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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 35  |  Issue : 2  |  Page : 214-217

Corneal epithelial thickness changes as imaged by Fourier-domain optical coherence tomography in eyes with keratoconus


Ophthalmology Department, Faculty of Medicine, Benha University, Benha, Egypt

Date of Submission07-Mar-2017
Date of Acceptance06-Apr-2017
Date of Web Publication17-Aug-2018

Correspondence Address:
Dr. Ahmed Y Fekry
Flat 8, Floor 3, 24 El Gomhoria St, El Mansourah, 35511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bmfj.bmfj_46_17

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  Abstract 


Purpose The purpose of this study was to document changes in the corneal epithelium as imaged by Fourier-domain optical coherence tomography (OCT) in cases of keratoconus.
Patients and methods This is a comparative cross-sectional study including 20 eyes of 14 patients with keratoconus (n=20, study group) and 16 eyes of eight normal individuals (n=16, control group). Both groups were imaged using Scheimpflug imaging corneal topography and Fourier-domain AS-OCT system. Corneal epithelial thickness maps obtained by the AS-OCT system were studied and compared between the two groups.
Results There was no statistically significant difference in mean corneal epithelial thickness between study and control groups (unpaired Student’s t-test, P<0.05). Minimum corneal epithelial thickness was statistically significantly less and maximum corneal epithelial thickness was statistically significantly more in the study group compared with the control group (unpaired Student’s t-test, P<0.05). Corneal epithelial thickness was least in the central, temporal, and inferotemporal sectors of the study group. A distinct pattern of epithelial thinning over the thinnest pachymetry and highest back elevation with varying degrees of surrounding epithelial thickening located in the inferotemporal quadrant was observed in 71.43% of the study group.
Conclusion Recognizable corneal epithelial thickness changes are seen in keratoconic eyes. The diagnostic potential of such changes need to be further investigated.

Keywords: corneal ectasia, corneal epithelium, keratoconus, optical coherence tomography


How to cite this article:
Fekry AY, Fayed AA, El Shayeb AA, Hamed AM. Corneal epithelial thickness changes as imaged by Fourier-domain optical coherence tomography in eyes with keratoconus. Benha Med J 2018;35:214-7

How to cite this URL:
Fekry AY, Fayed AA, El Shayeb AA, Hamed AM. Corneal epithelial thickness changes as imaged by Fourier-domain optical coherence tomography in eyes with keratoconus. Benha Med J [serial online] 2018 [cited 2018 Oct 18];35:214-7. Available from: http://www.bmfj.eg.net/text.asp?2018/35/2/214/239196




  Introduction Top


The epithelium is the outermost layer of the cornea and consists of five to seven layers of cells with an accepted central thickness of ∼50–52 µm [1]. The corneal epithelium is a highly active, self-renewing layer; a complete turnover occurs in ∼5–7 days [2].

Corneal epithelium contributes to the refractive power of the cornea by an average of 1.03 D (range: 0.55–1.85 D) over the central 2-mm-diameter zone and 0.85 D (range: 0.29–1.60 D) at the 3.6-mm-diameter zone [3].

It is known that the corneal epithelium has the ability to alter its thickness profile to re-establish a smooth, symmetrical optical surface and either partially or totally mask the presence of an irregular stromal surface from front surface topography [4].

Such compensatory epithelial changes are seen in cases of asymmetric LASIK flaps [4], microfolds [4], flap malposition, short flap, free cap malrotation, and irregular stromal surface following multiple refractive procedures [5].

Epithelial changes have also occurred in response to myopic [6] or hyperopic [7] LASIK, radial keratotomy [8], and intracorneal ring segment implantation [9].

Moreover, procedures such as corneal cross-linkage and intracorneal ring segment implantation ICRS both require a minimum corneal depth to prevent corneal endothelial damage for corneal cross-linkage or segment extrusion for intrastromal corneal ring segments (ICRS). In both procedures, corneal thickness is routinely initially measured with the epithelium intact. Therefore, lack of knowledge about corneal epithelial thickness distribution preoperatively may result in overestimation of corneal thickness and unfavorable postoperative outcomes [10].

In this study, we aim to document changes in the corneal epithelium as imaged by Fourier-domain optical coherence tomography in cases of keratoconus, for the possibility of using which as a diagnostic utility in the future.


  Patients and methods Top


This descriptive cross-sectional study was approved by the ethics committee. The participants provided a written informed consent before examination. The consent form was approved by the ethics committee. This study adhered to the tenets of the Declaration of Helsinki.

Participants of the study were recruited from subjects seeking laser refractive surgery. All of the participants underwent full cycloplegic refraction, spectacle best-corrected distance visual acuity, comprehensive slit-lamp biomicroscopy, and fundoscopy. Exclusion criteria included history or signs of previous corneal disease, previous refractive or intraocular surgery, late keratoconic changes such as corneal scars or hydrops, and patients unwilling to sign a written informed consent.

