Herpes Simplex Keratitis Medication
- Author: Jim C Wang (王崇安), MD; Chief Editor: Hampton Roy, Sr, MD more...
Topical corticosteroids are effective in suppressing the inflammatory response of herpetic keratitis. However, their inappropriate use may result in severe epithelial disease or stromal necrosis, corneal perforation, increased tendency toward recurrence, secondary microbial infections, elevation of the intraocular pressure, and lenticular changes.
Patients requiring topical corticosteroids for suppression of the inflammatory response usually require the drug for a period of months, and withdrawal often is complicated by a recurrence of inflammation. The immunosuppressive complications of steroid administration (eg, recurrent epithelial disease) largely can be avoided by the concurrent administration of antiviral therapy.
Patient cooperation is a prerequisite for the safe administration of corticosteroids in herpetic keratitis. An extremely slow corticosteroid taper typically is required.
Antiviral agents, topical or oral, are prescribed to inhibit viral replication in infected cells. All topical antiviral medications available for clinical use in the United States are toxic, with signs of toxicity being similar for all such drugs. Punctate epithelial keratopathy, limbal follicles, a follicular conjunctival response, ptosis, punctal stenosis, and contact dermatitis can occur at any time after 10-14 days of therapy.
In mild cases of antiviral toxicity, epithelial changes may be the only manifestation. The toxic potential of antiviral agents always should be considered in patients who heal poorly, because these agents are inhibitors of cell division.
These agents inhibit herpes simplex virus (HSV) replication. Treatment of viral infections begins with mechanical débridement of the involved rim along with a rim of normal epithelium. This is followed by the topical instillation of antiviral medications (eg, trifluridine, ganciclovir).
A structural analogue of thymidine, this agent inhibits viral DNA polymerase. Viroptic has better penetration through the cornea and greater efficacy (95% heal rate) than other topical agents. If no response occurs in 7-14 days, consider other treatments.
Valacyclovir is a prodrug that is rapidly converted to the active drug acyclovir. It produces a greater serum concentration of acyclovir with smaller oral dosing. Valacyclovir is more expensive than acyclovir but can be as effective with a more convenient dosing regimen. The optimal dose for ocular disease has not been determined.
This agent is a prodrug that, when biotransformed into its active metabolite, penciclovir, may inhibit viral DNA synthesis/replication. It has been used successfully in the suppression of genital herpes. Its efficacy in HSV keratitis currently is under study.
Acyclovir is a synthetic guanosine analogue that requires activation by viral thymidine kinase. The activated acyclovir triphosphate, concentrated 50-100 times in HSV-infected cells, suppresses viral replication by preferentially inhibiting viral DNA polymerase, serving as a DNA chain terminator and inducing irreversible binding between polymerase enzyme and the interrupted DNA chain.
Acyclovir is a potent inhibitor of viral growth with minimal toxicity to uninfected epithelial cells. Oral acyclovir at a dose of 2 g/day for 10 days has been reported to be as effective as topical agents for epithelial keratitis, with the advantage of no ocular toxicity.
This agent is an acyclic nucleoside analogue of 2'deoxyguanasine. It phosphorylates first to monophosphate form by a viral-encoded protein kinase homologue, and then to diphosphate and triphosphate forms by cellular kinases. This allows for greater concentration of ganciclovir in virus-infected cells, possibly because of preferential phosphorylation of this agent in infected cells.
Ganciclovir is thought to inhibit HSV replication by competitive inhibition of viral DNA polymerases and by incorporating itself into viral DNA, causing termination of viral DNA elongation. Like acyclovir, ganciclovir is virostatic and exerts its effect only on replicating virus.
Wilhelmus KR. Diagnosis and management of herpes simplex stromal keratitis. Cornea. 1987. 6(4):286-91. [Medline].
Zaher SS, Sandinha T, Roberts F, Ramaesh K. Herpes simplex keratitis misdiagnosed as rheumatoid arthritis-related peripheral ulcerative keratitis. Cornea. 2005 Nov. 24(8):1015-7. [Medline].
