FocalPoints Clinical Modules for Ophthalmologists VOLUME XXVI, NUMBER 8 SEPTEMBER 2008 (MODULE 2 OF 3) Herpetic Corneal Infections Sonal S. Tuli, MD Reviewers and Contributing Editors Consultants George A. Stern, MD, Editor for Cornea & External Disease James Chodosh, MD, MPH Kristin M. Hammersmith, MD, Basic and Clinical Science Course Faculty, Section 8 Kirk R. Wilhelmus, MD, PhD Christie Morse, MD, Practicing Ophthalmologists Advisory Committee for Education Focal Points Editorial Review Board George A. Stern, MD, Missoula, MT Claiming CME Credit Editor in Chief, Cornea & External Disease Thomas L. Beardsley, MD, Asheville, NC Academy members: To claim Focal Points CME cred- Cataract its, visit the Academy web site and access CME Central (http://www.aao.org/education/cme) to view and print William S. Clifford, MD, Garden City, KS Glaucoma Surgery; Liaison for Practicing Ophthalmologists Advisory your Academy transcript and report CME credit you Committee for Education have earned. You can claim up to two AMA PRA Cate- gory 1 Credits™ per module. This will give you a maxi- Bradley S. Foster, MD, Springfield, MA Retina & Vitreous mum of 24 credits for the 2008 subscription year. CME credit may be claimed for up to three (3) years from Anil D. Patel, MD, Oklahoma City, OK date of issue. Non-Academy members: For assistance Neuro-Ophthalmology please send an e-mail to [email protected] or a Eric P. Purdy, MD, Fort Wayne, IN fax to (415) 561-8575. Oculoplastic, Lacrimal, & Orbital Surgery Steven I. Rosenfeld, MD, FACS, Delray Beach, FL Refractive Surgery, Optics & Refraction C. Gail Summers, MD, Minneapolis, MN Focal Points (ISSN 0891-8260) is published quarterly by the American Academy of Ophthalmology at 655 Beach St., San Francisco, CA 94109-1336. Print Pediatric Ophthalmology & Strabismus and online 1 year subscription is $175 for Academy members (2 years, $315; Albert T. 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All rights reserved. ii FOCAL POINTS : MODULE 8, 2008 Learning Objectives Upon completion of this module, Contents the reader should be able to: Introduction 1 • Describe the different clinical presentations of herpes simplex and herpes zoster corneal Herpes Simplex Keratitis 2 infections, including unusual presentations and • Life Cycle of Herpes Simplex Virus 2 complications of these diseases • Epithelial and Stromal Keratitis 3 • Discuss the Herpetic Eye Disease Study, its • Diagnosis 5 outcomes, and its limitations • Long-Term Complications 5 • Explain the current therapies available for herpetic • Treatment 5 eye disease, including surgery, understand the rationale for using these treatments, and outline Herpes Zoster Ophthalmicus 7 their complications • Diagnosis 8 • Acute Keratitis 8 • Chronic/Relapsing Keratitis 8 Financial Disclosures • Long-Term Complications 9 The authors, reviewers, and consultants disclose the following finan- • Treatment 9 cial relationships. James Chodosh, MD, MPH: (S) National Eye Institute. Kristin M. Hammersmith, MD: (L) Allergan. Steven I. Conclusion 11 Rosenfeld, MD, FACS: (L) Allergan. Albert T. Vitale, MD: (C) Bausch & Lomb. Clinicians’ Corner 13 The following contributors state that they have no significant financial interest or other relationship with the manufacturer of any commer- cial product discussed in their contributions to this module or with the manufacturer of any competing commercial product: Introduction Thomas L. Beardsley, MD; William S. Clifford, MD; Bradley S. Foster, MD; Christie Morse, MD; Anil D. Patel, MD; Eric P. Purdy, The word herpes is derived from the Greek word meaning MD; George A. Stern, MD; C. Gail Summers, MD; Sonal S. Tuli, MD; “to crawl,” because of the serpiginous nature of herpetic Kirk R. Wilhelmus, MD, PhD. lesions. Herpes viruses affecting humans include herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella- C = consultant fee, paid advisory boards, or fees for attending a zoster virus (VZV), cytomegalovirus, and Epstein- Barr meeting virus. These double- stranded DNA viruses have a viral- L = lecture fees (honoraria), travel fees, or reimbursements when derived capsid enclosed in a host cell–derived envelope speaking at the invitation of a commercial entity with viral- derived glycoprotein projections (Figure 1). S = grant support Figure 1 Structure of herpes simplex virus. FOCAL POINTS : MODULE 8, 2008 1 For the ophthalmologist, the three most important of these viruses are HSV-1, HSV-2, and VZV, all of which are neurotrophic. Once primary infection occurs, they enter the sensory nerve ganglia and reside there permanently. Periodic reactivations result in the morbidity seen with these viruses. In the United States, estimates note 60,000 new and recurrent cases of HSV keratitis and 50,000 to 100,000 cases of VZV keratitis, also called herpes zoster ophthalmicus (HZO), per year. Not only are these viruses a significant medical problem, but the economic implica- tions are staggering. Studies have estimated that treat- ment of each acute episode of HSV costs $200 to $300 and that systemic antiviral prophylaxis costs $8500 per event averted. In addition, there are intangible losses related to HSV infection, such as the loss of manpower. Herpes Simplex Keratitis Keratitis caused by HSV, or herpes simplex keratitis (HSK), is the most common cause of corneal blindness in devel- oped nations. It was previously thought that HSV-1 had Figure 2 Life cycle of herpes simplex virus. TG = trigeminal a predilection for the trigeminal ganglion and HSV-2, for ganglion. the sacral ganglion. However, an increasing number of cases of ocular herpes are caused by HSV-2, and anec- dotal reports suggest that ocular HSV-2 infections may Primary HSV Infection. Primary HSV ocular infection be more severe and cause more scarring. is frequently missed and rarely affects the cornea. The most common pattern of infection is blepharoconjunc- Life Cycle of Herpes Simplex Virus tivitis that heals without scarring. The associated fol- Primary HSV infection occurs by direct contact with licular conjunctivitis is often mistaken for adenoviral infected secretions. On contact, the virus enters epithe- conjunctivitis. However, unilateral, nonepidemic follic- lial cells and starts replicating. Within hours, it enters ular conjunctivitis should always make one suspect HSV,