UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Herpes simplex keratitis

Author
Alan Sugar, MD
Section Editors
Jonathan Trobe, MD
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

Keratitis (corneal infection and inflammation) caused by herpes simplex virus (HSV) is a major cause of blindness from corneal scarring and opacity worldwide [1].

HSV keratitis typically presents as an infection of the superficial layer of the cornea, with punctate or diffuse branching (dendritic) lesions of the epithelium that do not usually involve the stroma. Applying topical glucocorticoid drops to the infected eye (without use of concomitant antiviral medication) can exacerbate the infection and potentially lead to involvement of deeper stromal structures with threat to vision [2].

The diagnosis and treatment of HSV corneal infections will be discussed here. Discussion of the epidemiology and pathogenesis of HSV-1-related infections in general, as well as other clinical manifestations of HSV-1 infection, is presented separately. (See "Epidemiology of herpes simplex virus type 1 infection" and "Pathogenesis of herpes simplex virus type 1 infection" and "Clinical manifestations and diagnosis of herpes simplex virus type 1 infection".)

PATHOGENESIS

Herpes simplex virology — Two clinically important herpes simplex virus (HSV) types exist in the subfamily alpha herpesviridae, HSV-1 and HSV-2. Humans are the only natural host for both types. HSV-1 accounts for most oral, labial, and ocular infections and HSV-2 for most genital infections, although there is considerable and increasing overlap in these distributions.

Primary infection with HSV-1 occurs following inoculation of mucosal or skin surfaces by direct contact. Most ocular disease is thought to represent recurrent HSV disease following the establishment of viral latency in the host, rather than a primary ocular infection. Latency develops after the virus enters sensory neurons and travels to sensory ganglia (usually the trigeminal ganglion for ocular disease) by retrograde axoplasmic flow [3]. The virus remains in ganglia for the lifetime of the host. It has been proposed that HSV-1 latency may also be established in the cornea, although this is controversial [4-6]. (See "Pathogenesis of herpes simplex virus type 1 infection".)

                       

