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A Crosslinked HA-Based Hydrogel Ameliorates Dry Eye Symptoms in Dogs

DOI: 10.1155/2013/460437

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Abstract:

Keratoconjunctivitis sicca, commonly referred to as dry eye or KCS, can affect both humans and dogs. The standard of care in treating KCS typically includes daily administration of eye drops to either stimulate tear production or to hydrate and lubricate the corneal surface. Lubricating eye drops are often applied four to six times daily for the life of the patient. In order to reduce this dosing regimen yet still provides sufficient hydration and lubrication, we have developed a crosslinked hydrogel based on a modified, thiolated hyaluronic acid (HA), xCMHA-S. This xCMHA-S gel was found to have different viscosity and rheologic behavior than solutions of noncrosslinked HA. The gel was also able to increase tear breakup time in rabbits, indicating a stabilization of the tear film. Further, in a preliminary clinical study of dogs with KCS, the gel significantly reduced the symptoms associated with KCS within two weeks while only being applied twice daily. The reduction of symptoms combined with the low dosing regimen indicates that this gel may lead to both improved patient health and owner compliance in applying the treatment. 1. Introduction Keratoconjunctivitis sicca (KCS), commonly referred to as dry eye syndrome, is an ophthalmic disorder common in humans and dogs. The reported incidence of KCS in humans varies from 5 to 33%, depending on the report and how the data were obtained, while the incidence in dogs is approximately 1–4% [1]. In general, KCS results from a dysfunction in a component of the lacrimal functional unit, leading to changes in the volume, composition, or clearance of the tear film [2]. The lacrimal functional unit is composed of the lacrimal glands (both main and accessory), the ocular surface, and the interconnecting innervations [3]. In dogs, the most common cause of KCS is immune-related lacrimal gland disease [4, 5]. Other causes include congenital aplasia of the gland, drug-induced or traumatic injury to the gland, and neurologic dysfunction affecting the gland [4, 5]. With immune-mediated KCS in dogs, there is a predisposition for specific breeds having a higher prevalence. These breeds include English Bulldogs, West Highland White Terriers, Cavalier King Charles Spaniels, American and English Cocker Spaniels, and Pugs, with the prevalence reaching as high as 20% in these breeds [4, 5]. There is little information about the progression of dry eye symptoms in dogs with KCS as they age, but a gradual lowering of Schirmer tear test values in normal dogs has previously been shown as they age [6]. Although KCS is not considered a

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