title: Clinical utility of voriconazole eye drops in ophthalmic fungal keratitis.
abstract: Fungal keratitis is one of the major causes of ophthalmic mycosis and is difficult to treat. The range of common antifungal agents available for fungal keratitis remains inadequate and is generally associated with poor clinical outcomes. Voriconazole is a new generation triazole antifungal agent. Only marketed in systemic formulation and, with broad-spectrum activity and high intraocular penetration, voriconazole has demonstrated effectiveness against fungal keratitis. Systemic voriconazole, however, is not without side effects and is costly. Voriconazole eye drops have been prepared extemporaneously and used for the treatment of ophthalmic fungal keratitis. The current article sought to review the literature for evidence related to the effectiveness and safety of topical voriconazole and its corneal penetration into the aqueous humor of the eye. The voriconazole eye drops used are typically of 1% concentration, well tolerated by the eye, and are stable. Despite existing evidence to suggest that the eye drops are effective in the treatment of fungal keratitis, more studies are needed, especially in relation to using the eye drops as first-line and stand-alone treatment, preparation of higher concentrations, and optimal dosing frequency.
authors.affiliation: Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Victoria, Australia.
authors.forename: Daoud
authors.initials: D
authors.lastname: Al-Badriyeh
authors.forename: Chin Fen
authors.initials: CF
authors.lastname: Neoh
authors.forename: Kay
authors.initials: K
authors.lastname: Stewart
authors.forename: David C M
authors.initials: DC
authors.lastname: Kong
references.citation: Curr Opin Ophthalmol. 2004 Aug;15(4):321-7
references.pmid: 15232472
references.citation: Clin Exp Ophthalmol. 2009 Mar;37(2):197-200
references.pmid: 19723128
references.citation: Am J Vet Res. 2006 Feb;67(2):296-301
references.pmid: 16454636
references.citation: Ann Pharmacother. 2004 Mar;38(3):414-7
references.pmid: 14755065
references.citation: Br J Ophthalmol. 2002 Jul;86(7):829-30
references.pmid: 12084760
references.citation: Clin Infect Dis. 1997 Nov;25(5):1222-9
references.pmid: 9402385
references.citation: Br J Ophthalmol. 2008 Jul;92(7):871-8
references.pmid: 18577634
references.citation: Ophthalmology. 1991 Jun;98(6):847-53
references.pmid: 1866135
references.citation: Antimicrob Agents Chemother. 2007 Jan;51(1):239-44
references.pmid: 17060517
references.citation: Ophthalmology. 1998 Mar;105(3):522-6
references.pmid: 9499785
references.citation: Aust N Z J Ophthalmol. 1994 May;22(2):105-10
references.pmid: 7917262
references.citation: Adv Drug Deliv Rev. 2006 Nov 15;58(11):1131-5
references.pmid: 17097758
references.citation: Cornea. 1996 Jul;15(4):373-5
references.pmid: 8776563
references.citation: J Antimicrob Chemother. 1994 Feb;33(2):203-13
references.pmid: 8182001
references.citation: Curr Eye Res. 2003 Feb;26(2):113-7
references.pmid: 12815530
references.citation: Am J Ophthalmol. 1991 Nov 15;112(5):562-6
references.pmid: 1951595
references.citation: J Clin Microbiol. 1980 Sep;12(3):455-61
references.pmid: 7217337
references.citation: Indian J Ophthalmol. 1987;35(5-6):157-60
references.pmid: 2854820
references.citation: Am J Ophthalmol. 2004 May;137(5):820-5
references.pmid: 15126145
references.citation: J Med Vet Mycol. 1994;32(4):235-56
references.pmid: 7983569
references.citation: J Ocul Pharmacol Ther. 2008 Feb;24(1):87-90
