|Year : 2023 | Volume
| Issue : 1 | Page : 7-14
Role of epithelial mapping in the differentiation between early keratoconus and high regular astigmatism using spectral-domain optical coherence tomography
Sameh M Abdelfadeel, Noha M Khalil, Lobna M Khazbak, Mohamed Karim Sidky
Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||19-Oct-2022|
|Date of Decision||07-Nov-2022|
|Date of Acceptance||13-Nov-2022|
|Date of Web Publication||30-Mar-2023|
MD Mohamed Karim Sidky
Kasr Al Ainy School of Medicine, Cairo University, PO Box 109, Al Malek Al Saleh, Cairo 11559
Source of Support: None, Conflict of Interest: None
Pur6pose To detect epithelial thickness-based diagnostic variables to detect early keratoconus (KC) and differentiate cases of early KC from high regular astigmatism, especially if abnormal topographic changes are present.
Patients and methods A total of 84 eyes with high regular astigmatism on Scheimpflug imaging were evaluated by anterior segment optical coherence tomography (AS-OCT). Imaging of the cornea as well as pachymetry and epithelial thickness mapping was done using AS-OCT via a special lens mounted to a tomographic device. The same was done using Scheimpflug imaging (CSO Sirius device). Thickness of the corneal epithelium was automatically mapped using a computer algorithm. Calculations of the following diagnostic factors were recorded: minimum, superior–inferior, minimum–maximum, root-mean-square variation, root-mean-square pattern deviation, and thickness of the zonal epithelium.
Results This study analyzed 84 eyes divided into two groups: group A (n=56 eyes) had high regular astigmatism and group B (n=28 eyes) with early KC. The mean spherical refraction, cylindrical refraction, and central corneal thickness (Scheimpflug imaging) for group A were −1.16±1.02 D, −3.67±0.67, and 542.88±29.64 μm, respectively. In group A, the mean central corneal thickness and central epithelial thickness was 538.84±29.67 and 52.34±1.69 μm, respectively. The mean spherical refraction, cylindrical refraction, central corneal, and epithelial thickness mean for group B were −1.75±0.87, −4.02±0.69 D, 505.36±28.48, and 49.93±0.9 μm, respectively. A significant correlation between central epithelial thickness with anterior elevation was noted in group B (P=0.048).
Conclusion AS-OCT epithelial mapping may prove to be a useful diagnostic tool for determining early development of KC.
Keywords: anterior segment optical coherence tomography, keratoconus, regular stigmatism, Scheimpflug imaging
|How to cite this article:|
Abdelfadeel SM, Khalil NM, Khazbak LM, Sidky MK. Role of epithelial mapping in the differentiation between early keratoconus and high regular astigmatism using spectral-domain optical coherence tomography. J Egypt Ophthalmol Soc 2023;116:7-14
|How to cite this URL:|
Abdelfadeel SM, Khalil NM, Khazbak LM, Sidky MK. Role of epithelial mapping in the differentiation between early keratoconus and high regular astigmatism using spectral-domain optical coherence tomography. J Egypt Ophthalmol Soc [serial online] 2023 [cited 2023 May 30];116:7-14. Available from: http://www.jeos.eg.net/text.asp?2023/116/1/7/372945
| Introduction|| |
Keratoconus (KC) is a corneal pathology that results from ectasia and progressive thinning of the cornea, which subsequently results in progressive irregular astigmatism. KC is a noninflammatory condition that occurs bilaterally. Stages (moderate to severe) of KC are easily detectable using several devices. Nowadays, rotating Scheimpflug camera and orbscan are used to diagnose KC. However, early stages of KC remain a challenge.
When compared with corneal topography alone, epithelial thickness profiles may improve the specificity and sensitivity of screening for early KC. They may also be helpful in clinical practice. As epithelial changes will precede any topographic changes produced on the front surface of the cornea , corneal epithelial mapping is an attempt to develop epithelium-based diagnostic variables to facilitate early KC detection .
