Taking on surgery in HSV patients

Reviewed by Elizabeth Yeu, MD

Cataract and refractive surgeons should use prophylaxis to avoid reactivation of the herpes simplex virus (HSV) in patients with a history of infection with this virus, according to Elizabeth Yeu, MD.

“We have to be mindful of the examination process and make sure they have as healthy a cornea as possible,” said Dr. Yeu, assistant professor, Eastern Virginia Medical School, and partner, Virginia Eye Consultants, Norfolk, VA.

Dr. Yeu offered tips on treatment, topical steroid protocols, and postoperative warning signs that the virus has been activated.

HSV is ubiquitous, she said, citing a study-AAO Basic and Clinical Science Course, External Disease and Cornea, 2010-2011-that found HSV-1, a virus that causes cold sores, present in almost all autopsies of people over the age of 60 years in the United States.

HSV-1 generally starts with an oral-labial infection, whereas HSV-2 starts with a genital infection. The virus spreads from the site of the initial infection to neurons at other sites. The virus can lie dormant for years until a stressor reactivates it, potentially causing epithelial keratitis, Dr. Yeu said.

HSV is the one of the most common causes of corneal infections and can cause blindness.

The fewer episodes of HSV keratitis that the patient has experienced, and the more time has passed since these infections, the safer the surgery is likely to be, she noted.

Other considerations include the type of recurrence, whether epithelial, stromal, or endotheliitis; the degree of inflammation; and whether the infection developed despite prophylaxis.

Always risk

The risk never diminishes to zero.

“The scariest part is that the first episode can actually be stimulated by just having eye surgery,” Dr. Yeu said.

Surgeons and patients should weigh the risks against the benefits of the surgery under consideration.

“With cataract surgery, you know there’s actually a pathology there,” Dr. Yeu said. “Thus, the benefit of the likely improvement in vision can easily outweigh the risk of stimulating an HSV recurrence, whereas it is more difficult to justify this risk when considering a corneal refractive surgery candidate whose vision could easily worsen by a recurrent keratitis.”

Potentially devastating complications, albeit rare, can include fulminant herpetic keratouveitis with flap necrosis

Even less-severe infections, such as a short-lived course of epithelial keratitis, can lead to suboptimal vision from irregular astigmatism or scarring, she said.

People with HSV infections can be considered good candidates for cataract surgery if their infections have been inactive for at least 6 months, and the cataract extraction could lead to an overall vision improvement. Ultimately, any corneal pathology (corneal scarring or topographic irregularity) can lead to less-than-ideal vision, Dr. Yeu said.

Candidates for corneal refractive surgery, such as LASIK, should not have had an active infection in the past year, evidence of stromal disease, irregular topography, irregular pachymetry maps, or abnormal corneal sensitivity, she added.

HSV prophylaxis

For patients who have an inactive HSV infection, she recommended starting prophylaxis a day before surgery and maintaining it for 7 to 14 days afterward.

“If you can carry anti-viral prophylaxis through until they are reduced on their steroids to about once a day, that is a very smart thing to do because steroids themselves can trigger an episode of active viral epithelial keratitis,” Dr. Yeu said.

Prophylaxis anti-viral regimens to consider include valacyclovir 500 mg po BID, acyclovir 400 mg po BID, and topical ganciclovir 0.15% gel to the operative eye. The literature on ganciclovir is sparse, but using the ganciclovir gel as frequently as the steroid drop is used could be a reasonable protocol, Dr. Yeu said.

HSV keratitis

HSV keratitis

If HSV keratitis occurs after ocular surgery, treatment depends on whether the infection is caused by the live virus, an immune-mediated reaction, or a metaherpetic process, Dr. Yeu said.

She recommended maintaining enough topical steroids to facilitate recovery from the surgery, but to mitigate topical steroids in the setting of epithelial keratitis.

The active live virus can cause dendrites or geographic ulcers of the epithelium, necrotizing keratitis in the stroma, and keratouveitis in the anterior chamber. Immune-mediated HSV keratitis includes non-necrotizing stromal keratitis, disciform or linear endotheliitis, and possibly keratouveitis, she said.

