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. Author manuscript; available in PMC: 2023 Feb 1.
Published in final edited form as: J Refract Surg. 2022 Feb 1;38(2):112–119. doi: 10.3928/1081597X-20211116-01

Differentiating Between Contact Lens Warpage and Keratoconus Using OCT Maps of Corneal Mean Curvature and Epithelial Thickness

Elias Pavlatos 1, Brooke Harkness 1, Derek Louie 1, Winston Chamberlain 1, David Huang 1, Yan Li 1
PMCID: PMC8870421  NIHMSID: NIHMS1777803  PMID: 35156455

Abstract

Purpose:

To formulate an Epithelial Modulation index to differentiate between eyes with contact lens warpage and keratoconus.

Methods:

Normal eyes and eyes with either contact lens warpage or keratoconus were scanned by a Fourier-domain OCT system. Maps of epithelial thickness and anterior surface mean curvature were generated and converted to deviation maps by subtracting the average maps from a healthy population. The Epithelial Modulation index was defined as the covariance between the two types of deviation maps. A logistic regression model was used to classify eyes as non-keratoconus (normal or warpage) or keratoconus (manifest, subclinical, or forme fruste).

Results:

The average Epithelial Modulation index value for normal eyes was −0.6 ± 1.0 μm/m. Keratoconus eyes were characterized by coincident high anterior surface mean curvature and low epithelial thickness, resulting in a high Epithelial Modulation index (manifest: 103.0 ± 82.9 μm/m, subclinical: 37.0 ± 23.0 μm/m, forme fruste: 7.3 ± 13.2 μm/m). The Epithelial Modulation index was closer to normal for warpage eyes (−1.9 ± 4.0 μm/m). The classification accuracy of the Epithelial Modulation index during 5-fold cross-validation of the logistic regression model was 100 ± 0% for the normal eyes and 99.0 ± 2.0% for the warpage eyes. The accuracy was 100 ± 0%, 100 ± 0%, and 53.1 ± 1.5% for the manifest, subclinical, and forme fruste keratoconus groups, respectively.

Conclusions:

The Epithelial Modulation index is useful in distinguishing eyes with secondary epithelial modulation (keratoconus) from those with primary epithelial deformation (contact lens related warpage).

Introduction

The structure of the cornea is critical to the visual function of the eye. The cornea is composed of five layers: the epithelium, Bowman’s layer, the stroma, Descement’s membrane, and the endothelium. Accounting for roughly 90% of the cornea’s overall thickness, the stroma is the middle layer which contains the collagen fibers that give the cornea its mechanical strength. The epithelium is the outermost cellular layer and has a thickness of approximately 50 μm in healthy eyes. One of the primary functions of the epithelium is to maintain the smoothness of the outer surface of the cornea in response to changes in stromal structure.1

This smoothing effect of the epithelium can be observed in a number of scenarios. In keratoconus, the stroma thins and protrudes outward, resulting in a localized cone-shaped region of high curvature.2 The epithelium compensates for this increase in curvature by thinning in the region of the cone and thickening in the surrounding area, thereby attempting to smooth out the variation in curvature on the anterior surface of the cornea.3–6 A similar phenomenon can be observed as the cornea remodels after refractive surgery. For example, the epithelium can thicken centrally in an attempt to return the cornea to its pre-operative shape after myopic LASIK, which flattens the cornea by ablating a thin layer of the central stroma.7,8 These compensatory behaviors of the epithelium can be categorized as secondary epithelial modulation since they occur in response to a primary alteration of stromal structure.

In contrast to the secondary response of the epithelium, some conditions affect epithelial thickness directly. Epithelial basement membrane dystrophy (EBMD) is a degenerative disease that causes thickening of the basement membrane.9 Dry eye syndrome can also cause abnormal variations in epithelial thickness.10–13 The use of contact lenses is another source of epithelial distortion, as lenses may apply forces to the epithelium or cause metabolic stress. It is possible for contact lens-related warpage to be induced by both rigid and soft lenses.14,15 These conditions can be categorized as primary epithelial deformation.