Optical coherence tomography (OCT) is a non contrast technique that functions on the principle of low-coherence interferometer . High axial resolution of the OCT demonstrates enhanced corneal surface delineation. Spectral-domain anterior segment OCT (AS-OCT) systems can provide both epithelial and corneal thickness (pachymetry) mapping .
This study aims to detect the role of epithelial thickness mapping in early detection of KC and its role in the differentiation between early KC and high regular astigmatism.
| Patients and methods|| |
This is a cross-sectional observational study that included 84 eyes of patients recruited from the ophthalmology and laser unit of Kasr Al Ainy Hospital (Cairo University) in the period from February 2019 to October 2019. Institutional and ethical approval was granted for this study, which was conducted according to the Declaration of Helsinki guidelines.
The study included patients aged more than 18 years with high regular astigmatism more than or equal to −3 D cylinder and early KC as well as K readings between 45 and 49 D. Patients with frank KC and any pathological condition affecting the eye such as corneal opacities and fundus abnormalities were excluded.
This study included 84 eyes. All eyes had manifest astigmatism −3 D or more and K readings between 45 and 49 D in Scheimpflug imaging. Group A included 56 eyes showing high regular astigmatism, and group B included 28 eyes showing early KC according to the ABCD classification .
All patients underwent a detailed history and clinical examination that included the following: objective refraction (autorefractometer), subjective refraction by clinical trial, AS and fundus examination, uncorrected visual acuity, best-corrected visual acuity, and intraocular pressure measurement.
All patients underwent tomographic imaging using a Scheimpflug camera (CSO Sirius) device. (mod.Sirius for Sirius System, Serial No. 12031546, Florence, Italy). The following parameters were included: simulated K 1 and K2, central corneal thickness, S-I difference or I-S difference, central 5 mm of the anterior elevation map, and central 5 mm of the posterior elevation map.
Then patients were further subjected to AS-OCT imaging at Kasr Al Ainy Hospital using special lens mounted to an Optovue OCT device (Optovue, Visionix, Illinois, USA). The pachymetry and epithelial maps were analyzed. From the pachymetry map, we measured the central corneal thickness, and from the epithelial map, we measured central epithelial thickness, thickest location, thinnest location, and their distribution.
The Statistical Package for the Social Sciences (SPSS), version 25 (IBM Corp., Armonk, New York, USA) was used to code the data, which were summarized using SD, mean, and median for quantitative data and using frequency (count) and relative frequency (percentage) for categorical data. Quantitative data was analyzed and compared the nonparametric Mann–Whitney test . χ2 test was used to compare categorical data. When the expected frequency was less than 5, an exact test was used . Spearman correlation coefficient was used for determining the presence of any correlations in the quantitative variables . Receiver operating characteristic curve was constructed and an area under the curve analysis was performed to detect the best cutoff value for KC. P values less than 0.05 were significant.
| Results|| |
This study included 84 eyes, where all eyes had manifest astigmatism −3 D or more and K readings between 45 and 49 D in Scheimpflug imaging. Group A included 56 eyes showing high regular astigmatism, and group B included 28 eyes showing early KC according to the ABCD classification . The mean age group A was 25.09±4.65 years old, and in group B was 25.61±2.82 years old. In group A, the mean spherical refraction was −1.16±1.02 D, whereas in group B, the mean spherical refraction was −1.75±0.87 D.
The mean cylindrical refraction was −3.67±0.67 and −4.02±0.69 D in groups A and B, respectively. The mean central corneal thickness (Scheimpflug imaging) and minimum and maximum central corneal thicknesses for group A were 542.88±29.64, 480.00, and 620.00 μm, respectively. In group B, the mean central thickness of the cornea using Scheimpflug imaging was 505.36±28.48 μm, the minimum central corneal thickness was 425.00 μm, and the maximum central corneal thickness was 549.00 μm.
