Abstract:
Background: In spite of intensive antiviral and anti-inflammatory therapy, recovery is
not always achieved in patients with stromal herpes keratitis (HK). Inflammatory host
response and a complex immune defense system play a major role among the numerous
factors involved in herpes simplex virus (HSV) reactivation from latency. Inter-Cellular
Adhesion Molecule (ICAM-1) is best known for its role in mediating leukocyte adhesion to
endothelial cells and guiding leukocytes across the vascular wall. This factor is considered
as an inflammatoty biomarker. Given that signs of inflammation in recurrent stromal
keratitis are not always clinically manifest, additional diagnostics is required for wellfounded
anti-inflammatory treatment decisions.
Purpose: To assess the expression of ICAM-1 on blood lymphocytes in patients with
primary stromal HK and patients experiencing one or more annual recurrences of stromal
HK at different periods of disease.
Material and Methods: Fifty-six patients (age, 20 to 60 years) who had been consulted and
treated for stromal HK at the Department of Corneal Disorders and 27 systemically and
ophthalmologically healthy controls (age, 20 to 64 years) were involved in the study. Of the
56 patients, 10 had primary HK with disease duration ≤ 6 months, and 46 had recurrent
HK with disease duration ≤ 20 years. Individuals experiencing more than one recurrence
annually were defined as those with frequent recurrences. Absolute and relative ICAM-1
expression on lymphocytes was examined. Immunohistochemical staining with monoclonal
antibodies for ICAM-1 (CD-54) was performed.
Results: The median and interquartile range of the absolute expression level of ICAM,
and the mean (standard deviation) of the relative ICAM-1 expression on peripheral blood
lymphocytes in controls were 113.3 cells/μL, 87-168 cells/μL, and 8.5 (2.0)%, respectively.
Total patients with HSV keratitis exhibited significantly (4.0 times; p = 0.0001) higher
absolute counts of peripheral blood lymphocytes expressing ICAM-1 (median, 450 cells/
μL; interquartile range, 326-552 cells/μL) compared to controls. In patients in remission
with recurrent stromal HK, the relative ICAM-1 expression did not depend on the frequency
of recurrence and was 23.4 (4.0)%, which was 2.8 times higher than in controls (p =
0.000). Patients with active keratitis experiencing one recurrence annually had practically
the same relative ICAM-1 expression as those experiencing more than one recurrence
annually, with a mean value of 26.8 (4.6)%. This was 3.3 times higher than in controls (p =
0.000) and 15.8% higher than in patients in remission with recurrent HK (23.4 (4.1)%; p =
0.001). The relative ICAM-1 expression in patients with primary keratitis was 16% higher
than in patients on remission, and there was no significant difference in this parameter
between patients with primary keratitis and patients with active recurrent HK.
Conclusion: The absolute and relative ICAM-1 expression on peripheral blood lymphocytes
in patients with HSV keratitis was 4.0 times and 3.1 times, respectively, higher than in
controls. The relative expression of ICAM on lymphocytes in patients with active recurrent
disease and in patients with primary keratitis was 16% higher than in patients on remission.