references.pmid: 18370878
references.citation: Acta Ophthalmol Scand. 2004 Dec;82(6):762-4
references.pmid: 15606478
references.citation: J Cataract Refract Surg. 2008 Feb;34(2):183-4
references.pmid: 18242428
references.citation: Curr Eye Res. 1986 Nov;5(11):877-82
references.pmid: 3490954
references.citation: Clin Infect Dis. 2000 Apr;30(4):696-709
references.pmid: 10770732
references.citation: Graefes Arch Clin Exp Ophthalmol. 2006 Jul;244(7):782-7
references.pmid: 16133016
references.citation: Ann Pharmacother. 2009 Dec;43(12):2103-7
references.pmid: 19861430
references.citation: Cornea. 2002 Aug;21(6):555-9
references.pmid: 12131029
references.citation: Chin Med J (Engl). 2009 Aug 20;122(16):1884-8
references.pmid: 19781365
references.citation: Arch Ophthalmol. 2004 Jan;122(1):42-7
references.pmid: 14718293
references.citation: Surv Ophthalmol. 1994 Jul-Aug;39(1):3-22
references.pmid: 7974189
references.citation: Int Ophthalmol Clin. 2007 Spring;47(2):47-59
references.pmid: 17450006
references.citation: Sabouraudia. 1985 Aug;23(4):295-301
references.pmid: 3901331
references.citation: Arch Ophthalmol. 1997 Oct;115(10):1320-4
references.pmid: 9338682
references.citation: Arch Ophthalmol. 2008 Jan;126(1):18-22
references.pmid: 18195213
references.citation: Cornea. 1987;6(4):238-45
references.pmid: 3319407
references.citation: Arch Ophthalmol. 1981 Jun;99(6):1081-4
references.pmid: 6263236
references.citation: Cornea. 2009 Jan;28(1):116-9
references.pmid: 19092423
references.citation: Clin Exp Dermatol. 1989 Mar;14(2):110-3
references.pmid: 2689012
references.citation: Br J Ophthalmol. 1997 Nov;81(11):965-71
references.pmid: 9505820
references.citation: Eye (Lond). 2003 Nov;17(8):852-62
references.pmid: 14631389
references.citation: Clin Infect Dis. 2001 Mar 1;32(5):686-93
references.pmid: 11229835
references.citation: J Clin Pharmacol. 1996 May;36(5):452-61
references.pmid: 8739024
references.citation: Clin Microbiol Rev. 1994 Oct;7(4):479-504
references.pmid: 7834602
references.citation: Clin Microbiol Rev. 2000 Oct;13(4):662-85
references.pmid: 11023963
references.citation: Clin Exp Ophthalmol. 2007 Mar;35(2):124-30
references.pmid: 17362452
references.citation: Ophthalmology. 1997 Jul;104(7):1107-11
references.pmid: 9224461
references.citation: Expert Opin Pharmacother. 2004 Apr;5(4):865-74
references.pmid: 15102569
references.citation: Am J Health Syst Pharm. 2009 Aug 15;66(16):1478-83
references.pmid: 19667005
references.citation: Br J Ophthalmol. 1995 Nov;79(11):1024-8
references.pmid: 8534648
references.citation: Am J Ophthalmol. 1992 Oct 15;114(4):437-40
references.pmid: 1415454
references.citation: Antimicrob Agents Chemother. 2006 Jan;50(1):262-8
references.pmid: 16377696
references.citation: Ann Acad Med Singap. 1998 Jul;27(4):540-6
references.pmid: 9791663
references.citation: Clin Microbiol Rev. 2003 Oct;16(4):730-97
references.pmid: 14557297
references.citation: Pharmacoeconomics. 1995 Oct;8(4):350-61
references.pmid: 10155676
references.citation: Ophthalmology. 2000 Mar;107(3):555-8
references.pmid: 10711895
references.citation: Br J Ophthalmol. 2003 Oct;87(10):1235-7
references.pmid: 14507756
references.citation: Med Mycol. 2007 Jun;45(4):305-20
references.pmid: 17510855
references.citation: CLAO J. 1997 Oct;23(4):275-81
references.pmid: 9348453
references.citation: Cornea. 1997 Nov;16(6):700
references.pmid: 9395885
references.citation: CLAO J. 2002 Jul;28(3):111-8
references.pmid: 12144228
