Corneal Nerve Parameter Reference Values for Chinese Adults Assessed by Corneal Confocal Microscopy

Abstract

Background. Confocal corneal microscopy is an excellent new noninvasive tool for assessing diabetic peripheral neuropathy. We aimed to investigate the clinical variables associated with corneal nerve parameters and establish reference values for clinical use in healthy Chinese adults. Methods. The study enlisted 257 healthy volunteers (137 females and 120 males) from two clinical academic centers in China. Two experts captured and selected images of the central corneal subbasal nerve plexus at each center using the same corneal confocal microscopy instrument according to a commonly adopted protocol. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were measured using fully automated software (ACCMetrics). The correlation between clinical indicators and confocal corneal microscopy measures was determined using partial correlation. Quantile regression was used to calculate reference values and estimate the effects of clinical factors on the normative values of confocal corneal microscopy measures. Results. Females had significantly higher CNFD, CNBD, and CNFL than males. There was no correlation between age, glycated hemoglobin (HbA1c), height, weight, body mass index (BMI), and any corneal nerve fiber parameter in both sexes. In either sex, age, weight, height, BMI, and HbA1c did not affect the 0.05th quantile values of any corneal nerve parameter. Conclusions. This study establishes sex-adjusted reference values for corneal confocal microscopy measures in Chinese adults and provides a reference for clinical practice and research with this technique.

Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults

“…CNFL was the next most commonly studied parameter, with 2 studies demonstrating negative correlations between CNFL and advancing age, which is in line with our results. 20,23 CNFrD is a rather new automated nerve metric, which measures the topological complexity of main nerve fibers and branches. 42 It is expressed as a ratio of the logarithm of the total number of boxes that contain nerve fibers to the logarithm of the number of boxes of the image width.…”

“…17 Current studies have shown inconsistent results of the age effects on corneal nerves, with some demonstrating adverse effects of age on corneal nerve morphology such as decreasing subbasal nerve fiber density with age, [18][19][20] while others demonstrate no statistically significant changes in nerve fiber density, branch density, and length with age. [21][22][23] Regarding the corneal epithelium, Gambato et al and Niederer et al showed that there was no change in mean cell density of basal epithelial cells with age using IVCM evaluation. 21,24 Another study showed that a decrease in the density of limbal basal epithelial cells was observed with age because of the deteriorating proliferative ability with age, leading to a decrease in corneal epithelial thickness, although the central corneal epithelium was less susceptible to these age-related changes.…”