13  Part  4 Infectious uveitic conditions
Other Viral Diseases
Scott M. Whitcup
Key concepts
• Herpes simplex virus (HSV) is a common cause of
inflammatory eye disease.
• Keratitis and anterior uveitis are frequent manifesta-
tions of HSV disease; secondary glaucoma is an
important cause of vision loss.
• A number of randomized controlled trials help guide
therapy for HSV ocular disease. Topical antiviral
therapy is indicated for HSV keratitis. Although oral
aciclovir did not improve outcome in patients with
active epithelial keratitis receiving topical antiviral
therapy, it did reduce recurrence and progression of
HSV disease and appears to be beneficial for patients
with HSV-associated uveitis.
• Varicella causes two distinct forms of disease: primary
infection with varicella (chickenpox) and herpes zoster
disease. Uveitis most commonly occurs with herpes
zoster infection.
• Treatment with oral antiviral therapy appears to
improve outcome in patients with herpes zoster
infection.
• Viral infections associated with a transient mild uveitis
during the acute stages of infection include measles
(rubeola), mumps, influenza, dengue fever, Epstein–
Barr virus (EBV), and human T-lymphotropic virus type
I (HTLV-1).
Viruses are important causes of human disease and play a
pathogenic role in a number of inflammatory eye diseases.
Viruses were first identified in the late 1800s. The specific
viral etiology of diseases such as foot-and-mouth disease
and yellow fever soon followed. Viruses were first classified
as a distinct group based on their small size. We now
know that viral genomes are composed of either RNA or
DNA, and can encode several to hundreds of proteins
based on their size. By learning more about how viruses
attach, infect, and replicate in cells has allowed new thera­
peutic approaches to fighting viral infection. Importantly,
better detection of viruses has allowed us to determine a
viral etiology for diseases previously thought to be idio­
pathic. For example, high-throughput sequencing of RNA
obtained from the livers and kidneys of a cluster of
patients with fatal transplant-associated diseases allowed
the identification of a new arenavirus as the cause of the
outbreak.1
Herpes simplex virus kerititis
and keratouveitis
Although many viruses can induce intraocular inflamma­
tion, herpes simplex keratitis is probably the most common
ocular disease associated with uveitis. Patients with stromal
keratitis often have a concurrent anterior uveitis.1 Although
in some patients this uveitis develops during the initial onset
of epithelial disease, most patients have uveitis with stromal
involvement. Recurrent episodes are common and can se­
verely damage the eye. Anterior uveitis may also occur in
patients with a history of previous epithelial herpetic in­
fection without currently active corneal disease. Herpetic
keratouveitis manifests as a red, photophobic, and often
very painful eye with decreased vision.2 Secondary glaucoma
frequently accompanies severe inflammatory episodes and
can lead to vision loss.
Pathogenesis
It is difficult to know how much of the ocular inflammation
is due to direct viral infection, an immune response against
the virus, or induced autoimmunity as a result of molecular
mimicry. Each may play a role and vary between patients. A
similar disease to herpes stromal keratitis can be induced in
experimental animals by infecting them with HSV type 1.3,4
A herpes protein, UL6, has been identified as a viral protein
resembling corneal progein. Interestingly, both tolerance
and autoimmunity can be induced in the same model,
depending on host susceptibility to keratitis (Fig. 13-1).5
Diagnosis
The diagnosis of herpes simplex keratouveitis is most easily
made in patients with a known history of herpes simplex
keratitis confirmed by typical dendritic epithelial defects
(Fig. 13-2) or stromal disease confirmed by culture data. The
disease should also be suspected in patients with a signifi­
cant corneal opacity accompanied by synechiae and anterior
chamber cells. Keratic precipitates in the area of corneal
disease, hypopyon, and hyphema may be seen in some
patients. In some patients the corneal disease may obscure
the examination of the anterior chamber. Bacterial keratitis
must be ruled out, as well as the possibility of secondary
bacterial infection. The use of PCR is starting to help in
identifying HSV as the causative agent in patients with uveitis
of unknown etiology.6
It remains unclear whether the uveitis associated with
herpes simplex keratitis is a secondary inflammatory response