Topical antiviral gel treats herpetic keratitis

A new topical antiviral treatment for acute herpetic keratitis and associated corneal scarring will soon be widely available to patients in the U.S.

Bausch + Lomb acquired the U.S. assets and rights for Zirgan (ganciclovir ophthalmic gel 0.15%) from Sirion Therapeutics in early June. The U.S. Food and Drug Administration approved Zirgan for treatment of acute herpetic keratitis in September 2009.

Compared with the long-time standard treatment, Viroptic (trifluridine, Monarch Pharmaceuticals), ganciclovir is equally effective but less toxic, experts say.

“Zirgan is a highly effective, potent antiviral requiring less frequent application with significantly less toxicity to the ocular surface,” Richard L. Lindstrom, MD, OSN Chief Medical Editor, told Ocular Surgery News. “It is the first new antiviral to achieve FDA approval in 30 years. It has been used widely in Europe and is the preferred topical antiviral for the treatment of herpes simplex epithelial keratitis in many countries.”

In four studies comprising 377 patients with epithelial herpes simplex virus keratitis, ganciclovir yielded clinical resolution of herpetic keratitis in 72% to 77% of patients; trifluridine resolved infection in 69% to 72% of patients. The most common side effects were blurry vision, ocular irritation, punctate epithelial keratopathy and hyperemia, Dr. Lindstrom said.

Ganciclovir is used in conjunction with oral antiviral agents, especially in cases of herpes simplex virus stromal keratitis, uveitis and endotheliitis, he said.

Reduced toxicity, less frequent dosing

The recommended dosing regimen is one drop in the affected eye five times daily until the ulcer heals, followed by one drop three times daily for 7 days.

“The reason many ophthalmologists prefer [Zirgan] is that it is a potent antiviral with a lower dosing frequency than the predecessor drug, trifluridine, and is less toxic to the ocular surface,” Dr. Lindstrom said.

The new drug equals its predecessor in terms of efficacy and surpasses it in terms of safety, Stephen S. Lane, MD, said in an interview with OSN.

“I think the biggest advantage that Zirgan is going to offer is the advantage of being just as effective, if not more effective, than Viroptic, and having much less toxicity than Viroptic,” Dr. Lane said.

Although effective in treating herpetic keratitis, trifluridine is associated with a degree of toxicity and is known to cause ocular surface irritation, Dr. Lane said.

“First of all, you have to treat the herpes infection and, once you have that under control, then you have to treat the surface condition created by Viroptic in many cases,” he said.

Ganciclovir speeds recovery time and return of vision by rapidly resolving ocular surface irritation and discomfort, Dr. Lane said.

“Clearly we’ve got a medication that, I think, will substantially treat the herpetic infection and at the same time not lead to surface issues, so that when the herpes truly does come under control, the patient’s vision will be much closer to normal than it was as the herpetic disease is controlled,” he said.

The gel’s extended contact with the ocular surface enables less frequent dosing and offers more therapeutic benefit than eye drops, Dr. Lane said.

Corneal scarring, stromal keratitis

Ganciclovir significantly reduces corneal scarring, the primary indication for corneal transplantation in patients with herpetic keratitis, Dr. Lane said.

“If you’re going to anticipate that there’s going to be less transplantation as a result of this drug, then you have to anticipate that it will be a more effective treatment that will take care of the ulceration faster and will be a more potent antiviral than Viroptic,” Dr. Lane said.

“The new drug is indicated for the treatment of dendritic ulcers. Clinical studies show a similar efficacy to topical acyclovir but with less toxicity,” Edward J. Holland, MD, OSN Cornea/External Disease Board Member, told OSN.

“Toxicity has been a major problem with all previous topical antivirals. The longer the epithelium is abnormal, the more likely you are going to get scarring. With ganciclovir we should see a more rapid healing of the epitheliopathy that occurs after dendritic ulcers,” he said.

In addition, a faster resolution of the infectious epithelial lesion may reduce the incidence of stromal keratitis, which results from retention of viral antigens in the stroma, Dr. Holland said.

“If you clear the virus faster, we would potentially expect a potential lowering of the incidence of stromal keratitis,” Dr. Holland said. – by Matt Hasson

• Edward J. Holland, MD, can be reached at the Cincinnati Eye Institute, 580 South Loop Road, Edgewood, KY 41017; 859-331-9000; e-mail: eholland@holprovision.com. Dr. Holland is a consultant for Bausch + Lomb.
• Stephen S. Lane, MD, can be reached at 2950 Curve Crest Blvd., Stillwater, MN 55082; 651-275-3000; fax: 651-275-3099; e-mail: sslane@associatedeyecare.com. Dr. Lane is a paid consultant to Bausch + Lomb but has no proprietary interest in Zirgan.
• Richard L. Lindstrom, MD, can be reached at Minnesota Eye Consultants, 9801 DuPont Ave. S, Suite 200, Bloomington, MN 55431; 952-888-5800; fax: 952-567-6182; e-mail: rllindstrom@mneye.com.

Herpes simplex keratitis is a leading cause of corneal scarring in the U.S. and affects 10 million patients worldwide. The approval of ganciclovir 0.15% gel (Zirgan) offers our patients a new and better treatment. Previous-generation antiviral therapy was poorly soluble and incorporated into both human and viral DNA. Poor solubility required dosing schedules of nine times daily for the first week, and the nonselective nature of the antiviral therapy increased the risk of toxicity and poor healing. Zirgan is a viral-specific therapy with excellent solubility and low toxicity. Dosing is only five times a day for the first week and three times a day afterwards. Zirgan’s low toxicity and high solubility may make this drug a better prophylactic treatment for patients with chronic herpetic disease. Finally, Zirgan has been shown to have activity against epidemic keratoconjunctivitis, and while additional studies need to be performed, this is a new treatment opportunity that should be explored.

– Eric D. Donnenfeld, MD
OSN Cornea/External Disease Board Member