Distinguishing between conditions such as contact lens warpage (primary deformation) and keratoconus (secondary modulation) can be challenging because both of these conditions can induce topographic steepening (Figure 1).16 For this reason, new metrics are needed to assist with clinical decision-making. We have previously shown that optical coherence tomography (OCT) can be used to map epithelial thickness,4 and the epithelial pattern standard deviation (Epi PSD) can be used to detect abnormal epithelial thickness patterns.17 In this study, we propose a new parameter termed the Epithelial Modulation index which aims to differentiate between primary deformation and secondary modulation by quantifying the spatial relationship between epithelial thickness and the mean curvature of the anterior corneal surface.18

Figure 1.

Figure 1.

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Axial power maps from the Pentacam Scheimpflug topographer and epithelial thickness maps from the Avanti OCT device for representative warpage and keratoconus eyes. For the warpage case, the inferior topographic steepening is associated with thickening of the epithelium. For the keratoconus case, the topographic steepening is related to the cone-shaped structure of the cornea, and epithelial thinning is observed in the region of the cone. The different relationship between corneal curvature and epithelial thickness for the two conditions motivated the design of the Epithelial Modulation index.

Methods

Study Recruitment

Data was collected in the Casey Eye Institute at Oregon Health & Science University (Portland, Oregon) and the Affiliated Eye Hospital of Wenzhou Medical College (Wenzhou, China). The data collection protocols were approved by the institutional review boards of both institutions, and informed consent was obtained from all participants. The study adhered to the tenets of the Declaration of Helsinki and the Health Insurance Portability and Accountability Act of 1996.

Both eyes of each participant were examined at the slit lamp, tested for visual acuity, and scanned by either a Scheimpflug-based (Pentacam; Oculus Optikgeräte GmbH, Wetzlar, Germany) or scanning slit-based (Orbscan II; Bausch & Lomb, Bridgewater, New Jersey) corneal topographer. Eyes were divided into 5 groups based on clinical diagnosis:

  1. Normal: normal slit-lamp exam, corrected distance visual acuity (CDVA) ≥ 20/20, and normal topography appearance.

  2. Contact lens-related warpage: contact lens wear within 2 weeks of examination date, normal slit-lamp exam, and clinical evidence of warpage such as an ill-fitting lens, a reduction in CDVA, scissor reflex on retinoscopy, or abnormal anterior corneal topography (arcuate pattern of steepening, asymmetric bowtie with skewed radial axis, central or inferior steep zone).

  3. Manifest keratoconus: slit-lamp finding indicative of keratoconus (Vogt’s striae, Fleischer’s ring, Munson’s sign, Rizutti’s sign, apparent focal bulging and thinning); or CDVA < 20/20 and topographic pattern characteristic of keratoconus (asymmetric bowtie with skewed radial axis, central or inferior steep zone).

  4. Subclinical keratoconus: normal slit-lamp exam, CDVA ≥ 20/20, but topography characteristic of keratoconus.

  5. Forme fruste keratoconus: better eye of an asymmetric manifest or subclinical keratoconus patient with no signs of keratoconus (normal slit-lamp exam, CDVA ≥ 20/20, and normal topography).

All eyes with a history of surgery were excluded. Normal and keratoconus eyes with recent contact lens wear (soft contact lens within 2 weeks or rigid gas permeable lens within 3 weeks prior to examination) were also excluded to avoid overlap with the warpage group.

OCT Imaging

Tomographic images of the cornea were obtained using Fourier-domain OCT systems (RTVue or Avanti; Optovue Inc., Fremont, CA). A radial scan pattern was used to acquire images along 8 equally spaced meridians, centered on the pupil (Figure 2). The image width was approximately 6 mm, and the scan pattern was repeated 5 times within a single scan. Each eye was scanned at least twice. Scans with low signal intensity or significant artifacts caused by eyelid/eyelash interference were excluded.

Figure 2.

Figure 2.

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(A) Radial OCT scan pattern (yellow lines) overlaid on an en face photograph of the cornea. The scan pattern covered a 6mm diameter area. (B) Representative OCT image of a cornea with segmented boundaries.