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Wed Aug 17 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Liesegang TJ. Herpes simplex virus epidemiology and ocular importance. Cornea 2001; 20:1.
  2. Benz MS, Glaser JS, Davis JL. Progressive outer retinal necrosis in immunocompetent patients treated initially for optic neuropathy with systemic corticosteroids. Am J Ophthalmol 2003; 135:551.
  3. Cunningham AL, Diefenbach RJ, Miranda-Saksena M, et al. The cycle of human herpes simplex virus infection: virus transport and immune control. J Infect Dis 2006; 194 Suppl 1:S11.
  4. Kaye SB, Baker K, Bonshek R, et al. Human herpesviruses in the cornea. Br J Ophthalmol 2000; 84:563.
  5. Farooq AV, Shukla D. Corneal latency and transmission of herpes simplex virus-1. Future Virol 2011; 6:101.
  6. Higaki S, Fukuda M, Shimomura Y. Virological and molecular biological evidence supporting herpes simplex virus type 1 corneal latency. Jpn J Ophthalmol 2015; 59:131.
  7. Kaufman HE, Azcuy AM, Varnell ED, et al. HSV-1 DNA in tears and saliva of normal adults. Invest Ophthalmol Vis Sci 2005; 46:241.
  8. Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res 2006; 25:355.
  9. Predictors of recurrent herpes simplex virus keratitis. Herpetic Eye Disease Study Group. Cornea 2001; 20:123.
  10. Ludema C, Cole SR, Poole C, et al. Association between unprotected ultraviolet radiation exposure and recurrence of ocular herpes simplex virus. Am J Epidemiol 2014; 179:208.
  11. Pollara G, Speidel K, Samady L, et al. Herpes simplex virus infection of dendritic cells: balance among activation, inhibition, and immunity. J Infect Dis 2003; 187:165.
  12. Knickelbein JE, Khanna KM, Yee MB, et al. Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 2008; 322:268.
  13. Huang FF, Wang ZJ, Zhang CR. Tear HSV-specific secretory IgA as a potential indicator for recurrent stromal herpes simplex keratitis: a preliminary study. Cornea 2013; 32:987.
  14. Inoue Y. Immunological aspects of herpetic stromal keratitis. Semin Ophthalmol 2008; 23:221.
  15. Liedtke W, Opalka B, Zimmermann CW, Lignitz E. Age distribution of latent herpes simplex virus 1 and varicella-zoster virus genome in human nervous tissue. J Neurol Sci 1993; 116:6.
  16. Holland EJ, Mahanti RL, Belongia EA, et al. Ocular involvement in an outbreak of herpes gladiatorum. Am J Ophthalmol 1992; 114:680.
  17. Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol 2012; 57:448.
  18. Souza PM, Holland EJ, Huang AJ. Bilateral herpetic keratoconjunctivitis. Ophthalmology 2003; 110:493.
  19. Oral acyclovir for herpes simplex virus eye disease: effect on prevention of epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group. Arch Ophthalmol 2000; 118:1030.
  20. Liesegang TJ. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol 1989; 107:1160.
  21. Sobol EK, Fargione RA, Atiya M, et al. Case-Control Study of Herpes Simplex Eye Disease: Bronx Epidemiology of Human Immunodeficiency Virus Eye Studies. Cornea 2016; 35:801.
  22. Young RC, Hodge DO, Liesegang TJ, Baratz KH. Incidence, recurrence, and outcomes of herpes simplex virus eye disease in Olmsted County, Minnesota, 1976-2007: the effect of oral antiviral prophylaxis. Arch Ophthalmol 2010; 128:1178.
  23. Labetoulle M, Auquier P, Conrad H, et al. Incidence of herpes simplex virus keratitis in France. Ophthalmology 2005; 112:888.
  24. Stanzel TP, Diaz JD, Mather R, et al. The epidemiology of herpes simplex virus eye disease in Northern California. Ophthalmic Epidemiol 2014; 21:370.
  25. Liesegang TJ, Melton LJ 3rd, Daly PJ, Ilstrup DM. Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn, 1950 through 1982. Arch Ophthalmol 1989; 107:1155.
  26. Shuster JJ, Kaufman HE, Nesburn AB. Statistical analysis of the rate of recurrence of herpesvirus ocular epithelial disease. Am J Ophthalmol 1981; 91:328.
  27. Teng CC. Images in clinical medicine. Corneal dendritic ulcer from herpes simplex virus infection. N Engl J Med 2008; 359:e22.
  28. Kowalski RP, Gordon YJ, Romanowski EG, et al. A comparison of enzyme immunoassay and polymerase chain reaction with the clinical examination for diagnosing ocular herpetic disease. Ophthalmology 1993; 100:530.
  29. Kowalski RP, Karenchak LM, Shah C, Gordon JS. ELVIS: a new 24-hour culture test for detecting herpes simplex virus from ocular samples. Arch Ophthalmol 2002; 120:960.
  30. Satpathy G, Mishra AK, Tandon R, et al. Evaluation of tear samples for Herpes Simplex Virus 1 (HSV) detection in suspected cases of viral keratitis using PCR assay and conventional laboratory diagnostic tools. Br J Ophthalmol 2011; 95:415.
  31. McGilligan VE, Moore JE, Tallouzi M, et al. A comparison of the clinical and molecular diagnosis of herpes simplex keratitis. Open Ophthalmol J 2014; 4:65.
  32. Kuo MT, Fang PC, Yu HJ, et al. A Multiplex Dot Hybridization Assay For Detection and Differentiation of Acanthamoeba and Herpes Keratitis. Invest Ophthalmol Vis Sci 2016; 57:2158.
  33. Gonzalez-Gonzalez LA, Molina-Prat N, Doctor P, et al. Clinical features and presentation of infectious scleritis from herpes viruses: a report of 35 cases. Ophthalmology 2012; 119:1460.
  34. Liesegang TJ. Classification of herpes simplex virus keratitis and anterior uveitis. Cornea 1999; 18:127.
  35. Holland EJ, Schwartz GS. Classification of herpes simplex virus keratitis. Cornea 1999; 18:144.
  36. Cook SD. Herpes simplex virus in the eye. Br J Ophthalmol 1992; 76:365.
  37. Langston DP, Dunkel EC. A rapid clinical diagnostic test for herpes simplex infectious keratitis. Am J Ophthalmol 1989; 107:675.
