Treatment of Alternaria Keratitis with Intrastromal and Topical Caspofungin in Combination with Intrastromal, Topical, and Oral Voriconazole

Neoh, Chin Fen; Leung, Lok; Vajpayee, Rasik B; Stewart, Kay; Kong, David Chee Ming

doi:10.1345/aph.1p586

Cited by 28 publications

(23 citation statements)

References 7 publications

(8 reference statements)

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“…However, the body of clinical evidence for its use is not strong, and consists mainly of single case reports48–50 and small, or uncontrolled interventional case series 51–55. Other agents, namely caspofungin and amphotericin have also been reported for intrastromal use, but again only in case report format 56 57 Table 3. summarises published studies of intrastromal antifungals for fungal keratitis.…”

Section: Intrastromal Antimicrobialsmentioning

confidence: 99%

Established and emerging ancillary techniques in management of microbial keratitis: a review

2016

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Microbial keratitis is a sight-threatening condition and an ocular emergency, because of the potential for rapid progression. Intensive topical antimicrobials are the mainstay and the gold standard of treatment for microbial keratitis. However, despite appropriate diagnosis and therapy, treatment failure is still common, and can result in significant morbidity due to corneal perforation and/or scarring. For this reason, clinicians continue to seek novel treatment techniques in order to expand the armamentarium of tools available to manage microbial keratitis, and in doing so improve clinical outcomes. In this review, we examine the evidence for some established, as well as a few emerging ancillary techniques used to manage microbial keratitis. These include topical corticosteroids, corneal collagen cross-linking, intrastromal antimicrobials, amniotic membrane transplantation and miscellaneous other techniques. Of these, collagen cross-linking shows some promise for selected cases of infectious keratitis, although more research in the area is required before it is accepted as mainstream treatment for this potentially blinding condition.

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Section: Intrastromal Antimicrobialsmentioning

confidence: 99%

Established and emerging ancillary techniques in management of microbial keratitis: a review

2016

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“…Over the last few years, a few cases of Alternaria keratitis treated with a combination of topical and intrastromal/intracameral antifungals have been reported. [2][3][4][5] Voricanozole was first reported for the management of Alternaria keratitis by Ozbek et al 2 with resolution of the infection within 10 days of beginning therapy. Tu 4 reported three cases of Alternaria keratitis that responded rapidly to either topical fluconazole 0.02% or a combination of intrastromal voriconazole and topical caspofungin 0.5%.…”

mentioning

confidence: 99%

“…Tu 4 reported three cases of Alternaria keratitis that responded rapidly to either topical fluconazole 0.02% or a combination of intrastromal voriconazole and topical caspofungin 0.5%. Neoh et al 5 reported a case of Alternaria keratitis in a patient with a corneal graft that was successfully managed with intrastromal and topical caspofungin in combination with intrastromal, topical, and oral voriconazole. However, once the infection was under control, the patient underwent penetrating keratoplasty.…”

mentioning

confidence: 99%

Medical management of Alternaria keratitis with endophthalmitis in a patient with a corneal graft

Papakostas

Kohanim

Skondra

et al. 2013

Clinical Exper Ophthalmology

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“…After topical delivery in animals, caspofungin has good penetration into eyes with inflammation or corneal abrasion (4,20), and it has been shown previously to be effective in treating fungal keratitis in rabbits (5,12). While penetration into intact human eyes may be limited (10), successful application of topical caspofungin alone (7) or in combination with voriconazole (11,18) for patients with fungal keratitis has been reported. However, the stability of extemporaneously prepared caspofungin eye drops is unknown and the eye drops have to be freshly prepared and used within 24 h (7), making their use in clinical settings uneconomical.…”

mentioning

confidence: 99%

“…By following an intensive regime of one drop (0.05 ml) administered every 1 or 2 h in clinical practice (11,18), a total of 0.6 to 1.2 ml of eye drops would be applied daily. A single 50-mg caspofungin vial provides two 5-ml bottles of eye drops, each sufficient for 4 to 8 days of treatment.…”

mentioning

confidence: 99%

Stability of Extemporaneously Prepared 0.5-Percent Caspofungin Eye Drops: a Potential Cost-Savings Exercise