Segmentation of the anterior and posterior boundaries of the epithelium was performed to obtain maps of epithelial thickness. Mean curvature maps for the anterior corneal surface were generated by a custom OCT topography algorithm (MATLAB, MathWorks Inc., Natick, MA) which corrects image distortions and minimizes artifacts caused by eye motion.19 An elevation map was first constructed using the segmented boundary of the anterior corneal surface from the 8 meridians. The elevation map was then used to calculate the mean curvature which is defined as:

MC(x,y)=12[K1(x,y)+K2(x,y)] (2)

where K1 and K2 are the maximum and minimum surface curvatures at point (x,y) of the corneal elevation map, respectively.20 All maps were cropped to a diameter of 5 mm.

Thickness and Topography Measurements

Measurements were made on the OCT maps of anterior mean curvature and epithelial thickness to characterize the differences between the patient groups. The maximum mean curvature and minimum epithelial thickness values were recorded to demonstrate the amount of corneal steepening and epithelial thinning for each eye. The difference between the minimum and maximum values on the same map was also measured to show how this range differed between groups. The Epi PSD was calculated to quantify the extent of irregularity in the epithelial thickness. An Epi PSD measure of greater than 4.1% indicates abnormal epithelial thickness pattern.17

Epithelial Modulation Index

The Epithelial Modulation index was calculated using maps of both epithelial thickness and the mean curvature of the anterior corneal surface. Both maps for a given scan were converted to deviation maps by subtracting the respective healthy population map (Figure 3). The Epithelial Modulation index was calculated from the covariance of the epithelial thickness and mean curvature deviation maps:

EM index=−cov(ΔET,ΔMC)=−∑i(ΔETi−ΔET¯)(ΔMCi−ΔMC¯)n−1 (3)

where ΔETi and ΔMCi represent each of the values in the epithelial thickness (ET) and anterior mean curvature (MC) deviation maps, respectively, ΔET¯ and ΔMC¯ are the average values from each map, and n is the number of pixels in the maps. Epithelial Modulation index values for repeated scans were averaged.

Figure 3.

Figure 3.

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Calculation of anterior mean curvature (A) and epithelial thickness (B) deviation maps used to compute the EM index. The population maps were computed as the average maps from a group of normal eyes not analyzed in this study.

Statistical Analysis

The Shapiro-Wilk test was used to determine whether the measurements from the OCT maps and the Epithelial Modulation index values were normally distributed within each group. Two-tailed t-tests (normality confirmed) or Wilcoxon rank sum tests (normality rejected) were used to compare the differences in average values between normal eyes and each keratoconus group or the warpage group. One eye was chosen randomly if both eyes of a participant were involved. These analyses were performed in R (R Foundation for Statistical Computing, Vienna, Austria).

The Epithelial Modulation index was used to perform a binary classification of keratoconus versus non-keratoconus. A logistic regression model was used to establish the cutoff value for the Epithelial Modulation index corresponding to a probability of 0.5. For the binary classification, all 3 groups of keratoconus eyes were included as keratoconus cases, and the normal and warpage eyes were treated as non-keratoconus cases. To validate the logistic regression model, 5-fold cross-validation was repeated 5 times. The average classification accuracy and cutoff value were computed. The logistic regression model and cross-validation algorithm were built in Python using the scikit-learn library (version 0.21.3, Python Software Foundation).

Results

The minimum epithelial thickness was lower for the warpage eyes and all 3 keratoconus groups compared to normal (Table 1). All of the keratoconus groups differed from the normal eyes by having a greater difference between the maximum and minimum epithelial thickness values. The maximum mean curvature of the anterior corneal surface was significantly higher for the manifest and subclinical keratoconus groups, but a statistical difference was not found between the normal eyes and either the warpage or forme fruste keratoconus eyes. There was a greater difference between the maximum and minimum mean curvature values for the warpage group and all three keratoconus groups compared to normal.

Table 1.

