Aim-To study herpes simplex virus (HSV) DNA in tears from patients with atypical epithelial keratitis of unknown aetiology. Methods-Tear samples were collected from 17 aVected eyes of 17 consecutive patients suVering from epithelial keratitis in whom HSV keratitis was suspected but whose diagnosis was diYcult on the basis of clinical manifestations alone. Using reduced sensitivity polymerase chain reaction (PCR), tear samples were tested for HSV DNA. Tears from the unaVected eyes of the 17 patients were also examined, along with 38 tear samples from 19 normal volunteers. Southern blot analysis was performed to confirm that amplified DNA bands were specific for HSV. Clinical correlation with photographs of corneal lesions was also investigated. Results-HSV DNA was detected in tears from the aVected eyes of eight of the 17 patients with suspected HSV keratitis. Tears from the aVected eyes of the other patients were PCR negative, as were tears from the unaVected eyes of all 17 patients, and from the 38 normal eyes. There was no correlation between PCR results and clinical manifestation of keratitis. Conclusions-Based on the sensitivity of the PCR system, eight of 17 suspected HSV keratitis patients were confirmed as suVering from HSV keratitis. HSV keratitis should therefore be considered as a possible diagnosis in atypical epithelial keratitis. (Br J Ophthalmol 1999;83:957-960) Herpes simplex virus (HSV) epithelial keratitis, a leading cause of corneal blindness, is typified by dendritic or geographical corneal ulcers, which usually have dendritic edges with terminal bulbs and epithelial infiltration. This enables them to be diVerentiated from corneal ulcers due to other causes, and their clinical diagnosis as herpetic keratitis. Sometimes, however, such factors as duration since onset, previous medication, systemic diseases (atopic dermatitis, 1 for example), or history of corneal transplantation 2 can make the epithelial lesions appear diVerent from classic HSV lesions. The initial diagnosis is very important, since it decides the use of antiviral drugs, such as aciclovir. In atypical cases, however, it is often diYcult to make a correct diagnosis based solely on the clinical presentation.Since Saiki et al's 1985 report on the usefulness of the polymerase chain reaction (PCR) for diagnostic purposes, 3 it has often been used for diagnosing viral diseases of the eye. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Previously, we established a reduced sensitivity PCR for diagnosing HSV epithelial keratitis, [4][5][6][7] corneal endothelitis, 8 and HSV related uveitis.9 10 Using this PCR system, we are able to detect HSV DNA in tears from patients with clinically diagnosed HSV epithelial keratitis. The sensitivity of this system is higher than that of viral culture, while being low enough not to give a positive PCR result in normal tears. 4 5 In the present study, we used the reduced sensitivity PCR system to investigate HSV DNA in tears from suspected epithelial keratitis patie...