CLINICAL

  ANTERIOR

HASTEN HSV INTO HIBERNATION

RETURN THIS DNA VIRUS TO DORMANCY TO PREVENT VISION LOSS

JOSH JOHNSTON, O.D., F.A.A.O.

IN 2005, a 60-year-old female underwent unremarkable cataract surgery, and I managed her post-op care. The first week of recovery was unremarkable. Roughly 10 days later, she presented complaining of pain, photophobia, decreased vision and an irritated red eye OS.

Examination revealed her cornea had diffuse focal epithelial lesions and keratitis. These focal corneal lesions became more prominent upon fluorescein staining. In addition, her cornea appeared to have early stage dendritic formation with subsequent keratitis of the epithelium and anterior stroma. Given these findings and her post-cataract surgery steroid drop regimen, I suspected this patient had topical steroid-induced herpes simplex virus (HSV) keratitis.

Here, I discuss the etiology, symptoms, clinical signs, diagnosis/management options, as well as the ICD-10 codes for HSV keratitis and what happened with this patient.

ETIOLOGY

HSV keratitis occurs from HSV-1 and HSV-2 DNA viruses and can permanently decrease vision if not treated correctly.

HSV-1 is mainly transmitted via oral-to-oral contact and causes “cold sores,” though it can also induce genital herpes, says the World Health Organization. Meanwhile HSV-2 is transmitted sexually and causes genital herpes.

An estimated 500,000 people in the United States have HSV-related ocular disease, and there are approximately 20,000 new cases annually, according to Medscape.

HSV-1 and HSV-2 can involve the conjunctiva, corneal endothelium, corneal stroma, the lids, uveal tract and, most commonly, the corneal epithelial tissue. Less common ocular findings are endothelialitis, decreased corneal sensitivity from neurotrophic keratitis, stromal keratitis and uveitis.

After its first appearance, the virus hibernates in the nervous system until it is reactivated by stress, which causes an attack on the immune system.

SYMPTOMS

• Decreased vision

• Foreign-body sensation

• Pain

• Photophobia

• Tearing

CLINICAL SIGNS

• Characteristic branching of the corneal epithelium

• Conjunctival hyperemia

• Dendrites

• Large geographic ulcers

• Vesicular rash with or without pre-auricular lymphadenopathy (pertaining to lids and the periorbital area)

• Decreased corneal sensitivity from neurotrophic keratitis (less common)

• Endothelialitis (less common)

• Stromal keratitis (less common)

• Uveitis (less common)

DIAGNOSIS/MANAGEMENT

Obtain a corneal culture, particularly in a patient without a prior virus history, to definitively diagnose HSV keratitis. Culture results typically take several days to weeks. (The good news: Point-of-care diagnostics that promise greater efficiency, less expense and better sensitivity and specificity are in development.) A caveat: When you suspect HSV keratitis in a contact lens wearer, but the clinical presentation lacks the classic dendrites, rule out infectious keratitis from contact lens wear. Finally, use dyes, such as lissamine green, rose bengal and fluorescein, to assess epithelial lesions seen in HSV-caused epithelial keratitis. The lesions/dendrites take up the stain to let you see the dendritic pattern better, and this can also help you differentiate between zoster keratitis and HSV, as HSV has terminal end bulbs unlike zoster. You can also use the dyes to see whether the lesions are getting smaller and re-epithelization has occurred.

In terms of management options, four exist and are contingent on the condition’s severity:

• Topical antiviral. You can prescribe trifluridine 1% (Viroptic, Pfizer) or ganciclovir (Zirgan, Bausch + Lomb). Trifluridine is dosed one drop q2h during waking hours until the cornea has re-epithelialized. Then, the medication can be reduced to one drop q4h for the following seven to 10 days to reduce active viral replication. (Have the patient refrigerate trifluridine for the best efficacy.) Ganciclovir is dosed five times a day until the corneal ulcer has re-epithelialized and then three times a day for seven days until viral replication has ceased.

• Oral antiviral. For epithelial toxicity, primary HSV and severe stromal keratitis, prescribe oral acyclovir (Zovirax, GlaxoSmithKline) 400 mg five times a day. Further, consider prescribing an oral antiviral as prophylaxis with valacyclovir (Valtrex, GlaxoSmithKline) dosed at 500 mg t.i.d. PO for seven to 10 days and famciclovir (Famvir, Novartis) dosed at 250 mg t.i.d. PO for seven to 10 days. You can prescribe lower dosages, such as 250 mg or 500 mg Q.D. PO for months for recurring and chronic cases of HSV as well as before and after surgery. (Remember, surgery can cause stress and reactivate a latent virus. Many patients take steroids after surgery, so oral antivirals help decrease the chance of HSV reactivation.)

NaFl staining on a cornea with severe HSV keratitis. Note the classic dendritic appearance on the left with terminal end bulbs. The bottom right of the cornea is a large geographic ulcer that’s essentially an enlarged or expanding dendritic ulcer with scalloped borders.

• Topical steroid. Prescribe this for epithelial HSV keratitis that has healed dendritic lesions. Topical steroids are most commonly used to treat endotheliatitis, stromal keratitis and uveitis. Have this patient maintain antiviral coverage with both topical and oral antivirals while using the topical steroid. Dose topical steroids q.i.d., and taper with improvement.

• Amniotic membranes. Use these in conjunction with the treatments listed above when there is central keratitis with vision at risk, stromal and epithelial keratitis and chronic and poor-healing corneas. These tissues are placed on the cornea in an in-office procedure and have regenerative healing properties. They are left in place anywhere from five to 30 days, depending on the severity of the keratitis. The tissue does dissolve over time, and medications are still used as is. Place a dye, such as NaFL, and examine the cornea epithelium. If the keratitis has resolved, you remove the amniotic membrane.

THAT PATIENT

A corneal culture on the aforementioned patient confirmed HSV keratitis. I prescribed an antiviral drug. After the epithelial lesions began healing, I tapered the antiviral. Just when I thought everything was under control, the patient presented with complaints of pain, photophobia, decreased vision and an irritated red eye. Exam showed her cornea looked worse than before with a large area of diffuse punctate keratitis. She was having medicamentosa from the frequent use of the topical antiviral.

This case was challenging, as many variables were involved. The patient was on a topical steroid from the cataract surgery, the steroid suppressed her immune system and caused her latent HSV to reactivate, and the topical antiviral helped suppress viral replication, but caused medicamentosa and corneal toxicity. If I stopped the topical antiviral, the virus would increase in replication. If I stopped the steroid, the patient was at risk for postoperative inflammation and other issues, such as cystoid macular edema. Thankfully, the patient came out of this with her vision intact. Eleven years later, I’m thankful for the new therapeutic options available that help speed corneal healing and decrease corneal scarring to better prevent decreased vision. OM

DR. JOHNSTON practices at Georgia Eye Partners. He focuses on ocular surface disease and has extensive experience in co-managing cataract and refractive surgery patients. Email him at drj@gaeyepartners.com, or visit tinyurl.com/OMcomment to comment.