Average Map Characteristics for Each Patient Group

Group Number of Eyes (Patients) Minimum Epithelial Thickness (μm) Max - Min Epithelial Thickness (μm) Maximum Anterior Mean Curvature (1/m) Max - Min Anterior Mean Curvature (1/m) Epi PSD (%) EM Index (μm/m)
Normal 32 (16) 48.1 ± 3.0 7.9 ± 2.3 135.7 ± 3.1 11.3 ± 2.9 2.6 ± 0.7 −0.6 ± 1.0
Warpage 20 (10) 41.8 ± 5.5* 13.8 ± 7.4* 133.9 ± 6.0 13.2 ± 4.3* 4.7 ± 2.9* −1.9 ± 4.0
Manifest Keratoconus 89 (63) 38.7 ± 4.8* 22.7 ± 6.9* 172.8 ± 21.0** 80.9 ± 37.7** 12.4 ± 4.2* 103.0 ± 82.9**
Subclinical Keratoconus 16 (15) 42.8 ± 5.0* 18.0 ± 6.1* 157.5 ± 10.3** 47.4 ± 12.8* 9.2 ± 2.8* 37.0 ± 23.0**
Forme Fruste Keratoconus 26 (26) 45.5 ± 4.1** 11.0 ± 4.2** 138.3 ± 5.9 18.8 ± 6.4** 4.8 ± 2.8** 7.3 ± 13.2**
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*

2-tailed t-test p < 0.01,

**

Wilcoxon rank sum test p < 0.05

For normal eyes, deviations from the healthy population were small for maps of both epithelial thickness and mean curvature (Figure 4). In contrast, deviation maps for eyes with keratoconus showed larger magnitudes, with higher anterior mean curvature and lower epithelial thickness in the infero-temporal region compared to the healthy population. Larger deviations could also be observed for the maps of eyes with contact lens warpage. However, these eyes did not exhibit the coincident spatial relationship between high anterior mean curvature and low epithelial thickness that was characteristic of keratoconus eyes.

Figure 4.

Figure 4.

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Representative mean curvature and epithelial thickness deviation maps for an eye from each group. Epi PSD = Epithelial Thickness Pattern Standard Deviation, EM = Epithelial Modulation.

The average Epi PSD and Epithelial Modulation index values for normal eyes were 2.6 ± 0.7% and −0.6 ± 1.0 μm/m, respectively (Figure 5). For warpage eyes, the average Epi PSD was 4.7 ± 2.9% and the average Epithelial Modulation index was −1.9 ± 4.0 μm/m. Of the keratoconus eyes, the manifest group had the highest Epi PSD at 12.4 ± 4.2%, followed by the subclinical group at 9.2 ± 2.8% and the forme fruste group at 4.8 ± 2.8%. A similar trend was observed for the Epithelial Modulation index, with average values of 103.0 ± 82.9 μm/m for manifest keratoconus, 37.0 ± 23.0 μm/m for subclinical keratoconus, and 7.3 ± 13.2 μm/m for forme fruste keratoconus. Overall, the keratoconus groups displayed a characteristic pattern of a high Epi PSD and a high Epithelial Modulation index. Both the Epi PSD and Epithelial Modulation index were significantly different from normal for the 3 keratoconus groups (all p < 0.02). A statistical difference was found between the Epi PSD values of normal and warpage eyes (p = 0.03), but the mean values for the Epithelial Modulation index were similar (p = 0.74).

Figure 5.

Figure 5.

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Average Epi PSD and EM index values for each group. Epi PSD = Epithelial Thickness Pattern Standard Deviation, EM = Epithelial Modulation, * indicates a statistically significant difference from the normal group based on a t-test or a Wilcoxon rank sum test.

Repeated k-fold cross-validation of the logistic regression model revealed that the Epithelial Modulation index was effective in separating the keratoconus eyes (manifest, subclinical, and forme fruste) from the non-keratoconus eyes (normal and warpage) (Table 2). Evaluating the performance of the model within each group revealed that the classification accuracy was at or near 100% for the normal, warpage, manifest keratoconus, and subclinical keratoconus groups. Slightly more than half (53.1%) of the forme fruste keratoconus eyes were classified as keratoconus. The average cutoff value for the Epithelial Modulation index was 1.24 μm/m, with a more positive value being indicative of keratoconus and a more negative value indicating that an eye did not have keratoconus (i.e., the eye was normal or had contact lens warpage).

Table 2.

