Altered corneal nerves in aqueous tear deficiency viewed by in vivo confocal microscopy

Purpose: To define the alterations of corneal nerves in aqueous tear deficiency dry eye patients with or without Sjogren syndrome and to identify the relationship between the morphologic changes of corneal nerves and the extent of dry eye. Methods: Confocal microscopy was used to examine 38 consecutive aqueous tear deficiency patients (8 Sjogren syndrome and 30 non-Sjogren syndrome) and 30 age and gender-matched normal controls. Images taken by Confocal2 slit-scanning microscope at subbasal epithelial cell layer of central cornea were analyzed. The number and density of corneal nerves and their size, beads, tortuosity, and branching pattern were compared. These data were correlated with age and the degree of dry eye. Results: Sjogren syndrome patients showed a significant increase in average nerve number and tortuosity as compared with normal controls (P = 0.031 and 0.021, respectively). Severe nerve tortuosity (grade 4) and nerve branching appeared more frequently in aqueous tear deficiency than in normal subjects (P = 0.024 and 0.042, respectively). A decreased nerve number was observed with age in the normal controls (P = 0.002). However, such a correlation did not exist in aqueous tear deficiency. In aqueous tear deficiency, rose bengal staining score correlated positively with nerve density (P = 0.048) and nerve number (P = 0.001). Corneal fluorescein staining score was also positively correlated with nerve number (P = 0.027). Conclusions: Abnormal morphologic changes are observed in aqueous tear deficiency that are more severe in Sjogren syndrome. The distinct changes of corneal nerves include increased nerve number, tortuosity, and chances of branching, suggesting an attempted nerve regeneration. A strong correlation exists between the changes of nerve morphology and the degree of dry eye. These results provide some possible evidence for the abnormal corneal sensation in dry eye.