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Development of Herpes Simplex Virus Infectious Epithelial Keratitis During Oral Acyclovir Therapy and Response to Topical Antivirals

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Development of Herpes Simplex Virus Infectious Epithelial Keratitis During Oral Acyclovir Therapy and Response to Topical Antivirals CASE REPORT Development of Herpes Simplex Virus Infectious Epithelial Keratitis During Oral Acyclovir Therapy and Response to Topical Antivirals Stuart B. Carter, MD, and Elisabeth J. Cohen, MD clinician experience and preference. Here we present 3 cases Purpose: To describe 3 cases of herpes simplex virus (HSV) of HSV blepharoconjunctivitis that progressed to corneal vesicular blepharitis that progressed to infectious epithelial keratitis epithelial keratitis despite receiving treatment doses of oral despite treatment with oral acyclovir, but responded to topical acyclovir, and subsequently resolved with the addition of antiviral therapy. topical antiviral therapy. Methods: Retrospective review of a small case series. Results: One adult and 2 children presented with unilateral HSV MATERIALS AND METHODS vesicular blepharitis without evidence of corneal involvement. Each We retrospectively reviewed the medical records of 3 patient was placed on a therapeutic dose of oral acyclovir. While patients who presented to the New York University Ophthal- taking oral antiviral therapy, the patients developed HSV infectious mology Service with a diagnosis of HSV vesicular blepharitis epithelial keratitis, which was treated with trifluridine 1% solution 9 and subsequently developed HSV infectious epithelial kera- times daily in the adult and ganciclovir 0.15% ophthalmic gel 5 titis while on oral antiviral therapy. This case series is exempt times daily in the 2 children. All 3 cases showed resolution of from review by the New York University School of Medicine epithelial keratitis within 3 to 10 days after initiation of topical Institutional Review Board. antiviral treatment while oral acyclovir was continued. Conclusions: Oral antiviral therapy alone may not adequately RESULTS prevent progression of infectious ocular HSV blepharoconjunctivitis. Topical antiviral therapy appeared to enable resolution of HSV Case 1 epithelial keratitis that arose during oral acyclovir treatment. A 25-year-old female presented to the eye clinic with 1 day of painful vesicular rash on her left upper and lower Key Words: herpes simplex virus, infectious epithelial keratitis, eyelids. She complained of redness and tearing in the left eye, blepharitis, antiviral medication but denied any change in vision. Her past medical history was (Cornea 2016;35:692–695) significant for eczema and asthma, and she had experienced a mild exacerbation of facial eczema 3 days prior for which she had not sought treatment. She denied any recent use of erpes simplex virus (HSV) ocular disease may present topical or oral steroids, only using an albuterol inhaler Hwith a variety of anterior segment manifestations includ- occasionally as needed. She had a history of prior episodes ing blepharoconjunctivitis, epithelial keratitis, stromal kerati- of oral cold sores, but denied any previous history of ocular tis, endothelial keratitis, and iritis.1,2 Both topical and oral infections or similar lesions around the eyes. Vision was antiviral agents have shown efficacy in the treatment of HSV found to be 20/20 in OD and 20/25 in OS at distance with epithelial infections. Randomized controlled trials such as the spectacle correction. Slit lamp examination revealed crops of Herpetic Eye Disease Study (HEDS) have refined the clear vesicles along the left medial upper and lower eyelids, treatment of HSV keratitis over the past 20 years.3–5 Specific approaching the lid margins, with scattered ruptured vesicles. treatment for HSV blepharoconjunctivitis is often based on The eyelids were bilaterally erythematous and scaly. There was mild conjunctival injection of the left eye, but no follicles Received for publication December 7, 2015; revision received January 13, or staining on the palpebral or bulbar conjunctiva. The left 2016; accepted January 14, 2016. Published online ahead of print March cornea was clear without fluorescein staining. There was no 18, 2016. anterior chamber reaction, and intraocular pressure (IOP) and From the Department of Ophthalmology, New York University (NYU) School of Medicine, NYU Langone Medical Center, New York, NY. dilated fundus examination were within normal limits. Funded, in part, by the Liesegang Research Fund to publish the figure in Examination of the right eye revealed no abnormalities. The color. patient was administered oral acyclovir 400 mg 5 times daily, The authors have no conflicts of interest to disclose. bacitracin ophthalmic ointment to the left eye and lids 3 times Reprints: Stuart B. Carter, MD, Department of Ophthalmology, New York fi University School of