Skip to main content
NCBI home page
Transactions of the American Ophthalmological Society logoLink to Transactions of the American Ophthalmological Society
. 2000;98:285–303.

Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy.

P A Asbell 1
PMCID: PMC1298232  PMID: 11190029

Abstract

PURPOSE: A variety of factors have been reported as inducing the reactivation of latent herpes simplex virus (HSV), among them stress, trauma, and UV radiation. Excimer laser photorefractive keratectomy (PRK) is a surgical procedure utilizing a 193 nm ultraviolet light to alter the curvature of the cornea and hence correct vision. Reactivation of ocular herpes simplex keratitis following such excimer laser PRK has been reported. All published cases of HSV reactivation following excimer laser treatment in humans are reviewed. The present study evaluates whether stress, trauma of the corneal de-epithelialization prior to the laser, or the excimer laser treatment itself to the stromal bed induces this ocular reactivation of the latent HSV, and whether a systemic antiviral agent, valacyclovir, would prevent such laser PRK-induced reactivation of the HSV. METHODS: Forty-three normal 1.5- to 2.5-kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution, and then all animals were divided into 5 treatment groups: (1) de-epithelialization only, intraperitoneal (i.p.) saline for 14 days; (2) de-epithelialization plus laser, i.p. saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day i.p. for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day i.p. for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day i.p. for 14 days. Animals were evaluated in a masked fashion by clinical examination biweekly and viral cultures biweekly through day 28. RESULTS: The reactivation rates were as follows: group 1, 0%; group 2, 67%; group 3, 50%; group 4, 17%; and group 5, 0%. Viral titers were negative in animals that had no reactivation but persistently positive in those that had reactivation (day 6 through day 28). CONCLUSIONS: Excimer laser (193 nm) treatment can trigger reactivation of ocular herpes disease (67%) and viral shedding in the latently infected rabbit. De-epithelialization alone is not sufficient to cause reactivation or viral shedding. Prophylaxis with intraperitoneal valacyclovir decreases the recurrence rate in a dose-response fashion. At 150 mg/kg per day, there are no recurrences. The presence of persistent viral shedding in reactivated animals may correlate with cases of late HSV recurrence reported in humans undergoing excimer treatment. The data suggest that humans undergoing excimer laser procedures for correction of refractive errors or treatment of corneal scars with a history of herpetic keratitis are at increased risk for reactivation. Such patients, however, may appropriately be considered for prophylactic systemic antiviral medication at the time of the laser procedure in order to decrease the possibility of recurrence.

Full text

PDF
285

Images in this article

294FIGURE 6
on p.294
298FIGURE 7
on p.298

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbott K. C., McLendon E. F., Gangarosa L. P., Sr, Hill J. M. Adrenergic induction of HSV-1 ocular shedding in rabbits. J Ocul Pharmacol. 1986 Winter;2(1):41–54. doi: 10.1089/jop.1986.2.41. [DOI] [PubMed] [Google Scholar]
  2. Acosta E. P., Fletcher C. V. Valacyclovir. Ann Pharmacother. 1997 Feb;31(2):185–191. doi: 10.1177/106002809703100211. [DOI] [PubMed] [Google Scholar]
  3. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. Herpetic Eye Disease Study Group. N Engl J Med. 1998 Jul 30;339(5):300–306. doi: 10.1056/NEJM199807303390503. [DOI] [PubMed] [Google Scholar]
  4. Asbell P. A., Centifanto-Fitzgerald Y. M., Chandler J. W., Kaufman H. E. Analysis of viral DNA in isolates from patients with recurrent herpetic keratitis. Invest Ophthalmol Vis Sci. 1984 Aug;25(8):951–954. [PubMed] [Google Scholar]
  5. Asbell P. A., Kamenar T. The response of Langerhans cells in the cornea to herpetic keratitis. Curr Eye Res. 1987 Jan;6(1):179–182. doi: 10.3109/02713688709020087. [DOI] [PubMed] [Google Scholar]
  6. BLANK H., BRODY M. W. Recurrent herpes simplex; a psychiatric and laboratory study. Psychosom Med. 1950 Jul-Aug;12(4):254–260. doi: 10.1097/00006842-195007000-00007. [DOI] [PubMed] [Google Scholar]
  7. Baringer J. R., Swoveland P. Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med. 1973 Mar 29;288(13):648–650. doi: 10.1056/NEJM197303292881303. [DOI] [PubMed] [Google Scholar]
