Contralateral Clinically Unaffected Eyes of Patients with Unilateral Infectious Keratitis Demonstrate Subclinical Diminishment of Corneal Nerves and Increase in Dendritic Cell Density

Abstract

Purpose: : We have recently demonstrated significant diminishment in the subbasal corneal nerve plexus and an increase in dendritic cell (DC) density in the affected eyes of patients with infectious keratitis (IK). The aim of the current study was to analyze the contralateral unaffected eyes of patients with IK for any cellular or nerve changes by laser in vivo confocal microscopy (IVCM).

Methods: : A prospective study was performed in 28 patients with acute unilateral IK, including acute bacterial, fungal and Acanthamoeba keratitis. IVCM with the HRT3/RCM and corneal sensation with the Cochet-Bonnet esthesiometer of the central cornea were performed in 28 IK eyes, in their contralateral clinically unaffected eyes, as well as in 17 normal controls. Central corneal nerve density, nerve numbers, branching, tortuosity and corneal DC density were assessed by two masked observers.

Results: : The contralateral clinically unaffected eyes of IK, as compared to normal controls, demonstrated significant diminishment in nerve density (2396.0±1028.0 vs. 3652.8±596.3 µm/frame), total number of nerves (12.0±5.3 vs. 20.8±4.1), main nerve trunks (4.8±1.6 vs. 6.2±1.0) and branch nerve density (886.8±615.2 vs. 1718.1±486.9) (p<0.001 for all parameters). Corneal sensation was decreased as compared to controls (5.5±0.9 vs. 6.0±0 cm, p<0.04) but less severe than in eyes with acute IK (4.0±2.1 cm, p<0.001). Surprisingly, DC density in the unaffected eyes was significantly increased as compared to controls (117.5±105.1 vs. 42.4±40.4 cells/mm2, p<0.003), but not as dramatic as in the affected eyes with acute IK (384.4±295.1 cells/mm2).

Conclusions: : We demonstrate subclinical involvement in the contralateral clinically unaffected eye in patients with unilateral acute IK. IVCM reveals not only a diminishment of the subbasal corneal nerves and sensation, but also a surprising increase in DC density in the contralateral unaffected eyes of IK patients. These findings show a bilateral nerve and immune alteration in an apparently unilateral disease.

Keywords: keratitis • microscopy: confocal/tunneling • imaging/image analysis: clinical