Herpetic simplex keratitis is a form of
keratitis
Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
caused by recurrent
herpes simplex virus (HSV) infection in the
cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical ...
.
It begins with infection of
epithelial cells
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
on the surface of the eye and retrograde infection of nerves serving the cornea.
Primary infection typically presents as swelling of the
conjunctiva
The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...
and eyelids (
blepharoconjunctivitis), accompanied by small white itchy lesions on the corneal surface. The effect of the lesions varies, from minor damage to the epithelium (
superficial punctate keratitis), to more serious consequences such as the formation of
dendritic ulcers.
Infection is unilateral, affecting one eye at a time. Additional symptoms include dull pain deep inside the eye, mild to acute dryness, and
sinusitis
Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...
. Most primary infections resolve spontaneously in a few weeks. Healing can be aided by the use of oral and topical
antiviral
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do no ...
s.
Subsequent recurrences may be more severe, with infected epithelial cells showing larger dendritic ulceration, and lesions forming white plaques.
The epithelial layer is sloughed off as the dendritic ulcer grows, and mild inflammation (
iritis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
) may occur in the underlying
stroma of iris
The stroma of the iris is a fibrovascular layer of tissue. It is the upper layer of two in the iris.
Structure
The stroma is a delicate interlacement of fibres. Some circle the circumference of the iris and the majority radiate toward the pupi ...
. Sensation loss occurs in lesional areas, producing generalised corneal anaesthesia with repeated recurrences.
Recurrence can be accompanied by chronic dry eye, low grade intermittent conjunctivitis, or chronic unexplained sinusitis. Following persistent infection the concentration of viral DNA reaches a critical limit. Antibody responses against the viral
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
expression in the stroma can trigger a massive
immune
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
response in the eye. The response may result in the destruction of the
corneal stroma
The stroma of the cornea (or substantia propria) is a fibrous, tough, unyielding, perfectly transparent and the thickest layer of the cornea of the eye. It is between Bowman's membrane anteriorly, and Descemet's membrane posteriorly.
At its cent ...
,
resulting in loss of vision due to opacification of the cornea. This is known as immune-mediated stromal keratitis.
HSV infection is very common in humans. It has been estimated that one third of the world population have recurrent infection. Keratitis caused by HSV is the most common cause of cornea-derived
blindness
Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment†...
in developed nations. Therefore, HSV infections are a large and worldwide public health problem.
The global incidence (rate of new disease) of herpes keratitis is roughly 1.5 million, including 40,000 new cases of severe monocular visual impairment or blindness each year.
Signs and symptoms
Primary infection
![herpes simplex blepharitis](https://upload.wikimedia.org/wikipedia/commons/f/f3/Herpes_simplex_blepharitis.jpg)
Primary infection most commonly manifests as
blepharoconjunctivitis i.e. infection of lids and conjunctiva that heals without scarring. Lid vesicles and conjunctivitis are seen in primary infection. Corneal involvement is rarely seen in primary infection.
Recurrent eye infection
Recurrent herpes of the eye is caused by reactivation of the virus in a latently infected sensory ganglion, transport of the virus down the nerve axon to sensory nerve endings, and subsequent infection of ocular surface.
The following classification of herpes simplex keratitis is important for understanding this disease:
Dendritic ulcer (Epithelial keratitis)
![Herpes simplex geographic corneal ulcer](https://upload.wikimedia.org/wikipedia/commons/0/07/Herpes_simplex_geographic_corneal_ulcer.jpeg)
This classic herpetic lesion consists of a linear branching corneal ulcer (dendritic ulcer). During eye exam the defect is examined after staining with
fluorescein
Fluorescein is an organic compound and dye based on the xanthene tricyclic structural motif, formally belonging to triarylmethine dyes family. It is available as a dark orange/red powder slightly soluble in water and alcohol. It is widely used ...
dye. The underlying cornea has minimal inflammation.
Patients with epithelial keratitis complain of foreign-body sensation, light sensitivity, redness and blurred vision.
Focal or diffuse reduction in corneal sensation develops following recurrent epithelial keratitis.
In immune deficient patients or with the use of corticosteroids the ulcer may become large and in these cases it is called geographic ulcer.
Disciform keratitis (Endothelial keratitis)
Endothelial keratitis manifests a central
endothelitis in a disc-shaped manner. Longstanding corneal edema leads to permanent scarring and is the major cause of decreased vision associated with HSV.
Localized endothelitis (localized inflammation of corneal endothelial layer) is the cause of disciform keratitis.
Other forms
* ''Metaherpetic ulcer'' : is not due to live virus, results from inability of the corneal surface to heal.
* ''Necrotizing keratitis''
* ''Keratouveitis'' : is usually granulomatous
uveitis
Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and in ...
with large
keratic precipitates on the corneal endothelium.
Cause
HSV is a double-stranded DNA virus that has icosahedral capsid. HSV-1 infections are found more commonly in the oral area and HSV-2 in the genital area. Ocular herpes simplex is usually caused by HSV-1.