  8. Baringer J. R., Swoveland P. Recovery of herpes-simplex virus from human trigeminal ganglions. N Engl J Med. 1973 Mar 29;288(13):648–650. doi: 10.1056/NEJM197303292881303. [DOI] [PubMed] [Google Scholar]
  9. Becker T. M., Magder L., Harrison H. R., Stewart J. A., Humphrey D. D., Hauler J., Nahmias A. J. The epidemiology of infection with the human herpesviruses in Navajo children. Am J Epidemiol. 1988 May;127(5):1071–1078. doi: 10.1093/oxfordjournals.aje.a114883. [DOI] [PubMed] [Google Scholar]
  10. Beuerman R. W., Rózsa A. J. Collateral sprouts are replaced by regenerating neurites in the wounded corneal epithelium. Neurosci Lett. 1984 Jan 27;44(1):99–104. doi: 10.1016/0304-3940(84)90228-3. [DOI] [PubMed] [Google Scholar]
  11. Beyer C. F., Arens M. Q., Hill J. M., Rose B. T., Hill G. A., Lin D. T. Penetrating keratoplasty in rabbits induces latent HSV-1 reactivation when corticosteroids are used. Curr Eye Res. 1989 Dec;8(12):1323–1329. doi: 10.3109/02713688909013913. [DOI] [PubMed] [Google Scholar]
  12. Beyer C. F., Arens M. Q., Hill J. M., Rose B. T., Hill G. A., Lin D. T. Penetrating keratoplasty in rabbits induces latent HSV-1 reactivation when corticosteroids are used. Curr Eye Res. 1989 Dec;8(12):1323–1329. doi: 10.3109/02713688909013913. [DOI] [PubMed] [Google Scholar]
  13. Beyer C. F., Byrd T. J., Hill J. M., Kaufman H. E. Herpes simplex virus and persistent epithelial defects after penetrating keratoplasty. Am J Ophthalmol. 1990 Jan 15;109(1):95–96. doi: 10.1016/s0002-9394(14)75590-4. [DOI] [PubMed] [Google Scholar]
  14. Beyer C. F., Hill J. M., Reidy J. J., Beuerman R. W. Corneal nerve disruption reactivates virus in rabbits latently infected with HSV-1. Invest Ophthalmol Vis Sci. 1990 May;31(5):925–932. [PubMed] [Google Scholar]
  15. Beyer C. F., Hill J. M., Reidy J. J., Beuerman R. W. Corneal nerve disruption reactivates virus in rabbits latently infected with HSV-1. Invest Ophthalmol Vis Sci. 1990 May;31(5):925–932. [PubMed] [Google Scholar]
  16. Blatt A. N., Laycock K. A., Brady R. H., Traynor P., Krogstad D. J., Pepose J. S. Prophylactic acyclovir effectively reduces herpes simplex virus type 1 reactivation after exposure of latently infected mice to ultraviolet B. Invest Ophthalmol Vis Sci. 1993 Nov;34(12):3459–3465. [PubMed] [Google Scholar]
  17. Blyth W. A., Harbour D. A., Hill T. J. Effect of immunosuppression on recurrent herpes simplex in mice. Infect Immun. 1980 Sep;29(3):902–907. doi: 10.1128/iai.29.3.902-907.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Bodsworth N. J., Crooks R. J., Borelli S., Vejlsgaard G., Paavonen J., Worm A. M., Uexkull N., Esmann J., Strand A., Ingamells A. J. Valaciclovir versus aciclovir in patient initiated treatment of recurrent genital herpes: a randomised, double blind clinical trial. International Valaciclovir HSV Study Group. Genitourin Med. 1997 Apr;73(2):110–116. doi: 10.1136/sti.73.2.110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. CARTON C. A., KILBOURNE E. D. Activation of latent herpes simplex by trigeminal sensory-root section. N Engl J Med. 1952 Jan 31;246(5):172–176. doi: 10.1056/NEJM195201312460503. [DOI] [PubMed] [Google Scholar]
  20. Carroll J. M., Martola E. L., Laibson P. R., Dohlman C. H. The recurrence of herpetic keratitis following idoxuridine therapy. Am J Ophthalmol. 1967 Jan;63(1):103–107. doi: 10.1016/0002-9394(67)90583-1. [DOI] [PubMed] [Google Scholar]
  21. Cobo L. M., Coster D. J., Rice N. S., Jones B. R. Prognosis and management of corneal transplantation for herpetic keratitis. Arch Ophthalmol. 1980 Oct;98(10):1755–1759. doi: 10.1001/archopht.1980.01020040607002. [DOI] [PubMed] [Google Scholar]
  22. Cohen E. J., Laibson P. R., Arentsen J. J. Corneal transplantation for herpes simplex keratitis. Am J Ophthalmol. 1983 May;95(5):645–650. doi: 10.1016/0002-9394(83)90384-7. [DOI] [PubMed] [Google Scholar]
  23. Colin J., Robinet A., Malet F. Traitement préventif des kératites herpétiques par l'acyclovir en comprimés. J Fr Ophtalmol. 1993;16(1):6–9. [PubMed] [Google Scholar]
  24. Cook S. D., Hill J. H. Herpes simplex virus: molecular biology and the possibility of corneal latency. Surv Ophthalmol. 1991 Sep-Oct;36(2):140–148. doi: 10.1016/0039-6257(91)90127-2. [DOI] [PubMed] [Google Scholar]
  25. Corey L., Spear P. G. Infections with herpes simplex viruses (2). N Engl J Med. 1986 Mar 20;314(12):749–757. doi: 10.1056/NEJM198603203141205. [DOI] [PubMed] [Google Scholar]
