Eye diseases, such as dry eye syndrome, are commonly treated with eye drop formulations. However, eye drop formulations require frequent dosing with high drug concentrations due to poor ocular surface retention, which leads to poor patient compliance and high risks of side effects. We developed a mucoadhesive nanoparticle eye drop delivery platform to prolong the ocular retention of topical drugs, thus enabling treatment of eye diseases using reduced dosage. Using fluorescent imaging on rabbit eyes, we showed ocular retention of the fluorescent dye delivered through these nanoparticles beyond 24 h while free dyes were mostly cleared from the ocular surface within 3 h after administration. Utilizing the prolonged retention of the nanoparticles, we demonstrated effective treatment of experimentally induced dry eye in mice by delivering cyclosporin A (CsA) bound to this delivery system. The once a week dosing of 0.005 to 0.01% CsA in NP eye drop formulation demonstrated both the elimination of the inflammation signs and the recovery of ocular surface goblet cells after a month. Thrice daily administration of RESTASIS on mice only showed elimination without recovering the ocular surface goblet cells. The mucoadhesive nanoparticle eye drop platform demonstrated prolonged ocular surface retention and effective treatment of dry eye conditions with up to 50- to 100-fold reduction in overall dosage of CsA compared to RESTASIS, which may significantly reduce side effects and, by extending the interdosing interval, improve patient compliance.

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An increasing number of patients are being referred to Allergy clinics for evaluation of mast cell activation syndrome (MCAS). A commonly cited complaint in this disorder is a non-specific condition commonly described as ''brain fog.'' Similar complaints have been noted in postural orthostatic tachycardia syndrome, and studies have found possible objective evidence of cognitive dysfunction in this disorder. Our overall goal is a quality improvement initiative to quantify symptom burden in patients with MCAS. For this part of the project, our aim is to evaluate whether cognitive dysfunction can be identified and monitored in a cohort of patients referred for MCAS. METHODS: In an ongoing quality improvement project (IRB exempt), patients referred to a University of Wisconsin Allergy clinic for evaluation of MCAS are being administered symptom questionnaires. Executive cognitive function is assessed via a previously validated computer battery (CogState), with individual tests including Detection, Identification, One Card Learning, One Back, and Groton Maze Learning. A PHQ-9 questionnaire is also administered to assess co-morbid depression. RESULTS: In a cohort of patients with presumed MCAS in the University of Wisconsin Allergy clinic, 25% of patient have self-reported symptoms of cognitive dysfunction and approximately one-third have physiciandiagnosed or self-reported depression. CONCLUSIONS: Referrals to the Allergy clinic for MCAS are increasing in number, and the diagnosis, monitoring and management of the disease remains challenging. Given the frequency of self-reported cognitive concerns, establishing objective measures is of utmost importance in monitoring and management of this disease.