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Updated: Jun 20, 2026
Ex Vivo Organotypic Corneal Model of Acute Epithelial Herpes Simplex Virus Type I Infection
Published on: November 3, 2012
Endothelial involvement in herpes simplex virus keratitis: an in vivo confocal microscopy study
Toine Hillenaar1, Christien Weenen, René J Wubbels
1Cornea and External Disease Service, The Rotterdam Eye Hospital, Rotterdam, The Netherlands; Rotterdam Ophthalmic Institute, Rotterdam, The Netherlands. t.hillenaar@oogziekenhuis.nl
Purpose:
To describe the appearance, frequency, and clinical consequences of corneal endothelial involvement in human herpes simplex virus (HSV) keratitis as seen by in vivo confocal microscopy (IVCM).
Design:
Prospective observational case series.
Participants:
A total of 285 patients with HSV keratitis who visited the cornea department of the Rotterdam Eye Hospital between May 2005 and May 2008. The control groups comprised the unaffected fellow eyes of patients with HSV keratitis, the eyes of 58 healthy volunteers, and the affected eyes of 62 patients with inflammatory corneal disorders other than HSV.
Methods:
We examined the eyes of all participants by IVCM and slit-lamp examination. For IVCM, corneas were scanned with Confoscan 3 or 4 (Nidek Technologies, Albignasego, Padova, Italy).
Main Outcome Measures:
All IVCM examinations were qualitatively reviewed for signs of endothelial deviations characteristic of endotheliitis. Endothelial cell density (ECD) was evaluated on the first and last visits of patients who were followed for more than 100 days. The differences in ECDs were calculated and converted to percent ECD change per year.
Results:
Endothelial alterations characteristic of endotheliitis were detected by IVCM in 107 of 250 patients with HSV keratitis (43%). These deviations consisted of pseudoguttata, enlarged intercellular gaps, infiltration of inflammatory cells into the endothelial layer, loss of defined cell boundaries, spot-like holes, and endothelial denudation. All of these signs disappeared with appropriate antiviral and anti-inflammatory treatment. However, the endothelium in eyes with endotheliitis-characteristic alterations showed a significant decrease in ECD (10.3% per year) compared with healthy fellow eyes.
Conclusions:
IVCM allows earlier detection of endothelial alterations in patients with HSV keratitis compared with slit-lamp examination. Although endotheliitis-specific alterations appear to resolve, the corneal endothelium can become irreversibly damaged.