Seitzman GD, Cevallos V, Margolis TP. Rose bengal and lissamine green inhibit detection of herpes simplex virus by PCR. Am J Ophthalmol. 2006 Apr. 141(4):756-8. [Medline].
Tabbara KF. Treatment of herpetic keratitis. Ophthalmology. 2005 Sep. 112(9):1640. [Medline].
Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006 Jul. 25(4):355-80. [Medline].
Jain V, Pineda R. Reactivated herpetic keratitis following laser in situ keratomileusis. J Cataract Refract Surg. 2009 May. 35(5):946-8. [Medline].
Khalili MR, Mehdizadeh M, Mehryar M. Herpetic epithelial keratitis after intravitreal injection of bevacizumab (avastin). Cornea. 2009 Apr. 28(3):360-1. [Medline].
Patel NN, Teng CC, Sperber LT, Dodick JM. New-onset herpes simplex virus keratitis after cataract surgery. Cornea. 2009 Jan. 28(1):108-10. [Medline].
Shtein RM, Stahl RM, Saxe SJ, Mian SI. Herpes simplex keratitis after intravitreal triamcinolone acetonide. Cornea. 2007 Jun. 26(5):641-2. [Medline].
Liesegang TJ, Melton LJ 3rd, Daly PJ, Ilstrup DM. Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989 Aug. 107(8):1155-9. [Medline].
Adhin MR, Grunberg MG, Labadie-Bracho M, Pawiroredjo J. Incidence of Alpha-Herpes virus induced ocular disease in Suriname. J Med Virol. 2012 Dec. 84(12):1937-42. [Medline].
Hsiao CH, Yeung L, Yeh LK, Kao LY, Tan HY, Wang NK, et al. Pediatric herpes simplex virus keratitis. Cornea. 2009 Apr. 28(3):249-53. [Medline].
Serna-Ojeda JC, Ramirez-Miranda A, Navas A, Jimenez-Corona A, Graue-Hernandez EO. Herpes Simplex Virus Disease of the Anterior Segment in Children. Cornea. 2015 Oct. 34 Suppl 10:S68-71. [Medline].
Saini JS, Agarwala R. Clinical pattern of recurrent herpes simplex keratitis. Indian J Ophthalmol. 1999 Mar. 47(1):11-4. [Medline].
Mocan MC, Irkec M, Mikropoulos DG, Bozkurt B, Orhan M, Konstas AG. In vivo confocal microscopic evaluation of the inflammatory response in non-epithelial herpes simplex keratitis. Curr Eye Res. 2012 Dec. 37(12):1099-106. [Medline].
Holland EJ, Schwartz GS. Classification of herpes simplex virus keratitis. Cornea. 1999 Mar. 18(2):144-54. [Medline].
Knickelbein JE, Hendricks RL, Charukamnoetkanok P. Management of herpes simplex virus stromal keratitis: an evidence-based review. Surv Ophthalmol. 2009 Mar-Apr. 54(2):226-34. [Medline].
Zhao G, Chen M, Liu T, Sun SY, Zhao J, Xie LX. Association of HSV-1 antigen distribution in the cornea with clinical characteristics of herpetic stromal keratitis. Eur J Ophthalmol. 2012. 22 Suppl 7:S40-5. [Medline].
Inoue Y, Shimomura Y, Fukuda M, Miyazaki D, Ohashi Y, Sasaki H, et al. Multicentre clinical study of the herpes simplex virus immunochromatographic assay kit for the diagnosis of herpetic epithelial keratitis. Br J Ophthalmol. 2012 Oct 19. [Medline].
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 Oct. 144(4):547-51. [Medline].
Koelle DM, Ghiasi H. Prospects for developing an effective vaccine against ocular herpes simplex virus infection. Curr Eye Res. 2005 Nov. 30(11):929-42. [Medline].
Pepose JS, Keadle TL, Morrison LA. Ocular herpes simplex: changing epidemiology, emerging disease patterns, and the potential of vaccine prevention and therapy. Am J Ophthalmol. 2006 Mar. 141(3):547-557. [Medline].
Guess S, Stone DU, Chodosh J. Evidence-based treatment of herpes simplex virus keratitis: a systematic review. Ocul Surf. 2007 Jul. 5(3):240-50. [Medline].