  26. Crouse C. A., Pflugfelder S. C., Pereira I., Cleary T., Rabinowitz S., Atherton S. S. Detection of herpes viral genomes in normal and diseased corneal epithelium. Curr Eye Res. 1990 Jun;9(6):569–581. doi: 10.3109/02713689008999597. [DOI] [PubMed] [Google Scholar]
  27. Davidorf J. M. Herpes simplex keratitis after LASIK. J Refract Surg. 1998 Nov-Dec;14(6):667–667. doi: 10.3928/1081-597X-19981101-18. [DOI] [PubMed] [Google Scholar]
  28. Dawson C. R., Togni B. Herpes simplex eye infections: clinical manifestations, pathogenesis and management. Surv Ophthalmol. 1976 Sep-Oct;21(2):121–135. doi: 10.1016/0039-6257(76)90090-4. [DOI] [PubMed] [Google Scholar]
  29. Deutsch F. H. Recurrent herpes simplex keratitis treated with hormone-induced amenorrhea. Am J Ophthalmol. 1966 Jun;61(6):1527–1529. doi: 10.1016/0002-9394(66)90497-1. [DOI] [PubMed] [Google Scholar]
  30. Dhaliwal D. K., Barnhorst D. A., Jr, Romanowski E., Rehkopf P. G., Gordon Y. J. Efficient reactivation of latent herpes simplex virus type 1 infection by excimer laser keratectomy in the experimental rabbit ocular model. Am J Ophthalmol. 1998 Apr;125(4):488–492. doi: 10.1016/s0002-9394(99)80189-5. [DOI] [PubMed] [Google Scholar]
  31. Douglas J. M., Critchlow C., Benedetti J., Mertz G. J., Connor J. D., Hintz M. A., Fahnlander A., Remington M., Winter C., Corey L. A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection. N Engl J Med. 1984 Jun 14;310(24):1551–1556. doi: 10.1056/NEJM198406143102402. [DOI] [PubMed] [Google Scholar]
  32. Epstein R. J., Seedor J. A., Dreizen N. G., Stulting R. D., Waring G. O., 3rd, Wilson L. A., Cavanagh H. D. Penetrating keratoplasty for herpes simplex keratitis and keratoconus. Allograft rejection and survival. Ophthalmology. 1987 Aug;94(8):935–944. doi: 10.1016/s0161-6420(87)33356-1. [DOI] [PubMed] [Google Scholar]
  33. Fagerholm P., Ohman L., Orndahl M. Phototherapeutic keratectomy in herpes simplex keratitis. Clinical results in 20 patients. Acta Ophthalmol (Copenh) 1994 Aug;72(4):457–460. doi: 10.1111/j.1755-3768.1994.tb02796.x. [DOI] [PubMed] [Google Scholar]
  34. Fife K. H., Barbarash R. A., Rudolph T., Degregorio B., Roth R. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Results of an international, multicenter, double-blind, randomized clinical trial. The Valaciclovir International Herpes Simplex Virus Study Group. Sex Transm Dis. 1997 Sep;24(8):481–486. doi: 10.1097/00007435-199709000-00007. [DOI] [PubMed] [Google Scholar]
  35. Foster C. S., Duncan J. Penetrating keratoplasty for herpes simplex keratitis. Am J Ophthalmol. 1981 Sep;92(3):336–343. doi: 10.1016/0002-9394(81)90522-5. [DOI] [PubMed] [Google Scholar]
  36. Frueh B. E., Cadez R., Böhnke M. In vivo confocal microscopy after photorefractive keratectomy in humans. A prospective, long-term study. Arch Ophthalmol. 1998 Nov;116(11):1425–1431. doi: 10.1001/archopht.116.11.1425. [DOI] [PubMed] [Google Scholar]
  37. Gebhardt B. M., Kaufman H. E. Propranolol suppresses reactivation of herpesvirus. Antiviral Res. 1995 Jun;27(3):255–261. doi: 10.1016/0166-3542(95)00009-b. [DOI] [PubMed] [Google Scholar]
  38. Gerdes J. C., Smith D. S. Recurrence phenotypes and establishment of latency following rabbit keratitis produced by multiple herpes simplex virus strains. J Gen Virol. 1983 Nov;64(Pt 11):2441–2454. doi: 10.1099/0022-1317-64-11-2441. [DOI] [PubMed] [Google Scholar]
  39. Gordon Y. J., Araullo-Cruz T. P., Romanowski E., Ruziczka L., Balouris C., Oren J., Cheng K. P., Kim S. The development of an improved murine iontophoresis reactivation model for the study of HSV-1 latency. Invest Ophthalmol Vis Sci. 1986 Aug;27(8):1230–1234. [PubMed] [Google Scholar]
  40. Gordon Y. J., Araullo-Cruz T. P., Romanowski E., Ruziczka L., Balouris C., Oren J., Cheng K. P., Kim S. The development of an improved murine iontophoresis reactivation model for the study of HSV-1 latency. Invest Ophthalmol Vis Sci. 1986 Aug;27(8):1230–1234. [PubMed] [Google Scholar]
  41. Gordon Y. J., Romanowski E., Araullo-Cruz T. A fast, simple reactivation method for the study of HSV-1 latency in the rabbit ocular model. Invest Ophthalmol Vis Sci. 1990 May;31(5):921–924. [PubMed] [Google Scholar]
  42. Gordon Y. J., Romanowski E., Araullo-Cruz T. A fast, simple reactivation method for the study of HSV-1 latency in the rabbit ocular model. Invest Ophthalmol Vis Sci. 1990 May;31(5):921–924. [PubMed] [Google Scholar]
