Characterization of the Corneal Subbasal Nerve Plexus in Limbal Stem Cell Deficiency

Abstract

Purpose To quantify the changes of subbasal nerve plexus in patients with limbal stem cell deficiency (LSCD) using in vivo laser scanning confocal microscopy. Design: Retrospective cross-sectional comparative study Methods Confocal images of 51 eyes of 37 patients with LSCD collected between 2010 and 2015 by the Heidelberg Retina Tomograph III Rostock Corneal Module Confocal Microscope. Two independent observers evaluated the scans of the central cornea. Seventeen normal eyes of 13 patients served as controls. Total subbasal nerve density (SND), density of long nerves (i.e., nerves 200 μm or longer) and the degree of tortuosity were quantified. Results The mean (± SD) total SND and long nerve density were 48.0 ± 34.2 nerves/mm2 and 9.7 ± 10.9 nerves/mm2, respectively, in all eyes with LSCD and 97.3 ± 29.9 nerves/mm2 and 35.3 ± 25.3 nerves/mm2, respectively, in eyes of the control group (P<0.001 for both comparisons). Compared with SND in control subjects, SND was reduced by 34.9% in the early stage, 54.0% in the intermediate stage, and 73.5% in the late stage of LSCD. The degrees of nerve tortuosity were significantly greater in patients with LSCD than in control subjects and differed among the early, intermediate, and late stages of LSCD. Reductions in total SND and long nerve density were positively correlated with the severity of LSCD. Conclusions Reductions in total SND and long nerve density were accompanied by increases in nerve tortuosity in eyes with LSCD. These parameters could be used as quantifiable measures of LSCD severity.

Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency

“…Other features of IVCM findings suggestive of LSCD include epithelial thinning and reduction of subbasal nerve plexus and basal cell density. [107][108][109][110]…”

The diagnosis of limbal stem cell deficiency

“…1I, 1N, 1S). Compared with control subjects, subbasal nerve density was reduced by 34.9% in the early stage, 54.0% in the intermediate stage, and 73.5% in the late stage of LSCD [95]. Other distinct morphologic changes of the subbasal nerve plexus in patients with LSCD include severe nerve dropout, short nerve branches, and sharp turns of the branched nerve [95].…”

Classification of Limbal Stem Cell Deficiency Using Clinical and Confocal Grading

“…Other quantifiable parameters such as limbal BCD, subbasal nerve density, and epithelial thickness would be necessary to establish more accurate staging of LSCD. 11,12,14–17 In future investigations, the classification system could be further refined by including these quantifiable parameters. A larger prospective study would be necessary to further validate the classification system.…”

“…Recently, our group has demonstrated that epithelium thickness, central cornea BCD, limbus BCD, and sub-basal nerve density are significantly decreased in eyes with LSCD and that the degree of reduction correlates with the severity of LSCD. 15–17…”