OVERVIEW

What is herpes simplex virus keratitis?

It is a corneal infection caused by the herpes simplex virus, which is very common and the leading cause of corneal scarring and blindness due to corneal opacity worldwide. Most cases involve superficial corneal infection, presenting as punctate or diffuse branching (dendritic) lesions in the corneal epithelium, typically without affecting the corneal stroma. However, it can recur multiple times, progressively worsening corneal opacity and eventually leading to blindness.

Is herpes simplex virus keratitis common?

Herpes simplex virus type 1 (HSV-1) infection spreads through direct contact with mucous membranes, making the disease highly prevalent in humans. The annual incidence of HSV ocular disease ranges from 6.8 to 31 per 100,000 people. The prevalence in the United States is approximately 150 per 100,000.

Who is most susceptible to herpes simplex virus keratitis?

Individuals with recurrent herpes simplex virus infections are at higher risk. Factors such as fever, fatigue, UV exposure, trauma, stress, menstruation, and certain immunodeficiency disorders can trigger viral reactivation.

SYMPTOMS

What are the manifestations of herpes simplex viral keratitis?

Primary herpes simplex viral keratitis:

• Common in young children, over 94% of infected children show no symptoms and typically present with oral lesions, while the eyes remain unaffected.

• Affected children may exhibit systemic fever, preauricular lymphadenopathy, and lip or skin herpes. Lesions at this stage are often self-limiting.

• Ocular involvement manifests as acute follicular conjunctivitis, pseudomembranous conjunctivitis, eyelid skin herpes, or punctate or dendritic keratitis. Dendritic keratitis is characterized by short branches, late onset, and short duration.

• Primary infection mainly presents as corneal epithelial lesions with atypical clinical manifestations. Less than 10% of affected children develop stromal keratitis or uveitis.

Recurrent herpes simplex viral keratitis:

• Unlike primary infection, recurrent herpes simplex viral infection typically presents with classic symptoms. It is often unilateral, and due to reduced corneal sensitivity in early stages, symptoms may be mild, delaying medical attention.

• Common symptoms include photophobia, tearing, and eyelid spasms. Central corneal involvement significantly impairs vision. Variations in viral virulence and host immune responses lead to diverse clinical presentations of herpes simplex keratitis (HSK), which is classified into different types accordingly.

• Epithelial keratitis: Caused by viral reactivation and replication in epithelial cells. Secondary stromal scarring, dendritic or geographic marginal corneal ulcers may occur.

• Trophic keratopathy: Results from corneal nerve dysfunction, stromal infiltration, or drug toxicity. Ulcers lead to stromal scarring and persistent epithelial defects.

• Stromal keratitis: Caused by viral invasion and immune-inflammatory reactions. Tissue infiltration, necrosis, and neovascularization occur. Corneal thinning may accompany epithelial keratitis.

• Endothelial keratitis: Caused by immune reactions triggered by the virus. Endothelial dysfunction and chronic edema lead to stromal opacity, presenting as disciform, linear, or diffuse corneal endothelitis.

What complications can herpes simplex viral keratitis cause?

• Iridocyclitis;

• Secondary glaucoma: Corneal scarring with embedded iris tissue forms adherent corneal leukoma. Further adhesion to the iris may block the anterior chamber angle, obstructing aqueous outflow and increasing intraocular pressure, leading to secondary glaucoma;

• Corneal ulcers or perforation may form a corneal fistula, increasing the risk of intraocular infection, which can result in global atrophy and blindness.

CAUSES

What is the cause of herpes simplex viral keratitis?

The cause is infection with the herpes simplex virus (HSV).

• HSV is a DNA virus, and humans are its only host. It is divided into HSV-1 and HSV-2. Infections in the mouth and lips are mostly caused by HSV-1, with a minority caused by HSV-2.

• Primary HSV infection in the skin, mucous membranes, or other target tissues innervated by any branch of the trigeminal nerve can lead to HSV latency in the neurons of the trigeminal ganglion. When the body's resistance declines—such as during febrile illnesses like colds, or with systemic or local use of glucocorticoids or immunosuppressants—the latent virus reactivates. The reactivated virus travels retrograde along the trigeminal nerve to reach corneal epithelial cells, causing recurrent HSK.

