Cellular Changes of the Corneal Epithelium and Stroma in Herpes Simplex Keratitis

Abstract

Purpose

To analyze the morphology of corneal epithelial cells and keratocytes by in vivo confocal microscopy (IVCM) in patients with herpes simplex keratitis (HSK) as associated with corneal innervation.

Design

Prospective, cross-sectional, controlled, single-center study.

Participants

Thirty-one eyes with the diagnosis HSK and their contralateral clinically unaffected eyes were studied and compared with normal controls (n = 15).

Methods

In vivo confocal microscopy (Confoscan 4; Nidek Technologies, Gamagori, Japan) and corneal esthesiometry (Cochet-Bonnet; Luneau Ophthalmologie, Chartres, France) of the central cornea were performed bilaterally in all patients and controls. Patients were grouped into normal (>5.5 cm), mild (>2.5–5.5 cm), and severe (<2.5 cm) loss of sensation.

Main Outcome Measures

Changes in morphology and density of the superficial and basal epithelial cells, as well as stromal keratocytes were assessed by two masked observers. Changes were correlated to corneal sensation, number of nerves, and total length of nerves.

Results

There was a significant and gradual decrease in the density of superficial epithelial cells in HSK eyes, with 852.50±24.4 cells/mm2 in eyes with severe sensation loss and 2435.23±224.3 cells/mm2 in control eyes (p=0.008). Superficial epithelial cell size was 2.5-fold larger in HSK eyes (835.3 μm2) as compared to contralateral or normal eyes (407.4 μm2; p= 0.003). A significant number of hyperreflective desquamating superficial epithelial cells were present in HSK eyes with normal (6.4%), mild (29.1%) and severe (52.2%) loss of sensation, but were absent in controls. The density of basal epithelial cells, anterior keratocytes, and posterior keratocytes did not show statistical significance between patients and controls. Changes in superficial epithelial cell density and morphology correlated strongly with total nerve length, number, and corneal sensation. Scans of contralateral eyes did not show any significant epithelial or stromal changes as compared to controls.

Conclusions

IVCM reveals profound HSK-induced changes in the superficial epithelium, as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. We demonstrate that these changes strongly correlate with changes in corneal innervation.