Corneal tomography was performed using the WaveLight Oculyzer Diagnostic Device (Očna Bolnica Profesional, Tršćanska, Zemun, Beograd), which uses Scheimpflug imaging to provide simulated keratometry (diopters), anterior and posterior elevation maps, corneal pachymetric maps, AC-irregularity indices, and topographic keratoconus classification (TKC). To facilitate statistical analysis, numeric conversion scheme was introduced to TKC, grade (−) was set to 0, KC1 to 1, KC1–2 to 2, KC2 to 3, KC2–3 to 4, KC3 to 5, KC3–4 to 6, and KC4 to 7.

Corneal pachymetry and epithelial thickness maps were recorded using the Fourier-domain AS-OCT system (Optovue, Fremont, California, USA) with a scan rate of 26 000 axial scans per second, axial resolution of 5 μm, transverse resolution of 15 μm, and an add-on lens (CAM-L mode: 6.0−2.0 mm). A computer algorithm automatically maps total corneal thickness and corneal epithelial thickness across the central 6 mm of the corneal surface. Each total corneal thickness map (pachymetry map) and corneal epithelium thickness map (epithelial map) is divided into 17 sectors. Specifically, these are the 2-mm-diameter pupil-center disk of 12.56 mm2 area, eight sectors (octants) within the annulus between the 2- and 5-mm zones, each of 8.24 mm2 area, and eight sectors (octants) within the annulus of 5–6-mm zones, each of 4.32 mm2 area. For each one of these sectors, the average thickness is displayed numerically over the corresponding area.

The study included 36 eyes of 22 participants divided into two groups. The study group included 20 eyes of 14 participants with topographic evidence of keratoconus in the form of abnormal AC-irregularity indices and TKC of KC1 or more. The control group included 16 eyes of eight normal individuals with no topographic evidence of keratoconus. Several statistical tests were carried out on the data set.


  Results Top


The study group included 20 eyes of 14 patients with keratoconus. Mean corneal epithelial thickness for keratoconic eyes was 52.16±3.48 µm. Minimum corneal epithelial thickness was 43.87±5.35 µm and maximum corneal epithelial thickness was 61.95±4.88 µm.

The control group included 16 normal eyes of eight individuals. Mean corneal epithelial thickness for normal eyes was 55.06±2.44 µm. Minimum corneal epithelial thickness was 51.5±2.78 µm and maximum corneal epithelial thickness was 58.43±2.61 µm.

Applying unpaired Student’s t-test, there was no statistically significant difference in the mean corneal epithelial thickness between study and control groups (P=0.65). There was a statistically significant difference in minimum (P=0.00024) and maximum (P=0.00697) epithelial thicknesses. Minimum corneal epithelial thickness was less and maximum corneal epithelial thickness was more in the study group compared with the control group.

Corneal epithelial thickness was least in the central 2-mm circle, and in the temporal and inferotemporal octants between 2- and 5-mm circles at 51.9±5.18, 51.7±5.25, and 51.2±5.6 µm, respectively, in the study group. These zones also correspond to the least total corneal thickness at 485.95±34, 496.7±28.8, and 489.6±29.7 µm, respectively, and were less in the study group than in the control group (P=0.0167, 0.0338, and 0.0114, respectively). The remaining corneal zones showed no statistically significant difference between study and control groups.

The point of minimum corneal epithelium thickness in the study group was located in the inferior half of the corneal map in 15 (71.43%) eyes, all of which were located inferotemporal to the center of the cornea (within the central, inferotemporal, temporal, and inferior octants). The remaining five (28.57%) eyes were located in the superior half of the corneal map (the superior octant).

In the same 15 eyes, a distinct pattern of corneal epithelial thickness distribution can be observed. The point of minimum epithelial thickness lies in very close proximity to both the point of minimum total corneal thickness and the point of maximum back elevation. An area of epithelial thinning is centered around this point of minimum epithelial thickness and is surrounded by varying degrees of epithelial thickening. In other words, the corneal epithelium is thinnest over the apex of the cone and thickens in the area surrounding the apex of the cone ([Figure 1]).
Figure 1 Distinct corneal epithelial thickness pattern in keratoconus. Left pane shows corneal epithelial thickness map (a), total corneal thickness map (b) by Fourier-domain AS-OCT system RTVue 100, and back surface elevation map by WaveLight Oculyzer II Diagnostic Device (c). Right panel shows corneal thickness spatial profile (d) and AS-irregularity indices (e) by WaveLight Oculyzer II Diagnostic Device.

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  Discussion Top


It has been shown by in-vitro histopathologic analysis and light microscope examination that the keratoconic epithelium thins over the apex of the cone, and this may in advanced keratoconus lead to a breakdown of the epithelium [11]. Moreover, the corneal epithelium has been shown to have the ability to undergo compensatory changes in response to underlying stromal surface irregularities [4]. Examples of such scenarios include myopic [6] or hyperopic [7] LASIK, radial keratotomy [8], intracorneal ring segment implantation [9], and in cases with postoperative regression following refractive surgery [12].