Is herpes simplex virus contagious? How is it transmitted?

Yes, it is contagious. It spreads through skin or mucous membrane contact.

DIAGNOSIS

Which medical histories are important for doctors to diagnose herpes simplex viral keratitis?

Previous history of recurrent herpes simplex viral keratitis, history of immunosuppression such as long-term use of corticosteroids or immunosuppressants, history of immunodeficiency diseases, history of fever, and history of fatigue.

What tests are needed to diagnose herpes simplex viral keratitis?

• Corneal epithelial scraping: Detection of multinucleated giant cells;

• Corneal lesion: Isolation of herpes simplex virus;

• Immunofluorescence electron microscopy, monoclonal antibody immunohistochemical staining: Detection of viral antigens;

• Serology: Viral antibodies.

Which diseases can herpes simplex viral keratitis be easily confused with?

Keratitis caused by bacteria, fungi, amoebae, and non-infectious keratitis.

TREATMENT

Which department should I visit for herpes simplex viral keratitis?

Ophthalmology, Cornea Department.

How is herpes simplex viral keratitis treated?

Treatment goals: To suppress viral replication in the cornea and reduce corneal damage caused by inflammatory reactions. Treatment approaches vary for different types of HSK:

• Epithelial keratitis: Caused by viral replication and destruction of epithelial cells. Effective antiviral drugs are essential to inhibit viral activity and control the condition.

• Stromal keratitis: Primarily involves immune-mediated inflammation, so anti-inflammatory treatment is crucial in addition to antiviral therapy.

• Endothelial keratitis: Along with antiviral and anti-inflammatory treatment, measures to protect corneal endothelial cell function are necessary.

• Neurotrophic keratopathy: Managed similarly to neurotrophic corneal ulcers.

Medication:

• Antiviral drugs: Ganciclovir (GCV), Acyclovir (ACV), Trifluridine, and Cytarabine.

• During the acute phase, eye drops should be administered every 1–2 hours, and antiviral ointment should be applied at night.

• For severe cases, frequent recurrences, or post-keratoplasty patients, oral antivirals like ACV or GCV are required for at least 2 weeks.

• For disciform keratitis caused by immune reactions, corticosteroids may be used but must be combined with antiviral drugs.

• For iridocyclitis, atropine eye drops or ointment should be used promptly to dilate the pupil.

Surgical treatment:

• Penetrating keratoplasty may be performed for perforated corneas.

• For vision-impairing corneal scars after HSK healing, penetrating keratoplasty is an effective method to restore vision.

Preventing recurrence:

• Herpes simplex keratitis is prone to recurrence, with about 1/3 of recurrences occurring within 2 years of primary infection.

• Under strict medical supervision, oral ACV (typically 400 mg twice daily for months to a year) can reduce recurrence rates. However, liver and kidney function must be closely monitored due to potential drug toxicity.

• Oral ganciclovir, famciclovir, or valacyclovir may also lower recurrence rates.

• After surgery, topical corticosteroids should be combined with local and systemic antiviral drugs to prevent recurrence.

• Controlling triggering factors is also important for reducing recurrence.

Can herpes simplex viral keratitis be completely cured?

Early detection and treatment can lead to recovery, but the condition is prone to recurrence. Delayed treatment may worsen corneal ulcers, leading to perforation, secondary intraocular infections, and even vision loss or blindness.

DIET & LIFESTYLE

What should be paid attention to in diet after herpes simplex viral keratitis is cured?

There is no special need to pay attention to in diet, just maintain a healthy diet.

What should patients with herpes simplex viral keratitis pay attention to in daily life?

Adhere to a healthy diet, maintain a regular routine, avoid excessive fatigue, exercise, and improve immunity.

PREVENTION

How to Prevent Recurrent Herpes Simplex Viral Keratitis?

• Exercise regularly to boost immunity, maintain a regular schedule, and avoid excessive fatigue;

• Take oral antiviral medications such as acyclovir and ganciclovir;

• Control triggering factors like fever and exhaustion, and avoid long-term use of steroids and immunosuppressive drugs.