DETECTION OF HERPES-SIMPLEX VIRAL-DNA IN THE IRIDOCORNEAL ENDOTHELIAL SYNDROME

Objective: To test the hypothesis that the iridocorneal endothelial (ICE) syndrome has a viral origin by comparing the incidence of viral DNA in corneal specimens from patients with the ICE syndrome and from controls. Design: Thirty-one corneas obtained from 25 patients with the ICE syndrome and six with chronic herpetic keratitis (n=31) were compared with 30 control specimens obtained from 15 healthy donors and from 15 patients with other, nonviral chronic corneal diseases. Methods: Primer pairs and polymerase chain reaction methods were used to identify and amplify either a segment of the DNA polymerase gene in the case of the herpes simplex and tester viruses or a region of the nuclear antigen gene for the Epstein-Barr virus. The oligonucleotide amplified by polymerase chain reaction was fully characterized with the use of restriction enzyme, hybridization, and sequence analyses to determine that it contained the expected base pair sequence. Results: Sixteen of 25 ICE syndrome specimens and four of six herpetic keratitis specimens were positive for herpes simplex virus (HSV) DNA. All nine ICE syndrome specimens tested were negative for the presence of DNA from the herpes tester or the Epstein-Barr viruses. Controls were uniformly negative for HSV DNA whether they were obtained from ostensibly normal corneas (n=15) or from corneas with interstitial keratitis, aphakic bullous keratopathy, or keratoconus (n=15). Tissue samples cut from positive ICE syndrome specimens yielded negative results when retested after the endothelial layer was removed. These findings indicate that localization of HSV DNA is within the endothelium, the tissue primarily involved in the pathogenesis of the ICE syndrome. Conclusions: Polymerase chain reaction evidence shows that HSV DNA is present in a substantial percentage of ICE syndrome corneal specimens and that HSV-DNA is absent in normal corneas and in corneas from patients with three other chronic corneal diseases. These results provide direct evidence to support our hypothesis that the ICE syndrome has a viral origin. We discussed clinical implications, including possible therapeutic interventions.