Topical cyclosporine A formulations in ophthalmology: a literature review

Cyclosporine A (CsA) is a neutral, lipophilic, hydrophobic cyclic polypeptide derived from the fungal metabolites Tolypocladium inflatum and Beauveria nevus . Despite the widespread introduction of topical CsA formulations into clinical practice, their use in inflammatory ocular surface disorders and dry eye disease remains largely based on heterogeneous studies and empirical clinical experience, without a unified, systematic appraisal of the available evidence. The absence of a structured review comparing different CsA formulations, their immunomodulatory mechanisms, clinical indications, and limitations represents a significant scientific and clinical gap. Purpose : to systematize data from the scientific literature on topical CsA as a well-established therapeutic agent for inflammatory ocular surface disorders and dry eye disease. Materials and methods . Data from original studies were analyzed, and published findings from the most relevant works on CsA formulations used in ophthalmology were synthesized. Publications were identified using a comprehensive search strategy based on predefined keywords. A total of 93 articles indexed in the PubMed database were included in the review. Results . In ophthalmology, 0.05 % CsA was the first commercially available formulation approved for the treatment of dry eye disease and registered in the Russian Federation. Subsequently, a 0.1 % cationic emulsion was introduced for the same indication. The literature analysis demonstrates that topical CsA increases tear production and exerts a protective effect on the ocular surface epithelium and conjunctival goblet cells. Its therapeutic immunomodulatory action is associated with a reduction in HLA-DR expression, pro-inflammatory cytokine levels, apoptosis markers, and conjunctival T-lymphocyte infiltration. Conclusions . In ophthalmic practice, CsA should be used for a relatively narrow but therapeutically challenging group of ocular surface diseases, either in combination with topical glucocorticosteroids or as monotherapy in a steroid-sparing regimen. In addition to severe immune-mediated forms of dry eye disease, CsA is appropriate for the management of other T-cell-mediated inflammatory ocular surface conditions, including post-keratoplasty graft rejection, vernal and atopic keratoconjunctivitis, keratitis associated with autoimmune diseases, Thygeson’s superfi cial punctate keratitis, and meibomian gland dysfunction.