The Plasticity of the Human Cornea Epithelial Layer
- including in ocular surface disease -
Rob Davis OD FAAO
The corneal epithelium provides a smooth surface to absorb oxygen and nutrients from tears, which are then distributed to the other layers of the cornea. The corneal epithelium smooths over the corneal surface irregularity by filling in the depressions and thinning over the elevations. The epithelium also has the ability to alter its thickness profile to reduce surface irregularities and to reestablish a smooth optical surface.
Measuring Epithelial Thickness
Optical coherence tomography (OCT) is a noncontact imaging technique based on principles of low-coherence interferometry. Its high axial resolution allows precise thickness measurements of the different layers of the cornea. Commercial Fourier-domain OCT automatically maps the corneal epithelial thickness with good repeatability. Following LASEK surgery, the corneal epithelium alters its thickness to mask sub-epithelial stromal irregularities and to maintain a smooth anterior surface of the eye. This remodeling of the anterior epithelium is helpful after refractive surgery, altering the anterior corneal contour. It has also been seen in the initial stage of stromal thinning with corneal ectasia, in which the epithelial layer remodels to maintain normal corneal global thickness.
Corneal epithelium responds to thicken after LASEK surgery
In dry eye disease, remodeling of the epithelium occurs due to increased lid friction; the change in epithelial thickness signals the beginning of ocular surface disease. Corneal epithelial thickness mapping can provide useful information in identifying dry eye disease with the use of an anterior segment OCT system. Because of friction from the upper lid, the reduced tear film begins to thin the superior aspect of the cornea. As toxins accumulate in the lower fornix, the inferior epithelium also begins to thin.
Thinner Epithelium in Dry Eyes
The average corneal epithelial thickness for the normal patient was examined by Kanellopoulos and Asimellis. They reported an average pupil center epithelial thickness repeatability of 0.88 ± 0.71 µm. On average, the pupil center epithelial thickness was 53.28 ± 3.34 µm, superior was 51.78 ± 3.78 µm, and inferior was 53.81 ± 3.44 µm; minimum corneal epithelial thickness was 48.65 ± 4.54 µm, maximum was 56.35 ± 3.80 µm.
Kanellopoulos and Asimellis also observed augmented epithelial thickness in dry eye patients. For the control group, central epithelial thickness was 53.0 ± 2.7 µm (45-59 µm). Average epithelium thickness was 53.3 ± 2.7 µm (46.7-59.6 µm). Topographic thickness variability was 1.9 ± 1.1 µm (0.7-6.1 µm). For the dry eye group, central epithelial thickness was 59.5 ± 4.2 µm (50-72 µm), and average thickness was 59.3 ± 3.4 µm (51.4-70.5 µm). Topographic thickness variability was 2.5 ± 1.5 µm (0.9-6.9 µm). All pair tests of respective epithelium thickness metrics between the control and dry eye groups showed statistically significant differences (P < 0.05).
Cui reported in the dry eye patient the mean (± SD) central, superior, and inferior corneal epithelial thickness was 53.57 (± 3.31) μm, 52.00 (± 3.39) μm, and 53.03 (± 3.67) μm in normal eyes and 52.71 (± 2.83) μm, 50.58 (± 3.44) μm, and 52.53 (± 3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p = 0.037), whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, a wider range (p = 0.032), and greater deviation (p = 0.003).
Erdelyi examined clinical patients and reported that the corneal epithelial thickness tends to be thinner in dry eyes, which was attributed to the destruction of stem cells at the limbus.
The Inflammatory Processes in Ocular Surface Disease
During the initial stages of ocular surface disease, the inflammatory processes and epithelial proliferation have a significant impact on the average central epithelial thickness. At the same time, the superior aspect of the cornea became thinner due to the frictional force of the upper lid. Later in the disease process, as the stem cells at the limbus are affected, the central epithelium becomes thinner. As the disease progresses, changes in epithelial thickness will provide information as to the stage of dry eye syndrome and will thus provide direction for therapy.
There is a continuum in the progression of dry eye, first influenced by inflammation and epithelial thickening, then followed by limbal stem cell atrophy resulting in epithelial thinning. It is interesting to note that the stem cell population is greater in the superior and inferior region in the normal eye than it is in the nasal and temporal region. This anatomical variation is important due to greater frictional forces applied to the superior cornea and greater inflammatory toxins residing in the inferior tear film adjacent to the cornea. Epithelial thickness changes are more dramatic in the peripheral cornea than in the central.
Corneal epithelium thins in the superiorly in response to friction in Ocular Surface Disease
Malleability of the Corneal Epithelium
The normal corneal epithelial thickness profile is thinner in the superior quadrant than in other regions of the cornea. As the tear film becomes more deficient and lubrication is reduced, greater frictional force upon the superior cornea results in increased cell loss. It has also been shown that tear-deficient patients increase their blinking rate in an attempt to lubricate the ocular surface, resulting in greater frictional force placed upon the epithelium, which causes additional cell loss and thinning. It is also interesting to note that long-term soft contact lens wearers have also exhibited a thinning epithelia effect. The cause of thinning has been attributed to mechanical stress, hypoxia or both. It appears that the corneal epithelium is very plastic and can change rapidly due to influences of external factors.
Dr. Robert L. Davis practices in Oak Lawn Illinois and is director of the Contact Lens Clinic at Davis EyeCare.
He is also co-founder of EyeVis, Eye and Vision Research Institute developing novel contact lens designs as well as forging the knowledge of anterior segment pathophysiology. He is an adjunct faculty member at Southern California College of Optometry - Marshall B. Ketchum University, University of Missouri in St. Louis, Illinois College of Optometry, Pennsylvania College of Optometry at Salus University and Pacific University.
Dr. Davis has been recognized as a Diplomate in the Corneal, Contact Lens and Refractive Technology section of the American Academy of Optometry and as well as an inductee in National Academy Practice in Optometry. He has held leadership roles with the American Optometric Association, American Academy of Optometry, National Academy of Practice and other professional organizations.
Dr. Davis has published and lectured on topics related to Contact Lenses, Myopia Control, and the management of eye disorders.