  43. Green M. T., Rosborough J. P., Dunkel E. C. In vivo reactivation of herpes simplex virus in rabbit trigeminal ganglia: electrode model. Infect Immun. 1981 Oct;34(1):69–74. doi: 10.1128/iai.34.1.69-74.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Green M. T., Rosborough J. P., Dunkel E. C. In vivo reactivation of herpes simplex virus in rabbit trigeminal ganglia: electrode model. Infect Immun. 1981 Oct;34(1):69–74. doi: 10.1128/iai.34.1.69-74.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Harbour D. A., Hill T. J., Blyth W. A. Recurrent herpes simplex in the mouse: inflammation in the skin and activation of virus in the ganglia following peripheral stimulation. J Gen Virol. 1983 Jul;64(Pt 7):1491–1498. doi: 10.1099/0022-1317-64-7-1491. [DOI] [PubMed] [Google Scholar]
  46. Haruta Y., Maguire L. J., Rootman D. S., Hill J. M. Recurrent herpes simplex virus type 1 corneal epithelial lesions after radial keratotomy in the rabbit. Arch Ophthalmol. 1987 May;105(5):692–694. doi: 10.1001/archopht.1987.01060050110048. [DOI] [PubMed] [Google Scholar]
  47. Haruta Y., Rootman D. S., Xie L. X., Kiritoshi A., Hill J. M. Recurrent HSV-1 corneal lesions in rabbits induced by cyclophosphamide and dexamethasone. Invest Ophthalmol Vis Sci. 1989 Mar;30(3):371–376. [PubMed] [Google Scholar]
  48. Hill T. J., Blyth W. A. An alternative theory of herpes-simplex recurrence and a possible role for prostaglandins. Lancet. 1976 Feb 21;1(7956):397–399. doi: 10.1016/s0140-6736(76)90220-8. [DOI] [PubMed] [Google Scholar]
  49. Hill T. J., Blyth W. A., Harbour D. A. Trauma to the skin causes recurrence of herpes simplex in the mouse. J Gen Virol. 1978 Apr;39(1):21–28. doi: 10.1099/0022-1317-39-1-21. [DOI] [PubMed] [Google Scholar]
  50. Hill T. J., Field H. J., Blyth W. A. Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. J Gen Virol. 1975 Sep;28(3):341–353. doi: 10.1099/0022-1317-28-3-341. [DOI] [PubMed] [Google Scholar]
  51. Håkanson S. Trigeminal neuralgia treated by the injection of glycerol into the trigeminal cistern. Neurosurgery. 1981 Dec;9(6):638–646. doi: 10.1227/00006123-198112000-00005. [DOI] [PubMed] [Google Scholar]
  52. Kauffmann T., Bodanowitz S., Hesse L., Kroll P. Corneal reinnervation after photorefractive keratectomy and laser in situ keratomileusis: an in vivo study with a confocal videomicroscope. Ger J Ophthalmol. 1996 Nov;5(6):508–512. [PubMed] [Google Scholar]
  53. Kaufman H. E., Brown D. C., Ellison E. M. Recurrent herpes in the rabbit and man. Science. 1967 Jun 23;156(3782):1628–1629. doi: 10.1126/science.156.3782.1628. [DOI] [PubMed] [Google Scholar]
  54. Kaufman H. E., Varnell E. D., Centifanto-Fitzgerald Y. M., De Clercq E., Kissling G. E. Oral antiviral drugs in experimental herpes simplex keratitis. Antimicrob Agents Chemother. 1983 Dec;24(6):888–891. doi: 10.1128/aac.24.6.888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Kaye S. B., Lynas C., Patterson A., Risk J. M., McCarthy K., Hart C. A. Evidence for herpes simplex viral latency in the human cornea. Br J Ophthalmol. 1991 Apr;75(4):195–200. doi: 10.1136/bjo.75.4.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Klein R. J. Pathogenetic mechansims of recurrent herpes simplex virus infections. Arch Virol. 1976;51(1-2):1–13. doi: 10.1007/BF01317829. [DOI] [PubMed] [Google Scholar]
  57. Kohlhaas M. Corneal sensation after cataract and refractive surgery. J Cataract Refract Surg. 1998 Oct;24(10):1399–1409. doi: 10.1016/s0886-3350(98)80237-x. [DOI] [PubMed] [Google Scholar]
  58. Kurata T., Kurata K., Aoyama Y. Reactivation of herpes simplex virus (type 2) infection in trigeminal ganglia and oral lips with cyclophosphamide treatment. Jpn J Exp Med. 1978 Oct;48(5):427–435. [PubMed] [Google Scholar]
  59. Kwon B. S., Gangarosa L. P., Burch K. D., deBack J., Hill J. M. Induction of ocular herpes simplex virus shedding by iontophoresis of epinephrine into rabbit cornea. Invest Ophthalmol Vis Sci. 1981 Sep;21(3):442–449. [PubMed] [Google Scholar]
  60. Laibson P. R., Kibrick S. Reactivation of herpetic keratitis by epinephrine in rabbit. Arch Ophthalmol. 1966 Feb;75(2):254–260. doi: 10.1001/archopht.1966.00970050256020. [DOI] [PubMed] [Google Scholar]
  61. Laycock K. A., Lee S. F., Brady R. H., Pepose J. S. Characterization of a murine model of recurrent herpes simplex viral keratitis induced by ultraviolet B radiation. Invest Ophthalmol Vis Sci. 1991 Sep;32(10):2741–2746. [PubMed] [Google Scholar]
