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Nov 2012, Vol 130, No. 11 >

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Small Case Series | Nov 2012

Real-Time Polymerase Chain Reaction for Diagnosing Acyclovir-Resistant Herpetic Keratitis Based on Changes in Viral DNA Copy Number Before and After Treatment

Tomoyuki Inoue, MD; Rumi Kawashima, MD; Takashi Suzuki, MD; Yuichi Ohashi, MD
Arch Ophthalmol. 2012;130(11):1462-1464. doi:10.1001/archophthalmol.2012.1176.
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Acyclovir (ACV) is a specific anti–herpes simplex virus (HSV) and anti–varicella-zoster virus agent for herpetic infection; topical ACV ointment, 3%, has been the treatment of choice for HSV infection in Japan.1 Based on the widespread use of ACV, in some cases of recurrent herpetic keratitis, the disease was refractory to topical ACV treatment, which was previously reported as ACV-resistant herpetic keratitis.1- 3 Conventionally, definitive diagnosis of an ACV-resistant HSV keratitis requires a laboratory examination of viral cultures following in vitro drug sensitivity testing,1 which is generally difficult and complicated because of the low rates of replication of these viruses and the small number of ocular samples. A rapid, simple, and accurate method of diagnosing drug-resistant herpetic infection remains to be established. Real-time polymerase chain reaction (PCR) is a highly sensitive method for the detection and quantification of pathogens.4- 5 We report 4 cases of ACV-resistant HSV keratitis using real-time PCR analysis; these cases were diagnosed based on changes in the viral DNA copy numbers before and after ACV treatment.
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Figure. Relationship between the therapeutic outcomes with acyclovir (ACV) and trifluorothymidine (TFT) antiviral therapy and herpes simplex virus type 1 (HSV-1) DNA copy numbers. A, Slitlamp photograph with fluorescent staining shows geographic keratitis before topical ACV treatment (day 0). B, Slitlamp photograph with fluorescent staining shows that geographic keratitis has not improved after topical ACV treatment (day 14). C, Slitlamp photograph with fluorescent staining shows gradual improvement of lesions after topical TFT therapy (day 28). D, Slitlamp photograph with fluorescent staining shows resolution of the lesions (day 42). E, Although the ACV treatment was continued, the geographic lesions did not improve, and the HSV-1 DNA copy numbers did not decrease. After topical TFT was substituted for ACV, the lesions slowly healed, and the HSV-1 DNA copy number became undetectable.

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Real-time polymerase chain reaction for diagnosing acyclovir-resistant herpetic keratitis based on changes in viral DNA copy number before and after treatment.
Arch Ophthalmol 2012;;130(11):1462-4.
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