In group A, the central corneal thickness measured by AS-OCT was 538.84±29.67 μm, the minimum thickness was 417.00 μm, and the maximum thickness was 617.00 μm. In group B, the central corneal thickness was 496.71±32.43 μm, the minimum thickness was 409.00 μm, and the maximum thickness was 543.00 μm.
In group A, the central epithelial thickness measured by AS-OCT was 52.34±1.69 μm, the minimum thickness was 50 μm, and the maximum thickness was 59 μm. In group B, the mean central epithelial thickness was 49.93±0.9 μm, the minimum thickness was 48 μm, and the maximum thickness was 51 μm.
Correlation coefficient between central epithelial thickness of 56 eyes of group A and each of central corneal thickness (AS-OCT), central corneal thickness (Pentacam), K1, K2, anterior elevation, posterior elevation, and I-S difference or S-I difference (Pentacam) of group A was statistically insignificant, as shown in [Table 1]. The Pentacam and the epithelial map of case number 21 with high astigmatism are shown in [Figure 1] and [Figure 2], respectively.
|Table 1 Correlation coefficient between central epithelial thickness and each of central corneal thickness (anterior segment optical coherence tomography), central corneal thickness (Pentacam), K1, K2, anterior elevation, posterior elevation, and I-S difference (Pentacam) in group A|
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Correlation coefficient between central epithelial thickness of 28 eyes of group B and each of central corneal thickness (AS-OCT), central corneal thickness (Pentacam), K1, K2, posterior elevation, and I-S difference (Pentacam) of group B was statistically insignificant but with anterior elevation was statistically significant, as shown in [Table 2] (P=0.048). The Pentacam and the epithelial map of case number 24 with KC are shown in [Figure 3] and [Figure 4], respectively.
|Table 2 Correlation coefficient between central epithelial thickness and each of central corneal thickness (anterior segment optical coherence tomography), central corneal thickness (Pentacam), K1, K2, anterior elevation, posterior elevation, and I-S difference (Pentacam) in group B|
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A comparison between groups in the terms of age, refraction, K1, K2, central corneal thickness by Pentacam, anterior elevation, posterior elevation, I-S difference, S-I difference, central corneal thickness using AS-OCT, central epithelial thickness, and thinnest and thickest location using AS-OCT is demonstrated in [Table 3].
| Discussion|| |
KC is a predominant primary corneal ectatic pathology with an incidence of approximately one per 2000 in the general population in the USA. Identifying patients at risk for subclinical KC and distinguishing them from normal individuals had been an elusive goal for refractive surgeons .
Although many studies focused on the role of Scheimpflug imaging in the diagnosis of KC, the role of epithelial mapping in the early diagnosis of KC is still under investigation. When paired with corneal topography, epithelial thickness profiles may improve both the sensitivity and specificity of KC screening compared with corneal topography alone, which may be very helpful in the clinical setting.
Alterations in epithelia usually precede any topographic changes, so an early diagnosis of KC may be possible using epithelial information . Many authors had studied these variations in epithelial thickness in early KC ,. OCT, a precise, rapid, user-friendly, and noninvasive technology, can now be used to evaluate corneal epithelium and pachymetry profiles .
In this study, we compared epithelial thickness and pachymetry maps using AS-OCT with topographic findings using rotating Scheimpflug imaging in two groups: group A showing high regular astigmatism (up to −3.00 D astigmatism) and corneal steepening on rotating Scheimpflug imaging and group B with stage one KC according to the ABCD classification. Our study showed statistically significant results between the two groups regarding epithelial and central corneal thickness by AS-OCT and central corneal thickness, thinnest corneal thickness, keratometric readings, and anterior and posterior elevation maps by Scheimpflug imaging. Group B showed statistically significant central corneal thinning and corresponding epithelial thinning compared with group A.
