Figure 1. Central diffuse and focal peripheral corneal scarring secondary to stromal herpes simplex keratitis
Dr Michael Loughnan
MBBS PhD FRANZCO
The herpes viruses are a group of DNA viruses. The two main ocular pathogens are the herpes simplex virus (HSV) and varicella zoster virus (VZV), also commonly referred to as the herpes zoster virus. HSV is the most common human infection with greater than 95 per cent of people exhibiting antibodies to the virus. HSV is also the most common corneal pathogen, with about one in 650 people experiencing herpes simplex keratitis (HSK) at some time in their life.
After the initial infection with both HSV and VZX—either a sub-clinical vesicular skin rash or a follicular blepharoconjunctivitis with HSV, or chicken pox with VZX—the virus becomes latent within the neural cell body. For the cornea, this is within the ganglion of the trigeminal nerve, the fifth cranial nerve.
HSK manifests a wide spectrum of disease, ranging from primarily viral replicative disease such as an epithelial dendrite through to disease primarily due to the host's immune reaction to viral particles, as occurs with stromal necrotic keratitis.
VZV is the cause of herpes zoster ophthalmicus (HZO) shingles involving the second branch of the trigeminal nerve. While the cornea is commonly spared in HZO, a chronic kerato-uveitis can occur, often requiring years of topical steroid use to control the host immune reaction to residual viral antigen. Recent evidence also supports the idea that VZV may continue to replicate at a low level in such patients.1
One concern with the now common usage of varicella virus vaccines, such as Varivax, is that the normal exposure of adults with latent virus to VZV in the community will decrease as a result of the immunisation of younger people and as such, their immunity to VZV will fall and the prevalence of shingles within this group will increase.
A vaccine against VZV to prevent shingles is available. It is marketed in Australia by CSL Biotherapies and sold as Zostavax. It significantly reduces the risk of developing shingles as well as reducing the associated morbidity. In the USA, it is now recommended for standard use for people over the age of 55 years.
When to perform surgery
Chronic anterior segment inflammation, especially uveitis, commonly leads to an acceleration of nuclear sclerosis development. The long-term usage of topical corticosteroids can also lead to the development of a posterior subcapsular cataract (PSCC). As a consequence, patients with chronic kerato-uveitis requiring long-term topical steroids frequently develop visually significant cataract.
The timing of cataract surgery for people with VZV/HZO keratitis or HSV stromal keratitis, typically stromal necrotic disease or keratouveitis, is important. Most surgeons prefer to defer surgery until the cornea is not inflamed and easily controlled with minimal topical medication, usually one drop a day or less of corticosteroid; however, it is also preferable to remove the cataract before it becomes too dense and removal requires more phacoemulsification power.
Special considerations for surgery
Both HSV and VZV keratitis can lead to scarring and flattening of the cornea, resulting in lower keratometry readings. Standard keratometry may be inaccurate due to the focal nature of both the scarring and the resultant flattening. Topography and the use of simulated keratometry readings may be a more accurate measure of the true corneal anterior surface power.
Chronic uveitis can also lead to weakening of the zonules and scarring of the trabecular meshwork predisposing to glaucoma. Extra care should be taken during the surgery not to stress the zonules, one of the indications for femtosecond laser-assisted cataract surgery, and peri-operative anti-glaucoma medication is indicated.
Preventing recurrences around time of surgery
The recurrence of both inflammation (keratitis and anterior uveitis) and reactivation of viral replication are a concern around the time of surgery. Thankfully, modern cataract surgery is so non-traumatic to the eye that this is probably less of a concern now than it was with previous more invasive and pro-inflammatory techniques.
The Herpetic Eye Disease Studies (HEDS) were a series of prospective, randomised, multi-centre eye studies from the early 1990s that looked at several aspects of HSV keratitis and uveitis. One of the studies in HEDS was the acyclovir prevention trial (APT). This trial found that in people with HSK that taking 400 mg of the anti-viral agent acyclovir orally twice a day reduced their risk of recurrent HSK to about 50 per cent of the control group who took a placebo. However, acyclovir has a short serum half-life of approximately four hours and as such, standard treatment for an active infection is 800 mg five times daily.2
The concern with respect to viral recurrence around the time of surgery is reactivation of latent tissue or nerve cell body virus secondary to localised tissue damage. This would occur after the surgery. Treatment with acyclovir is needed immediately post-surgery and for a period afterwards until the tissue has recovered. For this reason, typical treatment is with 800 mg orally five times daily for seven days, commencing immediately following surgery.
Acycolvir is not approved by the PBS for this indication, so it needs to be bought as a private script. It is now off patent and can commonly be purchased for about $100. The alternative is to use another anti-viral drug with a longer serum half-life, such as valaciclovir or famciclovir; however, both of these are significantly more expensive than acyclovir, although they require only twice or three times daily dosing.
There is no good evidence of which patients will benefit from peri-operative oral acyclovir. As a rule of thumb, it tends to be used in those patients who are at higher risk of recurrence. That is, patients with recent (within the past year) stromal keratitis or uveitis secondary to either HSV or VZV.
In addition to oral acyclovir, topical corticosteroids may have to be used longer than usual post-operatively to reduce the risk of a flare-up of inflammation. A common approach is to use a topical corticosteroid such as prednisolone acetate (Prednefrin Forte) four times a day for one week, followed by three times a day for two weeks then two times daily for six weeks, then either ceasing or, if the patient requires topical corticosteroids prior to surgery, a return to the usual maintenance dose.
Modern uncomplicated cataract surgery is generally safe even with a history of HSV or HZO. Surgery is best performed when the eye is quiet, and topical corticosteroids and oral acyclovir can be used around the time of surgery to reduce the risk of viral reactivation or an increase in ocular inflammation.
- Hu AY et al. Late varicella-zoster virus dendriform keratitis in patients with histories of herpes zoster ophthalmicus. Am J Ophthalmol 2010; 149: 214-220.
- Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med 1998; 339: 300-306.