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Rodrigo T Muller, Roxanna Pourmirzaie, Shruti Aggarwal, Bernardo Menelau Cavalcanti, Arsia Jamali, Deborah Langston, Pedram Hamrah; In Vivo Confocal Microscopy Reveals Differential Corneal Immune Response in Patients with Central vs. Peripheral HSV Keratitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2846.
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Herpes simplex virus (HSV) keratitis results in recurrent immune-mediated keratitis, scarring and neurotrophic keratopathy. This study aimed to compare corneal sensation, nerve and immune cell changes using in vivo confocal microscopy (IVCM) between patients with HSV-induced central or peripheral scar.
A prospective, cross-sectional study was conducted in 21 patients with a central corneal scar, 16 patients with a peripheral scar, both with a clinical diagnosis of HSV keratitis, and 24 age-matched normal controls. Central and peripheral IVCM (HRT3/RCM) and corneal sensation (Cochet-Bonnet esthesiometer) were performed in all patients and controls. Confocal images were analyzed by 2 masked observers for subbasal corneal nerve density and numbers and dendritiform immune cell (DC) density.
The eyes with both central and peripheral scars demonstrated a significant decrease in corneal nerve density in the center (8.2±1.3 mm/mm2 and 12±14, p<0.0001) and periphery (5.0±6.9 and 4.2±0.7, p=0.006) of the cornea compared to controls (17.8±8.7 and 8.9±1.0). Similarly, central and peripheral corneal sensation did not differ between groups, although areas with peripheral corneal scar had lower sensation than corresponding areas in patients with a central scar. Surprisingly, patients with a central scar, demonstrated significantly higher mean DC density in both the central (155±40 cells/mm2) and peripheral (117±26) cornea as compared to controls (35±9; p=0.008 and 69±11; p=0.006). Patients in this group demonstrated correlation of DC density with number of immune-mediated recurrences (r=0.48). In contrast, in patients with peripheral scar, no significant difference in DC density was observed compared to controls for all areas. A significant correlation was seen between central DC density and subbasal nerve density for the central scar group (r=-0.61, p<0.001).
There is a differential corneal immune response in patients with HSV keratitis depending upon the location of the focal corneal scar. Patients with a central herpetic scar demonstrate a global increase in corneal immune response, which correlates significantly with nerve density and number of clinical recurrences. These findings suggest that the location of corneal scars in patients with HSV may have important clinical implications, such as the risk of recurrence and visual outcome.
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