September 2015




World Cornea Congress highlights

Understanding herpes zoster ophthalmicus

by Michelle Dalton EyeWorld Contributing Writer

  If patients are interested in healthy aging, they want to avoid this disease. Its often just the beginning of the end for older people. Elisabeth J. Cohen, MD  

An example of an eye with dendriform keratitis Source: Elisabeth J. Cohen, MD

Although theres a vaccine against shingles, cases of HZO are rising

Herpes zoster results in more than 1 million new cases in the U.S. each year, 1020% of those involving the trigeminal nerve. As people age, the likelihood of contracting zoster increases, rising from about 1 in 3 overall to more than 1 in 2 by age 85, said Elisabeth J. Cohen, MD, professor of ophthalmology, New York University Langone Medical Center, New York, but she added the greatest number of cases occurs in people in their 50s. While the disease is much more severe in those who are immunocompromised, 90% of those afflicted are not immunocompromised, leading to the number 1 misconception that healthy people are not at risk, she said. When the disorder affects the V1 distribution (herpes zoster ophthalmicus, HZO), it can cause acute and/or chronic anterior segment disease. HZO is caused by a reactivation of the latent varicella zoster virus (chicken pox), which has affected virtually everyone over the age of 40 whether they know it or not, Dr. Cohen said. HZO typically results in a painful, unilateral, vesicular rash, and can manifest in the eye. Pseudodendrites may be seen on the epithelium and are culture positive for HZV, said Clara Chan, MD, assistant professor of ophthalmology, University of Toronto. There is often decreased or loss of corneal sensation. Elevated intraocular pressure may occur due to a trabeculitis and can settle with use of topical steroids. Later findings may include iris transillumination defects and poor pupil reactivity. Immune stromal keratitis and uveitis may also be late findings after HZO requiring topical steroids and a slow taper over months, with risk of recurrence. HZO can lead to acute retinal necrosis or other retinal disorders.

However, Zostavax (Merck, Kenilworth, N.J.) is a live attenuated zoster vaccine that was approved almost a decade ago to prevent shingles in immunocompetent people over the age of 60.

Studies on the vaccine showed it reduced the recurrence of zoster about 50% in people between ages 60 and 69, said Jay Pepose, MD, founder and medical director of Pepose Vision Institute, Chesterfield, Mo., and professor of clinical ophthalmology, Washington University School of Medicine, St. Louis. Cell mediated immunity to zoster wanes with age. Prior to chicken pox vaccination, adults got boosts in their immunity to varicella zoster virus by exposure to wild type varicella shed by infected children in the community, periodically reactivating their own latent zoster, which was associated with brief periods of viremia. With the reduction of chicken pox in vaccinated children, we must rely more on a zoster vaccine to substitute for the immune boost that came from natural exposure to exogenous wild type virus, he said.

Understanding zoster

Before the chicken pox vaccination, adults continued to have their immunity against shingles boosted because of the continual exposure to the varicella virus. That continued exposure has virtually disappeared. The key now is educating older patients that they need to get vaccinated, said Bryan S. Lee, MD, Altos Eye Physicians, Los Altos, Calif. Dr. Cohen agreed that more education is necessary on the part of primary care physicians but that ophthalmologists should add a routine question about the vaccine to the initial workup.

Once a patient has developed plaques and pseudodendrites (some people believe the pseudodendrites or dendriform keratitis as they are now also calledare caused by a live virus, Dr. Pepose noted), there can be significant neurotrophic changes. Dr. Cohen added pseudodendrites are positive for the varicella zoster virus by PCR, and are evidence of chronic active infection, which was not known until 1995 and still not widely appreciated by ophthalmologists, she said. Stromal keratitis (with or without ulceration), endothelial keratitis, and uveitis are among the more common ophthalmic complications, Dr. Cohen said. For those who develop HZO, postherpetic neuralgia (PHN) will develop in about 25%, and zoster has been shown in population-based studies to be a risk factor for major depression; it is the most common cause of suicide due to pain in people 70 years and older, Dr. Cohen said. HZO results in a 4.5-fold increase in the risk of stroke and a 1.3-fold increase in the risk of stroke in patients with zoster in other locations. Further, there is a 9-fold higher risk for cancer within a year of an HZO diagnosis, Dr. Cohen said. Finally, she said, the most common time for the eye to become involved is about 24 weeks after the rash in the V1 distribution over the eye.

