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Terry G Coursey, Phillip A Vanlandingham, Ashley K. Sparkes, Drew Wassel, Alexander B Quiambao, Didier J Nuno, Rafal Farjo; Topical application of Cyclosporine-A-MiDROPS™ for treatment of Autoimmune Uveitis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):790.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the efficacy cyclosporine A (CsA) formulated in Microemulsion Drug Ocular Penetration System (MiDROPS™) to prevent immune cell infiltration, clinical severity, and loss of visual function in a mouse model of experimental autoimmune uveitis (EAU).
B10.RIII mice were immunized with human IRBP peptide to induce EAU. Immunized mice were treated either systemically by oral gavage of CsA (25 mg/kg, QD), or via bilateral topical administration with 0.1% CsA-MiDROPS™ (2 µl/eye, BID). Groups of non-immunized or untreated EAU-induced mice were enrolled as controls. Efficacy was assessed by measuring visual acuity with optokinetic tracking (OKT), immune cell infiltration by optical coherence tomography (OCT), and severity of clinical inflammation by color fundoscopic examination. Baseline levels were assessed prior to immunization, visual acuity was assessed on Day 15, and immune cell infiltration and clinical severity were assessed on Day 16 post immunization.
Previous studies demonstrate that CsA-MiDROPS™ confers superior ocular drug delivery of CsA compared to conventional eye drops and is very efficacious in a mouse model of dry eye disease. Rabbit studies demonstrate that CsA-MiDROPS™ transiently modulate opening of tight junctions in the ocular surface epithelium, without impacting cellular integrity, to allow for increased drug delivery. In this study, whereas UT mice show a significant (71%) loss in visual acuity from baseline to Day 15, no significant change was observed in the systemic CsA, or topical CsA-MiDROPS™ treatment groups. Measurement of cellular infiltrates visualized by OCT showed a significant, 8-fold reduction in immune cells present in the vitreous following either oral (p=0.0028), or topical (p=0.0033) administration of CsA compared to UT mice. Mean clinical scores were also higher in UT mice (1.95) compared to the oral CsA administration group (1.04) and topical CsA-MiDROPS™ administration group (1.12). Naïve mice showed no loss of visual acuity or clinical indications of EAU.
In a mouse model of EAU, topical treatment with CsA-MiDROPS™ has a profound effect reduce severity of clinical pathology, immune cell infiltration, and loss of visual function similar or more potently than systemic CsA. These results suggest that topical delivery of CsA by CsA-MiDROPS™ may be an effective treatment of uveitis without the side effects of systemic CsA.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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