Detection of herpes simplex viral DNA in the iridocorneal endothelial syndrome
J. A. Alvarado, J. L. Underwood, W. R. Green, S. Wu, C. G. Murphy, D. G. Hwang, T. E. Moore and D. O'Day
Department of Ophthalmology, University of California, San Francisco.
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
zoster 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 zoster 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 intestinal 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.