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.
BACKGROUND
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.


METHODS



METHODS
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.


METHODS
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.


METHODS
Data independently extracted from identified articles by two authors of this manuscript.


RESULTS
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.


RESULTS
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).


CONCLUSIONS
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.
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, Durham, NC, 27709, USA. diane.e.balderson@gsk.com.
Diane E
DE
Balderson
GlaxoSmithKline, 2301 Renaissance Boulevard, King of Prussia, Upper Merion, PA, 19406-2772, USA. Gengqian.2.Cai@gsk.com.
Gengqian
G
Cai
CSL Behring Biotherapies for Life, 1020 First Avenue, King of Prussia, Upper Merion, PA, 19406-0901, USA. michael.alan.fries@gmail.com.
Michael A
MA
Fries
Flaum Eye Institute, University of Rochester, Rochester, NY, USA. dave@davidkleinman.com.
David M
DM
Kleinman
GlaxoSmithKline, 2301 Renaissance Boulevard, King of Prussia, Upper Merion, PA, 19406-2772, USA. Megan.M.McLaughlin@gsk.com.
Megan M
MM
McLaughlin
GlaxoSmithKline, 2301 Renaissance Boulevard, King of Prussia, Upper Merion, PA, 19406-2772, USA. trivedisports@gmail.com.
Trupti M
TM
Trivedi
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, Durham, NC, 27709, USA. john.i.wurzelmann@gsk.com.
John I
JI
Wurzelmann
GlaxoSmithKline, 2301 Renaissance Boulevard, King of Prussia, Upper Merion, PA, 19406-2772, USA. sheila.b.young@gsk.com.
Sheila B
SB
Young
D000212:Acyclovir / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007065:Idoxuridine / Q000008:administration & dosage*; D016849:Keratitis, Herpetic / Q000188:drug therapy*; D009824:Ointments; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D009824:Ointments; D007065:Idoxuridine; D000212:Acyclovir