A Double-blind, Multicenter Clinical Trial of Acyclovir vs Idoxuridine for Treatment of Epithelial Herpes Simplex Keratitis

McCulley, James P.; Binder, Perry S.; Kaufman, Herbert E.; O’Day, Denis M.; Poirier, R. H.

doi:10.1016/s0161-6420(82)34668-0

Cited by 36 publications

(35 citation statements)

References 17 publications

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“…Sixty-three trials enrolled patients with dendritic epithelial keratitis, including two trials that may have also enrolled other types of HSV epithelial keratitis (Chen 2008; Yang 2000); 38 trials enrolled participants with either dendritic or geographic epithelial keratitis (Blake 1977; Carmassi 1993; Colin 1981; Colin 1984; Colin 1997a; Colin 1997b; Colin 2007a; Colin 2007b; Coster 1976; Coster 1980; Daniel 1972; de Koning 1983; Denis 1983; Fulhorst 1972; Genée 1987; Guerra 1979; Haut 1983; Hoang-Xuan 1984; Huang 2008a; Jackson 1984; Kitano 1985; Laibson 1964; Li 2008; Markham 1977; Maychuk 1988; McCulley 1982; McGill 1974; Patterson 1967a; Pavan-Langston 1976; Pavan-Langston 1981; Serifoglu 1987; Sugar 1980; Sundmacher 1984a; Van Bijsterveld 1989; Wellings 1972; Yeakley 1981; Young 1982); two trials were restricted to patients with geographic keratitis (Collum 1985; Coster 1979); and three trials provided insufficient information to ensure that all participants had dendritic epithelial keratitis (Burns 1963; Davidson 1964; Klauber 1982). Of studies that enrolled eyes with either dendritic or geographic epithelial keratitis, 24 trials provided information on the numbers with dendritic epithelial keratitis (1469) and with geographic epithelial keratitis (326), yielding a median dendritic to geographic epithelial keratitis ratio of 5.0:1 (interquartile range, 3.5:1 to 9.5:1).…”

Section: Resultsmentioning

confidence: 99%

“…Females are under-represented in clinical trials of chemotherapy (Van Spall 2007), and women of child-bearing potential may have been selectively excluded from ophthalmic antiviral treatment trials because of an unproven concern of teratogenicity during pregnancy (Chung 2004; Itoi 1975; Pasternak 2010). Neither gender nor age influences corneal healing during antiviral therapy (de Koning 1982; de Koning 1983; Jackson 1984; McCulley 1982; Van Bijsterveld 1980; Van Bijsterveld 1989). …”

Section: Discussionmentioning

confidence: 99%

“…Neither the number of previous episodes nor the duration of symptoms prior to initiating antiviral treatment affected healing rate in most studies that evaluated these preceding factors (Blake 1977; Høvding 1989; Jensen 1982; La Lau 1982; McCulley 1982; Pavan-Langston 1981; Sugar 1980; Van Bijsterveld 1989; Yeakley 1981). The prior use of antiviral agents did not affect relative treatment response (Jensen 1982; McCulley 1982).…”

Section: Discussionmentioning

confidence: 99%

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Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

Wilhelmus

2010

Cochrane Database of Systematic Reviews

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

Wilhelmus

2010

Cochrane Database of Systematic Reviews

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“…16 Topical acyclovir 3% ointment is more effective and better tolerated than idoxuridine, vidarabine, and trifluridine; [17][18][19] it is commonly used in Europe for the treatment of HSK. Although acyclovir can be prescribed in the US for oral and dermatological administration, no ophthalmic preparation is available.…”

Section: Acyclovirmentioning

confidence: 99%

Ganciclovir Gel—A New Topical Treatment for Herpetic Keratitis

Foster¹

2012

US Ophthalmic Review

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“…Herpes simplex virus (HSV) is the etiologic agent responsible for a variety of diseases, including ocular herpetic keratitis, an illness that can lead to severe corneal scarring and blindness (16,23). Patients with this condition may be treated with several drugs, including the nucleoside analogs acyclovir (ACV) and trifluorothymidine (TFT) (21,31).…”

mentioning

confidence: 99%

In vitro toxicological evaluation of ISIS 1082, a phosphorothioate oligonucleotide inhibitor of herpes simplex virus

Crooke

Hoke

Shoemaker

1992

Antimicrob Agents Chemother

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ISIS 1082, a phosphorothioate oligonucleotide targeted to a translation initiation codon of herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) virion capsid protein UL13 inhibits in vitro viral replication. To better understand the pharmacological properties of ISIS 1082, we examined its effects in nonvirally infected HeLa cells by using a number of cytotoxicity assays. Our data indicate that ISIS 1082 had no effect on HeLa cell viability as measured by cellular proliferation and clonogenic assays at concentrations as high as 100 p1M. Additionally, DNA, RNA, and protein syntheses were only inhibited by 25% in cells treated with 100 FM ISIS 1082. The effects of ISIS 1082 on DNA synthesis were compared with those of acyclovir and trifluorothymidine, two clinically used antiherpetic agents. Acyclovir displayed effects similar to that of ISIS 1082. However, trifluorothymidine, which has been reported to be a potential mutagen and teratogen, significantly altered DNA replication at concentrations from 1 to 100 p,M. Isolated HeLa DNA polymerases were inhibited by the compound, with a 50%o inhibitory concentration of 2 pM. The in vitro antiviral (K.Draper and V. Brown-Driver, submitted for publication; K. G. Draper and V. Brown-Driver, Antiviral Res. Suppl. 1:106, 1991) and cytotoxicity studies suggest that ISIS 1082 is a selective, nontoxic, antiherpetic therapeutic agent.Herpes simplex virus (HSV) is the etiologic agent responsible for a variety of diseases, including ocular herpetic keratitis, an illness that can lead to severe corneal scarring and blindness (16,23). Patients with this condition may be treated with several drugs, including the nucleoside analogs acyclovir (ACV) and trifluorothymidine (TFT) (21, 31). Although each of the antiviral drugs has displayed clinical efficacy, the emergence of resistant strains of HSV and the occurrence of toxic and hypersensitivity reactions to the compounds underscore the need for more specific, potent, and less toxic antiviral therapy (25).The theoretical selectivity of antisense oligonucleotides for specific genomic and viral RNA targets makes their use as therapeutic agents extremely attractive (17,29,32). Our laboratory has designed and tested several sequence-specific oligonucleotides targeted to the translation initiation regions of HSV mRNAs (9, 10). ISIS 1082, a phosphorothioate oligonucleotide 21 nucleotides in length (5' GCCGAGGTC CATGTCGTACGC 3') is complementary to a translation initiation codon region within the UL13 open reading frame of HSV. The UL13 sequence is highly conserved within strains of HSV, and the target sites for ISIS 1082 are identical in HSV type 1 (HSV-1) and HSV-2, except for the 3'-terminal base of the target mRNAs. On the basis of sequence homology with other virus RNAs, the UL13 gene product is postulated to be a virion capsid protein with phosphotransferase activity (7,24). ISIS 1082 inhibited HSV-1 replication in cell culture in a dose-dependent manner, with 50% inhibitory concentrations (IC50s) ranging from 0.4...

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A Double-blind, Multicenter Clinical Trial of Acyclovir vs Idoxuridine for Treatment of Epithelial Herpes Simplex Keratitis

Cited by 36 publications

References 17 publications

Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis

Ganciclovir Gel—A New Topical Treatment for Herpetic Keratitis

In vitro toxicological evaluation of ISIS 1082, a phosphorothioate oligonucleotide inhibitor of herpes simplex virus

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