Issue: February 2013
November 01, 2012
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Topical antiviral ointment may treat adenoviral conjunctivitis

Clinical trial will investigate whether ganciclovir can prevent the infection from spreading and decrease the number of days of viral shedding.

Issue: February 2013
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Based on earlier studies that showed ganciclovir is active against adenovirus, the most common cause of acute follicular conjunctivitis, a clinical trial was launched to determine whether treatment with topical ganciclovir would reduce the effects of the condition.

According to Jay S. Pepose, MD, PhD, lead investigator, the use of Zirgan (topical ganciclovir, Bausch + Lomb) may also lessen the spread of adenoviral conjunctivitis.

“I wouldn’t at all be surprised if Zirgan not only decreases the number of days of shedding but that it might also lower the incidence of developing subepithelial infiltrates, because that is an immune response to the antigen,” Pepose said. “If you can shut down the viral proliferation earlier on, we may have less of an immune response.”

Adenovirus vs. herpes simplex virus

Topical ganciclovir is not approved by the U.S. Food and Drug Administration for the treatment of adenoviral conjunctivitis; it was, however, approved by the FDA in 2009 for the treatment of acute herpetic keratitis, which is caused by herpes simplex virus (HSV).

According to Pepose, adenovirus can spread epidemically, while HSV is self-limiting. Additionally, adenovirus infection occurs more commonly in summer and winter, whereas HSV does not have a seasonal variation.

Topical ganciclovir works by penetrating the infected cell and preventing the viral DNA from replicating, Pepose said.

Jay S. Pepose, MD, PhD

Jay S. Pepose

Because topical ganciclovir is an effective treatment for HSV, Pepose said he believes it may also be helpful in treating adenoviral conjunctivitis.

“Even though ophthalmologists might presume that cause of a patient’s acute follicular conjunctivitis is adenovirus, about 20% of acute follicular conjunctivitis is caused by herpes simplex, and the beauty of ganciclovir is that it is effective against herpes simplex,” he said. “So, if proven effective, they would have cross-coverage in the case that the etiological diagnosis wasn’t right and the virus is not adeno but herpes.”

Clinical trial

According to ClinicalTrials.gov, Pepose and colleagues will examine whether topical ganciclovir gel can reduce the number of days of adenovirus shedding, the chances of fellow eye involvement, the spread of the virus to other people and objects, the incidence and severity of subepithelial infiltrates, and the degree of bulbar conjunctival injection and ocular discomfort.

The randomized, double-masked clinical trial will enroll approximately 80 participants who have tested positive for adenoviral infection. Forty participants will receive 0.15% ganciclovir, and the other 40 will receive placebo 0.3% hypromellose gel.

Both gels will be applied five times daily for the first 7 days, then three times daily for the subsequent 7 days. Final follow-up will be at 21 days of treatment.

In an earlier study to investigate ganciclovir for the treatment of herpetic keratitis, Tabbara compared 0.15% ganciclovir to preservative-free artificial tears. Study results indicated that the average recovery time for ganciclovir-treated patients was 7.7 days, compared to 18.5 days for patients using artificial tears.

Complete resolution of herpetic keratitis was observed in all 16 patients — within 7 days for 11 patients and within 3 weeks for the remaining five patients.

Pepose said he is also interested in the results of a study investigating a combination therapy of dexamethasone and povidone-iodine to treat viral conjunctivitis.

“Will it activate both the intracellular and extracellular adenovirus, or is it just going to activate extracellular?” he asked. “They both may be important in controlling the life cycle of viral applications.” – by Ashley Biro

References:
Pepose JS, Price FW Jr., Goldberg D, et al. A placebo controlled comparison of topical Zirgan versus Genteal gel for the treatment of adenovirus conjunctivitis. http://www.clinicaltrials.gov/ct2/show/NCT01533480. Accessed August 9, 2012.
Tabbara KF. Treatment of herpetic keratitis. Ophthalmology. 2005;112(9):1640.
U.S. Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 22-211. Summary review. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022211s000_SumR.pdf. Accessed September 12, 2012.
For more information:
Jay S. Pepose, MD, PhD, can be reached at Pepose Vision Institute, 1815 Clarkson Road, Chesterfield, MO 63017; 636-728-0111; email: jpepose@peposevision.com.
Disclosure: Pepose is a consultant for Bausch + Lomb.