Tacrolimus for Dry Eye Disease: Translational Insights from Animal Models and Clinical Studies into Molecular Pathways and Anti-Inflammatory Mechanisms

Tacrolimus (TAC) is recognized as a promising therapy for Dry Eye Disease (DED). Recent experimental studies indicate that TAC formulations, such as nanoemulsions and liposomes, notably improve tear production, stabilize the tear film, and reduce corneal damage in animal models. TAC achieves these effects by inhibiting T-cell activation and suppressing the production of inflammatory cytokines, primarily through the NF-κB signaling pathway. Clinical trials report that topical TAC, especially at 0.03% concentration, significantly alleviates both symptoms and signs in patients with Sjögren's syndrome and ocular graft-versushost disease. Critical clinical improvements include higher Schirmer test values, prolonged tear film break-up time, and decreased ocular surface staining. Comparative analyses suggest that TAC is at least as effective as cyclosporine and offers a favorable safety profile. Combining TAC with agents such as sodium hyaluronate may further enhance therapeutic outcomes. Despite the need for further studies to optimize dose and longterm safety, current evidence supports the use of TAC as an effective solution for individuals with refractory or severe DED, providing a vital option where conventional treatments may fail.