  62. Liesegang T. J. Epidemiology and natural history of ocular herpes simplex virus infection in Rochester, Minnesota, 1950-1982. Trans Am Ophthalmol Soc. 1988;86:688–724. [PMC free article] [PubMed] [Google Scholar]
  63. Liesegang T. J. Epidemiology of ocular herpes simplex. Natural history in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989 Aug;107(8):1160–1165. doi: 10.1001/archopht.1989.01070020226030. [DOI] [PubMed] [Google Scholar]
  64. Liesegang T. J., Melton L. J., 3rd, Daly P. J., Ilstrup D. M. Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn, 1950 through 1982. Arch Ophthalmol. 1989 Aug;107(8):1155–1159. doi: 10.1001/archopht.1989.01070020221029. [DOI] [PubMed] [Google Scholar]
  65. Linna T. U., Pérez-Santonja J. J., Tervo K. M., Sakla H. F., Alió y Sanz J. L., Tervo T. M. Recovery of corneal nerve morphology following laser in situ keratomileusis. Exp Eye Res. 1998 Jun;66(6):755–763. doi: 10.1006/exer.1998.0469. [DOI] [PubMed] [Google Scholar]
  66. Linna T., Tervo T. Real-time confocal microscopic observations on human corneal nerves and wound healing after excimer laser photorefractive keratectomy. Curr Eye Res. 1997 Jul;16(7):640–649. doi: 10.1076/ceyr.16.7.640.5058. [DOI] [PubMed] [Google Scholar]
  67. Mannis M. J., Plotnik R. D., Schwab I. R., Newton R. D. Herpes simplex dendritic keratitis after keratoplasty. Am J Ophthalmol. 1991 Apr 15;111(4):480–484. doi: 10.1016/s0002-9394(14)72384-0. [DOI] [PubMed] [Google Scholar]
  68. Mattison H. R., Reichman R. C., Benedetti J., Bolgiano D., Davis L. G., Bailey-Farchione A., Remington M., Winter C., Corey L. Double-blind, placebo-controlled trial comparing long-term suppressive with short-term oral acyclovir therapy for management of recurrent genital herpes. Am J Med. 1988 Aug 29;85(2A):20–25. [PubMed] [Google Scholar]
  69. Mattison H. R., Reichman R. C., Benedetti J., Bolgiano D., Davis L. G., Bailey-Farchione A., Remington M., Winter C., Corey L. Double-blind, placebo-controlled trial comparing long-term suppressive with short-term oral acyclovir therapy for management of recurrent genital herpes. Am J Med. 1988 Aug 29;85(2A):20–25. [PubMed] [Google Scholar]
  70. McDonnell P. J., Moreira H., Clapham T. N., D'Arcy J., Munnerlyn C. R. Photorefractive keratectomy for astigmatism. Initial clinical results. Arch Ophthalmol. 1991 Oct;109(10):1370–1373. doi: 10.1001/archopht.1991.01080100050041. [DOI] [PubMed] [Google Scholar]
  71. McGill J., Williams H., McKinnon J., Holt-Wilson A. D., Jones B. R. Reassessment of idoxuridine therapy of herpetic keratitis. Trans Ophthalmol Soc U K. 1974 Jul;94(2):542–552. [PubMed] [Google Scholar]
  72. McLeish W., Rubsamen P., Atherton S. S., Streilein J. W. Immunobiology of Langerhans cells on the ocular surface. II. Role of central corneal Langerhans cells in stromal keratitis following experimental HSV-1 infection in mice. Reg Immunol. 1989 Jul-Aug;2(4):236–243. [PubMed] [Google Scholar]
  73. Mertz G. J., Jones C. C., Mills J., Fife K. H., Lemon S. M., Stapleton J. T., Hill E. L., Davis L. G. Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial. JAMA. 1988 Jul 8;260(2):201–206. [PubMed] [Google Scholar]
  74. Mertz G. J., Jones C. C., Mills J., Fife K. H., Lemon S. M., Stapleton J. T., Hill E. L., Davis L. G. Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial. JAMA. 1988 Jul 8;260(2):201–206. [PubMed] [Google Scholar]
  75. Moreira L. B., Sanchez D., Trousdale M. D., Stevenson D., Yarber F., McDonnell P. J. Aerosolization of infectious virus by excimer laser. Am J Ophthalmol. 1997 Mar;123(3):297–302. doi: 10.1016/s0002-9394(14)70124-2. [DOI] [PubMed] [Google Scholar]
  76. Nesburn A. B., Dickinson R., Radnoti M. The effect of trigeminal nerve and ganglion manipulation on recurrence of ocular herpes simplex in rabbits. Invest Ophthalmol. 1976 Sep;15(9):726–731. [PubMed] [Google Scholar]
  77. Nesburn A. B., Elliott J. H., Leibowitz H. M. Spontaneous reactivation of experimental herpes simplex keratitis in rabbits. Arch Ophthalmol. 1967 Oct;78(4):523–529. doi: 10.1001/archopht.1967.00980030525021. [DOI] [PubMed] [Google Scholar]
  78. Newton A. A. Inhibitors of prostaglandin synthesis as inhibitors of herpes simplex virus replication. Adv Ophthalmol. 1979;38:58–63. [PubMed] [Google Scholar]
  79. Norn M. S. Dendritic (herpetic) keratitis. I. Incidence--seasonal variations--recurrence rate--visual impairment--therapy. Acta Ophthalmol (Copenh) 1970;48(1):91–107. doi: 10.1111/j.1755-3768.1970.tb06577.x. [DOI] [PubMed] [Google Scholar]
