Herpetic Eye Disease: The Tide is Turning

Herpetic eye disease is a common and potentially devastating manifestation of a class of viruses that include herpes simplex virus (HSV) and herpes zoster virus (HZV). Although HZV is contradistinct from HSV, the treatment of herpetic eye disease has been experiencing a slow but inexorable shift towards the use of oral antiviral therapy with an increasing focus on prophylaxis for herpex simplex keratitis and a varicella-zoster vaccine for herpes zoster ophthalmicus. Indeed, a recent comparison between oral valacyclovir and topical acyclovir by Sozen and colleagues found that systemic antiviral therapy is more effective as a therapy for acute herpes simplex keratitis. Specifically, patients treated with oral valacyclovir resolved more quickly and had a more rapid decrease in symptoms such as photophobia, and the infrequency of adverse reactions associated with systemic acyclovir or valacyclovir has made the administration of topical acyclovir an uncommon scenario in all but those patients who are unable to tolerate oral antivirals. Meanwhile, the introduction of a varicella-zoster vaccine has opened up new possibilities for the treatment of herpes zoster ophthalmicus.

An Ounce of Prevention

An important issue affecting the treatment of herpes simplex concerns the effectiveness of antivirals as prophylaxis against the recurrence of acute herpes simplex keratitis. Many cornea specialists feel that long-term prophylaxis is indicated in all patients with stromal keratitis, and oral acyclovir has been the mainstay of therapy for this purpose, but its short half-life and requisite frequent dosing have prompted some to use valacyclovir or famciclovir as prophylactic agents. Both valacyclovir and famciclovir are pro-drugs that can be converted to active forms which accumulate intracellularly, allowing therapeutic intracellular levels to be obtained without large doses or frequent administration.

No adequately designed studies have compared these agents in herpes simplex keratitis, but several studies of genital herpes have established the efficacy of these 2 pro-drugs for preventing recurrences of both asymptomatic viral shedding and symptomatic outbreaks. One recent study, for example, revealed a slight advantage of valacyclovir over famciclovir, with fewer patients developing virologically confirmed recurrences. Given the longer half-life and better oral absorption of these medicines, they both represent a modest improvement over oral acyclovir, albeit at a significantly increased cost. Common side effects of valacyclovir and famciclovir include nausea, which is usually related to the lactose component of the pill, and headache. More serious side effects are rare and may occur in patients with renal insufficiency. Therefore, usage in these patients requires alteration of the dose accordingly.

The ideal intervention for any disease is prevention, and herpetic simplex keratitis is a prime candidate for this approach. Despite the availability of effective prophylactic and therapeutic medications, prevention of infection would obviate the need for these drugs with their associated cost and risk of adverse effects. Unfortunately, an effective vaccine for HSV-1, the primary strain implicated in ocular infections, has yet to clear the hurdles of rigorous clinical study. Meanwhile, candidate vaccines for HSV-2, the primary cause of genital herpes and an occasional ocular pathogen, are demonstrating some efficacy in early clinical trials, demonstrating “proof of concept” for potential future herpes vaccines.

The Varicella-Zoster Vaccine

The Zostavax vaccine is a live, attenuated, varicella-zoster virus that has been shown to decrease the incidence of herpes zoster infection by 51% over an average follow-up of 3 years. The landmark study, which prospectively enrolled 38,546 patients 60 years of age and older, clearly demonstrated that in the short term the vaccine can dramatically reduce the burden of HZV, and it is likely that this effect will extend to ocular zoster infections. The effects of mass varicella-zoster vaccinations for children will take decades to appreciate, but it has been postulated that decreasing the incidence of primary infection (and therefore latent infections) would effectively reduce the burden of herpes zoster. It may be too soon to add varicella-zoster to the list of eradicated viruses, but even a modest reduction in the number of patients with latent infection could potentially be of great benefit.

Current treatment options for herpetic eye disease are much more effective than what was available in the past. In an ideal world, patients would be protected from the devastating sequelae of herpes zoster ophthalmicus such as neurotrophic keratopathy, keratouveitis, postherpetic neuralgia, and even acute retinal necrosis. Given the difficulty in treating each of these disease manifestations, however, the arrival of the Zostavax vaccine is welcome news, and an effective immunization program which incorporates a varicella-zoster vaccine may forever alter current approaches to the treatment of herpes zoster ophthalmicus by decreasing the burden of this often devastating disease and making obsolete many current therapies. Although an effective vaccine for herpes simplex keratitis has yet to be perfected, it is likely just a matter of time before it too is preventable via immunization. Until then, oral antivirals will remain a valuable method to treat and prevent the many presentations of herpes simplex keratitis.

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Author Disclosure

The authors state that they have no financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service.