Herpes Simplex Keratitis (HSK)


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Herpes simplex virus (HSV) infection is extremely common, though usually latent

  • up to 90% of UK population is seropositive for HSV

HSV-1 generally infects ‘above the waist’ (lips, face, eyes)

  • primary infection usually in childhood, then virus lies dormant in trigeminal ganglion
  • when virus reactivates it travels along branches of the trigeminal nerve to cause local infection (e.g. cold sore or herpes keratitis)

HSV-2 generally infects ‘below the waist’ and is usually sexually acquired

  • but may also be a cause of herpetic keratitis

Ocular HSV infection (of which the incidence of new cases is 5-15 per 100,000 per annum) can manifest as blepharoconjunctivitis, keratitis, anterior uveitis or acute retinal necrosis. The most common form is epithelial keratitis, accounting for 50% to 80% of cases

Ocular HSV infection can be categorised into primary and recurrent disease

Herpes simplex keratitis (HSK) is the leading cause of corneal blindness in developed countries. In UK, responsible for 1 in 10 corneal transplants

Predisposing factors

Poor general health, immunodeficiency, fatigue
Systemic or topical steroids, or other immunosuppressive drugs
Possible aggravating factors

  • sunlight (UV), fever, extreme heat or cold, infection (systemic or ocular), trauma (ocular)

History of previous attacks of ocular herpes simplex infection (key diagnostic feature)
Severe atopic disease

Symptoms of herpes simplex keratitis

Usually affects one eye; may be bilateral, especially in severely atopic patients
Severity of symptoms very variable
Pain, burning, irritation, photophobia, reduced visual acuity, redness

Signs of herpes simplex keratitis

HSK has a highly variable and unpredictable course
Can be considered as a spectrum of four distinct disease entities (with differing management strategies):

Initially punctate lesions, coalescing into dendriform pattern

  • dendritic ulcer, single or multiple
  • opaque cells arranged in a stellate pattern progressing to a linear branching ulcer; terminal bulbs may be visible
  • associated with reduced corneal sensitivity
  • continued enlargement may result in an ‘amoebic’ or ‘geographic’ ulcer (especially following inappropriate use of topical steroids)

Stromal infiltrates, vascularisation, necrosis, scarring, uveitis and keratic precipitates, possibly raised intraocular pressure

Disciform keratitis
Central or eccentric zone of epithelial oedema overlying an area of stromal thickening
Folds in Descemet’s membrane, uveitis and keratic precipitates

Metaherpetic ulcer (trophic keratitis) 
Due to a combination of denervation, drug toxicity, persistent defects in epithelial basement membrane

Differential diagnosis

Herpes zoster keratitis
Bacterial, fungal or amoebic keratitis (NB Dendritic keratitis in a contact lens wearer should raise the index of suspicion of an Acanthamoeba infection)
Healing corneal epithelial defect (e.g. abrasion): may have stellate or dendritic profile

Management by optometrist

Practitioners should recognise their limitations and where necessary seek further advice or refer the patient elsewhere

Non pharmacological

Exclude viral retinitis following pupil dilatation (especially in immunocompromised patients) as this would warrant emergency (same day) referral

  • peripheral infiltrates
  • vasculitis
  • intra-retinal haemorrhages
  • vitreous inflammation


Acute Herpes Simplex: in non-contact lens wearing adults and where HSK is confined to the epithelium with classic dendritic appearance, commence antiviral therapy with one of the following: 

  • oc. aciclovir 3%, e.g. Aciclovir Agepha, ophthalmic preparation (unpreserved)
  • ganciclovir 0.15% ophthalmic gel (Virgan) (BAK preserved preparation only)

NB: HSK is a potentially blinding disease and optometrists should consistently apply a low threshold for referral for this condition
(GRADE*: Level of evidence=moderate, Strength of recommendation=strong)

Recurrent Herpes Simplex: where there is:

  • a clear history of previous attacks
  • no doubt about the diagnosis and
  • only epithelial involvement
    • commence antiviral therapy (as above)

(GRADE*: Level of evidence=moderate, Strength of recommendation=strong)

Management category

B2 (modified) (acute or recurrent epithelial HSK with no stromal involvement): alleviation or palliation; monitor closely within first 72 hours to evaluate healing, but refer urgently (within one week) to ophthalmologist if epithelium has not healed after seven days
A1 (if stroma involved, or in children or contact lens wearers, or in bilateral cases): emergency (same day) referral to ophthalmologist

Possible management by ophthalmologist

Isolation and characterisation of virus from corneal swab or biopsy
PCR identification of HSV DNA or viral culture
Antivirals (topical and/or systemic antivirals such as aciclovir or famciclovir)
Topical steroid
Epithelial débridement
Penetrating keratoplasty in some quiescent cases with scarring

Evidence base

*GRADE: Grading of Recommendations Assessment, Development and Evaluation (see www.gradeworkinggroup.org)

Sources of evidence

Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes keratitis. Prog Retin Eye Res. 2013;32:88-101

Roozbahani M, Hammersmith KM. Management of herpes simplex virus
epithelial keratitis. Curr Opin Ophthalmol. 2018;29:360-4

Sibley D, Larkin DFP. Eye (Lond). Update on Herpes simplex keratitis management. 2020;34(12):2219-2226

Tsatsos M, MacGregor C, Athanasiadis I, Moschos MM, Hossain P, Anderson D. Herpes simplex virus keratitis: an update of the pathogenesis and current treatment with oral and topical antiviral agents. Clin Exp Ophthalmol. 2016;44(9):824-837

White ML, Chodosh J. Herpes Simplex Virus Keratitis: A Treatment Guideline 2014

Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev. 2015;1:CD002898

Plain language summary

Up to 90% of people in the UK have an inactive nerve infection caused by herpes simplex virus type 1. This infection is usually acquired in childhood by contact with an adult. The viruses penetrate the skin and travel along the nerves of sensation to the central part of the nervous system (brain or spinal cord) where they become ‘latent’ and produce no symptoms. The infection cannot be eliminated and there is no protective vaccine. Another variety, herpes simplex type 2, is usually sexually transmitted, but can also affect the eye.

The infection remains inactive until some factor such as poor health, disturbance of the body’s immune system or certain drugs allow the virus to become active and then travel back down the nerves to the surface of the body. If this happens in the trigeminal nerve (the nerve that gives sensation to the head and neck), an infection of the skin such as a cold sore on the lip, or an infection of the eye surface, can occur. If the cornea (the clear window at the front of the eye) is involved, the condition is known as Herpes Simplex Keratitis. Usually only one eye is affected.

Several different forms of corneal infection are possible, ranging from slight to severe. One of them, affecting the surface skin of the cornea, produces ulcers with a characteristic branching outline and this is known as a dendritic ulcer. The infection can recur and if this happens scarring may result, which can cause blurring of vision.

A new case, with involvement of the surface skin of the cornea only, will usually be treated by the optometrist with anti-viral eye ointment. In children, contact lens wearers and where the condition affects both eyes, same-day referral to the ophthalmologist is recommended. This is a condition which tends to recur from time to time. Recurrences involving only the surface skin of the cornea can often be managed by the optometrist, who will usually prescribe anti-viral eye ointment, but if this is not effective after a week, urgent referral to the ophthalmologist is recommended. If the vision has become badly affected by scarring of the cornea, a patient may be offered a corneal transplant.

Herpes Simplex Keratitis (HSK)
Version 15
Date of search 27.08.21
Date of revision 27.08.21
Date of publication 14.09.21
Date for review 22.01.23
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