  80. Norn M. S. Dendritic (herpetic) keratitis. I. Incidence--seasonal variations--recurrence rate--visual impairment--therapy. Acta Ophthalmol (Copenh) 1970;48(1):91–107. doi: 10.1111/j.1755-3768.1970.tb06577.x. [DOI] [PubMed] [Google Scholar]
  81. Patel R., Bodsworth N. J., Woolley P., Peters B., Vejlsgaard G., Saari S., Gibb A., Robinson J. Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. International Valaciclovir HSV Study Group. Genitourin Med. 1997 Apr;73(2):105–109. doi: 10.1136/sti.73.2.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Pavan-Langston D., Rong B. L., Dunkel E. C. Extraneuronal herpetic latency: animal and human corneal studies. Acta Ophthalmol Suppl. 1989;192:135–141. doi: 10.1111/j.1755-3768.1989.tb07104.x. [DOI] [PubMed] [Google Scholar]
  83. Pazin G. J., Ho M., Jannetta P. J. Reactivation of herpes simplex virus after decompression of the trigeminal nerve root. J Infect Dis. 1978 Sep;138(3):405–409. doi: 10.1093/infdis/138.3.405. [DOI] [PubMed] [Google Scholar]
  84. Pepose J. S. Herpes simplex keratitis: role of viral infection versus immune response. Surv Ophthalmol. 1991 Mar-Apr;35(5):345–352. doi: 10.1016/0039-6257(91)90184-h. [DOI] [PubMed] [Google Scholar]
  85. Pepose J. S. Herpes simplex keratitis: role of viral infection versus immune response. Surv Ophthalmol. 1991 Mar-Apr;35(5):345–352. doi: 10.1016/0039-6257(91)90184-h. [DOI] [PubMed] [Google Scholar]
  86. Pepose J. S., Laycock K. A., Miller J. K., Chansue E., Lenze E. J., Gans L. A., Smith M. E. Reactivation of latent herpes simplex virus by excimer laser photokeratectomy. Am J Ophthalmol. 1992 Jul 15;114(1):45–50. doi: 10.1016/s0002-9394(14)77411-2. [DOI] [PubMed] [Google Scholar]
  87. Perna J. J., Mannix M. L., Rooney J. F., Notkins A. L., Straus S. E. Reactivation of latent herpes simplex virus infection by ultraviolet light: a human model. J Am Acad Dermatol. 1987 Sep;17(3):473–478. doi: 10.1016/s0190-9622(87)70232-1. [DOI] [PubMed] [Google Scholar]
  88. Perry C. M., Faulds D. Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections. Drugs. 1996 Nov;52(5):754–772. doi: 10.2165/00003495-199652050-00009. [DOI] [PubMed] [Google Scholar]
  89. Pfister R. R., Richards J. S., Dohlman C. H. Recurrence of herpetic keratitis in corneal grafts. Am J Ophthalmol. 1972 Feb;73(2):192–196. doi: 10.1016/0002-9394(72)90132-8. [DOI] [PubMed] [Google Scholar]
  90. Polack F. M., Kaufman H. E. Penetrating keratoplasty in herpetic keratitis. Am J Ophthalmol. 1972 Jun;73(6):908–913. doi: 10.1016/0002-9394(72)90460-6. [DOI] [PubMed] [Google Scholar]
  91. Raborn G. W., McGaw W. T., Grace M., Tyrrell L. D., Samuels S. M. Oral acyclovir and herpes labialis: a randomized, double-blind, placebo-controlled study. J Am Dent Assoc. 1987 Jul;115(1):38–42. doi: 10.14219/jada.archive.1987.0211. [DOI] [PubMed] [Google Scholar]
  92. Reitano M., Tyring S., Lang W., Thoming C., Worm A. M., Borelli S., Chambers L. O., Robinson J. M., Corey L. Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. International Valaciclovir HSV Study Group. J Infect Dis. 1998 Sep;178(3):603–610. doi: 10.1086/515385. [DOI] [PubMed] [Google Scholar]
  93. Rodriguez A., Power W. J., Neves R. A., Foster C. S. Recurrence rate of herpetic uveitis in patients on long-term oral acyclovir. Doc Ophthalmol. 1995;90(4):331–340. doi: 10.1007/BF01268121. [DOI] [PubMed] [Google Scholar]
  94. Rong B. L., Pavan-Langston D., Weng Q. P., Martinez R., Cherry J. M., Dunkel E. C. Detection of herpes simplex virus thymidine kinase and latency-associated transcript gene sequences in human herpetic corneas by polymerase chain reaction amplification. Invest Ophthalmol Vis Sci. 1991 May;32(6):1808–1815. [PubMed] [Google Scholar]
  95. Rooney J. F., Straus S. E., Mannix M. L., Wohlenberg C. R., Alling D. W., Dumois J. A., Notkins A. L. Oral acyclovir to suppress frequently recurrent herpes labialis. A double-blind, placebo-controlled trial. Ann Intern Med. 1993 Feb 15;118(4):268–272. doi: 10.7326/0003-4819-118-4-199302150-00004. [DOI] [PubMed] [Google Scholar]
  96. Rózsa A. J., Beuerman R. W. Density and organization of free nerve endings in the corneal epithelium of the rabbit. Pain. 1982 Oct;14(2):105–120. doi: 10.1016/0304-3959(82)90092-6. [DOI] [PubMed] [Google Scholar]
  97. Rózsa A. J., Guss R. B., Beuerman R. W. Neural remodeling following experimental surgery of the rabbit cornea. Invest Ophthalmol Vis Sci. 1983 Aug;24(8):1033–1051. [PubMed] [Google Scholar]
