Dry eye syndrome: developments and lifitegrast in perspective

Abstract

Dry eye (DE) is a chronic ocular condition with high prevalence and morbidity. It has a complex pathophysiology and is multifactorial in nature. Chronic ocular surface inflammation has emerged as a key component of DE that is capable of perpetuating ocular surface damage and leading to symptoms of ocular pain, discomfort, and visual phenomena. It begins with stress to the ocular surface leading to the production of proinflammatory mediators that induce maturation of resident antigen-presenting cells which then migrate to the lymph nodes to activate CD4 T cells. The specific antigen(s) targeted by these pathogenic CD4+ T cells remains unknown. Two emerging theories include self-antigens by autoreactive CD4 T cells or harmless exogenous antigens in the setting of mucosal immunotolerance loss. These CD4 T cells migrate to the ocular surface causing additional inflammation and damage. Lifitegrast is the second topical anti-inflammatory agent to be approved by the US Food and Drug Administration for the treatment of DE and the first to show improvement in DE symptoms. Lifitegrast works by blocking the interaction between intercellular adhesion molecule-1 and lymphocyte functional associated antigen-1, which has been shown to be critical for the migration of antigen-presenting cells to the lymph nodes as well as CD4+ T cell activation and migration to the ocular surface. In four large multicenter, randomized controlled trials, lifitegrast has proven to be effective in controlling both the signs and symptoms of DE with minimal side effects. Further research should include comparative and combination studies with other anti-inflammatory therapies used for DE.

The Immunological Basis of Dry Eye Disease and Current Topical Treatment Options

“…25 Lifitegrast has the potential to act on both afferent and efferent arms of the immunomodulatory pathway in DED. 84 In the afferent arm (to the lymph node), it may block LFA-1:ICAM-1 interaction between dendritic cells on the ocular surface and endothelial cells of lymphatic tissues, thereby inhibiting migration and homing of naive dendritic cells to draining lymph nodes or activation of resting T cells at the ocular surface. 25 In the efferent arm (from the lymph node), lifitegrast may inhibit migration of activated T cells into the conjunctiva, recruitment in conjunctival epithelium, and secondary activation in ocular tissues.…”

Menopause and Dry Eye Syndrome

“…Dry eye syndrome involves the ocular surface, and there are two different etiologies that affect tear film stability (Lollett & Galor, 2018). One is aqueous deficiency, which is the decreased production of the aqueous component of tear film (Lollett & Galor, 2018).…”

“…Osmolarity is the osmotic concentration of electrolytes of the ocular surface and is a biomarker for a healthy ocular surface. Hyperosmolarity creates a progressive inflammatory process with the release of proinflammatory cytokines and tumor necrosis factor a (Lollett & Galor, 2018).…”

Sjögren’s Syndrome as an Ocular Problem: Signs and Symptoms, Diagnosis, Treatment

“…Interaction between LFA-1 and ICAM-1 leads to T-lymphocyte adhesion to endothelial cells, migration to tissue, antigen presentation and recognition facilitating the formation of an immunological synapse. It releases inflammatory mediators, cytokines, chemokines, TNF-α, and IL-1 which are responsible for perpetuation and intensification DED inflammation [2,22,[75][76][77][78][79]. The clinical efficacy of lifitegrast in patients with DED has been reported: improvement in symptom scores and ocular staining score in patients using it for 12 weeks.…”

“…The clinical efficacy of lifitegrast in patients with DED has been reported: improvement in symptom scores and ocular staining score in patients using it for 12 weeks. No serious ocular adverse events occurred [22,[75][76][77][78][79]. However, there are no studies comparing lifitegrast and other anti-inflammatory agents, evaluating whether lifitegrast in combination therapy could work better in DED-those problems need further studies [79].…”