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.

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

“…[10][11][12][13] Furthermore, in addition to providing trophic and sensory functions, corneal nerves have been shown to play an important role in the maintenance of ocular surface epithelial health and function. [14][15][16][17] As epithelial DCs and subbasal nerves may change in a variety of ocular surface and corneal conditions, such as dry eye disease, neurotrophic keratopathy, infectious keratitis, diabetes, and contact lens wear, 3,5,[18][19][20][21][22] quantification of these two structures, which can be achieved by IVCM, is of significant importance. The high resolution of IVCM images is inherently associated with a drawback, which is a relatively small field of view of the images.…”

In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

“…IVCM had been performed on both eyes of patients with MGD-associated persistent dry eye symptoms, and on one randomly selected eye of controls, as previously described. 21 IVCM of the palpebral conjunctiva had been performed on the center of both upper and lower everted eyelids, approximately half way between the eyelid fold and the eyelid margin. A total of four to eight sequence scans obtained were reviewed per eyelid.…”

Anterior Segment Applications of In Vivo Confocal Microscopy

“…59,63 Moreover, IVCM reveals the corneal superficial epithelial alterations in herpes simplex keratitis as demonstrated by increase in cell size, decrease in cell density, and squamous metaplasia. 64 …”