Corneal Subbasal Nerve Plexus Research Articles

Corneal Diabetic Neuropathy: A Confocal Microscopy Study

To evaluate the role of corneal confocal microscopy in the diagnosis of morphologic damage of the corneal sub-basal nerve plexus in diabetic patients and to correlate corneal confocal microscopy findings with peripheral diabetic neuropathy. Corneal sub-basal nerve plexus parameters were quantified by corneal confocal microscopy in 42 diabetic patients and 27 age-matched controls. The parameters quantified were the number of fibers, the tortuosity of fibers, the number of beadings, and the branching pattern of the fibers. Peripheral neuropathy was also quantified using the Michigan Neuropathy Screening Instrument. The number of fibers, number of beadings, and branching pattern of fibers significantly decreases in diabetic patients versus control subjects (P<.0001; P<.0001; P=.0006, respectively), whereas nerve tortuosity significantly increases (P<.0001). The same corneal sub-basal nerve plexus parameters show a statistical trend, suggesting progression of corneal neuropathy with peripheral diabetic neuropathy. Corneal confocal microscopy represents a new tool in the diagnosis, clinical evaluation, and follow-up of peripheral diabetic neuropathy. This study found that diabetes damages corneal nerves, particularly the corneal sub-basal nerve plexus. This damage may be easily and accurately documented using corneal confocal microscopy.

Mapping the Corneal Sub-basal Nerve Plexus in Keratoconus by In Vivo Laser Scanning Confocal Microscopy

To produce a two-dimensional reconstruction map of the living corneal sub-basal nerve plexus in keratoconus with in vivo confocal microscopy. Four eyes of four subjects with keratoconus were examined by slit lamp biomicroscopy, Orbscan II slit-scanning elevation topography (Bausch & Lomb Surgical, Rochester, NY), and laser scanning in vivo confocal microscopy with the Heidelberg Retina Tomograph II, Rostock Corneal Module (Heidelberg Engineering, Heidelberg, Germany). Subjects were asked to fixate on targets arranged in a grid to enable in vivo confocal microscopy of the cornea in a wide range of positions. A mean of 402 +/- 57 images were obtained for each cornea, to create confluent montages. The mean dimensions of the corneal areas mapped were 6.60 +/- 0.70 mm horizontally and 5.91 +/- 0.72 mm vertically. All corneas exhibited abnormal sub-basal nerve architecture compared with patterns previously observed in normal corneas. At the apex of the cone, a tortuous network of nerve fiber bundles was noted, many of which formed closed loops. At the topographic base of the cone, nerve fiber bundles appeared to follow the contour of the base, with many of the bundles running concentrically in this region. Central sub-basal nerve density was significantly lower in keratoconus corneas (10,478 +/- 2,188 microm/mm2) compared with normal corneas (21,668 +/- 1,411 microm/mm2; Mann-Whitney; P < 0.01). This is the first study to elucidate the overall distribution of sub-basal nerves in the living central to midperipheral human cornea in keratoconus, using laser scanning in vivo confocal microscopy.

Mapping of the Normal Human Corneal Sub-Basal Nerve Plexus by In Vivo Laser Scanning Confocal Microscopy

To produce a two-dimensional reconstruction map of the living human sub-basal corneal nerve plexus using in vivo confocal microscopy. Laser scanning in vivo confocal microscopy was performed on three normal eyes of three healthy human subjects. Subjects were asked to fixate on targets arranged in a grid to enable examination of the cornea in a wide range of positions. Using the section mode, a mean of 573 +/- 176 images of the sub-basal plexus were obtained for each subject. The data were arranged and images were mapped for each subject into confluent montages. Mean dimensions of the corneal areas mapped were 4.95 +/- 0.53 mm horizontally and 5.14 +/- 0.53 mm vertically. In all subjects, the sub-basal nerve plexus appeared to radiate toward a whorl-like complex centered 1 to 2 mm inferior to the corneal apex. Outside this area, the nerve fiber bundles in the remainder of the cornea were arranged in a radiating pattern. Mean nerve density was significantly higher in the inferocentral whorl region (25,249 +/- 616 microm/mm2) compared with the central cornea (21,668 +/- 1411 microm/mm2) (Mann-Whitney U test; P = 0.05). This is the first study to elucidate the overall distribution of sub-basal nerves in the healthy, live central to mid-peripheral human cornea by laser scanning in vivo confocal microscopy. The whorl pattern of the sub-basal nerves is similar to that seen in the epithelium in corneal verticillata and may lend support to the theory that epithelial cells and nerves migrate centripetally in tandem.

The Effect of Age on the Corneal Subbasal Nerve Plexus

To measure subbasal nerve density and orientation in normal human corneas across a broad age range. Sixty-five normal corneas of 65 subjects were examined by using tandem scanning confocal microscopy. Ages of subjects ranged from 15 to 79 years (mean 46 +/- 19 years), with 5 subjects from each hemidecade. Subbasal nerve fiber bundles appeared as bright, well-defined linear structures in confocal images of the central cornea. Images from 3 to 8 scans per eye (mean 4.6 +/- 1.8 scans) were randomly presented to a masked observer for analysis. The mean subbasal nerve density (total nerve length [microm] within a confocal image [area = 0.166 mm]), the mean nerve number per confocal scan, and the mean nerve orientation were determined by using a custom software program. Correlations between age and nerve density and age and nerve orientation were assessed by using Pearson correlation coefficients. The subbasal nerve plexus was visible in the central cornea of all subjects. The mean subbasal nerve density was 8404 +/- 2012 microm/mm (range 4735 to 14,018 microm/mm). The mean subbasal nerve number was 4.6 +/- 1.6 nerves (range 1 to 8 nerves). The mean subbasal nerve orientation was 94 +/- 16 degrees (range 58 to 146 degrees). There was no correlation between age and subbasal nerve density (r = 0.21, P = 0.09) or between age and subbasal nerve orientation (r = -0.19, P = 0.12). The density and orientation of the subbasal nerve plexus in the central human cornea does not change with age.