Clinical Ophthalmology (Feb 2020)
A Review of Topical Cyclosporine A Formulations—A Disease-Modifying Agent for Keratoconjunctivitis Sicca
Abstract
Gary W Jerkins,1 Guruprasad R Pattar,2 Shane R Kannarr3 1Advancing Vision Research, Nashville, TN, USA; 2The Eye Care Institute, Louisville, KY, USA; 3Kannarr Eye Care, Pittsburg, KS, USACorrespondence: Gary W JerkinsAdvancing Vision Associates, 4306 Harding Pike, Nashville, TN 37205, USATel +1 615 502-2871Email [email protected]: Keratoconjunctivitis sicca (KCS) is a multifactorial disease characterized by tear hyperosmolarity, inflammation, and ocular surface damage. Cyclosporine A (CsA) is used as an effective disease-modifying agent to improve the signs and symptoms of KCS by reducing inflammation, which interferes with tear production. This review provides an overview of efficacy, safety, and limitations of currently marketed topical CsA formulations—including CsA ophthalmic emulsion, cationic nanoemulsion, and aqueous nanomicelles—and highlights newer technologies for controlled ocular delivery of CsA and their clinical implications. Long available emulsion formulations of CsA are oil-based and have several limitations, including slow onset of efficacy and low intraocular penetration and bioavailability. Aqueous CsA nanomicelle carriers produce rapid improvement in objective signs of KCS such as corneal and conjunctival staining as early as 4 weeks and have acceptable safety profiles. CsA formulations using semifluorinated alkanes or polyaphrons are currently in clinical development, having recently completed Phase 2 studies. Other carriers for CsA currently in the preclinical phase include microemulsions, polymeric aqueous and lyophilized micelles, and hydrogels; these novel formulations have yet to undergo clinical trials. Formulations that improve tissue availability of CsA may be beneficial in clinical practice by providing faster onset of relief and improving patient adherence.Keywords: cyclosporine A, keratoconjunctivitis sicca, emulsion, nanomicelles, OTX-101
