Refractive Eyecare — September 2010
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Ganciclovir Gel 0.15%: An Important New Option For The Treatment Of Herpetic Keratitis (Dendritic Ulcers)
Ron Melton, OD, FAAO, and Randall Thomas, OD, FAAO

Herpetic ocular infections remain a leading infectious cause of corneal blindness and a potential indication for corneal transplant. After years of waiting for a topical treatment, we now have ZIRGAN® (ganciclovir ophthalmic gel) 0.15% for the treatment of dendritic herpetic keratitis. Its combination of efficacy, safety, and product attributes now makes it our drug of choice for the treatment of acute herpetic keratitis (dendritic ulcers).

Since 1995, European doctors have had ganciclovir ophthalmic gel 0.15% available for the treatment of herpes keratitis, and recently Bausch + Lomb launched this topical ocular antiviral in the United States under the trade name ZIRGAN®.

Overall, US clinicians see approximately 50,000 new or recurrent cases of herpes keratitis each year.1 While few comprehensive optometrists see more than an occasional case of herpetic keratitis, its classic presentation with dendritic ulcers remains high on our radar due to its potential to progress, causing corneal scarring and permanently compromised eyesight (Figures 1 and 2). Indeed, herpetic keratitis remains a leading infectious cause of corneal blindness and one of the most frequent indications for corneal transplant in the United States.1

A New Option

In late 2009, the FDA approved ZIRGAN for the treatment of acute herpetic keratitis (dendritic ulcers) based on the results of several clinical trials conducted in Europe, Africa, and Asia. The first was an open-label, randomized, controlled multicenter trial with 164 patients.2,3 At day 7, treatment with ganciclovir gel produced clinical resolution (healed ulcers) in 77% (55/71) of patients vs 72% (48/67) of patients receiving Acyclovir 3% ophthalmic ointment. (Acyclovir ointment is only available outside the United States).

An additional three randomized, single-masked, controlled, multicenter clinical trials enrolled a total of 213 patients. Again ZIRGAN proved “non-inferior” to acyclovir ointment in patients with dendritic ulcers, with clinical resolution at day 7 in 72% (41/57) of those treated with ZIRGAN vs 69% (34/49) acyclovirtreated patients.2,4-7

As clinicians, we were particularly impressed with the patient tolerability ratings that came out of these studies, with 75% of patients rating the tolerability of ZIRGAN as “excellent” and 97% rating it “good” or “excellent” (Table 1).

Important Risk Information for ZIRGAN

ZIRGAN is indicated for topical use only, and patients should not wear contact lenses if they have signs or symptoms of herpetic keratitis or during the course of therapy with ZIRGAN. The most common adverse reactions reported in patients were blurred vision (60%), eye irritation (20%), punctate keratitis (5%), And conjunctival hyperemia (5%). Please see the complete information about ZIRGAN in the brief summary of the ZIRGAN full prescribing information provided on page 4.

Optimizing Treatment of Dendritic Keratitis

Diagnosis of epithelial herpes keratitis rests on its classic dendritic presentation, generally evident with fluorescein staining. Without treatment, most cases of superficial dendritic keratitis will resolve without permanently damaging vision. But as clinicians, we have no way of predicting which infections will progress, so early and effective treatment is imperative to minimize the risk of secondary stromal immune keratitis, corneal scarring, and lasting vision damage.

Treatment likewise speeds relief of the symptoms that motivate patients to seek medical care. These typically include pain, a gritty or “foreign body” sensation, and redness. A serous discharge may be present, and the clinician may see a follicular-type reaction to the inferior palpebral conjunctiva.

It is a general truth in medicine that the sooner effective treatment is initiated, the more rapid will be the clinical resolution. This is particularly important in a condition like herpes keratitis where the sequelae can be devastating. It behooves clinicians to be vigilant in their diagnostic observations and to treat dendritic keratitis without hesitation as soon as the diagnosis is made.

The patient should instill one drop of ZIRGAN in the affected eye five times per day (every 3 hours while awake) until the corneal ulceration heals, then one drop three times per day for another 7 days. Follow-up is important. Signs of inadequate resolution may indicate patient noncompliance and the need for further counseling in this regard.

The gel formulation helps retain the drug on the eye and is advantageous for adult and pediatric use. (ZIRGAN was clinically evaluated in patients 2 years and older.)

