Abstract
Purpose :
Topical application of cyclosporin A (CsA) is a widely adopted method for treating ocular inflammatory diseases. However, achieving therapeutic levels of CsA in ocular tissues is challenging due to its significant molecular weight and hydrophobicity and the natural defense system of the eye. The purpose of this study was to investigate the effects of two different types of pH-responsive CsA-eluting contact lenses on the ocular surface of experimental dry eye (EDE) in rabbits.
Methods :
CsA-eluting contact lenses were developed using two pH-responsive materials (pH-responsive immine cross-linking hyaluronic acid and pH-responsive cellulose polymer drug-eluting systems). Dry eye was induced using 0.1% benzalkonium chloride in rabbits, subdivided into the normal, EDE, 0.05% CsA, naïve soft contact lens (CL), immine cross-linking hyaluronic acid contact lens (CL type 1), or cellulose polymer contact lens (CL type 2) groups (n=18). CsA release profiles of the CsA-eluting contact lenses were evaluated with high-performance liquid chromatography analysis at pH 7.4 and 37°C, the same environment as the human ocular surface. Tear volume, tear film break-up time (TBUT), and corneal staining scores (CSS) were measured after 7 and 14 days. Periodic acid-Schiff staining for conjunctival goblet cells and TUNEL assay for corneal apoptotic positive cells were performed after 14 days.
Results :
CsA was continuously released without an initial rapid release for 24 hours in both types of CsA-eluting contact lenses. All treatment groups showed a significant improvement in tear volume, TBUT, and CSS compared to the EDE group at 7 and 14 days. The CL type 1 and CL type 2 groups exhibited a significant improvement in the clinical parameters than the 0.05% CsA and CL groups after 7 and 14 days. In addition, compared to the EDE group, the CL type 1 and CL type 2 groups had higher goblet cell density and fewer TUNEL positive cells after 14 days (p < 0.05).
Conclusions :
Two types of CsA-eluting contact lenses manufactured using two pH-responsive substances showed sustained drug release under conditions similar to the ocular surface. Both CsA-eluting contact lens types 1 and 2 could improve clinical signs, increase conjunctival goblet cells, and decrease TUNEL positive cells in a rabbit model of experimental dry eye.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.