As imaging technologies continue to develop, OCT brings us anterior segment applications. On the forefront is anterior segment OCT of the epithelial layer of the cornea. Optovue (FREMONT, CA) obtained U.S. Food and Drug Administration (FDA) approval for its epithelial thickness mapping software (“epi-mapping”) on Aug. 8, 2017. This technology provides quantitative measurements of the epithelial and stromal layers of the cornea. It is the first FDA-approved product indicated to provide measurements of the corneal epithelium and stroma to aid in the diagnosis, documentation, and management of ocular health and diseases in the adult population.

Epithelial mapping is not a new concept. Historically, epithelium was evaluated using OCT, slit-lamp adapted OCT, confocal microscopy, optical pachymetry, and focusing confocal microscopy. It is reported that the epithelial layer will alter its thickness to maintain a smooth, symmetrical optical surface to compensate for changes in the stroma. Epithelial thickening has been reported following myopic LASIK, and epithelial thinning has been reported overlying a keratoconic cone. (1)

Reinstein, et. al. evaluated epithelial maps of 110 normal eyes in 56 patients. They found the epithelium was 5.7µ thicker inferiorly than superiorly, and 1.2µ thicker nasally than temporally. The average layer thickness was 53.4µ with a standard deviation of only 4.6µ. It was suggested the eyelid might chaffe the surface during blinking, applying greater forces to the superior cornea, thinning it slightly. (2)

The same group then studied 54 keratoconic eyes and found their epithelial pattern to be more irregular than in normal eyes. It was typically thinnest at the apex of the cone, surrounded by an annulus of thickened epithelium. The thinnest area was displaced inferiorly temporally slightly, and the overall thickness was slightly less than that of normal eyes at 45.7µ. (3)

They then investigated using epithelial thickness profiles as an early indicator for keratoconus. Keratoconus is often represented with tomography as an elevation on the best fit sphere map. The posterior float typically shows this prior to the anterior float. They suggested that the thin center surrounded by the thicker annulus acts to minimize the manifestation of the cone on the anterior surface. (1)

Kanellopoulos, et. al., found increased overall epithelial thickness in ectatic corneas and suggested overall average increased epithelial thickness may be an early biological marker of corneal biomechanical instability. (4) They found that significantly irregular epithelium may be an indicator for ectasia, that the epithelium is thinner over the keratoconic elevation, and that keratoconic corneas tend to have thicker epithelial layers.

Schallhorn JM, et. al. investigated topographical changes in contact lens warpage cases and compared them to keratoconic eyes. They determined that areas of corneal steepening in contact lens warpage were associated with focal epithelial thickening, while focal epithelial thinning was associated with the areas of corneal steepening in keratoconus.

Temstet, et. al. investigated epithelial mapping to detect forme fruste keratoconus using optical coherence tomography (OCT). Forme fruste keratoconus is a condition in which the anterior elevation and curvature are normal, which the posterior best-fit sphere demonstrates an area of elevation. Normal corneas, forme fruste keratoconic eyes, and moderate to severe keratoconic eyes were measured using Fourier-domain OCT, scanning slit-corneal topography, and a Scheimpflug camera. Forme fruste keratoconic corneas had less epithelial thickness in the thinnest area than normal corneas and greater epithelial thickness in the thinnest area than keratoconic corneas (P < .005). The thinnest area of epithelium in forme fruste corneas was located inferiorly (P < .005), corresponding with the zone of minimum epithelial thickness and maximum posterior elevation (P < .005). It was suggested that epithelial thickness of 52μ threshold value for discriminating forme fruste keratoconic corneas from normal corneas, but the standard deviation does not support using this as a strong indicator.

Changes in epithelium following refractive surgery have also been studied. Corneal epithelial changes are suspected to play a role in refractive regression. Corneal epithelium contributes to the corneal refractive power. The refractive index of the epithelium differs from the stroma (1.401 vs 1.377 respectively), resulting in an average power contribution of -3.60D.

