Development of Autologous Serum Ocular Insert for Chronic Dry Eye Disease

<b>Background:</b> Dry eye disease is a multifactorial disease of the ocular surface and/or tear film. It is one of the leading causes of ocular morbidity worldwide. Current therapy primarily consists of topical application of artificial tears and anti-inflammatory drugs. Autologous serum eye drops are an alternative treatment typically reserved for severe dry eyes mainly due to the limitations associated with access, storage, and the need for frequent application. <b>Methods:</b> Herein we describe the design and characterization of a bilayer carboxymethylcellulose/serum ocular insert that may expand the utility and accessibility of this treatment method. The insert, designed to be placed in the inferior fornix of the eye, has a unique carboxymethylcellulose backing layer to enhance comfort and direct protein release to the ocular surface. <b>Results:</b> Released serum proteins were able to protect corneal cells in vitro after treatment with hydrogen peroxide, demonstrated by a significantly higher cell viability compared to both serum eye drops and untreated cells. Our in vivo studies showed that the ocular inserts were able to deliver epitheliotrophic growth factors to treated animals at a level similar to standard serum eyedrops at an 8-fold reduction in dosing frequency that was well-tolerated in the treated eyes. In comparison to the control, serum ocular inserts demonstrated improvement in dry eye signs and symptoms in a rabbit model. <b>Conclusions:</b> Our results demonstrate that the novel inserts prolong the delivery of key proteins and growth factors for treating dry eye disease and significantly enhance shelf stability.