Non-necrotizing HSV stromal keratitis is associated with the highest and most severe ocular morbidity, Dr. Yeu said, and can include stromal edema, vascularization or lipid deposition with the epithelium intact, and an antibody-complement cascade against retrained viral antigens in the stroma.

All endotheliitis should be treated with aggressive topical steroids, she said.

The disciform is the most common form. It is immune-mediated and can be recognized by its disc-shaped area of edema and keratic precipitates, Dr. Yeu added.

The diffuse form, which is also immune-mediated, is characterized by dense retrocorneal plaque. Linear endotheliitis, on the other hand, may be a sign of a live virus.

Metaherpetic disease

A metaherpetic keratitis process, such as a neurotrophic ulcer or drug toxicity, should be considered where the cornea fails to re-epithelialize after 14 to 21 days of treatment, Dr. Yeu said.

“Metaherpetic means something transitional,” she explained. “You know something else going on.

“It could be neurotrophic,” she said. “It could be that the nerves are so damaged from prior HSV infections that the cornea itself doesn’t sense that something is wrong so it doesn’t trigger the processes in order to heal that wound. Or it could be treatments that are too toxic for it.”

Trifluridine, which was considered a treatment of choice prior to topical gancyclovir, “is extremely toxic and was a common culprit for a poorly healing corneal epithelium,” Dr. Yeu said. A secondary infection could be another reason for metaherpetic keratitis.

Signs of neurotrophic keratopathy include confinement within the interpalpebral fissure; epithelization that has been delayed for more than 2 to 3 weeks; poor sensation; and oval, rolled edges with smooth borders.

HSV ulcer

HSV ulcer

If an HSV ulcer persists for more than 2 weeks, Dr. Yeu recommends stopping topical anti-viral treatment and changing to an oral anti-viral prophylaxis, aggressive preservative-free lubrication, a therapeutic bandage over the lens (with particular caution on a neurotrophic ulcer), topical anti-bacterial coverage, self-retaining amniotic membrane, and vitamin C, omega-3 fatty acids, and doxycycline.

Treatments for keratitis caused by the live virus include valcyclovir 500 to 1,000 mg po TID, acyclovir 400 mg po 5× daily, acyclovir 0.3% ointment 5× daily (not available in the United States), ganciclovir 0.15% gel 5× daily, and trifuridine 1% every 2 hours (with caution because of toxicity), with a potential concomitant epithelial debridement to debulk the viral load.

HSV epithelial keratitis is a self-limited disease, but treating it as a live viral infection for 21 days can help expedite recovery and limit nerve damage or future immunological disease, Dr. Yeu said.

For keratitis caused by an immune-mediated reaction, antiviral prophylaxis should be instituted at the lower prophylaxis protocol as aforementioned to prevent re-activation of the active virus from the topical steroid use, according to Dr. Yeu.

Topical steroids with a very slow taper over months should be used to treat the inflammation, and may be needed once or twice a week indefinitely to maintain remission. Common high-dose topical steroids are needed, such as topical difluprednate 0.05% or prednisolone 1%, every 2 to 3 hours with a very slow taper down to weaker steroids and less frequency.

Elizabeth Yeu, MD

P: 757/622-2200     E: eyeu@vec2020.com

This article was adapted from Dr. Yeu’s presentation during Cornea Day at the 2017 meeting of the American Society of Cataract and Refractive Surgery. Dr. Yeu is a consultant or advisor to Alcon Laboratories, Allergan, ArcScan, Bausch + Lomb/Valeant, BioTissue, iOptics, Johnson & Johnson Vision, LENSAR, Kala Pharmaceuticals, Ocular Science, Ocular Therapeutix, Omeros, Ocusoft, Shire, SightLife Sun, Surgical, TearLab Corp., and TearScience. Her research has been sponsored by Alcon, Allergan, iOptics, Kala, and Topcon. She has ownership interest in ArcScan, Modernizing Medicine, Ocular Science, RPS, SightLife Surgical, and Strathspey Crown.