Dry-eye-associated inflammation may change the corneal microenvironment. It has been well documented that the inflammation occurs in the subbasal cornea, conjunctiva, and Meibomian and lacrimal glands. Recently, Kheirkhah et al.
113 reported reduced corneal endothelial cell density (CECD) and nerve density in patients with dry eye. They speculated that a lower CECD is due to the reduction of corneal nerves in dry eye, because a concomitant decrease in corneal nerve and CECD has been reported in other etiologies, such as herpetic keratitis,
114,115 and Fuchs' endothelial corneal dystrophy.
116 Further, Kheirkhah et al.
117 showed that low corneal nerve density is associated with a higher reduction rate of CECD in patients with dry eye. We recently found elevated levels of aqueous cytokines in chronic ocular surface diseases, which suggests the existence of chronic inflammatory conditions in the anterior chamber, leading to cataract formation or reduction of CECD, if the corneal epithelial barrier function breaks down.
63 Furthermore, we demonstrated a connection among iris pigment damage, elevated cytokine levels in the aqueous humor and CECD in eyes with various ocular conditions, including bullous keratopathy and post-penetrating keratoplasty,
118–121 providing evidence that a “chronic inflammatory” microenvironment in the anterior segment of the eye supports the pathogenesis of these conditions. With chronic inflammation, various changes occur: loss of goblet cells in the conjunctiva, limbal stem cell loss, aqueous tear deficiency, immune cell infiltration into the corneal stroma, decreased CECD, corneal nerve loss and elevated cytokine levels in the tears and aqueous humor. The cornea, lacrimal glands, tears, conjunctiva, iris and aqueous humor are anatomically close and the pathogenic alteration of one can affect another. Goblet cells, for example, maintain DCs in an immature state and modulate the local immune response.
122 They also present antigens to underlying APCs via goblet cell associated antigen passages without a break in epithelial integrity.
123,124 Research on the aqueous humor found that the inflammatory cytokine levels increased by a 1000-fold in some eyes, compared to those of healthy controls, which influences not only IOP, but also corneal neovascularization, tear composition, and the condition of the corneal nerves, corneal immune cells and epithelium. In other words, in normal eyes, there appears to be some mechanism for orchestrating homeostasis among tear production, nerves, and immune cells in the cornea. Although the results of these articles can be influenced by confounding factors, such as prior intraocular surgery and preexisting iris damage, future studies on their association with dry eye will be important to understand their physiologic and pathologic impacts. Because dry eye presents as tear film instability, future studies on how ocular surface inflammation changes the corneal microenvironment through its etiopathogenesis, especially in eyes with severe types of dry eye, such as SJS, OCP, or chemical burn, despite the absence of apparent and subclinical inflammation, will be valuable.