WHY DID THIS PATIENT GET WORSE, RATHER THAN BETTER?

A FEW years ago, a 55-year-old male contact lens-wearing patient with a history of herpes simplex viral (HSV) stromal and epithelial keratitis presented with ocular pain, photophobia, hyperemia and decreased vision.

He was referred by a doctor who diagnosed him as having a case of reactivated HSV stromal and epithelial keratitis and was, therefore, prescribed topical antiviral ophthalmic drops, oral antiviral pills and topical steroids. The patient saw me because his clinical signs and symptoms had worsened.

Here, I discuss the etiology, symptoms, clinical signs and diagnosis/management of HSV stromal keratitis and why this patient’s signs and symptoms worsened.

ETIOLOGY

HSV viral keratitis occurs from HSV-1 DNA and HSV-2 DNA viruses and can permanently decrease vision, if not treated correctly. Both forms can affect the ocular adnexa, conjunctiva, corneal endothelium, corneal stroma, uveal tract and the corneal epithelium.

HSV keratitis can present in these forms: HSV epithelial keratitis, HSV stromal keratitis without ulceration, HSV stromal keratitis with ulceration and HSV endothelial keratitis. All can occur at the same time.

Studies examining the presence of HSV-1 DNA in the trigeminal ganglia have determined that at least 90% of the world’s population is infected with latent HSV-1 by the age of 60, according to the American Academy of Ophthalmology’s (AAO) Herpes Simplex Virus Keratitis: A Treatment Guideline – 2014. Most ocular HSV infections are due to HSV-1. Rare ocular HSV-2 transmissions occur during childbirth. A total of 22% of pregnant women were seropositive for HSV-2, reveals September 2012’s Survey of Ophthalmology. In general, the various manifestations of ocular infection occur in an estimated 13% to 20% of neonates with HSV.

Once transmission occurs, some patients may get their first viral “attack,” known as primary HSV. This may present as general malaise or a mild fever, but most of the time no symptoms are experienced, and the classic signs (explained below) don’t occur. The virus then goes into hibernation in the nervous system until it is reactivated by stress, causing an attack on the immune system.

SYMPTOMS

• Decreased vision
• Foreign-body sensation
• Pain
• Photophobia
• Tearing

CLINICAL SIGNS

• Corneal edema
• Corneal infiltrates
• Corneal thinning
• Decreased corneal sensitivity
• Decreased VA
• Perforation
• Stromal scarring/haze
• Ulceration (possible)

DIAGNOSIS/MANAGEMENT

Because the viral antigens of HSV stromal keratitis reside in the stroma, a definitive diagnosis via culturing the cornea is not possible. Thus, diagnosis is made via case history and slit lamp exam, looking for the aforementioned clinical signs.

To differentiate HSV stromal keratitis from the ulcerative form and HSV epithelial keratitis, employ fluorescein dye for slit lamp biomicroscopy. In addition, doing so, will enable you to know how to balance antiviral and topical corticosteroid treatment, reports the AAO’s treatment guide.

The preferred treatment of HSV stromal keratitis is typically a 10-week course of a topical corticosteroid (prednisolone four to eight times or difluprednate ophthalmic emulsion 0.05% [Durezol, Novartis] b.i.d. to q.i.d.), in conjunction with a two-month course of an oral anti-viral (acyclovir 400 mg b.i.d. PO, valacyclovir 500 mg q.d. PO or famciclovir 250 mg b.i.d. PO), according to the AOA’s treatment guide. You need to balance using both oral antiviral treatments along with topical corticosteroids, adjusting both treatments, depending on clinical improvement. That said, if you see staining with epithelial involvement, topical corticosteroids are contraindicated, and you must use a topical antiviral alone.

In addition, the off-label use of cyclosporine .05% is used for long-term therapy to decrease reoccurrence and treat inflammation after topical steroids have been discontinued.

Of note: a referral for surgical intervention (penetrating keratoplasty and corneal transplants) is often warranted when patients present with HSV-caused corneal damage. Keratoprostheses are used as a last resort in repeat graft failures because of chronic HSV reoccurrences.

WHY THE WORSENING

The 55-year-old was diagnosed with HSV stromal keratitis with ulceration. The ulceration occurred from a failure to prescribe adjunctive antibacterial treatment with topical antibiotics — something required for contact lens-wearers who have HSV stromal keratitis, as the immunosuppressive nature of topical steroids in contact lens wearers can cause secondary infections.

Once I assessed the patient, I continued the prescribed antiviral treatment, but added adjunctive antibacterial treatment (besifloxacin, [Besivance, Bausch + Lomb] Q1, polymyxin B [Polytrim, Allergan] q.i.d. and bacitracin zinc and polymyxin B sulfate [Polysporin UNG ointment, Monarch] q.h.s.). This treated both gram-positive pathogens and anaerobes as well as gram-positive and gram-negative bacterial isolates, including MRSA, deemed widely resistant to fluoroquinolones. (Other topical fourth generation fluoroquinolones that can be used: ciprofloxacin 0.3 [Ciloxan, Alcon], levofloxacin 1.5% [Iquix Santen], ofloxacin 0.3% [Ocuflox, Allergan] moxifloxacin 0.5 [Vigamox, Alcon] and gatifloxacin 0.3%, [Zymar, Allergan].)

The results of a corneal culture prompted me to modify the patient’s antibacterial treatment to fortified vancomycin and besifloxacin (Besivance, Bausch + Lomb). An amniotic membrane was placed in the eye on the second office visit to speed healing and prevent additional scarring. Removal occurred five days later after the epithelial defect and infectious ulcer with dellen had resolved. (All topical treatments were maintained during the amniotic membrane placement.)

The cornea healed well with no additional scarring.

The lesson: When treating a contact lens-wearing patient who has HSV stromal keratitis, be sure to cover these patients with antibiotics to prevent secondary infections. 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. He is a consultant and speaker for Abbott, Alcon, Allergan, BioTissue and Shire. Email him at drj@gaeyepartners.com.