Medicine, 462 First Avenue, NBV 5N 18 (Bellevue daily, and arti cial tears as needed. Hospital Building), New York, NY 10016 (e-mail: [email protected]). The patient was seen in clinic 3 days later with Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. improvement in symptoms and reported compliance with 692 | www.corneajrnl.com Cornea Volume 35, Number 5, May 2016 Copyright Ó 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. Cornea Volume 35, Number 5, May 2016 Herpes Simplex Virus Epithelial Keratitis her medications. Examination revealed resolving vesicular good compliance. She denied any medical or ocular history, lesions of the left eyelids, trace conjunctival injection, and but had a history of oral cold sores. On examination in the clear corneal examination without fluorescein staining. The emergency room, the patient’s vision was 20/40 OD and 20/ patient was continued on oral acyclovir. The next day, the 20 OS without correction at near. The right upper lid was patient reported acute worsening of symptoms and increased edematous with a few erosive epidermal lesions without pain and foreign body sensation in the left eye with decreased evidence of marginal involvement. There was moderate vision. She presented for evaluation 2 days later, and vision conjunctival injection. Corneal examination revealed a prob- had decreased to 20/100 OS. Slit lamp examination revealed able geographic central epithelial lesion with multiple discrete multiple dendritic lesions of the central cornea without corneal dendrites nasally without stromal involvement (Fig. stromal involvement (Fig. 1A). The anterior chamber was 1B). There was no anterior chamber reaction, and the IOP and quiet and the IOP was normal. Trifluridine 1% ophthalmic dilated fundus examination were within normal limits. The solution 9 times daily and cyclopentolate 1% ophthalmic left eye was unremarkable. solution 3 times daily were added to the regimen for treatment The patient was administered ganciclovir 0.15% oph- of HSV infectious epithelial keratitis. thalmic gel 5 times daily to the right eye and continued on On follow-up examination the next day, the dendritic oral acyclovir and topical tobramycin ointment. On follow-up lesions of the cornea had decreased in size. After 4 days of examination 3 days later, the patient’s symptoms had trifluridine treatment, there were only trace epithelial defects completely resolved. Vision improved to 20/15 OU at remaining. The patient reported minimal pain, and cyclo- distance without correction and the right eyelid lesions had pentolate was discontinued. After 10 days of topical treat- healed. Corneal examination revealed trace residual superfi- ment, the dendritic lesions had completely resolved with faint cial punctate keratopathy in the right eye and no evidence of residual central superficial punctate keratopathy and underly- stromal disease or uveitis. Ganciclovir gel was then tapered to ing subepithelial haze. After 15 days of treatment, trifluridine 3 times daily for 1 week and the patient was instructed to was decreased to 5 times daily and stopped completely 2 complete a 14-day course of oral acyclovir. weeks later. The patient completed a 20-day course of oral acyclovir at 400 mg 5 times daily. Fluorometholone 0.1% ophthalmic solution was initiated 4 times daily during the Case 3 third week of treatment for residual subepithelial haze, which An 8-year-old male presented to the clinic with a 1-day resolved over the next month. At 7 weeks after initiation of history of a vesicular rash of the right upper and lower topical antiviral therapy, vision had recovered to 20/20 OS eyelids. His parents denied any redness, tearing, or changes in with correction. Fluorometholone was then tapered over vision. He had no past medical or ocular history, recent 3 weeks. illnesses, or history of cold sores. On examination, vision was 20/30 OU at distance without correction. Slit lamp examina- tion revealed multiple vesicles on the right central upper and Case 2 lower eyelids with surrounding edema. The conjunctiva was A 16-year-old female presented to the emergency room white and quiet. The cornea was clear without fluorescein with a 2-day history of right eye redness, blurry vision, and staining. There was no anterior chamber reaction, and the IOP pain. She had a painful vesicular rash of her right upper eyelid and dilated fundus examination were within normal limits. 5 days before presentation, without any ocular symptoms or The left eye was unremarkable. The patient was administered changes in vision. She saw her pediatrician who began oral acyclovir elixir 300 mg 3 times daily (30 mg$kg21$d21; treatment with tobramycin 0.3% ophthalmic ointment to the patient weight = 30 kg) and bacitracin ophthalmic ointment to right eyelids and oral acyclovir 400 mg 5 times daily with the right eyelids 3 times daily. FIGURE 1. A, Slit lamp photograph of the left
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