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

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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 (IP) saline for 14 days; (2) de-epithelialization plus laser, IP saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day IP for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day IP for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day IP 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.

Original languageEnglish (US)
Pages (from-to)285-303
Number of pages19
JournalTransactions of the American Ophthalmological Society
Volume98
StatePublished - Dec 1 2000

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valacyclovir
Laser Corneal Surgery
Excimer Lasers
Eye Diseases
Virus Diseases
Simplexvirus
Lasers
Herpetic Keratitis
Photorefractive Keratectomy
Virus Shedding
Recurrence
Cornea
Antiviral Agents
Therapeutics
Rabbits
Refractive Errors
Human Herpesvirus 1
Ultraviolet Rays

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

@article{42fe6dbba4a340efa1a9b55c081a0768,
title = "Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy",
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 (IP) saline for 14 days; (2) de-epithelialization plus laser, IP saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day IP for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day IP for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day IP 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.",
author = "Penny Asbell",
year = "2000",
month = "12",
day = "1",
language = "English (US)",
volume = "98",
pages = "285--303",
journal = "Transactions of the American Ophthalmological Society",
issn = "0065-9533",
publisher = "American Ophthalmological Society",

}

TY - JOUR

T1 - Valacyclovir for the prevention of recurrent herpes simplex virus eye disease after excimer laser photokeratectomy

AU - Asbell, Penny

PY - 2000/12/1

Y1 - 2000/12/1

N2 - 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 (IP) saline for 14 days; (2) de-epithelialization plus laser, IP saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day IP for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day IP for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day IP 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.

AB - 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 (IP) saline for 14 days; (2) de-epithelialization plus laser, IP saline for 14 days; (3) de-epithelialization plus laser, valacyclovir 50 mg/kg per day IP for 14 days; (4) de-epithelialization plus laser, valacyclovir 100 mg/kg per day IP for 14 days; (5) de-epithelialization plus laser, valacyclovir 150 mg/kg per day IP 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.

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