Case 1 is representative of the 4 cases. The patient was a 37-year-old man with a history of herpetic keratitis in the left eye that was diagnosed at another clinic. Initially, the herpetic keratitis resolved with periodic treatment using ACV ointment and a topical steroid. He had reported a foreign-body sensation and redness in his left eye and periodically received topical antibiotics and a steroid for 1 month. Because the symptoms gradually worsened despite treatment, he was referred to our clinic. At his first examination, his affected eye had a best-corrected VA of 20/1000 and an intraocular pressure of 15 mm Hg. A slitlamp examination revealed epithelial erosion in the central cornea that manifested as geographic lesions with corneal infiltrates, moderate ciliary injection, and no anterior chamber inflammation (day 0) (Figure, A). Using a Cochet-Bonnet esthesiometer, we determined that the sensitivity of the left cornea decreased to 10 mm in the left eye compared with 60 mm in the right eye. The right eye was normal. A wide corneal scraping was performed for cytopathologic examination and culturing to detect any pathogenic microorganisms such as bacteria, fungi, or Acanthamoeba, and real-time PCR analysis was performed to detect human herpesviruses (HSV type 1 or 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6, 7, and 8).4,5 Light microscopy failed to identify any pathogens. The PCR results were positive only for HSV-1 DNA (8.7 × 107 copies/sample) (Figure, E). The culture results were negative for any pathogens. Based on the positive PCR results for HSV-1 DNA, the patient was suspected to have HSV keratitis and was treated with topical ACV ointment, 3%, 5 times a day and topical levofloxacin, 0.5%, 3 times a day for 2 weeks. However, the geographic lesions did not heal (day 14) (Figure, B). A second epithelial scraping was performed for real-time PCR analysis and cytopathologic examination and culturing, which resulted in detection of only HSV-1 DNA (1.2 × 108 copies/sample) (Figure, E) from the diseased lesions without other pathogens. Because ACV is a specific anti-HSV and anti–varicella-zoster virus agent, it usually is effective against herpetic keratitis, and, simultaneously, it can decrease HSV copy numbers compared with pretreatment (data not shown). However, the HSV viral load in this case did not decrease as a result of ACV treatment, and the only detected pathogen was HSV. Because these findings indicated that the HSV detected in these lesions might be an ACV-resistant strain, we substituted topical trifluorothymidine (TFT) solution, 1%, prepared from TFT, which was reported to be effective against ACV-resistant HSV keratitis.1,2 The levels of ocular pain and photophobia gradually decreased, and the lesions slowly healed by day 28 (Figure, C). Real-time PCR of the samples obtained from epithelial scraping 14 days after the start of TFT therapy did not detect HSV-1 DNA (Figure, E), and by day 42, the keratitis resolved with corneal scarring (Figure, D).