Neoh

Jacob

Leung

et al. 2012

Antimicrob Agents Chemother

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cWhile the successful use of topical caspofungin for patients has been reported, topical caspofungin is not commercially available and its stability is unknown, limiting its usefulness in treating fungal keratitis. Caspofungin (0.5%) eye drops were aseptically prepared, and the concentrations were measured using a validated high-performance liquid chromatography (HPLC) analysis. The preparations remained stable for 28 days under refrigerated condition but not at 25.0°C. Our study supports the cost-saving use of caspofungin eye drops in the clinical setting.F ungal keratitis is difficult to treat, with Candida, Aspergillus, and Fusarium species (1, 16) as the common causative pathogens. Current treatment options for keratomycosis are inadequate (3) given the restricted range of effective topical preparations (e.g., natamycin is the only commercially available antifungal eye drop). Caspofungin is active against a broad spectrum of fungi (MIC 90 , 60 to 2,000 ng/ml) (8,20). After topical delivery in animals, caspofungin has good penetration into eyes with inflammation or corneal abrasion (4, 20), and it has been shown previously to be effective in treating fungal keratitis in rabbits (5, 12). While penetration into intact human eyes may be limited (10), successful application of topical caspofungin alone (7) or in combination with voriconazole (11, 18) for patients with fungal keratitis has been reported. However, the stability of extemporaneously prepared caspofungin eye drops is unknown and the eye drops have to be freshly prepared and used within 24 h (7), making their use in clinical settings uneconomical. This study investigated the stability of 0.5% caspofungin eye drops to support the clinical use of topical caspofungin.The eye drops were prepared aseptically; 10.5 ml of water for injection was added to a 50-mg vial of caspofungin acetate (Cancidas) (2). Aliquots (0.5 ml) of the reconstituted 0.5% solution were then transferred into presterilized, lightproof, low-density polyethylene eye dropper bottles (Sik Hong Holding Pty. Ltd.). The bottles were kept sealed until the day of analysis, stored either (i) under refrigeration (at 4.0 Ϯ 1.0°C; n ϭ 18) or (ii) at room temperature (25.0 Ϯ 1.0°C; n ϭ 18). On days 0, 3, 7, 14, 28, and 56, 50 l of 0.5% caspofungin from each bottle was diluted with 450 l of water to obtain a concentration of 0.5 mg/ml; 10-l aliquots were injected into a high-performance liquid chromatograph (HPLC). Three bottles were analyzed in triplicate for each condition at the designated time points.The HPLC method of Spriet et al. (15) was adapted. A liquid chromatography (LC) system (Shimadzu, Japan) comprised an LC-10AD pump, a DGU-14A degasser, and a CTO-10AC column oven. A PhenoSphere-NEXT C 18 column (pore size, 120 Å; dimensions, 150 by 4.6 mm; and particle size, 5 m; Phenomenex) and a guard column (dimensions, 4 by 2 mm; Phenomenex) were used. The column temperature was 35.0°C, and the flow rate was 1.5 ml/min. The mobile phase comprised Milli-Q water-trifluoroacetic acid (mobile phase ...

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Treatment of Alternaria Keratitis with Intrastromal and Topical Caspofungin in Combination with Intrastromal, Topical, and Oral Voriconazole

Abstract: Intrastromal and topical caspofungin were employed in combination with voriconazole for the management of refractory Alternaria keratitis, with no observed adverse effects.

Cited by 28 publications

References 7 publications

Established and emerging ancillary techniques in management of microbial keratitis: a review

Established and emerging ancillary techniques in management of microbial keratitis: a review

Medical management of Alternaria keratitis with endophthalmitis in a patient with a corneal graft

Stability of Extemporaneously Prepared 0.5-Percent Caspofungin Eye Drops: a Potential Cost-Savings Exercise

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