© 2006 American College of Veterinary Ophthalmologists Veterinary Ophthalmology (2006) 9, 1, 1–5 Blackwell Science, Ltd Constant rate infusion for topical ocular delivery in horses: a pilot study Kathern E. Myrna and Ian P. Herring Department of Small Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061-0442, USA Abstract Objective To assess the efficacy and kinetics of a continuous infusion modality for topical ophthalmic drug delivery via subpalpebral lavage in horses. Animals studied Five ophthalmically normal horses Procedures A constant-rate continuous delivery pump was used to apply 0.01% fluorescein solution to the eyes of five ophthalmically normal horses via subpalpebral lavage. Fluorescein was applied at a rate of 0.14 mL/h for 72 h. Tear samples were collected from the ventral conjunctival fornix at regular intervals via capillary tube and tear fluorescein concentrations were determined via spectral assay. Laboratory studies to evaluate the procedures used in the study also were performed. Results Overall mean tear film fluorescein concentration was approximately 20% of the applied concentration of fluorescein. However, tear film fluorescein concentrations varied considerably between horses and over time. Dilution varied from 0.62% to 60% of the applied concentration. Air pockets sporadically appeared in subpalpebral lavage tubing lines, resulting in discontinuous topical application of fluorescein. Conclusions Constant-rate delivery of ophthalmic medications using a continuous infusion pump may provide a valuable method of topical drug delivery if tear film dilution of drugs is taken into account. Key Words: continuous infusion pump, equine, pharmacokinetics, subpalpebral lavage, tear film Address communications to: I. P. Herring Tel.: (540) 231-4621 Fax: (540) 231-1676 e-mail: iherring@vt.edu INTRODUCTION Topical delivery of ophthalmic medications in horses can be challenging, particularly when frequent application is indicated. Traditionally, ophthalmic medications in solution form are applied via a single drop. 1 However, this single, high-dose modality has a number of drawbacks. Most of the dose is quickly drained through the nasolacrimal duct, with an ocular residence time of only 2–23 min. 2–4 This low residence time allows ophthalmic bioavailability of approxi- mately 10%. 5 Increased lacrimation may also be induced by irritant properties of the medication or application method, which will speed drug loss from the tear film. 6 Painful ocular disorders such as corneal ulcers are associated with increased lacrimation and, thereby, increased rate of loss of topically applied medication via the nasolacrimal duct and epiphora. Although frequent dosing may overcome this, it often is not feasible to treat a horse at frequencies recommended for melting corneal ulcers. 7 Ocular lavage systems are temporary implant devices designed to deliver liquid topical medication to the eye. A subpalpebral lavage placed in the dorsal conjunctival fornix of the affected eye through an incision in the upper lid allows medication to be flushed into the conjunctival sac from the distal end of the tubing. 8 Although ocular lavage systems facilitate topical application, they still require physical appli- cation of medication through the system at regular intervals. The use of an automated constant rate fluid delivery pump attached to a subpalpebral lavage system offers a promising alternative to repeated instillations of topical solutions. Potential benefits include improved ease of treatment and relatively stable tear film and ocular tissue concentrations of applied medications. The concept of continuous infusion of topical drugs through ophthalmic delivery systems is not a novel one. Human studies have investigated the concept in the form of subcutaneous abdominal pumps and lacrimal duct cannulation and external infusion pumps. 9–12 However, these methods