Reactivation of Latent Herpes Simplex Virus by Excimer Laser Photokeratectomy Jay S. Pepose, M.D., Keith A. Laycock, Ph.D., Judith Kelvin Miller, Ph.D., Ekktet Chansue, M.D., Eric J. Lenze, Larry A. Gans, M.D., and Morton E. Smith, M.D. We tested whether excimer laser photore- fractive and phototherapeutic keratectomy may reactivate latent herpes simplex and cause recurrent keratitis in mice. Two of ten latently infected mice that were treated with ten excimer laser pulses to the corneal epithe- lium shed herpes simplex virus type 1, as did four of ten mice that were treated with 50 excimer laser pulses. Ocular shedding of her- pes simplex virus was detected in four of ten mice that were treated with ethylenediamine- tetraacetic acid (EDTA) scraping of the corneal epithelium without laser keratectomy, and in six of ten mice on which combined EDTA- facilitated epithelial removal was performed followed by the application of ten excimer laser pulses. In both EDTA-treated groups, viral shedding was prolonged and 18 of 20 mice developed marked corneal opacification or neovascularization, or both. Corneal photo- ablation with the excimer laser may induce reactivation of latent herpes simplex virus, even in mice with clear and smooth-appearing corneas, and should be considered in the dif- ferential diagnosis of humans with persistent corneal epithelial defects after refractive or therapeutic excimer procedures. THE HERPES SIMPLEX VIRUS, after primary infec- tion of a host, becomes latent and establishes a Accepted for publication April 8, 1992. From the Departments of Ophthalmology and Visual Sciences (Drs. Pepose, Laycock, Miller, Chansue, Gans, and Smith; and Mr. Lenze) and Pathology (Drs. Pepose and Smith), Washington University School of Medicine, St. Louis, Missouri. This study was supported in part by a grant from Research to Prevent Blindness, Inc., New York, New York. Reprint requests to Jay S. Pepose, M.D., Department of Ophthalmology and Visual Sciences, Box 8096, Wash- ington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110. finely balanced and unique host-pathogen rela- tionship. 1 Humans are the only natural hosts for herpes simplex virus. Periodic reactivation of the dormant virus in neuronal tissue and subsequent axonal transport to the ocular sur- face, mucous membranes and skin, allows repli- cating virus to spread and infect other members of the community. Only in unusual circum- stances that result in systemic viral dissemina- tion or encephalitis, does herpetic reactivation result in death, which simultaneously ends its own life cycle. See also p. 96 Many factors and stimuli can reactivate latent herpes simplex. These include mechani- cal, 2,3 chemical, 4 " 6 or photodynamic 710 injuries to the skin or ocular surface; systemic immuno- suppression 11 " 13 ; hyperthermia 14 ; and mechani- cal, 15 surgical, 16 electrical, 17 or chemical stimula- tion 1821 of nerves of latently infected sensory or autonomie ganglia. Penetrating keratoplasty, 22 radial keratotomy, 23 anterior superficial kera- tectomy, cryogenic injury of the cornea, tran- section of corneal nerves at the corneoscleral limbus, 24 and intrastromal injections 25 have effi- ciently induced herpes simplex recurrences in animals. Persistent epithelial defects have been culture-positive for herpes simplex after pene- trating keratoplasty in patients in whom surgi- cal procedures were performed because of pre- vious herpetic scarring, 2632 as well as in patients with nonherpetic indications. 3335 Considerable attention has been recently fo- cused on the argon-fluoride excimer laser, a device that has entered phase III trials in the United States for photorefractive and photo- therapeutic keratectomy. The laser emits 193- nm ultraviolet light at a high fluence, delivering sufficient energy to break carbon-carbon bonds within the superficial corneal cells that absorb the laser energy. 8687 We used a well-character- ©AMERICAN JOURNAL OF OPHTHALMOLOGY 114:45-50, JULY, 1992 45