Review
Clinical utility of caspofungin eye drops in fungal keratitis

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Abstract

Treatment of fungal keratitis remains challenging. To date, only the polyenes and azoles are commonly used topically in the management of fungal keratitis. Natamycin, a polyene, is the only antifungal eye drop that is commercially available; the remainder are prepared in-house and are used in an ‘off-label’ manner. Failure of medical treatment for fungal keratitis is common, hence there is a need for more effective topical antifungal therapy. To increase the antifungal eye drop armamentarium, it is important to investigate the utility of other classes of antifungal agents for topical use. Caspofungin, an echinocandin antifungal agent, could potentially be used to address the existing shortcomings. However, little is known about the usefulness of topically administered caspofungin. This review will briefly explore the incidence, epidemiology and antifungal treatment of fungal keratitis. It will focus primarily on evidence related to the efficacy, safety and practicality of using caspofungin eye drops in fungal keratitis.

Introduction

Infections of the cornea are a major cause of blindness worldwide, especially in developing countries; fungal infections are a particularly noteworthy cause of morbidity [1], [2]. In certain parts of the world, more than one-half of corneal ulcers are due to fungal infections [3]. Fungal keratitis, also known as mycotic keratitis or keratomycosis, is characterised by a defect of the corneal epithelium with inflammation of the underlying stroma owing to fungal aetiology [4] and is particularly difficult to treat [5]. It responds poorly or not at all to antifungal treatment and may require surgical intervention [6]. Although the outcome for patients with early-stage fungal keratitis is reasonably good, for moderate-to-severe cases the chances of successful restoration of vision are ≤50% [7], [8], [9]. The limited range of antifungal eye drops available for treatment and the lack of favourable outcomes with existing antifungal eye drops [10] are major hurdles to successfully treating fungal keratitis; hence, alternatives are urgently needed. Topical application of newer antifungal agents that are currently available only for injection, such as the echinocandins (e.g. caspofungin), is worthy of consideration. In addition to increasing therapeutic options, this approach is likely to be more economically favourable than parenteral administration. While focusing on the efficacy, safety and practicality of using caspofungin eye drops in treating fungal keratitis, this review will also provide an overview of the incidence, epidemiology and current antifungal treatment options for this condition.

Section snippets

Incidence and epidemiology of fungal keratitis

The incidence of and causative pathogens associated with fungal keratitis vary by geographical region [11], more specifically by latitudinal variation, local climate, extent of urbanisation, occupational and/or economic factors [12], [13]. Fungal keratitis occurs more frequently in developing countries and in the tropics, including India [14], [15], [16], [17], Ghana [18], Nepal [19] and Burma [20], and accounts for ca. 50% of corneal infections in these regions. Other nations, including

Antifungal treatment

Use of appropriate topical antifungal agents remains the first-line therapeutic option [5]. It has been recommended that topical antifungal therapy should be initiated hourly around the clock for the first 24–48 h and then gradually tapered according to the clinical response [10] once laboratory confirmation of the causative fungal pathogen is available [44]. In most cases prolonged therapy of ≥6 weeks is required, with 12 weeks for filamentous and deep stromal infections [31]. The two key

Conclusions and future research direction

Topical treatment for fungal keratitis remains inadequate, and alternative antifungal eye drops are urgently needed. Caspofungin eye drops appear to be a potentially useful alternative for fungal keratitis. However, information related to the treatment outcome of using different concentrations of caspofungin eye drops as well as the optimal dosing frequency and duration of treatment remains scant. Indeed, there is a paucity of clinical experience in using caspofungin eye drops in treating

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