A systematic review and meta-analysis to compare the efficacy of acyclovir 3% ophthalmic ointment to idoxuridine in curing herpetic keratitis by Day 7 of treatment
Diane E BaldersonGengqian CaiMichael FriesDavid KleinmanMegan McLaughlinTrupti TrivediJohn I. WurzelmannSheila B Young
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Abstract:
This objective of the review and analysis is to demonstrate that acyclovir (ACV) 3% ophthalmic ointment is superior to idoxuridine (IDU) in treating herpetic keratitis (HK) presenting as dendritic and geographic ulcer sub-types. Data sources: Publications in human subjects were identified by searching the Ovid MEDLINE database through April 2011, combining medical subject headings (MESH) "Keratitis, Herpetic/" AND "Acyclovir/" limiting by the key words "topical" OR "ointment" and also restricted to MESH "Administration, Topical/" OR "Ointments/". The results were cross checked with the references used in the Cochrane Database Syst Rev. 1:1–134, 2009 and GlaxoSmithKline clinical documents related to acyclovir. Study selection: Randomized, double-masked studies in subjects diagnosed with HK with head to head comparator arms of ACV ophthalmic ointment and topical IDU that had actual or calculable healing rates at Day seven. Data extraction: Data independently extracted from identified articles by two authors of this manuscript. Data synthesis: Data from seven randomized, controlled trials (RCT) evaluating 432 subjects that met inclusion criteria (214 were treated with ACV and 218 were treated with IDU) and had Day seven healing rates calculable. All sub-classified lesions were identified as either dendritic ulcers (n = 185) or geographic ulcers (n = 35). The Cochran-Mantel-Haenszel (CMH) method in Biometrics 10:417-51, 1954 and JNCI 22:719-48, 1959, controlling for study, was performed as the primary analysis using SAS v9. Homogeneity was assessed using Breslow-Day-Tarone (BDT) test in IARC 1:1-32, 1980 and Biometrika 72:91-5, 1985. The analysis was performed with outliers removed to assess their impact. ACV showed statistically significant greater odds of healing HK at Day seven in all subjects (Odds Ratio 3.95, 95% CI2.60, 6.00, p <0.0001), in dendritic ulcers (Odds Ratio 4.22, 95% CI: 2.14, 8.32; p < 0.0001) and geographic ulcers (Odds Ratio 5.31, 95% CI: 1.09, 25.93; p =0.0244). ACV 3% ophthalmic ointment is a valuable intervention for dendritic and geographic corneal ulcers. ACV and IDU were generally well tolerated in the studies reviewed.Keywords:
Idoxuridine
Aciclovir
Topical medication
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A double controlled clinical study comparing idoxuridine (IDU) and vidarabine (ara-A) in the treatment of uncomplicated herpes simplex keratitis was carried out with 10 patients. No statistically significant differences occurred in the healing time between IDU (6.8 days) and ara-A (8.0 days). Two moderately adverse reactions to IDU were observed, but no demonstrable ocular toxicity was noted with ara-A.
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Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of aciclovir-resistant herpes simplex virus keratitis treated with systemic foscarnet and present a review of the pharmacological options available to manage this condition.
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Valaciclovir
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OBJECTIVE To study the application of Carbopol gel to be used as the base of aciclovir ophthalmic gel. METHODS The aciclovir eye ointment was used as control group,and the gel as test group, the drug action on treatment of experimental rabbits herpes simplex keratitis (HSK) was compared. RESULTS There was no significant difference between the two groups (P0.05). CONCLUSIONS The drug action of the gel containing carbopol base on the treatment of experimental rabbits herpes simplex keratitis (HSK) is same as the eye ointment.
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Bilateral herpes simplex keratitis was induced in rabbit corneas. The infected corneas were treated with either neutral red dye followed by exposure to fluorescent light or with idoxuridine ointment. Dye-light treatment produced a faster cure rate than idoxuridine.
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Poly I:C-IDU treatment was given to 26 eyes with superficial, and 20 eyes with stromal herpetic keratitis. In superficial keratitis the results were not superior to those of conventional IDU treatment. The favourable results observed in stromal keratitis were attributed to penetration of poly I:C into the corneal stroma, which also can explain the small number of recurrences. Side effects were not observed.
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Idoxuridine
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In experimental herpetic keratitis in rabbits, aciclovir proved to have a high antiviral activity, superior to that of idoxuridine. Viral encephalitis was partly prevented by local treatment and fully by systemic treatment with aciclovir.
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Idoxuridine
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• Patients with active dendritic herpetic keratitis that was unresponsive to topical idoxuridine or vidarabine therapy were treated topically with a 1% solution of trifluridine. The dendritic ulcers healed in an average time of 6.1 days. All patients tolerated the drug well except for one patient in whom a reversible crystalline epithelial keratitis developed.
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