Average Cutoff Value and Classification Accuracy for Each Group from Repeated 5-fold Cross-Validation of the EM Index

Classification Accuracy (%)
Non-Keratoconus Keratoconus
Cutoff Normal Warpage Manifest Subclinical Forme Fruste
1.24 ± 0.02 100 ± 0 99.0 ± 2.0 100 ± 0 100 ± 0 53.1 ± 1.5
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In the logistic regression model, the negative class was composed of the normal and warpage eyes, and all of the keratoconus eyes were included in the positive class.

A scatter plot of Epithelial Modulation index versus Epi PSD for all of the eyes in each group is shown in Figure 6. All of the normal eyes fell below the respective cutoff values for the Epithelial Modulation index and Epi PSD. In contrast, all of the subclinical and manifest keratoconus eyes had Epithelial Modulation index and Epi PSD values that were larger than the cutoff. Both the forme fruste keratoconus and warpage groups showed a wide range of values for Epi PSD. Of the 129 warpage and keratoconus eyes with an abnormal Epi PSD, only 3 were misclassified by the Epithelial Modulation index, and all 3 of these eyes were forme fruste keratoconus cases.

Figure 6.

Figure 6.

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Scatter plot of Epi PSD and EM index values for all eyes in the study. The cutoff values for the two metrics are indicated by the dashed lines. Keratoconus and warpage eyes with a high Epi PSD were able to be differentiated by the EM index. Epi PSD = Epithelial Thickness Pattern Standard Deviation, EM = Epithelial Modulation.

Discussion

Using OCT topography and epithelial thickness maps, we have developed a new diagnostic metric, the Epithelial Modulation index, for the classification of corneal irregularities. The premise of the Epithelial Modulation index is that corneal shape abnormalities can be categorized into two groups: primary epithelial deformation (shape change originates in the corneal epithelium layer) and secondary epithelial modulation (epithelial thickness change is a result of epithelial modulation due to a change in stromal shape). We computed the Epithelial Modulation index for normal eyes and eyes with either contact lens warpage (primary epithelial deformation) or keratoconus (secondary epithelial modulation).

Irregular and asymmetric epithelial thickness distributions have been proposed for keratoconus detection in previous studies.4,21,22 In this study, after identifying eyes with abnormal epithelial thickness, the Epithelial Modulation index was used to determine whether the epithelial irregularities were related to contact lens warpage or keratoconus. Since warpage and keratoconus eyes both exhibit irregular map patterns,23–25 it can be challenging to distinguish between the two conditions based on an individual map.16 The Epithelial Modulation index was therefore designed to identify differences between the two groups of eyes based on the spatial relationships between the anterior mean curvature and epithelial thickness deviation maps. Mean curvature was used because it is not affected by astigmatism which improves visualization of the keratoconic cone.18

The Epithelial Modulation index differed between eyes with primary epithelial deformation and secondary epithelial modulation because it captured the inverse relationship between anterior mean curvature and epithelial thickness that is characteristic of secondary modulation (i.e. epithelial smoothing). For keratoconus eyes specifically, this inverse relationship was characterized by high curvature of the anterior corneal surface and low epithelial thickness near the cone location, resulting in a large Epithelial Modulation index (Figure 4). Warpage eyes did not exhibit such a consistent relationship. This is because for warpage eyes, regions of steep anterior mean curvature were related to focal decreases in epithelial thickness rather than the curvature of the stroma. These rapid decreases could occur in transition zones from either high to normal thickness or from normal to low thickness. In this way, the warpage eyes were more similar to the normal eyes and could be differentiated from the keratoconus eyes (Figure 6). The magnitude of the Epithelial Modulation index depended on the magnitudes in the deviation maps and the strength of the spatial relationships between the two maps. These two factors combined to produce the largest Epithelial Modulation index values for the manifest keratoconus eyes (Figure 5).