In 2015, Temstet et al.  investigated the role of epithelial thickness mapping in the detection of forme fruste KC. Their study involved 145 eyes divided into three groups: a group showing forme fruste KC diagnosed only by the presence of KC in the fellow eye whereas the rest of the topographic and orbscan indices as well as clinical examination showed no positive results, another group showing frank KC based on positive topographic and orbscan as well as clinical indices, and a third control group of normal individuals. Their results agreed with the findings of our study regarding the decreased central corneal and central epithelial thicknesses in the early KC group compared with the normal group. However, Temstet used the Orbscan II in addition to the rotating Scheimpflug camera and the AS-OCT, whereas in our study, we only used rotating Scheimpflug camera in addition to AS-OCT. In addition, the investigated groups in the Temstet study differed from those in our study as they included a control group, which is lacking in our study, and individuals with forme fruste KC (only positive finding was the presence of KC in the fellow eye) as well as individuals showing frank KC. Despite this difference in the studied groups and the machines used, there was an agreement in the results reinforcing the presence of epithelial changes in cases of early KC.
Fekry et al.  included 20 eyes of 14 patients showing frank KC and a control group of normal patients. They concluded that the corneal epithelium is thinnest over the apex of the cone and thickens in the area surrounding the cone apex in the KC group. This agreed with the results of our study; however, they included patients with frank KC, whereas in our study, patients with stage one KC were included, and they included a control group, which lacks in our study. They also described a pattern of epithelial thickness distribution in patients with KC, thus giving their study an advantage over ours. However, the aim of our study was mainly discriminating patients with high corneal astigmatism from patients with early KC especially if both groups show corneal steepening on Scheimpflug imaging, which could be of great advantage especially in candidates of refractive surgery.
Another similar study conducted by Silverman et al. , analyzed 111 normal and 30 patients with KC using Artemis and Pentacam data. Their study showed similar results to our study regarding coexisting central epithelial thinning and central corneal thinning when combining data obtained from both machines. However, in their study, they used ultrahigh-resolution ultrasonography (Artemis) to measure corneal epithelial thickness and rotating Scheimpflug imaging (Pentacam) to measure corneal thickness and other keratoconic indices, whereas in our study, we used AS-OCT and rotating Scheimpflug imaging. In addition, the studied groups differed from those of our study; however, the aim of our study differed from that of the study of Silverman and colleagues, as they aimed at developing and testing a KC classifier combining information from both methods, therefore the investigated groups were frank KC cases and a control group. However, the epithelial information obtained from the ultrahigh-resolution ultrasonography used in their study was like those obtained from the AS-OCT used in our study, thus validating our results. Moreover, AS-OCT, in our study could perform both corneal thicknesses using pachymetry map and epithelial thickness using the epithelial thickness map, which could be considered more cost-effective and of easier accessibility as the availability of AS-OCT is more compared with that of Artemis machines. This could serve as a better screening tool for early KC.
Serrao and colleagues investigated the role of epithelial thickness profiles in the detection of KC by analyzing pachymetry and epithelia thickness maps obtained from AS-OCT in 86 patients with stable/progressive KC (confirmed via repeated corneal topographies over 1-year follow-up period) and 182 normal patients . The results of their study agreed with those of our study regarding the presence of epithelial thinning over the thinnest corneal location. However, their study differed from our study in including patients with progressive KC, confirmed by repeated corneal topography over one year, whereas our study studied patients with early KC not taking into consideration the progression of the disease, which is important in the treatment of KC.
Another similar study and the closest to ours was that conducted by Ostadian et al. , which investigated patients with high myopic astigmatism without KC and patients with early and subclinical KC using epithelial thickness profiles of AS-OCT. Their results agreed with those of our study regarding the epithelial thinning in the subclinical patients. They performed their study on three groups including patients with KC, whereas our study excluded all patients with frank KC. They measured the mean epithelial thickness of the central, superior, inferior, nasal, and temporal regions, whereas our study focused on measuring central epithelial thickness mainly as well as central corneal thickness. Moreover, the study by Ostadian and colleagues used two different machines. They performed corneal Scheimpflug imaging with Pentacam and corneal epithelial thickness mapping with SD-OCT (Spectralis Heidelberg Engineering), whereas we used CSO (CSO Sirius device) for Scheimpflug imaging and Optovue AS-OCT device (Optovue, Visionix) for measurement of central epithelial.