  38. Wilhelmus KR, Coster DJ, Donovan HC, et al. Prognostic indicators of herpetic keratitis. Analysis of a five-year observation period after corneal ulceration. Arch Ophthalmol 1981; 99:1578.
  39. Knickelbein JE, Hendricks RL, Charukamnoetkanok P. Management of herpes simplex virus stromal keratitis: an evidence-based review. Surv Ophthalmol 2009; 54:226.
  40. Wishart MS, Darougar S, Viswalingam ND. Recurrent herpes simplex virus ocular infection: epidemiological and clinical features. Br J Ophthalmol 1987; 71:669.
  41. Green LK, Pavan-Langston D. Herpes simplex ocular inflammatory disease. Int Ophthalmol Clin 2006; 46:27.
  42. Rowe AM, St Leger AJ, Jeon S, et al. Herpes keratitis. Prog Retin Eye Res 2013; 32:88.
  43. Suzuki T, Ohashi Y. Corneal endotheliitis. Semin Ophthalmol 2008; 23:235.
  44. Koizumi N, Inatomi T, Suzuki T, et al. Clinical features and management of cytomegalovirus corneal endotheliitis: analysis of 106 cases from the Japan corneal endotheliitis study. Br J Ophthalmol 2015; 99:54.
  45. Hamrah P, Cruzat A, Dastjerdi MH, et al. Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology 2010; 117:1930.
  46. Williams HP, Falcon MG, Jones BR. Corticosteroids in the management of herpetic eye disease. Trans Ophthalmol Soc U K 1977; 97:341.
  47. DAVIDSON SI, EVANS PJ. IDU AND THE TREATMENT OF HERPES SIMPLEX KERATITIS. Br J Ophthalmol 1964; 48:678.
  48. Wilhelmus KR. Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database Syst Rev 2015; 1:CD002898.
  49. A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. The Herpetic Eye Disease Study Group. Arch Ophthalmol 1996; 114:1065.
  50. Collum LM, McGettrick P, Akhtar J, et al. Oral acyclovir (Zovirax) in herpes simplex dendritic corneal ulceration. Br J Ophthalmol 1986; 70:435.
  51. Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf 2007; 5:240.
  52. A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The Epithelial Keratitis Trial. The Herpetic Eye Disease Study Group. Arch Ophthalmol 1997; 115:703.
  53. Colin J, Hoh HB, Easty DL, et al. Ganciclovir ophthalmic gel (Virgan; 0.15%) in the treatment of herpes simplex keratitis. Cornea 1997; 16:393.
  54. Kaufman, HE. Ganciclovir: a promising topical antiviral gel for herpetic keratitis. Expert Rev Ophthalmol 2009; 4:367.
  55. Tabbara KF, Al Balushi N. Topical ganciclovir in the treatment of acute herpetic keratitis. Clin Ophthalmol 2010; 4:905.
  56. Chou TY, Hong BY. Ganciclovir ophthalmic gel 0.15% for the treatment of acute herpetic keratitis: background, effectiveness, tolerability, safety, and future applications. Ther Clin Risk Manag 2014; 10:665.
  57. Duan R, de Vries RD, Osterhaus AD, et al. Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis. J Infect Dis 2008; 198:659.
  58. Piret J, Boivin G. Antiviral resistance in herpes simplex virus and varicella-zoster virus infections: diagnosis and management. Curr Opin Infect Dis 2016; 29:654.
  59. Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology 1994; 101:1883.
  60. Barron BA, Gee L, Hauck WW, et al. Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology 1994; 101:1871.
  61. Rao SN. Treatment of herpes simplex virus stromal keratitis unresponsive to topical prednisolone 1% with topical cyclosporine 0.05%. Am J Ophthalmol 2006; 141:771.
  62. Gündüz K, Ozdemir O. Topical cyclosporin as an adjunct to topical acyclovir treatment in herpetic stromal keratitis. Ophthalmic Res 1997; 29:405.
  63. Heiligenhaus A, Steuhl KP. Treatment of HSV-1 stromal keratitis with topical cyclosporin A: a pilot study. Graefes Arch Clin Exp Ophthalmol 1999; 237:435.
  64. Sheppard JD, Wertheimer ML, Scoper SV. Modalities to decrease stromal herpes simplex keratitis reactivation rates. Arch Ophthalmol 2009; 127:852.
  65. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med 1998; 339:300.
  66. Uchoa UB, Rezende RA, Carrasco MA, et al. Long-term acyclovir use to prevent recurrent ocular herpes simplex virus infection. Arch Ophthalmol 2003; 121:1702.
  67. Miserocchi E, Modorati G, Galli L, Rama P. Efficacy of valacyclovir vs acyclovir for the prevention of recurrent herpes simplex virus eye disease: a pilot study. Am J Ophthalmol 2007; 144:547.
  68. Lairson DR, Begley CE, Reynolds TF, Wilhelmus KR. Prevention of herpes simplex virus eye disease: a cost-effectiveness analysis. Arch Ophthalmol 2003; 121:108.
  69. Chong EM, Wilhelmus KR, Matoba AY, et al. Herpes simplex virus keratitis in children. Am J Ophthalmol 2004; 138:474.
  70. van Velzen M, van de Vijver DA, van Loenen FB, et al. Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis. J Infect Dis 2013; 208:1359.
  71. Toma HS, Murina AT, Areaux RG Jr, et al. Ocular HSV-1 latency, reactivation and recurrent disease. Semin Ophthalmol 2008; 23:249.
  72. Stanfield B, Kousoulas KG. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections. Curr Clin Microbiol Rep 2015; 2:125.
  73. Halberstadt M, Machens M, Gahlenbek KA, et al. The outcome of corneal grafting in patients with stromal keratitis of herpetic and non-herpetic origin. Br J Ophthalmol 2002; 86:646.
  74. Ren Y, Wang H, Zheng Q, et al. Long-Term Outcomes of Deep Anterior Lamellar Keratoplasty Treating Posterior Stroma-Implicated Herpetic Corneal Opacities. Cornea 2016; 35:299.
  75. Garcia DD, Farjo Q, Musch DC, Sugar A. Effect of prophylactic oral acyclovir after penetrating keratoplasty for herpes simplex keratitis. Cornea 2007; 26:930.
  76. Brown CR, Wagoner MD, Welder JD, et al. Boston keratoprosthesis type 1 for herpes simplex and herpes zoster keratopathy. Cornea 2014; 33:801.