Download Insight on herpetic keratitis management accumulating, but

Special Focus
Insight on herpetic keratitis management
accumulating, but gaps remain
Cheryl Guttman
in Vienna
Viral replication and pathologic immune response
Late damage by herpes keratitis
Courtesy of Lies Remeijer MD, PhD
FINDINGS from the Herpetic Eye Diseases Studies
(HEDS) have provided some answers on treatment
of herpes simplex virus (HSV) keratitis, but several
frequently asked questions about the management
of these sight-threatening infections remain to be
answered, said Lies Remeijer, MD, PhD, at the 2007
Joint Congress of the European Society of
Ophthalmology and American Academy of
Ophthalmology.
The HEDS programme included several cohort
and randomised clinical trials conducted through a
cooperative agreement between the National Eye
Institute and the National Institutes of Health in
the US. Originally organised to investigate oral
acyclovir as a treatment for stromal disease, the
HEDS programme was expanded to include studies
evaluating topical steroids for stromal keratitis and
oral acyclovir for HSV iridocyclitis, epithelial
keratitis, and the prevention of recurrent active
infection in patients with any history of ocular HSV
disease.
Speaking during a symposium on corneal
infectious disease, Dr Remeijer, cornea and
external eye disease department, Rotterdam Eye
Hospital, the Netherlands, reviewed the results
from the HEDS programme and other independent
studies that have provided insight on management
of HSV ocular disease.
She noted one important finding from HEDS is
that patients with epithelial keratitis can be easily
treated with topical antiviral agents and do not
require ongoing oral acyclovir prophylaxis to
prevent future stromal disease. However, eyes with
stromal keratitis, endothelitis, uveitis, scleritis,
and/or trabecultis present a greater challenge for
long-term management.
“In eyes where more than just the corneal
epithelium is affected, the pathogenic process
involves not only viral replication but also a
chronic pathologic immune response that makes
them susceptible to recurrence,” Dr Remeijer said.
In the acute management of stromal keratitis,
one HEDS trial showed that patients randomised
to topical corticosteroid treatment with
prednisolone sodium phosphate benefited with
significantly reduced progression of stromal
inflammation and a shortened time to resolution of
stromal keratitis compared with controls using the
topical antiviral plus placebo. However, the study
also showed there is no need to initiate
corticosteroids immediately.
“Steroid treatment can be postponed for a few
days without compromising the vision outcomes
while the patient is monitored for efficacy of the
topical antiviral treatment. In my own practice, I
wait for two to three days after starting topical
treatment with acyclovir ointment and trifluridine
drops, but initiation of the corticosteroid can even
be delayed a few weeks without detriment to the
patient,” Dr Remeijer said.
Choice of a steroid regimen may take into
account the size of the area of inflammation.
However, Dr Remeijer advised against using
prednisolone acetate and recommended
prescribing dexamethasone 0.1 per cent instead,
beginning with three times daily instillation and
increasing to six times a day if inflammation
progresses.
She also emphasised the importance of avoiding
abrupt discontinuation of the corticosteroid.
EuroTimes,Vol 13, Issue 3, March 2008 – Not for reprinting
Tapering should be performed by decreasing the
strength or frequency in increments of no more
than 50 per cent, and once a low intensity regimen
is reached, it should be continued for a prolonged
period. For example, a patient using
dexamethasone 0.1 per cent three times a day may
be tapered to twice and then once-daily dosing at
monthly intervals, then tapered to every other day
administration or daily treatment with
fluorometholone to be continued for at least six
months.
Another HEDS study of eyes with acute stromal
keratitis evaluated the addition of systemic antiviral
treatment with oral acyclovir to topical antiviral
and corticosteroid treatment. The results showed
oral acyclovir provided no benefit over the topical
regimen alone in eyes with immune stromal
keratitis and no tissue loss, although it appeared to
have value when there was necrotising disease. In
another HEDS trial, there was a trend for a benefit
of using oral acyclovir in eyes with herpetic uveitis
(iridocyclitis).
Perhaps the most important finding from the
HEDS programme about the role of oral acyclovir
in the management of ocular HSV disease was the
identification of its benefit for preventing
recurrence of herpetic stromal keratitis. In the
study investigating that use, patients treated with
acyclovir had significantly fewer recurrences during
one year of therapy compared with placebotreated controls, and there was no rebound after
discontinuation of acyclovir.
“The usual prophylactic dose of acyclovir is
400mg twice daily, but it may be adjusted according
to body weight or changed to valacyclovir or
famciclovir if acyclovir is not tolerated,” Dr
Remeijer noted.
She added that a retrospective study of 160
patients treated at the Rotterdam Eye Hospital
found a 50 per cent rate of recurrent stromal
disease within a year when antiviral prophylaxis
was discontinued.
“This information suggests that it is important
to discuss with patients that they are at risk to
develop a recurrence within one year of stopping
their oral antiviral treatment. The answer to the
question of how long to continue treatment is
unknown, but might take into account the severity
of the corneal lesion, treatment side effects, and
the consequences of recurrence,” Dr Remeijer
said.
Based on those factors, long-term prophylaxis
with acyclovir might be considered in eyes with a
history of stromal disease and more than one
recurrence a year as well as in eyes where the
lesions are threatening the optical axis. Whether
there are deleterious effects of long-term, lowdose acyclovir are not known. One issue to
consider in that regard is whether it promotes the
emergence of HSV resistance to antiviral agents,
noted Dr Remeijer.
It also appears that steroids need to be
maintained long-term to prevent recurrence in
eyes with stromal keratitis. The exact reason why
the keratitis returns when the steroid is stopped is
not known, but the finding that polymorphonuclear
cells, T-cells, and viral DNA are present in the
stroma up to five years after initial infection
indicates stromal keratitis is a chronic
inflammatory condition. Furthermore, HSV-1 DNA
is found in 50 per cent of corneas transplanted for
HSV keratitis and HSV specific T-cells remain in the
cornea for more than 37 months.
“The presence of this chronic immune response
suggests we may not be able to stop
corticosteroids completely but rather may need to
maintain low-dose treatment permanently,” Dr
Remeijer said.
[email protected]
EuroTimes,Vol 13, Issue 3, March 2008 – Not for reprinting