The ocular surface in dry eye: a therapeutic target

Background: Most dry eye symptoms are a result of an abnormal, nonlubricative ocular surface (OS) resulting in increased shear forces under the eye lids and a diminished ability of the OS to respond to environmental challenges. This may result from immunocompromise due to systemic autoimmune disease or locally from a decrease in systemic androgen support to the lacrimal gland Seen with aging, primarily in the female. Hypothesis: Evidence indicates that external stimuli to the OS in the presence of an unsupported lacrimal gland, may initiate the dry eye pathology. The inhibition of normal neural traffic between the lacrimal glands and OS can initiate an autonomically mediated shutdown of normal glandular function yielding an altered tear film. The finding that OS trauma can initiate MHC II expression in the lacrimal gland may explain the lymphocytic infiltration in the gland of Sjogren's patients. Lymphokines further inflame the OS. Studies have demonstrated, that surface epithelial cells produce a variety of cytokines altering interactions with the extracellular matrix. Therapy: Restoration of lacrimal function and resolution of lymphocytic infiltrates has been demonstrated in the 1pr mouse using systemic androgens and in the dry eye dog using topical cyclosporine. Additionally, topical cyclosporine can suppress lacrimal acinar apoptosis seen in the dry eye dog. The efficacy of cyclosporine may be due to its immunomodulatory and anti inflammatory (phosphatase inhibitory capability) functions on the OS, resulting in a normalization of nerve traffic. Conclusion: Though the etiologies of dry eye are varied, common to all OS disease is an underlying cytokine/receptor mediated inflammatory process. By treating this process it may be possible to normalize the OS/lacrimal neural reflex and facilitate OS healing.