Contralateral Clinically Unaffected Eyes of Patients With Unilateral Infectious Keratitis Demonstrate a Sympathetic Immune Response.

The in vivo study and assessment of corneal inflammation and innervation is important due to its clinical applicability in the management and treatment of ocular surface diseases.1 Dendritic cells are the most potent antigen-presenting cells (APCs) of the body and mediators of both innate and adaptive immune responses. Given their strategic location in the epithelium and anterior stroma, they are ready to respond to invading pathogens in the cornea and ocular surface.2,3 Corneal inflammation results in increased dendritic cell density, and their upregulation of major histocompatibility complex class (MHC)-II expression, as dendritic cells mature and become activated to generate immune responses.3,4 Until recently, the assessment of corneal inflammation has been possible only through slit-lamp biomicroscopic examination. However, the current availability of clinical in vivo confocal microscopy (IVCM) provides an opportunity to study corneal changes after microbial keratitis (MK) at a cellular level.5–7 The use of this noninvasive imaging technique provides a resolution of images comparable to that with histochemical methods. In vivo confocal microscopy allows systematic studies of corneal epithelial, stromal, and endothelial cells and nerve morphology and density, as well as the study of immune cells such as corneal epithelial dendritiform cells in patients.8–11 Increased corneal dendritiform cell density has been observed by IVCM in patients with dry eye,9 with infectious keratitis,5 in immune-mediated inflammatory diseases,10 and in patients with pterygia.11 The role of corneal innervation is of great interest to clinicians and scientists due to its protective function on the ocular surface through regulation of corneal sensation and the blinking reflex, epithelial integrity, proliferation, and wound healing with the precise release of trophic factors.12 Several recent studies on humans and animals have shown an association between corneal innervation and both apoptosis and corneal stem cell homeostasis.13 Specific changes in corneal nerve function and morphology after infection, corneal surgery, and other ocular or systemic pathologies (e.g., diabetes, dry eye disease, contact lens [CL] use, keratoconus, corneal dystrophies) have received increased attention in recent times.1 Indeed, recently our group has shown that patients with unilateral herpes simplex keratitis (HSK)6 and herpes zoster ophthalmicus (HZO)7 have a significant bilateral loss of the corneal nerve plexus as compared to controls, demonstrating bilateral changes in clinically unilateral diseases. These findings were confirmed in an experimental study of trigeminal axotomy using a new mouse model for neurotrophic keratopathy, which demonstrated the loss of subbasal nerves in both the axotomized and contralateral eyes as soon as 24 hours after unilateral axotomy.14 More recently, we demonstrated that patients with MK have a significant reduction in the subbasal corneal nerve plexus and a concurrent increase in dendritiform cell density.5 Therefore, given our previously observed contralateral changes in corneal nerves in patients with HSK and HZO, we hypothesized that in nonherpetic MK, corneal nerve alterations in contralateral clinically unaffected eyes would be present and would be associated with concurrent increase in inflammatory cells, such as dendritiform cells. Thus, the aim of the current study was to analyze the contralateral clinically unaffected eyes of patients with MK for corneal immune cell alterations and their correlation to subbasal corneal nerve changes by laser IVCM.