It should be noted that the age group in our study was younger as compared with many studies, where the mean age of the KC group was 25.61±2.82 years and that of the normal group showing astigmatism was 25.09±4.65 years. This younger age group was of particular importance in the early diagnosis of KC, especially in the younger individuals, thus preventing its future progression.
In 2020, Fahmy concluded that there was a statistically significant difference between the two devices measuring CCT, where Pentacam is more accurate. This difference was not highly significant clinically, and therefore, the Pentacam and AS-OCT can be used interchangeably in clinics . Nam et al.  also concluded that the results of the Pentacam were more accurate as the results of the Pentacam and AS-OCT both were compared with the results of the ultrasonic pachymetry.
Corneal epithelium is the first protective layer of the cornea. Analysis of this layer and determining its thickness as well as its distribution play a pivotal role in refractive surgery, as it may help in the screening of normal individuals for early KC, especially if showing suspicious criteria in Scheimpflug imaging, thus helping to differentiate early KC from mimicking conditions on corneal topography such as high corneal astigmatism.Our study investigated the role of epithelial thickness of the cornea in the early diagnosis of KC especially in young individuals using Fourier domain OCT and correlated it with other indices detected in Scheimpflug imaging.
OCT is a noncontact and reliable method, can remarkably delaminate the surface of the cornea, and accurately demonstrate the thickness pattern of the corneal epithelium, owing to its high axial resolution .
The OCT has a fast acquisition time and appears to be a promising method for assessing high astigmatic cornea, such as in cases of early KC . Reports of cases of ectasia following LASIK in healthy eyes without any extra risk factors show that topography alone is unable to detect early stages of KC ,,,.
In comparison with corneal topography alone, epithelial thickness profiles may improve the sensitivity and specificity of screening for early KC, which is helpful in clinical practice. As epithelial changes can be detected before any topographic changes of the cornea , corneal epithelial mapping is a step to create epithelium-based diagnostic variables for early KC detection .
| Conclusion|| |
AS-OCT is a user friendly, noncontact instrument that can provide a screening tool for the early diagnosis of KC, especially in the suspicious group of young individuals experiencing high corneal astigmatism. This could further help in the early detection of KC thus providing early measures to halt progression of KC.
However, our study lacked the presence of a control group of normal patients which could highlight the results and establish a more reliable evaluation comparing early KC patients and patients with high corneal astigmatism with normal individuals. Moreover, our study did not describe the pattern of epithelial thickness distribution and compare it between both groups, which is important, as patients with early KC often show increased epithelial thickness surrounding central epithelial thinning as described in other aforementioned studies. Therefore, a second study is recommended with a larger sample size and a control group, in which in addition to studying epithelial thickness and their correlation with Pentacam and corneal thickness profiles, the epithelial thickness distribution is analyzed as well. This could provide more data to serve the detection of early KC and its progression to establish screening methods which are cost-effective, user friendly, and easily accessible, which could be the core of prevention plans of progression of KC.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Lee BW, Jurkunas UV, Harissi-Dagher M, Poothullil AM, Tobaigy FM, Azaral DT. Ectatic disorders associated with a claw-shaped pattern on corneal topography. Am J Ophthalmol 2007; 144:154–156.
Haque S, Jones L, Simpson T. Thickness mapping of the cornea and epithelium using optical coherence tomography. Optom Vis Sci 2008; 85:E963–E976.
Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W et al.
Optical coherence tomography. Science 1991; 254:1178–1181.
Christopoulos V, Kagemann L, Wollstein G, Ishikawa H, Gabriele ML, Wojtkowski M et al.