For now, Zostavax has yet to affect the global epidemiology because of a low uptake in most nations. According to Dr. Cohen, the global incidence is increasing with no clear-cut cause. Initial studies seem to suggest vaccine efficacy for about 6 years in people older than 60 years, Dr. Pepose said, and this remains a question the Centers for Disease Control (CDC) is trying to ascertainalong with any recommendations for revaccination.

The vaccine is approved by the FDA for people age 5059, when it reduces zoster by 70%, but the duration of vaccine efficacy is unknown in this age group, Dr. Cohen said.

Treating HZO

Within 72 hours of the shingles rash onset, oral antivirals should be prescribed, including valacyclovir 100 mg/3 times daily for 7 days, famciclovir 500 mg/3 times daily for 7 days, or acyclovir 800 mg/5 times daily for 7 days, although the latter is not as effective. And while they reduce chronic eye disease from 50% to 30%, Dr. Cohen said, they do not reduce PHN. The correct dose is crucial to treating the diseaseand this is twice the level as what is used to treat herpes simplex infections.

Antiviral treatment should be given to all people with zoster as soon as possible, since complications typically develop more than 72 hours after onset when treatment should be given, and occur in relatively young and healthy people, Dr. Cohen said, who would still implement the antivirals if a patient presented outside that 72-hour window with active disease.

Patients with zoster do need steroids, and often need steroid drops indefinitely, Dr. Lee said. Some of his patients may only need one drop a week, but thats what keeps their eye comfortable. Its crucial to set the expectation early on that theyll be on steroids for a long time with a very slow taper and to discuss the potential side effects from long-term steroid use.

Debate is ongoing about vaccination if a patient has developed HZO; Dr. Lee does not recommend vaccination, but others support vaccination as long as shingles occurred more than 12 months previously. Immunocompetent patients can recontract shingles or zoster ophthalmicus even shortly after the initial episode, so I personally recommend vaccination in select cases that are at least a year out without signs of ocular disease, even if theyve previously developed shingles, Dr. Pepose said. While more studies are indicated, it may lessen the severity of another recurrence, even if it doesnt completely eliminate the recurrence. It bolsters immunity in patients where age is depleting natural immunity. It should not be given to immunosuppressed patients or to individuals allergic to components of the vaccine. Dr. Chan disagreed, as the safety and efficacy for preventing recurrences in patients who have a history of HZO is unknown. If a patient has had a zoster recurrence, to me that is already indicative of an immune boost similar to that induced by the vaccine, thus the vaccine is unlikely to offer any additional protection in a patient with recurrent HZO. She also would not recommend the vaccine to a patient who has a history of ocular complications related to HZO. The vaccine increases the bodys cellular mediated immunity against varicella zoster virus (VZV), which can target any persistent herpes zoster DNA in ocular tissues resulting in a T-lymphocyte mediated recurrence of ocular manifestations in patients with a history of HZO, she said. VZV can trigger inflammation of giant cell arteritis; the latter is a VZV vasculopathy of the temporal artery, Dr. Cohen said, and antiviral treatment may be beneficial in these instances, and requires study. Dr. Cohens group is submitting an application to the National Eye Institute to conduct a multicenter, placebo, randomized, controlled clinical study to determine whether prolonged, suppressive valacyclovir treatment reduces complications of HZO, including chronic ocular disease and PHN, she said. If approved, more than 1,050 patients with HZO in more than 60 U.S. centers will be enrolled. If patients are interested in healthy aging, they want to avoid this disease, she said. Its often just the beginning of the end for older people.

Editors note: The physicians have no financial interests related to this article.

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