Inflammation is increasingly recognized as a central – although not universal – driver of dry eye disease (DED). A new review in Expert Review of Ophthalmology examines how lifitegrast ophthalmic solution 5% fits into that inflammatory pathway, drawing together clinical trial, safety, pharmacovigilance, and real-world evidence accumulated since the drug’s development.
Lifitegrast is a lymphocyte function-associated antigen-1 (LFA-1) antagonist indicated for the treatment of both signs and symptoms of DED. By blocking the interaction between LFA-1 and intercellular adhesion molecule-1 (ICAM-1), it interferes with T-cell activation, migration, and inflammatory cytokine release at several points in the ocular surface inflammatory cascade. The mechanism is illustrated in the review, which contrasts lifitegrast’s cell-surface action with the intracellular immunomodulatory mechanism of cyclosporine.
Much of the efficacy evidence comes from the three 12-week phase 3 OPUS trials. In OPUS-1, lifitegrast significantly improved inferior corneal fluorescein staining versus vehicle, while secondary endpoints included improvements in eye dryness and ocular discomfort. OPUS-2 did not meet its corneal staining coprimary endpoint but demonstrated a significant reduction in eye dryness, with an effect apparent by day 14.
OPUS-3 reinforced the symptom findings: eye dryness improved significantly versus vehicle by day 14 and remained improved at later assessments. A pooled post hoc analysis of OPUS-2 and OPUS-3 also found greater odds of clinically meaningful improvement in both corneal staining and eye dryness among lifitegrast-treated patients. The divergent sign and symptom outcomes across trials, the review authors note, reflect the often weak relationship between objective findings and patient-reported symptoms in this heterogeneous disease.
Safety data from five randomized trials comprising 2,464 patients were found to be broadly consistent. The most common ocular adverse events with lifitegrast were instillation-site irritation, reaction, and pain; dysgeusia was the most frequent nonocular event, occurring in 14.5% of lifitegrast-treated patients versus 0.3% receiving vehicle. Overall discontinuation because of adverse events remained relatively low.
Real-world evidence generally supported the clinical trial findings. Surveys and observational studies have reported improvements in symptoms, clinical signs, and quality of life, although treatment persistence remains a challenge. In one prospective case series, mean OSDI score improved from 52.2 at baseline to 31.2 after 12 weeks, accompanied by improvements in tear osmolarity, Schirmer testing, tear breakup time, and staining.
The review also highlights emerging applications, including preoperative ocular surface optimization before cataract surgery, where lifitegrast has been associated with improved keratometry reproducibility and refractive accuracy.
The review authors ultimately position lifitegrast as one component of an increasingly personalized DED treatment landscape, in which inflammatory biomarkers and advanced imaging may help identify patients most likely to benefit. The review was supported by Bausch + Lomb-funded medical writing assistance, and the authors are company employees, with several others reporting consultancy relationships, and these disclosures should be considered when interpreting its conclusions.