Wilhelmus KR, Gee L, Hauck WW, Kurinij N, Dawson CR, Jones DB, et al. Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis. Ophthalmology. 1994 Dec. 101(12):1883-95; discussion 1895-6. [Medline].
Kaufman HE, Martola EL, Dohlman CH. Herpes simplex treatment with IDU and corticosteroids. Arch Ophthalmol. 1963. 69:468-72.
Rao SN. Treatment of herpes simplex virus stromal keratitis unresponsive to topical prednisolone 1% with topical cyclosporine 0.05%. Am J Ophthalmol. 2006 Apr. 141(4):771-2. [Medline].
Chaurasia S, Murthy S, Ramappa M, Mohamed A, Garg P. Outcomes of Descemet's stripping endothelial keratoplasty in eyes with failed therapeutic penetrating keratoplasty. Acta Ophthalmol. 2013 Feb 7. [Medline].
Spelsberg H, Reichelt JA. [Amniotic membrane transplantation in proven ulcerative herpetic keratitis: successful anti-inflammatory treatment in time]. Klin Monbl Augenheilkd. 2008 Jan. 225(1):75-9. [Medline].
Cobo LM, Coster DJ, Rice NS, Jones BR. Prognosis and management of corneal transplantation for herpetic keratitis. Arch Ophthalmol. 1980 Oct. 98(10):1755-9. [Medline].
Maier AK, Ozlügedik S, Rottler J, Heussen FM, Klamann MK, Huber KK, et al. Efficacy of postoperative immunosuppression after keratoplasty in herpetic keratitis. Cornea. 2011 Dec. 30(12):1398-405. [Medline].
Garcia DD, Farjo Q, Musch DC, Sugar A. Effect of prophylactic oral acyclovir after penetrating keratoplasty for herpes simplex keratitis. Cornea. 2007 Sep. 26(8):930-4. [Medline].
de Rojas Silva MV, Díez-Feijóo E, Javaloy J, Sánchez-Salorio M. Prophylactic perioperative antiviral therapy for LASIK in patients with inactive herpetic keratitis. J Refract Surg. 2006 Apr. 22(4):404-6. [Medline].
Herpetic Eye Disease Study Group. 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. Arch Ophthalmol. 1997 Jun. 115(6):703-12. [Medline].
Herpetic Eye Disease Study Group. A controlled trial of oral acyclovir for iridocyclitis caused by herpes simplex virus. Arch Ophthalmol. 1996 Sep. 114(9):1065-72. [Medline].
Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med. 1998 Jul 30. 339(5):300-6. [Medline].
Levy J, Lapid-Gortzak R, Klemperer I, Lifshitz T. Herpes simplex virus keratitis after laser in situ keratomileusis. J Refract Surg. 2005 Jul-Aug. 21(4):400-2. [Medline].
Lu CK, Chen KH, Lee SM, Hsu WM, Lai JY, Li YS. Herpes simplex keratitis following excimer laser application. J Refract Surg. 2006 May. 22(5):509-11. [Medline].
de Rojas Silva V, Rodríguez-Conde R, Cobo-Soriano R, Beltrán J, Llovet F, Baviera J. Laser in situ keratomileusis in patients with a history of ocular herpes. J Cataract Refract Surg. 2007 Nov. 33(11):1855-9. [Medline].
van Lint AL, Torres-Lopez E, Knipe DM. Immunization with a replication-defective herpes simplex virus 2 mutant reduces herpes simplex virus 1 infection and prevents ocular disease. Virology. 2007 Nov 25. 368(2):227-31. [Medline]. [Full Text].
Kaiserman I, Kaiserman N, Nakar S, Vinker S. Herpetic eye disease in diabetic patients. Ophthalmology. 2005 Dec. 112(12):2184-8. [Medline].
Sozen E, Avunduk AM, Akyol N. Comparison of efficacy of oral valacyclovir and topical acyclovir in the treatment of herpes simplex keratitis: a randomized clinical trial. Chemotherapy. 2006. 52(1):29-31. [Medline].