In vivo corneal high-speed, ultra high-resolution optical coherence tomography. Arch Ophthalmol 2007; 125:1027–1035.
Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrósio RJr, Guell JL et al.
Group of Panelists for the Global Delphi panel of Keratoconus and Ectatic diseases. Global consensus on keratoconus and ectatic diseases. Cornea 2015; 34:359–369.
Chan YH. Biostatistics102: quantitative data − parametric & non-parametric tests. Singapore Med J 2003a; 44:391–396.
Chan YH. Biostatistics 103: qualitative data − tests of independence. Singapore Med J 2003b; 44:498–503.
Chan YH. Biostatistics 104: correlational analysis. Singapore Med J 2003c; 44:614–619.
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):284–95.
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. J Refrac Surg 2010; 26:259–271.
Li HF, Petrol WM, Pedersen TM, Maurer JK, Cavanagh HD, Jester JV. Epithelial and corneal thickness measurements by in vivo confocal microscopy through focusing. Curr Eye Res 1997; 16:214–221.
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; 119:2425–2433.
Temstet C, Sandali O, Bouheraoua N, Hamiche T, Galan A, El Sanharawi M et al.
Corneal epithelial thickness mapping using Fourier_domain OCT for detection of form fruste keratoconus. J Cataract Refract Surg 2015; 41:812–820.
Fekry A, Fayed A, Shayeb A, Hamed AM. Corneal epithelial thickness changes as imaged by Fourier_domain optical coherence tomography in eyes with keratoconus. Benha Med J 2018; 35:214–217. [Full text]
Silverman RH, Urs R, RoyChoudhury A, Archer TJ, Gobbe M, Reinstein DZ. Combined tomography and epithelial thickness mapping for diagnosis of keratoconus. Eur J Ophthalmol 2017; 27:129–134.
Serrao S, Lombardo M, Cali C, Lombardo M. Role of corneal epithelial thickness mapping in the evaluation of keratoconus . Cont Lens Anterior Eye 2019; 42:662–665.
Ostadian F, Farrahi H, Rad AM. Comparison of corneal epithelial thickness map measured by spectral domain OCT in healthy, subclinical and early keratoconus subjects. Med Hypothesis Discov Innov Ophthalmol 2019; 8:85–91.
Fahmy RM. Comparative study between Pentacam and anterior segment OCT in measuring anterior segment parameters in myopic patients. J Med Med Sci 2022; 11:1–6.
Nam SM, Im CY, Lee HK, Kim EK, Kim TI, Seo KY. Accuracy of RTVue optical coherence tomography, Pentacam, and ultrasonic pachymetry for the measurement of central corneal thickness. Ophthalmology 2010; 117:2096–2103.
Elhennawi FM, Alzankalony YA, Abdellatif MK, Ibrahim AMT. Role of anterior segment optical coherence tomography in the diagnosis of subclinical keratoconus in comparison with the Pentacam. Egypt J Hosp Med 2018; 72:3712–3715.
Catalan S, Cadarso L, Esteves F, Salgado-Borges J, Lopez M, Cadarso C. Assessment of corneal epithelial thickness in asymmetric keratoconic eyes and normal eyes using fourier domain optical coherence tomography. J Ophthalmol 2016; 2016:5697343.
Ambrosio RJr, Dawson DG, Salomao M, Guerra FP, Caiado AL, Belin MW. Corneal ectasia after LASIK despite low preoperative risk: tomographic and biomechanical findings in the unoperated, stable, fellow eye. J Refract Surg 2010; 26:906–911.
Klein SR, Epstein RJ, Randleman JB, Stulting RD. Corneal ectasia after laser in situ keratomileusis in patients without apparent preoperative risk factors. Cornea 2006; 25:388–403.
Seiler T, Quurke AW. Iatrogenic keratectasia after LASIK in a case of forme fruste keratoconus. J Cataract Refract Surg 1998; 24:1007–1009.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]