Asbell P A
Department of Ophthalmology, Mount Sinai School of Medicine, New York, USA.
Trans Am Ophthalmol Soc. 2000;98:285-303.
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.
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.
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).
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.
据报道，多种因素可诱导潜伏的单纯疱疹病毒（HSV）重新激活，其中包括压力、创伤和紫外线辐射。准分子激光屈光性角膜切削术（PRK）是一种利用193nm紫外线改变角膜曲率从而矫正视力的外科手术。已有报道称准分子激光PRK术后会出现眼部单纯疱疹性角膜炎的重新激活。本文回顾了所有已发表的人类准分子激光治疗后HSV重新激活的病例。本研究评估激光治疗前角膜上皮去除术的压力、创伤或对基质床的准分子激光治疗本身是否会诱发潜伏HSV的眼部重新激活，以及全身性抗病毒药物伐昔洛韦是否能预防准分子激光PRK诱导的HSV重新激活。
将43只体重1.5至2.5千克的正常新西兰白兔角膜表面感染HSV-1 RE株。对动物进行监测直至病情缓解，然后将所有动物分为5个治疗组：（1）仅行上皮去除术，腹腔内注射生理盐水14天；（2）上皮去除术加激光治疗，腹腔内注射生理盐水14天；（3）上皮去除术加激光治疗，伐昔洛韦50mg/kg每日腹腔内注射14天；（4）上皮去除术加激光治疗，伐昔洛韦100mg/kg每日腹腔内注射14天；（5）上皮去除术加激光治疗，伐昔洛韦150mg/kg每日腹腔内注射14天。每两周通过临床检查和病毒培养以盲法对动物进行评估，直至第28天。
重新激活率如下：第1组为0%；第2组为67%；第3组为50%；第4组为17%；第5组为0%。未重新激活的动物病毒滴度为阴性，但重新激活的动物（第6天至第28天）病毒滴度持续为阳性。
准分子激光（193nm）治疗可引发潜伏感染兔的眼部疱疹疾病重新激活（67%）和病毒脱落。单独的上皮去除术不足以导致重新激活或病毒脱落。腹腔内注射伐昔洛韦进行预防可呈剂量反应性降低复发率。每天150mg/kg时无复发。重新激活的动物中持续病毒脱落的存在可能与接受准分子治疗的人类中报道的HSV晚期复发病例相关。数据表明，有疱疹性角膜炎病史的患者接受准分子激光手术矫正屈光不正或治疗角膜瘢痕时，重新激活的风险增加。然而，此类患者在激光手术时可适当考虑使用全身性抗病毒药物进行预防，以降低复发的可能性。