A logistic regression model was used for binary classification of the keratoconus eyes (manifest, subclinical, and forme fruste) and the non-keratoconus eyes (normal and warpage) based on the Epithelial Modulation index values. The classification accuracy from 5-fold cross-validation of the logistic regression model was excellent for all groups except the forme fruste keratoconus group. This result is expected because forme fruste keratoconus is difficult to detect as it was defined in this study, and some of the eyes may not have differed significantly enough from normal eyes to be detectable.26

The Epi PSD was measured to evaluate the performance of the Epithelial Modulation index across the spectrum of epithelial thickness irregularity. An Epi PSD value larger than 4.1% indicates an abnormal epithelial thickness pattern that could have been caused by either keratoconus or contact lens warpage. While some of the warpage and forme fruste keratoconus eyes were not severe enough to have an abnormal Epi PSD, nearly all of the eyes with a high Epi PSD were classified correctly by the Epithelial Modulation index. Furthermore, four of the warpage eyes exhibited an abnormal Df value (≥ 1.6) on the Enhanced Belin-Ambrosio Display,27 and one had an I-S asymmetry of > 1.4 D on the axial power map.28 All of these warpage eyes were classified as non-keratoconus cases by the Epithelial Modulation index. Based on this result, the Epithelial Modulation index appears to be effective in determining the underlying cause of a detected corneal surface abnormality. Importantly, this could allow clinicians to rule out keratoconus in eyes with suspicious topography maps caused by contact lens warpage or another source of primary epithelial deformation (Figure 1).

A few other methods have been published to distinguish between contact lens warpage and keratoconus. Earlier studies made use of videokeratography to derive topography-based classification metrics.29,30 More recently, Patrao and others suggested that BAD-D could be used to rule out keratoconus in eyes with warpage since it includes information about the posterior surface of the cornea.31 Our group has previously described methods using topography maps obtained by standard topographers and epithelial thickness maps measured by OCT to differentiate between contact lens warpage and keratoconus.32,33 The current study improves upon our previous efforts by integrating OCT topography maps, removing the need for two devices to compute the diagnostic index. Moreover, the Epithelial Modulation index was optimized to characterize the different map patterns in warpage and keratoconus eyes.

There were a few limitations to this study. A technological limitation was the 6 mm diameter of the maps. A larger map size would ensure that corneal features over a larger area are captured. Another limitation of the OCT device was that it only scanned 8 meridians of the cornea. Due to this limitation, our OCT topography maps currently only capture up through 4th order Zernike terms and some of the higher order shape abnormalities may have been missed. Last, contact lens warpage and keratoconus were the only conditions included in this study. We expect that the Epithelial Modulation index could be applied more broadly to other cases of primary epithelial deformation (e.g. EBMD, dry eye) and secondary epithelial modulation (e.g. corneal scarring, stromal dystrophy, refractive surgery).34

In summary, we have developed a novel metric for the classification of corneal irregularities and shown its effectiveness in distinguishing between contact lens warpage and keratoconus. The Epithelial Modulation index could therefore be used to assist clinicians with diagnostic decision making. It also has the potential to be combined with other corneal measurements35 and indices36 to create a comprehensive classification system for corneal irregularities.

Acknowledgements

The authors would like to thank Dr. Shihao Chen and Dr. Qinmei Wang for their contributions to participant recruitment and data collection.

Source of Funding:

Supported by the National Institutes of Health, Bethesda, MD (grant no.: R01EY028755, R01EY029023, T32EY023211, P30EY010572); a research grant and equipment support from Optovue, Inc., Fremont, CA; unrestricted grants to Casey Eye Institute from Research to Prevent Blindness, Inc., New York, NY.

Footnotes

Conflicts of Interest: Oregon Health and Science University (OHSU) and Drs. Huang and Li have a significant financial interest in Optovue, Inc., a company that may have a commercial interest in the results of this research and technology. These potential conflicts of interest have been reviewed and managed by OHSU.

