Herpes Simplex Virus Keratitis
Assigned status Update Pending by Vatinee Bunya, MD on July 4, 2015.
- 1 Disease Entity
- 2 Diagnosis
- 3 Management
- 4 Additional Resources
- 5 References
Herpes Simplex Virus is a very common viral infection that has been reported to be present in the trigeminal ganglion of nearly 100% of patients greater than age 60 at autopsy. In regards to ocular disease, HSV- I and HSV- II may cause blepharoconjunctivitis, epithelial keratitis, stromal keratitis (necrotizing or non-necrotizing), iridocyclitis, or retinal infection. This EyeWiki will focus on corneal manifestations of the herpes simplex virus.
Herpetic epithelial keratitis may occur unilaterally or bilaterally (most often in patients with atopic disease) and may be accompanied by a blepharoconjunctivitis, involving lesions of the lid and a follicular response of the conjunctiva. In addition, a palpable preauricular lymph node may be present.
HSV Keratitis is caused by the herpes simplex virus, a double stranded DNA virus made up of an icosahedral shaped capsid surrounding a core of DNA and phosphoproteins of viral chromatin. HSV I and HSV II are differentiated by virus specific antigens. HSV I typically affects the oropharynx region while HSV II usually involves the genital area, though studies have shown that both viruses may affect either location.
Ocular herpetic disease is more frequently caused by HSV I, which is presumed to gain access to the cornea via direct contact or via the trigeminal nerve from oral infection. Initial infection typically remains asymptomatic. The virus then travels via sensory nerve axons to establish latent infection-- in ocular disease this usually involves the trigeminal ganglion. The virus is then capable of reactivation along any branch of the trigeminal ganglion, especially during immunocompromised states.
Risk factors for development of primary HSV involve direct contact with infected lesions, but also may result as exposure to asymptomatic viral shedding.
Risk factors for reactivation of disease have been postulated to include:
- Infectious disease and immunocompromised states.
Corneal scrapings of HSV keratitis prepared with Giemsa stain may reveal the presence of intranuclear viral inclusion bodies. Multinucleated giant cells may also be found. With complete stromal inflammation, a granulomatous reaction may be seen, usually at the level of Descemet's membrane.
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Prevention of herpetic infection includes avoidance of direct contact with known HSV.
Diagnosis of HSV is usually made clinically, however, definitive diagnosis can be made using tissue culture or serum antigen detection techniques.
Key aspects to inquire about in the history of patients with suspected HSV include past infections (history of recurrent "red eye", particularly unilateral), underlying systemic diseases, immunosupression or immunocompromised state, history of lid lesions, and history of oral ulcers.
In addition to a standard biomicrospic slit lamp examination, special attention should be paid to the presence of a preauricular lymph node, vesicular lesions on the lids or adnexa, bulbar follicles, decreased corneal sensation, and most notably the presence of epithelial dendrites on the cornea.
The hallmark of HSV keratitis is the presence of multiple small branching epithelial dendrites on the surface of the cornea, although often times it first presents as a coarse, punctuate epithelial keratitis (and may be mistaken for a viral keratitis). The HSV dendrite possesses terminal bulbs (that distinguish it from HZO) and follows the nerve pattern throughout the cornea.
Typically, patients with HSV keratitis present with blurry vision, extreme photophobia, pain, redness, and tearing.
The clinical diagnosis of HSV may be suggested by the presence of the multiple arborizing dendritic epithelial ulcers with terminal bulbs. The bed of the ulcer stains with fluorescein, while the swollen corneal epithelium at the edge of the ulcer typically stains with rose bengal. Several dendrites may also coalesce to form a geographic epithelial ulcer. In addition, there may be mild conjunctival injection, ciliary flush, mild stromal edema and subpeithelial white blood cell infiltration. Following resolution of the primary infection, a "ghost dendrite" may be visible just beneath the prior area of epithelial ulceration.
