HERPETIC KERATITIS

A case of herpes ophthalmicus with several vesicules on the skin, including the tip of the nose, predictive of a high of ocular involvement (Hutchinson’s sign) . Courtesy of Marc Labetoulle MD.

Herpes simplex keratitis (HSK) and herpes zoster ophthalmicus (HZO) are not so uncommon conditions, which account for a high cost to society in terms of visual disability and medical and surgical intervention. However, recurrences and the conditions’ more devastating ocular effects can be prevented in about half of patients through the use of antiviral therapy, said Marc Labetoulle MD, Bicêtre Hospital, South Paris University, Paris, France, in a keynote lecture at a Cornea Day Session at the
19th ESCRS Winter Meeting in Istanbul, Turkey.

HSK usually occurs after 20 years of age. In the European populations studied, the lifetime risk of it is 0.23 per cent by 30 years, 0.49 per cent by 50 years, 0.94 per cent by 80 years, he noted. The incidence of the disease is about 30 per 100,000 population per year and the prevalence is about 150 per 10,000. Herpes zoster generally occurs in patients older than 60 years. The lifetime risk of the disease is 10-30 per cent of people, and that of zoster ophthalmicus is one per cent to four per cent.

Very severe damage to the cornea is not uncommon in the natural history of both diseases. In the case of HSK, there is an 11 per cent risk of vision less than 20/200 in an affected eye at 20 years following the first occurrence. In addition, HSK accounts for about 10 per cent of graft indications and for about a third of graft failures. The rate of HSK recurrence following a corneal graft is 25 per cent at one year and 45 per cent at two years.

Dr Labetoulle noted that almost everyone is at some risk for HSK and HZO. Studies suggest that antibodies to the viruses are present in up to 90 per cent of people by the age of 50 years. In addition, PCR studies of cadaveric tissues, especially the trigeminal ganglia, have detected the virus in around one in five individuals at 20 years of age and in all patients at 60 years of age, even in the rare patients without serum antibodies to the virus.

After the first episode of herpetic keratitis, the risk for recurrence rises steadily during the years following the first episode, from 10 per cent at one year to 20 per cent at two years, 40 per cent at five years and 60 per cent at 20 years. Dr Labetoulle noted that a study he conducted with the late Prof Joseph Colin showed that among patients presenting with HSK at office, recurrences accounted for around 60 per cent of cases, and 30 per cent of the episodes of herpes keratitis were related to identified triggering factors.

“The risk factors for recurrence may be divided between physical and biological. The physical factors may be ultraviolet light and ocular surgery, but also biological factors due to immunosuppressive treatment, as well as ophthalmic solutions that may reduce the immunity or increase (or simulate) the inflammation, for example steroids and prostaglandins respectively," he added.

Eyes of patients with a previous history of herpes simplex that are undergoing keratoplasty therefore represent the perfect scenario for HSK. The procedure involves a huge severing of corneal nerves, an acute inflammation following surgery and the application of steroids postoperatively to reduce this inflammation.

For those reasons, antiviral prophylaxis against HSK is mandatory in patients with a history of HSV who are undergoing keratoplasty. Research going back 20 years shows that
acyclovir 400mg twice daily reduces the recurrence rate of herpes simplex by half.

There is some evidence that increasing the duration of treatment from 12 months to 18 months will reduce the recurrence rate further. There are also alternative agents to consider such as valacyclovir, which is more bioavailable than acyclovir and can be taken with food without loss of effect.

OCULAR COMPLICATIONS

The same antiviral agents may be used for occurrences of varicella zoster keratitis, especially in the days to weeks following HZO. Research has established that a dosage of 800mg acyclovir five times a day for seven days reduces the incidence of ocular complications of the keratitis and corneal hypoesthesia and neurotrophic keratitis.

More recent studies have indicated that 1000mg valacyclovir three times a day for seven days may produce better results in terms of reducing pain and inflammatory complications during occurrences of HZO. Famciclovir produces equivalent results to valacyclovir, as does brivudine, he noted.

In those who have not yet had a reactivation of the varicella virus, the best way to prevent HZO is to use the varicella vaccine during childhood and zoster vaccine during adult age. In the Shingles Prevention study, which involved over 38,000 patients over 60 years of age, a highly concentrated investigational vaccine halved the incidence of herpes zoster and reduced the neurological aggressiveness of the virus in cases where the disease occurred: unlike antiviral therapy, the vaccine also halved the incidence of post-herpetic neuralgia.

Marc Labetoulle: marc.labetoulle@bct.aphp.fr