References

  • 1.Dillon EC, Eagle R, Laibson P. Compensatory epithelial hyperplasia in human corneal disease. Ophthalmic Surg. 1992;23 11:729–732. [PubMed] [Google Scholar]
  • 2.Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ. The pathogenesis of keratoconus. Eye (Lond). Feb 2014;28(2):189–195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Reinstein DZ, Archer Tj - Gobbe M, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg. 2009;25(7):604–610. [DOI] [PubMed] [Google Scholar]
  • 4.Li Y, Tan O, Brass R, Weiss JL, Huang D. Corneal epithelial thickness mapping by Fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology. 2012;119(12):2425–2433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Kanellopoulos AJ, Asimellis G. Anterior segment optical coherence tomography: assisted topographic corneal epithelial thickness distribution imaging of a keratoconus patient. Case Rep Ophthalmol. Jan 2013;4(1):74–78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Franco J, White CA, Kruh JN. Analysis of Compensatory Corneal Epithelial Thickness Changes in Keratoconus Using Corneal Tomography. Cornea. 2020;39(3):298–302. [DOI] [PubMed] [Google Scholar]
  • 7.Reinstein DZ, Archer TJ, Gobbe M. Change in epithelial thickness profile 24 hours and longitudinally for 1 year after myopic LASIK: three-dimensional display with Artemis very high-frequency digital ultrasound. J Refract Surg. Mar 2012;28(3):195–201. [DOI] [PubMed] [Google Scholar]
  • 8.Tang M, Li Y, Huang D. Corneal Epithelial Remodeling after LASIK Measured by Fourier-Domain Optical Coherence Tomography. J Ophthalmol. 2015;2015:860313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.El Sanharawi M, Sandali O, Basli E, et al. Fourier-Domain Optical Coherence Tomography Imaging in Corneal Epithelial Basement Membrane Dystrophy: A Structural Analysis. Am J Ophthalmol. 2015/04/01/ 2015;159(4):755–763.e751. [DOI] [PubMed] [Google Scholar]
  • 10.Kanellopoulos AJ, Asimellis G. In vivo 3-dimensional corneal epithelial thickness mapping as an indicator of dry eye: preliminary clinical assessment. Am J Ophthalmol. Jan 2014;157(1):63–68.e62. [DOI] [PubMed] [Google Scholar]
  • 11.Cui X, Hong J, Wang F, et al. Assessment of corneal epithelial thickness in dry eye patients. Optom Vis Sci. Dec 2014;91(12):1446–1454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Kanellopoulos AJ, Asimellis G. In pursuit of objective dry eye screening clinical techniques. Eye Vis (Lond). 2016;3:1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Abou Shousha M, Wang J, Kontadakis G, et al. Corneal epithelial thickness profile in dry-eye disease. Eye (Lond). May 2020;34(5):915–922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Tsai PS, Dowidar A, Naseri A, McLeod SD. Predicting time to refractive stability after discontinuation of rigid contact lens wear before refractive surgery. J Cataract Refract Surg. 2004/11/01/ 2004;30(11):2290–2294. [DOI] [PubMed] [Google Scholar]
  • 15.Rayess Y, Arej N, Abdel Massih Y, Antoun J, Waked N. Influence of soft contact lens material on corneal warpage: prevalence and time to resolution. Can J Ophthalmol. 2018/04/01/ 2018;53(2):135–138. [DOI] [PubMed] [Google Scholar]
  • 16.Tseng SS, Hsiao JC, Chang DC. Mistaken diagnosis of keratoconus because of corneal warpage induced by hydrogel lens wear. Cornea. Oct 2007;26(9):1153–1155. [DOI] [PubMed] [Google Scholar]
  • 17.Li Y, Chamberlain W, Tan O, Brass R, Weiss JL, Huang D. Subclinical keratoconus detection by pattern analysis of corneal and epithelial thickness maps with optical coherence tomography. J Cataract Refract Surg. 2016;42(2):284–295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Tang M, Shekhar R, Huang D. Mean curvature mapping for detection of corneal shape abnormality. IEEE Trans Med Imaging. Mar 2005;24(3):424–428. [DOI] [PubMed] [Google Scholar]
  • 19.Pavlatos E, Huang D, Li Y. Eye motion correction algorithm for OCT-based corneal topography. Biomed Opt Express. Dec 1 2020;11(12):7343–7356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.do Carmo MP. Differential Geometry of Curves and Surfaces: Revised and Updated Second Edition: Dover Publications; 2016. [Google Scholar]