The diagnosis of HSV is often made clinically, however, laboratory tests are available to confirm the diagnosis in difficult cases (and in all cases of neonatal herpetic infection). Serologic testing may be performed but is usually not helpful in recurrent disease as most adults are laterally infected with HSV. However, conjunctival scrapings, impression cytology specimens and scrapings from vesicular lesions on the skin may be tested by cytology, culture, or polymerase chain reaction (PCR) for the presence of HSV.
See Diagnostic Procedures
The differential diagnosis of HSV includes herpes zoster ophthalmicus, viral keratitis (usually adenovirus), neurotrophic keratopathy, epithelial regeneration line, iatrogenic (topical drops such as antivirals), acanthamoeba, soft contact lens overwear, Thygeson’s superficial punctuate keratits.
Primary HSV epithelial keratitis usually resolves spontaneously, however, treatment with antiviral medication does indeed shorten the course of the disease and may therefore reduce the long term complications of HSV.
The mainstay of therapy is antiviral treatment either in the form of topical therapy with trifluridine 1% eight to nine times a day or oral administration of acyclovir or valacyclovir for 10 to 14 days. If trifluridine drops are used, care is to be taken to ensure antiviral drops are discontinued within 10-14 days due to corneal toxicity. Epithelial debridement of the dendrites may also be utilized in conjunction with antiviral therapy to help reduce viral load. Topical corticosteroids are contraindicated in the treatment of active HSV epithelial keratitis.
Please see General Treatment. In addition, if the disease is restricted to the conjunctiva, topical vidarabine 3% ophthalmic ointment may be utilized five times a day for 10 days.
Medical follow up
The patient should be closely monitored and if no response to treatment occurs after 1 week of therapy, the possibility of resistance to antiviral therapy, antiviral toxicity, neurotrophic disease, poor compliance with medication or an alternative diagnosis should be considered.
If there is visually significant stromal scarring, a penetrating keratoplasty may be performed once the disease is quiescent. Depending on the location and size of the scar, a lamellar keratoplasty may also be used to clear the visual axis. Of note, in eyes that are unable to sustain a clear graft, a Boston keratoprosthesis may be a viable option.
Surgical follow up
Follow-up should be performed as standard of practice for penetrating keratoplasty. Special attention should be paid to signs of recurrence of herpetic disease. Oral antiviral therapy may improve rate of graft survival by decreasing number of recurrences.
Corneal complications of herpetic eye disease range from epitheliopathy to frank neurotrophic or metaherptic ulcers. Long standing disciform keratitis may also result in bullous keratopathy. Late complications of deep vascular stromal scarring include secondary lipid keratopathy. Finally, stromal inflammation may lead to visually significant corneal scarring and irregular astigmatism.
Prognosis is usually good, but greatly varies depending on severity and number of recurrences of the disease.
Region Specific Information (from the AAO's Global Ophthalmology Guide):
Porter D, Jimenez EM. Herpes Keratitis. American Academy of Ophthalmology. EyeSmart® Eye health. https://www.aao.org/eye-health/diseases/herpes-keratitis-list. Accessed March 13, 2019.
American Academy of Ophthalmology. Core Ophthalmic Knowledge: Herpes simplex virus keratitis Practicing Ophthalmologists Learning System, 2017 - 2019 San Francisco: American Academy of Ophthalmology, 2017.
- Krachmer J, Mannis M, Holland E: CORNEA, 2nd ed.Elsevier Mosby, 2005, 1043-1074.
- AAO Basic and Clinical Science Course, External Disease and Cornea, 2005-2006, 134-145.
- AAO Basic and Clinical Science Course, Ophthalmic Pathology and Intraocular tumors, 2005-2006, 65-66.
- Rapuano C, Heng W, Cornea, Color Atlas and Synopsis of Clinical Ophthalmology, Wills Eye Hospital, 2003 159-170.
- Agarwal, A, Handbook of Ophthalmology, 2006, Slack Inc, 279-281.