references.citation: Am J Ophthalmol. 2007 Feb;143(2):222-227
references.pmid: 17258521
references.citation: Bull World Health Organ. 2001;79(3):214-21
references.pmid: 11285665
references.citation: Br J Ophthalmol. 2000 Aug;84(8):932-3
references.pmid: 10979655
references.citation: Cornea. 2001 Jul;20(5):505-8
references.pmid: 11413407
references.citation: Am J Ophthalmol. 2005 Jan;139(1):135-40
references.pmid: 15652837
references.citation: Clin Infect Dis. 2003 Mar 1;36(5):630-7
references.pmid: 12594645
references.citation: Trans Am Ophthalmol Soc. 2003;101:183-9; discussion 189
references.pmid: 14971576
references.citation: J All India Ophthalmol Soc. 1969 Oct;17(5):171-200
references.pmid: 4914371
references.citation: Cochrane Database Syst Rev. 2012 Feb 15;(2):CD004241
references.pmid: 22336802
references.citation: Am J Ophthalmol. 1985 Aug 15;100(2):293-8
references.pmid: 4025470
references.citation: Lancet. 1998 May 2;351(9112):1312-6
references.pmid: 9643793
references.citation: Lancet Infect Dis. 2005 Dec;5(12):775-85
references.pmid: 16310149
references.citation: Clin Exp Pharmacol Physiol. 2000 Jul;27(7):558-62
references.pmid: 10874518
references.citation: Antimicrob Agents Chemother. 2009 Feb;53(2):798-9
references.pmid: 19001119
references.citation: Int J Antimicrob Agents. 2006 Apr;27(4):274-84
references.pmid: 16563707
references.citation: Antimicrob Agents Chemother. 2005 Apr;49(4):1359-63
references.pmid: 15793112
references.citation: Arch Ophthalmol. 2008 Mar;126(3):343-6
references.pmid: 18332313
references.citation: Ann Pharmacother. 2009 Jun;43(6):1139-42
references.pmid: 19435962
references.citation: Ophthalmology. 1994 Jun;101(6):1005-13
references.pmid: 8008340
references.citation: Antimicrob Agents Chemother. 2009 Jul;53(7):3153-5
references.pmid: 19433565
references.citation: Antimicrob Agents Chemother. 1987 Jan;31(1):6-10
references.pmid: 3032091
references.citation: Surv Ophthalmol. 1996 Sep-Oct;41(2):142-54
references.pmid: 8890440
references.citation: Arch Ophthalmol. 2004 Nov;122(11):1687-92
references.pmid: 15534131
references.citation: Expert Opin Pharmacother. 2001 Nov;2(11):1849-57
references.pmid: 11825321
references.citation: Antimicrob Agents Chemother. 2006 Feb;50(2):658-66
references.pmid: 16436724
references.citation: Ophthalmic Surg. 1985 May;16(5):296-300
references.pmid: 4011116
references.citation: Arch Ophthalmol. 1979 Sep;97(9):1703-6
references.pmid: 475641
references.citation: Medicine (Baltimore). 1991 Nov;70(6):398-409
references.pmid: 1956281
references.citation: Am J Ophthalmol. 1984 Nov;98(5):552-7
references.pmid: 6541878
references.citation: Mycoses. 1991 May-Jun;34(5-6):251-4
references.pmid: 1795722
references.citation: Clin Infect Dis. 2005 Jun 15;40(12):e110-2
references.pmid: 15909252
references.citation: Cornea. 2007 Oct;26(9):1082-6
references.pmid: 17893539
references.citation: Arch Ophthalmol. 2007 Jun;125(6):789-93
references.pmid: 17562990
references.citation: J Clin Microbiol. 2003 May;41(5):2261-4
references.pmid: 12734297
references.citation: Ann Pharmacother. 1997 Apr;31(4):445-56
references.pmid: 9101008
references.citation: Cornea. 2000 May;19(3):307-12
references.pmid: 10832689
references.citation: Cornea. 1997 May;16(3):295-9
references.pmid: 9143801
references.citation: Am J Ophthalmol. 1975 May;79(5):719-51
references.pmid: 1096622
references.citation: Ophthalmology. 2000 Mar;107(3):574-80
references.pmid: 10711898
references.citation: Am J Pathol. 1977 Dec;89(3):718-808
references.pmid: 339743