Here’s an unexpected differential diagnosis for anyone who’s ever had pink eye – eye herpes. As nasty as that sounds, at least you can tell everyone the strain of herpetic eye disease is typically type I, which is the same strain that causes cold sores, rather than the type II strain of the herpes down there.

The herpes simplex virus (HSV) is exceedingly common throughout the world, considered globally endemic by the World Health Organization (WHO). Most primary HSV type I infections occur during childhood via transmission of saliva carrying the virus, though many children won’t exhibit any symptoms at the time of receiving the virus. Because the virus then remains in the body throughout life, whether in a dormant state or actively causing you problems, the prevalence of HSV infection worldwide, whether type I or II or both, is around 90%. In the Americas, WHO estimates 40-50% of the population under the age of 50 are host to the HSV type I virus. Sounds like the start of a zombie horror movie, doesn’t it? It gets (just a little bit) worse – an estimated 400,000 Americans have had eye herpes at some point, and every year we see around 50,000 new or repeated cases.

 
So, What Does Eye Herpes Look Like?
There are a few different categorizations of eye herpes based on the location within the eye. Because these categorizations have different underlying pathological processes – whether an actively replicating virus or immunologically-driven inflammation – it is important to identify which tissues of the eye are affected so as to appropriately guide treatment.

The most common form of eye herpes occurs in the epithelium of the cornea, which refers to the superficial outermost layers of cells (the epithelium) of the clear dome of tissue at the front of the eye (the cornea). HSV epithelial keratitis can often be easily identified by a trained eyecare clinician under a specialized microscope known as a slit lamp. With the use of certain dyes, a specific pattern of lesions created on the cornea by the virus can be visualized, appearing as a tree-like branching ulcer. Epithelial HSV infections arise from actively replicating live virus and should be treated with oral or topical antiviral medications. Some doctors will also choose to gently scrape away the epithelium to remove the amount of live virus present on the eye in a technique known as debridement; this can reduce the number of days on antiviral treatment from 7 to 2.5. In some cases, the treating doctor may elect to add an antibiotic eye drop to prevent a secondary bacterial infection as the epithelium heals. HSV epithelial keratitis generally heals without problems if appropriately treated.

HSV stromal keratitis is driven by an over-enthusiastic immune response to viral particles within the stroma (the middle layers) of the cornea, rather than an active infection from HSV. Stromal disease presents as clouding and swelling of the cornea when viewed under the slit lamp. There may also be the formation of new blood vessels into the corneal tissue, which is typically supposed to be avascular (without any blood vessels); the formation of vessels not only affects the transparency of the cornea but also brings in more potentially damaging immune cells into this tissue. HSV stromal keratitis may involve ulceration and subsequent vision-damaging scarring of the cornea. Because the underlying mechanism of stromal keratitis is predominantly inflammatory, treatment of this type of eye herpes is usually with steroid eye drops but also oral antiviral medications as a preventative in case the virus activates during that time.

HSV endotheliitis involves active virus in the space between the cornea and the colored iris within the eye, known as the anterior chamber. A patient with endotheliitis will demonstrate swelling of the cornea and an active inflammatory reaction in the anterior chamber, seen as floating white cells and cloudiness of this normally clear fluid. These inflammatory cells may clog up the drainage structures of the anterior chamber, causing the eye pressure to rise as fluid can no longer drain properly from the eye. An increase in pressure can damage the optic nerve in a disease called secondary glaucoma, which may result in peripheral vision loss if left uncontrolled. HSV endotheliitis is treated with oral antiviral medications to treat the live virus, and also topical steroids to address the inflammation.

Herpetic eye infections usually occur in one eye only, which may help to differentiate the pink eye from the more garden variety viral conjunctivitis. Despite this, symptoms tend to be non-specific:

• Sudden eye pain
• Blurry vision from swelling and clouding of the cornea
• Red eye
• Watery discharge
• Swelling of the eyelids
• Light sensitivity

Another interesting symptom of HSV keratitis is a loss of corneal sensitivity. As the virus replicates, it damages the nerve cells, leading to reduced sensitivity. This can be tested by a doctor by simply gently touching the eye with a wisp of cotton tip and noting how well this sensation can be felt across different points on the cornea.

 
Recurrent HSV Eye Disease
Reccurring HSV infection is the real culprit behind vision loss associated with the herpes simplex virus, causing corneal scarring, thinning, and the formation of new blood vessels, leading to potential blindness. As the virus never fully leaves the body once the initial infection occurs despite treatment with antiviral medications, the virus may reactivate at any time and cause a recurrent eye infection. Untreated eye herpes infections have a likelihood of recurring of about 40-50%, whether within weeks, months, or even years. Studies have found that while one episode of HSV epithelial keratitis does not increase the likelihood of experiencing it again, an HSV stromal keratitis episode increases the chance of recurrent stromal eye disease by ten times, and the degree of risk is strongly associated with the number of previous episodes.

Many cases of eye herpes reoccur at random without any known triggers but there are a few identifiable risk factors for recurrence:

• UV light exposure
• Fever or illness
• Deficient immune system, whether from stress or other causes such as chemotherapy
• Menstrual period
• Refractive surgery, including LASIK and PRK

Some doctors advocate the use of long-term oral antiviral medications to reduce the risk of a repeated eye herpes episode in an attempt to prevent vision loss from recurrent infection in certain patients.

Though neither are particularly desirable, the potentially blinding implications of recurrent eye herpes seem to make the herpes of down there the lesser of two evils. Because herpetic eye disease can mimic other causes of pink eye and has a high rate of misdiagnosis, it is important to be checked out by a qualified eye doctor, especially if you already have a history of herpes infection – just in case that zombie virus is starting to emerge.

References
Herpes simplex virus. https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus
Pediatric herpes simplex virus infection. https://emedicine.medscape.com/article/964866-overview#a7
Eye herpes (ocular herpes). https://www.allaboutvision.com/conditions/ocular-herpes.htm
Herpes simplex eye infections. https://www.nhs.uk/conditions/herpes-simplex-eye-infections/
Demystifying the ocular herpes simplex virus. https://www.aao.org/eyenet/article/demystifying-ocular-herpes-simplex-virus
What is herpes keratitis? https://www.aao.org/eye-health/diseases/herpes-keratitis
Herpes simplex virus stromal keratitis and endotheliitis. https://eyewiki.aao.org/Herpes_simplex_virus_stromal_keratitis_and_endotheliitis
Predictors of recurrent herpes simplex virus keratitis. Herpetic Eye Disease Study Group. https://www.ncbi.nlm.nih.gov/pubmed/11248812
How is recurrent herpes simplex virus (HSV) keratitis prevented? https://www.medscape.com/answers/1194268-102143/how-is-recurrent-herpes-simplex-virus-hsv-keratitis-prevented
Ocular herpes simplex virus: how are latency, reactivation, recurrent disease and therapy interrelated? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403814/