OPHTHALMOLOGY


Ketoconazole is an imidazole with fairly limited spectrum but good corneal and intraocular penetration.4,5 Miconazole has variable reported activity against the filamentous fungi.2,4 It comes as a 1% compounded suspension; however, the over-the- counter 2% dermatologic and 2% vaginal cream preparations have also been used as an ophthalmic treatment. Please see the below discussion for ad- ditional details on these formulations. The second group of azoles is the triazoles, again


named for their parent ring structure. Despite being well absorbed, fluconazole primar-


ily targets yeast, which limits its usefulness in equine keratomycosis. Itraconazole is a triazole with a broader spec-


trum but has a reduced penetration relative to flu- conazole. This penetration is believed to be improved by the addition of 30% dimethyl sulfoxide (DMSO) and is commonly available. This formula- tion has been seen to penetrate into the corneal stroma but has not been found in measurable levels within the aqueous humor.8 In a study by Mathes et al, itraconazole andDMSOwere found to have the least keratocyte damage relative to miconazole and natamycin.9 With excellent penetration and good efficacy against yeast and hyphae, voriconazole has emerged as a good option for antifungal therapy. Clode et al tested three concentrations (0.5%, 1%, and 3%) and found 1% delivered the best combination of penetra- tion and mitigation of side effects.10 Voriconazole was found to outperform natamycin, fluconazole, itraconazole, ketoconazole, and miconazole against in vitro isolates in a study by Pearce et al.4


Betadine (Povidone-Iodine) Solution


Betadine solution is an antiseptic with both anti- bacterial and antifungal properties. Widely used as a surgical preparation, there is also some who advocate its use as a therapy. Concentrations from 0.5% to 1.0% betadine have been validated to disin- fect the surgical site or donor cornea as a protocol for preoperative antisepsis.11 The use of a 2% dilute betadine solution every 24 hours has been suggested in the treatment of fungal keratitis.12 However, this should be limited to adjunctive therapy only. A large metastudy concluded that 5% betadine solu- tion did not reduce the bacterial load of human corneal ulcers significantly. This was theorized to be due to the lack of penetration into the corneal stroma.13


Silver Sulfadiazine


Silver sulfadiazine (SSD) is a 1% dermatologic cream with broad antibacterial and antifungal ac- tivity historically used to treat burns. Use as a corneal antifungal with topical application every 12 to 24 hours has been suggested.12 There has been limited in vitro data in horses14 that it is fungicidal when used as an ophthalmic topical. A large meta


34 2014  Vol. 60  AAEP PROCEEDINGS


study15 investigated topical drug trials for fungal keratitis in people. This study showed that based on the trials included, there was no evidence that any particular drug was more effective in the man- agement of fungal keratitis. One specific compari- son was topical SSD vs miconazole. However, the study noted that the trials included in this review were of variable quality and were generally under- powered. Therefore, the evidence behind use of SSD as an antifungal ophthalmic remains inconclusive.


Dosage: Frequency and Duration


Dosage of ophthalmic drugs is significantly different from other pharmacokinetics. Most topical drugs follow first-order kinetics (maximum concentration then exponential decline). Unlike systemic drugs where usually 75% is bioavailable, after topical application of an ophthalmic solution less than 1% and no more than 10% of the dose enters the eye. Furthermore, the lacrimal lake limits the volume that can be administered, and the concentration is limited by what is tolerable to the corneal surface. Therefore, frequent application of low-volume, di- lute solution is a mainstay to equine topical treat- ment. For example, a dosing regime may use topical antifungals every 2 to 4 hours initially and only reducing to six-times a day once clinical im- provement is seen. Ointments are a good option for decreasing the frequency of application. Rate of dissipation from the precorneal tear film of drugs administered in an ointment is significantly slower than a liquid. This is because less of the drug is immediately lost to nasolacrimal drainage, increasing bioavailability. Eye ointments can be dosed anywhere from every 4 to 12 hours. Disadvantages include danger if cor- neal perforation is imminent, imprecise dosing, and a creation of a film on the cornea significantly dis- torting vision. Regardless of topical of choice, a positive cytology


or culture of fungus should necessitate a continued course of topical antifungal therapy. Recrudes- cence is common. Durations from 3 to 8 weeks depending on response have been reported. Pre- paring clients for a minimum of 6 weeks of topical therapy is usually realistic.


Specific Questions


Is vaginal and athlete’s foot preparation of miconazole acceptable to apply topically to the horse eye?


Two percent miconazole is available as a dermato- logic and vaginal cream over-the-counter (OTC) preparation. These have been used as topical med- ications in horses. While this is an economic op- tion, these formulations are not designed for the ocular surface. There are anecdotal reports of oph- thalmic problems resulting from its use in horses and, therefore, use is with risk. The primary inac- tive ingredient in vaginal miconazole is benzoic acid.


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