Antiviral treatment best defence for ocular herpes
By Roibeard O'hÉineacháin
NICE - Oral antiviral therapy can greatly reduce the recurrence
rate of corneal herpetic disease whether used as a treatment for
its clinical manifestations or as a prophylaxis in eyes undergoing
potentially recurrence-inducing treatment such as penetrating keratoplasty
(PK) or LASIK.
French ophthalmologist Joseph Colin MD said the major objectives
of treating herpes simplex virus (HSV) keratitis are the preservation
of normal vision because untreated disease recurrences can lead
to visual loss.
"Antiviral therapy for HSV keratitis has gradually evolved
and the challenge is now to determine the most appropriate strategies
for using the antiviral options available," Dr Colin told the
XX ESCRS Congress.
Keratitis due to the herpes simplex virus (HSV) is the leading cause
of corneal blindness in Western countries. For example, the incidence
of new cases per year in the US is 8.4 per 100,000 population and
that of recurrences is 20.7 per 100,000 population.
Even if a vaccine for HSV-1 should become available, its uptake
would have to be almost universal to be effective in preventing
An estimated 20% of children younger than five years and 40% to
60% of adults are infected with the virus. However, only 20% to
30% of those infected manifest clinical disease. Ocular manifestations
develop in less than 1%, he pointed out.
"Thus, although a highly effective prophylactic vaccine could
potentially impact on the incidence of ocular HSV disease, it is
unlikely that efforts to prevent HSV-1 transmission and acquisition
would be practical or effective," Dr Colin said.
Ophthalmologists must therefore concentrate their efforts on careful
management of the disease in patients with ocular manifestations
of the HSV and the prevention of recurrences.
In addition, they should be aware of iatrogenic factors that can
provoke both the initial manifestations and the recurrences of the
"We know that recurrences can be induced by treatments including
UV light in the form of excimer laser surgery, topical and systemic
corticosteroids and latanoprost.
"Everything must be done to avoid trigger factors when we know
the trigger factor for a specific patient. Of course we must be
very careful and cautious when using drugs or instruments that can
induce recurrences," he explained.
The severity of HSV keratitis generally increases with recurrence.
In addition, the rate of recurrences after the first episode increases
progressively with follow-up, reaching 40% after five years.
However, there is now good evidence that antiviral treatment not
only reduces the duration and severity of HSV-keratitis but also
helps prevent recurrences.
In a prospective study by the Herpetic Eye Disease Group (New England
Journal of Medicine 1998; 339: 300-306), the rate of recurrences
in 357 patients who received 400 mg oral acyclovir twice a day was
That compared to a rate of 32% among 346 who received placebo. Furthermore,
the rate of stromal recurrences was only 13% in the active treatment
group compared to 27% for placebo.
"Therefore we can decrease the number of recurrences but currently
we cannot entirely eliminate the recurrences. The optimum dose of
oral acyclovir therapy has yet to be determined although the Herpetic
Eye Disease Group trial demonstrated that a dose of oral acyclovir
400 mg twice daily was effective in preventing recurrences,"
Dr Colin added.
In cases with epithelial dendritic keratitis, the symptoms generally
resolve within a week of the initiation of topical or oral antiviral
However, when the infection has begun to invade the stroma the situation
becomes much more difficult and dangerous. In extreme cases, the
scarring becomes so severe that penetrating keratoplasty (PK) becomes
necessary and this in itself can increase the risk of further recurrences.
Moreover, patients undergoing PK for HSV keratitis present a different
clinical profile from those with ocular HSV disease.
They are usually at the most severe end of the disease spectrum,
and their disease will be influenced by iatrogenic factors involved
in surgery and the use of topical corticosteroids. Therefore, the
results of the patients in the Herpetic Eye Disease Group study
cannot be directly extrapolated to patients with PK.
On the other hand, a study presented by Dr Van Rooij at last year's
meeting of the American Academy of Ophthalmology indicated that
a six month regimen of oral acylovir at a dosage of 400 mg twice
can reduce the recurrence rate of the disease.
Dr Colin noted that oral treatment might have some advantages over
topical therapy as it achieves higher drug levels in the anterior
chamber and other sites of infection.
Furthermore, oral acyclovir does not interfere with healing after
PK. He also suggested that there is a strong rationale for continuing
the prophylactic regimen for up to one year
"Prophylactic antiviral therapy should be considered for all
patients undergoing PK for ocular HSV disease. The optimum duration
of prophylactic antiviral therapy following PKP for HSV keratitis
has yet to be determined.
"Since most recurrences of ocular HSV disease occur in the
first year, one year of postoperative antiviral therapy may be a
reasonable minimum," he added.
In addition to the risk of provoking recurrences in patients with
HSV, PK also has the potential to transmit the virus to previously
The virus is strongly implicated in a recently identified form of
graft rejection called primary graft failure syndrome.
The features of the condition include a diffusely oedematous corneal
graft on the first postoperative day which fails to clear without
any known precipitating cause.
The syndrome occurs in 2% of corneal grafts. As many as one-third
of donor corneas involved in such cases test positive for HSV DNA.
"Although graft-to-recipient transmission of HSV is extremely
rare, the storage of corneas in eye banks offers the opportunity
to safeguard against transmission of HSV.
"Routine visual examination of the endothelium will identify
corneal buttons with obvious necrosis that may be caused by HSV.
This should prevent infected tissue being released for transplant,"
Dr Colin said.
UV light from the sun is a well-recognised trigger for the re-activation
of HSV. New research suggests the UV rays of the excimer laser have
a similar effect on corneas infected with the disease.
This has been reported in humans undergoing refractive surgery and
in the laboratory with rabbit eyes. However, rabbit eye studies
also suggest that antiviral therapy in infection lowers the risk
of HSV recurrence following laser surgery.
"The effect of antiviral prophylaxis on ocular HSV disease
recurrence rates should be investigated in a clinical trial.
"But for now I would recommend antiviral prophylaxis following
excimer laser surgery of the cornea in all cases of phototherapeutic
keratectomy (PTK) for herpetic scar, in all cases of PRK-LASIK in
patients with an history of HSV keratitis and in all patients with
a corneal scar of unknown origin," Dr Colin said.
He predicted that the future would see further trials with antiviral
agents to more precisely determine their role in the treatment of
In addition, valacyclovir, a pro-drug of acyclovir, will most likely
come to the fore by virtue of its superior penetration into intraocular
structures, he said.
Finally the prevention and cure of the condition may one day become
possible in the form of vaccines and new means of suppressing or
preventing viral latency.