Dry eye disease (DED) is associated with a wide range of contributing factors, including female sex, older age, menopause, and lifestyle influences such as prolonged screen time, exposure to ocular irritants, contact lens use, and underlying systemic inflammatory diseases (eg, Sjögren’s syndrome, rheumatoid arthritis). For most patients, the origins of DED are multifactorial, with several overlapping drivers.

Despite variability in triggers, many of the underlying pathogenic processes are shared among etiologies, including the activation and perpetuation of inflammation. DED has been described as a “vicious cycle of inflammation,” wherein ocular surface inflammation is both a cause and consequence of DED. In this cycle, ocular surface stress from intrinsic and/or extrinsic sources initiates an inflammatory cascade that begins with proinflammatory cytokine release. These cytokines activate antigen-presenting cells (APCs), which migrate to regional lymph nodes where they activate naïve T cells. The activated T cells migrate to the ocular surface, where they induce epithelial damage and tear film dysfunction. At the ocular surface, T cells may undergo secondary activation through interactions with local APCs, helping to sustain their effector function and perpetuate ocular surface inflammation.

Xiidra (lifitegrast ophthalmic solution 5.0%) is a first-in-class LFA-1 antagonist developed to act on several steps that propagate ocular surface inflammation in DED, including activation of naïve T cells by APCs, ocular surface migration of T cells, sustained/secondary activation of T cells, and recruitment and retention of T cells within the conjunctival epithelium, ultimately reducing the release of proinflammatory cytokines. The ability of Xiidra to act on both naïve and activated T cells is believed to contribute to its rapid amelioration of ocular surface inflammation. In clinical trials, measurable improvements in DED symptoms were observed as early as 2 weeks after starting Xiidra treatment.