. 2,3 Therefore, there remains a significant need for objective tests, which can be used to accurately diagnose DED and/or monitor therapeutic response in DED and its underlying changes. Recent studies have shown that the immune changes play an important role in the pathogenesis of DED. To evaluate changes in DCs in patients with DED, corneal in vivo confocal microscopy (IVCM) has lately been used. In vivo confocal microscopy is a noninvasive imaging modality that enables studying the cornea at a cellular level