  98. SCHMIDT J. R., RASMUSSEN A. F., Jr Activation of latent herpes simplex encephalitis by chemical means. J Infect Dis. 1960 Mar-Apr;106:154–158. doi: 10.1093/infdis/106.2.154. [DOI] [PubMed] [Google Scholar]
  99. Salisbury J. D., Berkowitz R. A., Gebhardt B. M., Kaufman H. E. Herpesvirus infection of cornea allografts. Ophthalmic Surg. 1984 May;15(5):406–408. [PubMed] [Google Scholar]
  100. Santos C. I. Herpes keratitis after radial keratotomy. Am J Ophthalmol. 1982 Mar;93(3):370–370. doi: 10.1016/0002-9394(82)90546-3. [DOI] [PubMed] [Google Scholar]
  101. Santos C. R. Herpetic corneal ulcer following radial keratotomy. Ann Ophthalmol. 1983 Jan;15(1):82–85. [PubMed] [Google Scholar]
  102. Sawtell N. M., Thompson R. L. Rapid in vivo reactivation of herpes simplex virus in latently infected murine ganglionic neurons after transient hyperthermia. J Virol. 1992 Apr;66(4):2150–2156. doi: 10.1128/jvi.66.4.2150-2156.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Seiler T., McDonnell P. J. Excimer laser photorefractive keratectomy. Surv Ophthalmol. 1995 Sep-Oct;40(2):89–118. doi: 10.1016/s0039-6257(95)80001-8. [DOI] [PubMed] [Google Scholar]
  104. Sher N. A., Bowers R. A., Zabel R. W., Frantz J. M., Eiferman R. A., Brown D. C., Rowsey J. J., Parker P., Chen V., Lindstrom R. L. Clinical use of the 193-nm excimer laser in the treatment of corneal scars. Arch Ophthalmol. 1991 Apr;109(4):491–498. doi: 10.1001/archopht.1991.01080040059027. [DOI] [PubMed] [Google Scholar]
  105. Shimeld C., Hill T. J., Blyth W. A., Easty D. L. Reactivation of latent infection and induction of recurrent herpetic eye disease in mice. J Gen Virol. 1990 Feb;71(Pt 2):397–404. doi: 10.1099/0022-1317-71-2-397. [DOI] [PubMed] [Google Scholar]
  106. Shimeld C., Hill T., Blyth B., Easty D. An improved model of recurrent herpetic eye disease in mice. Curr Eye Res. 1989 Nov;8(11):1193–1205. doi: 10.3109/02713688909000044. [DOI] [PubMed] [Google Scholar]
  107. Shimomura Y., Gangarosa L. P., Sr, Kataoka M., Hill J. M. HSV-1 shedding by lontophoresis of 6-hydroxydopamine followed by topical epinephrine. Invest Ophthalmol Vis Sci. 1983 Dec;24(12):1588–1594. [PubMed] [Google Scholar]
  108. Shimomura Y., Gangarosa L. P., Sr, Kataoka M., Hill J. M. HSV-1 shedding by lontophoresis of 6-hydroxydopamine followed by topical epinephrine. Invest Ophthalmol Vis Sci. 1983 Dec;24(12):1588–1594. [PubMed] [Google Scholar]
  109. Shuster J. J., Kaufman H. E., Nesburn A. B. Statistical analysis of the rate of recurrence of herpesvirus ocular epithelial disease. Am J Ophthalmol. 1981 Mar;91(3):328–331. doi: 10.1016/0002-9394(81)90285-3. [DOI] [PubMed] [Google Scholar]
  110. Simon A. L., Pavan-Langston D. Long-term oral acyclovir therapy. Effect on recurrent infectious herpes simplex keratitis in patients with and without grafts. Ophthalmology. 1996 Sep;103(9):1399–1405. doi: 10.1016/s0161-6420(96)30492-2. [DOI] [PubMed] [Google Scholar]
  111. Spruance S. L., Freeman D. J., Stewart J. C., McKeough M. B., Wenerstrom L. G., Krueger G. G., Piepkorn M. W., Stroop W. G., Rowe N. H. The natural history of ultraviolet radiation-induced herpes simplex labialis and response to therapy with peroral and topical formulations of acyclovir. J Infect Dis. 1991 Apr;163(4):728–734. doi: 10.1093/infdis/163.4.728. [DOI] [PubMed] [Google Scholar]
  112. Spruance S. L., Hamill M. L., Hoge W. S., Davis L. G., Mills J. Acyclovir prevents reactivation of herpes simplex labialis in skiers. JAMA. 1988 Sep 16;260(11):1597–1599. [PubMed] [Google Scholar]
  113. Spurney R. V., Rosenthal M. S. Ultraviolet-induced recurrent herpes simplex virus keratitis. Am J Ophthalmol. 1972 Apr;73(4):609–610. doi: 10.1016/0002-9394(72)90019-0. [DOI] [PubMed] [Google Scholar]
  114. Starr M., Donnenfeld E., Newton M., Tostanoski J., Muller J., Odrich M. Excimer laser phototherapeutic keratectomy. Cornea. 1996 Nov;15(6):557–565. [PubMed] [Google Scholar]
  115. Steinert R. F. Wound healing anomalies after excimer laser photorefractive keratectomy: correlation of clinical outcomes, corneal topography, and confocal microscopy. Trans Am Ophthalmol Soc. 1997;95:629–714. [PMC free article] [PubMed] [Google Scholar]
  116. Straus S. E., Takiff H. E., Seidlin M., Bachrach S., Lininger L., DiGiovanna J. J., Western K. A., Smith H. A., Lehrman S. N., Creagh-Kirk T. Suppression of frequently recurring genital herpes. A placebo-controlled double-blind trial of oral acyclovir. N Engl J Med. 1984 Jun 14;310(24):1545–1550. doi: 10.1056/NEJM198406143102401. [DOI] [PubMed] [Google Scholar]
