<i>In Vivo</i> Confocal Microscopy Analysis of the Corneal Layers in Adenoviral Epidemic Keratoconjunctivitis

Abstract

Objectives:To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy (IVCM) in patients with adenoviral epidemic keratoconjunctivitis (EKC).Materials and Methods:The study included 20 eyes of 12 patients who presented to the Kocaeli University Medical Faculty, Department of Ophthalmology with complaints of watering, crusting, and stinging, were clinically diagnosed EKC, and were examined by slit-lamp biomicroscopy and IVCM during the prodromal phase and the punctate keratitis, deep epithelial keratitis, and subepithelial infiltration stages of EKC.Results:While biomicroscopic examination findings were normal during the prodromal period of EKC, IVCM showed an increase in Langerhans cell numbers in the subbasal plexus. After onset of clinical EKC, the punctate epithelial keratitis stage was characterized by findings of hyperreflective cell clusters in the basal epithelium layer, increased accumulation of Langerhans cells in Bowman’s layer, and hyperreflectivity in the anterior stromal layers. In the deep epithelial keratitis stage, the basal epithelial cells displayed peripheral hyperreflectivity and the hyperreflectivity of the anterior stromal surface increased and became more rounded. In the subepithelial keratitis stage, these findings persisted in addition to increased anterior stromal surface hyperreflectivity and focal round plaques.Conclusion:This study shows that the inflammatory process in the cornea starts in the prodromal period of EKC. Massive inflammation of the epithelium and stroma was observed in the active phase and focal changes were observed on the anterior stromal surface starting in the subepithelial infiltration period.

Sialic Acid-Containing Glycans as Cellular Receptors for Ocular Human Adenoviruses: Implications for Tropism and Treatment

“…Corneal cells infected by EKC-causing HAdVs secrete chemokines such as IL8 and MCP1, which induce the infiltration of various immune cells (subepithelial infiltrates) into the corneal stroma [3,4,16] and the presence of these subepithelial infiltrates in the stroma is a hallmark of EKC. These infiltrates can persist in the stroma from months to years and can lead to visual impairment [3,17]. EKC usually begins as a unilateral condition (infection of one eye), but in most cases, it becomes bilateral as a result of eye-to-hand-to-eye transmission [3].…”

<p>Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions</p>

“…Studies have indicated that the inflammatory process affecting the cornea begins in the prodromal period of adenoviral infections, thus questioning the theory of self-limitation and adding a potential factor immediate therapeutic management. 98 Dissemination of HAdV is also a significant health burden particularly in individuals with factors that put them at great risk of morbidity and mortality from adenoviral infection. These individuals include children, elderly, immunocompromised individual, patients with acute Graft versus Host disease, those on immunosuppressants, and so on.…”

Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface

“…Animal and human clinical studies have shown that SEIs form in the superficial stroma just below Bowman’s layer and including the corneal epithelial basement membrane (Figure 1), areas which are comprised of a variety of immune cells. Acutely, SEI are comprised of polymorphonuclear leukocytes, but T lymphocytes and dendritic cells have been identified at later time points [24,25,29,30,32,184,185]. Neutrophils are the first and by far the most abundant cell type recruited to the cornea, typically within the first 24 hours post-infection in the mouse model, and are a critical pathogenic event in this infection [31,32,172,181].…”

“…SEIs, the hallmark feature of EKC, occur in approximately one-third of all EKC cases and may persist or recur for months to years following infection [23,24,25,26]. SEIs impair vision by physically blocking the passage of light and by disrupting the arrangement of collagen fibrils and other extracellular matrix components of the meticulously organized and normally transparent corneal stroma [27,28,29,30,31,32].…”