Diagnosis
![cytology corneal herpes multinucleated cell](https://upload.wikimedia.org/wikipedia/commons/a/ad/Cytology_corneal_herpes_multinucleated_cell.jpeg)
A specific clinical diagnosis of HSV as the cause of dendritic keratitis can usually be made by
ophthalmologists and
optometrists based on the presence of characteristic clinical features. Diagnostic testing is seldom needed because of its classic clinical features and is not useful in stromal keratitis as there is usually no live virus. Laboratory tests are indicated in complicated cases when the clinical diagnosis is uncertain and in all cases of suspected neonatal herpes infection:
* Corneal smears or impression cytology specimens can be analyzed by culture, antigen detection, or fluorescent antibody testing. Tzanck smear, i.e.Papanicolaou staining of corneal smears, show multinucleated giant cells and intranuclear inclusion bodies, however, the test is low in sensitivity and specificity.
* DNA testing is rapid, sensitive and specific. However, its high cost limits its use to research centers.
* Demonstration of HSV is possible with viral culture.
* Serologic tests may show a rising antibody titer during primary infection but are of no diagnostic assistance during recurrent episodes.
Treatment
Treatment of herpes of the eye is different based on its presentation: epithelial keratitis is caused by live virus while stromal disease is an immune response and metaherpetic ulcer results from inability of the corneal epithelium to heal. But on the viral aciclovir eye ointment q.i.d can be used together a systemic antiviral drug t.d.s for 10/7. :
Epithelial keratitis
Epithelial keratitis is treated with topical antivirals, which are very effective with low incidence of resistance. Treatment of the disease with topical antivirals generally should be continued for 10–14 days.
Aciclovir
Aciclovir (ACV), also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following tra ...
ophthalmic ointment and
Trifluridine
Trifluridine (also called trifluorothymidine; abbreviation TFT or FTD) is an anti-herpesvirus antiviral drug, used primarily on the eye. It was sold under the trade name Viroptic by Glaxo Wellcome, now merged into GlaxoSmithKline. The brand is ...
eye drops have similar effectiveness but are more effective than
Idoxuridine
Idoxuridine is an anti-herpesvirus antiviral drug.
It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the iodine atom added to the uracil component blocks base pairin ...
and
Vidarabine
Vidarabine or 9-β-D-arabinofuranosyladenine (ara-A) is an antiviral drug which is active against herpes simplex and varicella zoster viruses.
Discovery
In the 1950s two nucleosides were isolated from the Caribbean sponge ''Tethya crypta'': spo ...
eye drops.
Oral acyclovir is as effective as topical antivirals for treating epithelial keratitis, and it has the advantage of no eye surface toxicity. For this reason, oral therapy is preferred by some ophthalmologists.
Ganciclovir
Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections.
Ganciclovir was patented in 1980 and approved for medical use in 1988.
Medical use
Ganciclovir is indicated ...
and
brivudine
Brivudine (trade names Zostex, Mevir, Brivir, among others) is an antiviral drug used in the treatment of herpes zoster ("shingles"). Like other antivirals, it acts by inhibiting replication of the target virus.
Medical uses
Brivudine is used fo ...
treatments were found to be equally as effective as acyclovir in a systematic review.
[
Valacyclovir, a pro-drug of acyclovir likely to be just as effective for ocular disease, can cause thrombotic ]thrombocytopenic purpura
Thrombocytopenic purpura are purpura associated with a reduction in circulating blood platelets which can result from a variety of causes, such as kaposi sarcoma.
Types
By tradition, the term idiopathic thrombocytopenic purpura is used when t ...
/ Hemolytic-uremic syndrome in severely immunocompromised patients such as those with AIDS; thus, it must be used with caution if the immune status is unknown.
Topical corticosteroids are contraindicated in the presence of active herpetic epithelial keratitis; patients with this disease who are using systemic corticosteroids for other indications should be treated aggressively with systemic antiviral therapy.
The effect of interferon with an antiviral agent or an antiviral agent with debridement
Debridement is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue. Removal may be surgical, mechanical, chemical, autolytic (self-digestion), and by maggot therapy.
In p ...
needs further assessment.[
]
Stromal keratitis
Herpetic stromal keratitis is treated initially with prednisolone
Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthr ...
drops every 2 hours
accompanied by a prophylactic antiviral drug: either topical antiviral or an oral agent such as acyclovir or valacyclovir. The prednisolone drops are tapered every 1–2 weeks depending on the degree of clinical improvement. Topical antiviral medications are not absorbed by the cornea through an intact epithelium, but orally administered acyclovir penetrates an intact cornea and anterior chamber. In this context, oral acyclovir might benefit the deep corneal inflammation of disciform keratitis.
Metaherpetic ulcer
Treatment includes artificial tears and eye lubricants, stopping toxic medications, performing punctal occlusion, bandage contact lens and amniotic membrane transplant. These measures intend to improve corneal epithelial healing.
Antiviral medication may reduce the risk of HSV keratitis recurring in people having a graft due to HSV infection and may improve the chances of graft survival.
References
External links
{{Eye pathology
Ophthalmology
Herpes simplex virus–associated diseases