Following excimer ablation, the epithelium thickens to cover treatment (thinner) areas, effectively mirroring the change in stromal thickness. Central epithelial thickening following myopic excimer laser ablations has associated with myopic regression. (7,8) Changes following peripheral ablations in hyperopic LASIK follow the opposite pattern. Ultrasound mapping of epithelial thickness profiles after hyperopic LASIK demonstrated thinner epithelium centrally, and thicker epithelium paracentrally where more treatment was applied.(9) A hyperopic ablation attempts to steepen the central cornea, and the resulting central steepening resembles a keratoconic cornea. It is not surprising that the epithelial thickness profile after hyperopic ablation is like that seen in keratoconus.

Post-refractive surgery (PRK and LASIK) patients with residual refractive error may return to the surgeon to request a second treatment, or “enhancement.” A method to differentiate between regression due to epithelial hypertrophy and early corneal ectasia would be beneficial to determine which to enhance for residual refractive error.

Another application for epithelial mapping is orthokeratology, where lens-induced epithelial layer changes result in reduction of myopia. Compression of the central epithelium has been reported following ortho-K treatment.(1) Correlation of central flattening related to the amount of myopia reduction might aid clinicians in determining the limits to treatment within individual eyes.

An irregular epithelial layer has also been observed in patients with dry eye disease. (10) If both ocular surface disease and ectasia risk could be assessed using this technology, this might be another test commonly performed preoperatively to assess candidacy for keratorefractive procedures.


Footnotes

  1. Reinstein, D; Archer, TJ, Gobbe, M.  Artemis Epithelial Thickness Profile:  A Surrogate for Stromal Surface Topography. Corneal Topography:  A Guide for Clinical Application in the Wavefront Era, Second Edition.  Wang, M and Swartz, T; Editors.  2010. Slack Incorporated, Thorofare, NJ.

  2. Reinstein DZ, Archer TJ, Gobbe M, Silverman RH, Coleman DJ.  “Epithelial thickness in the normal cornea: three-dimensional display with Artemis very high-frequency digital ultrasound.”  Refract Surg.  2008; 24: 571-581. 

  3. Reinstein DZ, Gobbe M,  Archer TJ, Silverman RH, Coleman DJ.  “Epithelial, stromal and total corneal  thickness in keratoconus: three-dimensional display with Artemis very high-frequency digital ultrasound.”  Refract Surg.  2010; 26:  259-271. 

  4. Kanellopoulos AJ, Asimellis G. “Anterior segment optical coherence tomography – assisted topographic corneal epithelial thickness distribution imaging of a keratoconus patient.” Case Rep Ophthalmol. 2013;4:74-78.

  5. Schallhorn JM, et al. “Distinguishing between contact lens warpage and ectasia: Usefulness of optical coherence tomography epithelial thickness mapping.” J Cataract Refract Surg. 2017;43:60–66.

  6. Temstet C, Sandali O, Bouheraoua N, Hamiche T, Galan A, El Sanharawi MBasli ELaroche LBorderie V.  “Corneal epithelial thickness mapping using Fourier-domain optical coherence tomography for detection of forme fruste keratoconus.”  J Cataract Refract Surg. 2015 Apr;41(4):812-20. doi: 10.1016/j.jcrs.2014.06.043.

  7. Lohmann CP, Guell JL. “Regression after LASIK for the treatment of myopia: the role of the corneal epithelium.” Semin Ophthalmol. 1998;13:79–82.

  8. Reinstein DZ, et al. “Epithelial Thickness Profile Changes Induced by Myopic LASIK as Measured by Artemis Very High-frequency Digital Ultrasound.” J Refract Surg. 2009 May ;25(5):444–450.

  9. Reinstein DZ1, et al. “Epithelial thickness after hyperopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound.” J Refract Surg. 2010 Aug;26(8):555-64.

  10. Kanellopoulos AJ, Asimellis G. “Anterior segment optical coherence tomography – assisted topographic corneal epithelial thickness distribution imaging of a keratoconus patient.” Case Rep Ophthalmol. 2013;4:74-78.