  117. Takasu T., Furuta Y., Sato K. C., Fukuda S., Inuyama Y., Nagashima K. Detection of latent herpes simplex virus DNA and RNA in human geniculate ganglia by the polymerase chain reaction. Acta Otolaryngol. 1992 Nov;112(6):1004–1011. doi: 10.3109/00016489209137502. [DOI] [PubMed] [Google Scholar]
  118. Tervo K., Latvala T. M., Tervo T. M. Recovery of corneal innervation following photorefractive keratoablation. Arch Ophthalmol. 1994 Nov;112(11):1466–1470. doi: 10.1001/archopht.1994.01090230080025. [DOI] [PubMed] [Google Scholar]
  119. Tervo T., Tuunanen T. Excimer laser and reactivation of herpes simplex keratitis. CLAO J. 1994 Jul;20(3):152-3, 157. [PubMed] [Google Scholar]
  120. Trokel S. L., Srinivasan R., Braren B. Excimer laser surgery of the cornea. Am J Ophthalmol. 1983 Dec;96(6):710–715. doi: 10.1016/s0002-9394(14)71911-7. [DOI] [PubMed] [Google Scholar]
  121. Tyring S. K., Douglas J. M., Jr, Corey L., Spruance S. L., Esmann J. A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immunocompetent patients with recurrent genital herpes infections. The Valaciclovir International Study Group. Arch Dermatol. 1998 Feb;134(2):185–191. doi: 10.1001/archderm.134.2.185. [DOI] [PubMed] [Google Scholar]
  122. Underwood G. E., Weed S. D. Recurrent cutaneous herpes simplex in hairless mice. Infect Immun. 1974 Sep;10(3):471–474. doi: 10.1128/iai.10.3.471-474.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Varnell E. D., Kaufman H. E., Hill J. M., Thompson H. W. Cold stress-induced recurrences of herpetic keratitis in the squirrel monkey. Invest Ophthalmol Vis Sci. 1995 May;36(6):1181–1183. [PubMed] [Google Scholar]
  124. Vrabec M. P., Anderson J. A., Rock M. E., Binder P. S., Steinert R. F., Durrie D. S., Chase D. S. Electron microscopic findings in a cornea with recurrence of herpes simplex keratitis after excimer laser phototherapeutic keratectomy. CLAO J. 1994 Jan;20(1):41–44. [PubMed] [Google Scholar]
  125. Vrabec M. P., Durrie D. S., Chase D. S. Recurrence of herpes simplex after excimer laser keratectomy. Am J Ophthalmol. 1992 Jul 15;114(1):96–97. doi: 10.1016/s0002-9394(14)77418-5. [DOI] [PubMed] [Google Scholar]
  126. Wander A. H., Centifanto Y. M., Kaufman H. E. Strain specificity of clinical isolates of herpes simplex virus. Arch Ophthalmol. 1980 Aug;98(8):1458–1461. doi: 10.1001/archopht.1980.01020040310020. [DOI] [PubMed] [Google Scholar]
  127. Warren K. G., Brown S. M., Wroblewska Z., Gilden D., Koprowski H., Subak-Sharpe J. Isolation of latent herpes simplex virus from the superior cervical and vagus ganglions of human beings. N Engl J Med. 1978 May 11;298(19):1068–1069. doi: 10.1056/NEJM197805112981907. [DOI] [PubMed] [Google Scholar]
  128. Wentworth B. B., Alexander E. R. Seroepidemiology of infectious due to members of the herpesvirus group. Am J Epidemiol. 1971 Nov;94(5):496–507. doi: 10.1093/oxfordjournals.aje.a121347. [DOI] [PubMed] [Google Scholar]
  129. Whitcher J. P., Dawson C. R., Hoshiwara I., Daghfous T., Messadi M., Triki F., Oh J. O. Herpes simplex keratitis in a developing country. Natural history and treatment of epithelial ulcers in Tunisia. Arch Ophthalmol. 1976 Apr;94(4):587–592. doi: 10.1001/archopht.1976.03910030279006. [DOI] [PubMed] [Google Scholar]
  130. Wilcox C. L., Johnson E. M., Jr Nerve growth factor deprivation results in the reactivation of latent herpes simplex virus in vitro. J Virol. 1987 Jul;61(7):2311–2315. doi: 10.1128/jvi.61.7.2311-2315.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  131. Wilhelmus K. R., Coster D. J., Donovan H. C., Falcon M. G., Jones B. R. Prognostic indicators of herpetic keratitis. Analysis of a five-year observation period after corneal ulceration. Arch Ophthalmol. 1981 Sep;99(9):1578–1582. doi: 10.1001/archopht.1981.03930020452009. [DOI] [PubMed] [Google Scholar]
  132. Willey D. E., Trousdale M. D., Nesburn A. B. Reactivation of murine latent HSV infection by epinephrine iontophoresis. Invest Ophthalmol Vis Sci. 1984 Aug;25(8):945–950. [PubMed] [Google Scholar]
  133. Wishart M. S., Darougar S., Viswalingam N. D. Recurrent herpes simplex virus ocular infection: epidemiological and clinical features. Br J Ophthalmol. 1987 Sep;71(9):669–672. doi: 10.1136/bjo.71.9.669. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Transactions of the American Ophthalmological Society are provided here courtesy of American Ophthalmological Society

RESOURCES