Considering Alternatives

Before the recent introduction of ZIRGAN, US doctors had only one topical agent for treating herpes keratitis. That was 1% trifluridine solution, a drug with documented toxicity with continuous administration for periods exceeding 21 days.8 In addition, trifluridine solution incorporates the mercurial preservative thimerosal, which can produce sensitization and significant allergic reaction.9 This risk of sensitization increases with repeated use and is a significant concern in a potentially recurring condition like herpetic keratitis.

Used as directed, trifluridine also has less convenient dosing than ZIRGAN. At the inception of therapy, patients must instill trifluridine every 2 hours while awake, up to nine times a day. (Recommended dosing is every 3 hours, five times a day for the initial dosing regimen of ZIRGAN.) Trifluridine also must be kept refrigerated before dispensing, which can limit pharmacy availability. In our experience, this can delay the initiation of treatment and/or require office staff to help patients locate pharmacies that have the medication on hand.

Another option for treating dendritic keratitis is oral therapy with acyclovir, valacyclovir, or famciclovir. Unlike topical ganciclovir, the systemic administration of thesse drugs may cause nausea in some patients, and patients with impaired renal function may be at increased risk of overdose toxicity.10-12

Of particular interest to US eye physicians are the advantages associated with ganciclovir’s prodrug character and dual mechanism of action (see sidebar on page 3). Finally, an additional benefit of the ophthalmic gel formulation used in ZIRGAN is that patients with a compromised ocular surface may find gel formulations soothing.

Proven efficacy, reduced dosing frequency, gel formulation, and documented patient preference all make ZIRGAN an excellent option for the treatment of acute herpetic keratitis (dendritic ulcers).


Ron Melton, OD, FAAO, and Randall Thomas, OD, MPH, FAAO, lecture extensively as the principles of Educators in Primary Eye Care, LLC, in Concord, NC. They maintain private practices in Charlotte and Concord, NC, respectively, and serve as adjunct professors at the Pennsylvania College of Optometry (Salus University). Drs. Melton and Thomas serve as consultants to numerous ophthalmic companies, including Alcon, Bausch + Lomb, Carl Zeiss Meditec, ICARE - USA, Jobson Publishers, and RPS.


1. Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea. 2001 Jan;20(1):1-13.

2. Colin J, Hoh HB, Easty DL, Herbort CP, Resnikoff S, Rigal D, Romdane K. Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis. Cornea 1997;16(4):393-9.

3. Transphyto. Etude multicentrique comparative de l’effet de l’instillation de VIRGAN® dans l’herpès cornéen superficiel. Clermont-Ferrand. France: Rapport Clinique No 64GV 550/04.92- 66GV 550/06.92;1994. Dossier d’AMM.

4. Hoh HB, Hurley C, Claoue C, Viswalingham M, Easty DL, Goldschmidt P, Collum LM. Randomised trial of ganciclovir and acyclovir in the treatment of herpes simplex dendritic keratitis: a multicentre study. Br J Ophthalmol 1996;80:140-3.

5. Transphyto. Etude Clinique comparative multicentrique de l’effet de l’instillation de GV 550 dans l’herpès cornéen superficiel. Clermon-Ferrand. France: Rapport Clinique No 42-2.GV 550/02.90;1993. Dossier d’AMM.

6. Transphyto. Etude Clinique comparative multicentrique de l’effet de l’instillation de GV 550 dans l’herpès cornéen superficiel. Clermon- Ferrand. France: Rapport Clinique No 44.GV 550/12.90-46.GV 550/07.90;1993. Dossier d’AMM.

7. Transphyto. Etude Clinique comparative randomisée en simple insu de l’effet de l’instillation de ganciclovir gel ophtalmique dans le traitement de l’herpès cornéen superficiel. Clermont- Ferrand. France: Rapport clinique No 47.GV 550/09.90;1993. Dossier d’AMM.

8. Viroptic (trifluridine ophthalmic solution) Prescribing Information. Available from URL: [Accessed 2010 July 2].

9. Noecker R. Effects of common ophthalmic preservatives on ocular health. Adv Ther. 2001;18(5):205-15.

10. Zorivax (acyclovir) Prescribing Information. Available from URL: [Accessed 2010 July 2].

11. Valtrex (valacyclovir hydrochloride) Prescribing Information. Available from URL: [Accessed 2010 July 2].

12. Famvir (famciclovir) Prescribing Information. Available from URL: [Accessed 2010 July 2].

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