  • 21.Kanellopoulos AJ, Asimellis G. OCT corneal epithelial topographic asymmetry as a sensitive diagnostic tool for early and advancing keratoconus. Clin Ophthalmol. 2014;8:2277–2287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Zhou W, Stojanovic A. Comparison of corneal epithelial and stromal thickness distributions between eyes with keratoconus and healthy eyes with corneal astigmatism ≥ 2.0 D. PLoS One. 2014;9(1):e85994–e85994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Liu Z, Pflugfelder SC. The effects of long-term contact lens wear on corneal thickness, curvature, and surface regularity. Ophthalmology. 2000/01/01/ 2000;107(1):105–111. [DOI] [PubMed] [Google Scholar]
  • 24.Temstet C, Sandali O, Bouheraoua N, et al. Corneal epithelial thickness mapping using Fourier-domain optical coherence tomography for detection of form fruste keratoconus. J Cataract Refract Surg. 2015;41(4). [DOI] [PubMed] [Google Scholar]
  • 25.Kanellopoulos AJ, Aslanides IM, Asimellis G. Correlation between epithelial thickness in normal corneas, untreated ectatic corneas, and ectatic corneas previously treated with CXL; is overall epithelial thickness a very early ectasia prognostic factor? Clin Ophthalmol. 2012;6:789–800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Henriquez MA, Hadid M, Izquierdo L Jr. A Systematic Review of Subclinical Keratoconus and Forme Fruste Keratoconus. J Refract Surg. Apr 1 2020;36(4):270–279. [DOI] [PubMed] [Google Scholar]
  • 27.Ambrósio R Jr., Nogueira LP, Caldas DL, et al. Evaluation of Corneal Shape and Biomechanics Before LASIK. International Ophthalmology Clinics. 2011;51(2). [DOI] [PubMed] [Google Scholar]
  • 28.Cavas-Martínez F, De la Cruz Sánchez E, Nieto Martínez J, Fernández Cañavate FJ, Fernández-Pacheco DG. Corneal topography in keratoconus: state of the art. Eye Vis (Lond). 2016;3:5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Smolek MK, Klyce SD, Maeda N. Keratoconus and contact lens-induced corneal warpage analysis using the keratomorphic diagram. Invest Ophthalmol Vis Sci. 1994;35(13):4192–4204. [PubMed] [Google Scholar]
  • 30.Lebow KA, Grohe RM. Differentiating contact lens induced warpage from true keratoconus using corneal topography. CLAO J. Apr 1999;25(2):114–122. [PubMed] [Google Scholar]
  • 31.Patrão LF, Canedo AL, Azevedo JL, Correa R, Ambrósio R Jr. Differentiation of mild keratoconus from corneal warpage according to topographic inferior steepening based on corneal tomography data. Arq Bras Oftalmol. Jul-Aug 2016;79(4):264–267. [DOI] [PubMed] [Google Scholar]
  • 32.Schallhorn JM, Tang M, Li Y, Louie DJ, Chamberlain W, Huang D. Distinguishing between contact lens warpage and ectasia: Usefulness of optical coherence tomography epithelial thickness mapping. J Cataract Refract Surg. 2017;43(1):60–66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Tang M, Li Y, Chamberlain W, Louie DJ, Schallhorn JM, Huang D. Differentiating Keratoconus and Corneal Warpage by Analyzing Focal Change Patterns in Corneal Topography, Pachymetry, and Epithelial Thickness Maps. Invest Ophthalmol Vis Sci. 2016;57(9):544–549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Huang D, Tang M, Shekhar R. Mathematical model of corneal surface smoothing after laser refractive surgery. Am J Ophthalmol. 2003/03/01/ 2003;135(3):267–278. [DOI] [PubMed] [Google Scholar]
  • 35.Ambrosio R Jr., Caiado Al - Guerra FP, Guerra Fp - Louzada R, et al. Novel pachymetric parameters based on corneal tomography for diagnosing keratoconus. J Refract Surg. 2011;27(10):753–758. [DOI] [PubMed] [Google Scholar]
  • 36.Pavlatos E, Chen S, Yang Y, Wang Q, Huang D, Li Y. A Coincident Thinning Index for Keratoconus Identification Using OCT Pachymetry and Epithelial Thickness Maps. J Refract Surg. Nov 1 2020;36(11):757–765. [DOI] [PMC free article] [PubMed] [Google Scholar]

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