Anterior uveitis refers to inflammation affecting the anterior uvea, the rostral-most component of the vascular tunic of the eye. It is characterized by breakdown of the blood-aqueous barrier and other typical signs of inflammation. Anterior uveitis in dogs may result from a vast array of ocular and systemic disorders, including infection, neoplasia, trauma, and immune-mediated disease.1 In addition to causing pain, chronic or severe anterior uveitis may damage vision or the globe. Given its potentially dire consequences, anterior uveitis typically requires aggressive treatment with topically and systemically administered anti-inflammatory medications.
Corticosteroid medications form the mainstay of topical anti-inflammatory treatment for uveitis in both human and veterinary medicine.2,3 Aided by its good corneal penetration, 1% prednisolone acetate suspension is currently the most effective topical medication for moderate to severe anterior uveitis.1,4 Despite its efficacy, prednisolone acetate has some potentially important drawbacks, including those related to cost, compliance (frequent administration is required), administration (vigorous shaking of the suspension is required before instillation), and undesirable effects (eg, corneal lipid deposits).4–6 A need exists for topical corticosteroid medications that circumvent some of these drawbacks without compromising clinical efficacy.
Difluprednate is an extremely potent synthetic corticosteroid derived from prednisolone acetate. It differs from the parent compound in that fluorine moieties are substituted on carbons 6 and 9 of the prednisolone backbone and a butyrate is positioned on carbon 7.7,8 These substitutions act to improve corneal penetration and potency, respectively, compared with the effects of prednisolone acetate.8,9 Difluprednate was approved in 2008 by the US FDA for the treatment of postoperative ocular inflammation and pain in humans, and it was subsequently approved for the treatment of endogenous uveitis.9 Several clinical studies5,10–20 in humans have shown the efficacy of topically applied difluprednate for controlling various forms of uveitis and treatment of other intraocular diseases. Although studies6,14,20,21 have shown similar safety and efficacy between difluprednate and prednisolone acetate, several beneficial attributes have been ascribed to ophthalmic difluprednate, compared with prednisolone acetate, which notably include less frequent administration, an emulsion formulation that does not require shaking before instillation, dose uniformity, a preservative with potentially less irritation, and efficacy for treating posterior segment disease in humans.
Anterior chamber paracentesis (ie, aqueocentesis) refers to the removal of fluid from the anterior chamber of the eye for diagnostic or therapeutic purposes.22,23 The technique is performed by inserting a fine hypodermic needle into the anterior chamber through the perilimbal aspect of the cornea, with care taken to avoid contact with and trauma to intraocular tissues.24 Aqueocentesis induces intraocular inflammation in the treated eye, with larger needles causing a more pronounced anterior uveitis.23 The predictable intraocular inflammation caused by aqueocentesis has enabled this technique to be useful in research settings, particularly for the evaluation of medications used to treat uveitis.25,26
The blood-aqueous barrier is formed by the endothelium of the iris blood vessels, the nonpigmented layer of the ciliary epithelium, and the posterior pigmented epithelium of the iris.27 These structures typically prevent substances in the blood from entering the eye. When the barrier is disrupted, the blood vessels dilate and plasma proteins leak into the aqueous humor.28 Although a semiquantitative method for grading of the aqueous flare is most commonly used to assess the degree of blood-aqueous barrier breakdown in clinical settings, objective techniques have been described, including fluorophotometry, laser flare photometry, and measurement of aqueous humor protein concentrations. Anterior chamber fluorophotometry is used to noninvasively measure the fluorescein concentration in the anterior chamber after systemic administration of fluorescein. Greater amounts of fluorescein entering the anterior chamber indicate greater permeability of the blood-aqueous barrier; therefore, fluorophotometry can be used to quantify the degree of disruption of the blood-aqueous barrier.
The purpose of the study reported here was to evaluate the efficacy of topical administration of 0.05% difluprednate ophthalmic emulsion and 1% prednisolone acetate ophthalmic suspension for limiting the severity and duration of anterior uveitis. Efficacy was evaluated by use of a well-characterized fluorophotometric method for assessing the breakdown of the blood-aqueous barrier in dogs.22,23 Although investigators of a recent investigation29 found topically administered difluprednate superior to betamethasone for minimizing aqueous humor protein and prostaglandin E2 concentrations 1 hour after paracentesis, we are unaware of any veterinary studies in which topically administered difluprednate has been compared with topically administered prednisolone acetate for the control of iatrogenic or acquired uveitis in companion animals.
Supported in part by a Veterinary Clinical Sciences Research Incentive Grant through the College of Veterinary Medicine at Iowa State University.
The authors declare that there were no conflicts of interest.
Presented in abstract form at the 47th Annual Conference of the American College of Veterinary Ophthalmologists, Monterey, Calif, October 2016.
The authors thank Brian Harward for assistance with the statistical analysis.
Sandoz, Princeton, NJ.
Durezol, Alcon, Fort Worth, Tex.
Fluorotron Master, OcuMetrics, Mountain View, Calif.
AK-Fluor, Akorn Inc, Lake Forest, Ill.
SPSS Inc, Chicago, Ill.
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