It is this corneal epithelial compensatory ability that provoked interest in corneal epithelial thickness profiles in keratoconic eyes − that is, to help in close call clinical judgments over potentially ectatic corneas and in preoperative screening of laser refractive surgery. The cornea may project a smoother topography and an alleviated wavefront error map, compared with the underlying stroma alone. In the specific case of subclinical corneal ectasia, if the epithelium is thinner over the ectatic area profile maps may help a clinician who would otherwise be reading a total corneal pachymetry map to identify patients in whom corneal ablative procedures are contraindicated. However, if the epithelium is thicker centrally, an assessment based only on total corneal pachymetry − topography, with no knowledge of the specific epithelial depth − may result in an incorrect assessment of keratoconic progression. Regional epithelial thickness cannot be assumed to be uniform in ectatic corneas and therefore may require direct measurement when considering treatments for which underlying stromal thickness is particularly important, such as corneal collagen cross-linking or topography-guided excimer laser ablation.

In our study, we aimed to study the corneal epithelial thickness changes in keratoconic corneas. Although there was no difference in mean corneal epithelial thickness between normal and keratoconic eyes, minimum and maximum corneal epithelial thicknesses show significant difference. We report a distinct corneal epithelial pattern where the epithelium is thinnest over the apex of the cone, lying very close to the point of minimum total corneal thickness and maximum posterior elevation, in the inferotemporal quadrant (71%), with varying degrees of surrounding thickening, in the area surrounding the cone. These findings are in agreement with previous work carried out using Artemis very-high-frequency ultrasound, in which the epithelial doughnut pattern, characterized by a localized central zone of thinning surrounded by an annulus of thick epithelium, was slightly decentered inferotemporally, with the thinnest epithelial point located in the inferotemporal quadrant for 74% of the cases [13].

It is logical to assume that the corneal epithelium is thin over the thin protruding stroma over the apex of the cone, which chaffs the epithelium against the posterior surface of the eyelid during blinking, and thickens over the surrounding concave valleys by being remodeled to the smooth posterior surface of the eyelid or by compensatory hyperplasia to project a smooth anterior corneal surface. These corneal epithelial thickness changes become more apparent with increasing severity of the disease. Focal epithelial thinning is suggestive but not pathognomonic for keratoconus.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. Philadelphia, PA: Saunders Publishing; 1971.  Back to cited text no. 1
    
2.
Hanna C, O’Brien JE. Cell production and migration in the epithelial layer of the cornea. Arch Ophthalmol 1960; 64:536–539.  Back to cited text no. 2
    
3.
Simon G, Ren Q, Kervick GN, Parel JM. Optics of the corneal epithelium. Refract Corneal Surg 1993; 9:42–50.  Back to cited text no. 3
    
4.
Reinstein DZ, Archer T. Combined Artemis very high-frequency digital ultrasound-assisted transepithelial phototherapeutic keratectomy and wavefront-guided treatment following multiple corneal refractive procedures. J Cataract Refract Surg 2006; 32:1870–1876.  Back to cited text no. 4
    
5.
Reinstein DZ, Archer TJ, Silverman RH. Evaluation of irregular astigmatism with Artemis very high-frequency digital ultrasound scanning. In: Wang M, editor. Irregular astigmatism: diagnosis and treatment. Thorofare, NJ: SLACK Incorporated; 2007. pp. 29–42.  Back to cited text no. 5
    
6.
Reinstein DZ, Archer TJ, Gobbe M. Corneal epithelial thickness profile in the diagnosis of keratoconus. J Refract Surg 2009; 25:604–610.  Back to cited text no. 6
    
7.
Reinstein DZ, Silverman RH, Sutton HF, Coleman DJ. Very high-frequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery: anatomic diagnosis in lamellar surgery. Ophthalmology 1999; 106:474–482.  Back to cited text no. 7
    
8.
Lovisolo CF, Mularoni A, Calossi A. Complications of refractive keratotomy. In: Alio J, Azar DT, editors. Management of complications in refractive surgery. Berlin, Germany: Springer-Verlag; 2008. pp. 197–224.  Back to cited text no. 8
    
9.
Reinstein DZ, Srivannaboon S, Holland SP. Epithelial and stromal changes induced by intacs examined by three-dimensional very high-frequency digital ultrasound. J Refract Surg 2001; 17:310–318.  Back to cited text no. 9
    
10.
Rocha KM, Perez-Straziota CE, Stulting RD, Randleman JB. SD-OCT analysis of regional epithelial thickness profiles in keratoconus, postoperative corneal ectasia, and normal eyes. J Refract Surg 2013; 29:173–179.  Back to cited text no. 10
    
11.
Scroggs MW, Proia AD. Histopathological variation in keratoconic corneas. Cornea. 1992; 11:553–559.  Back to cited text no. 11
    
12.
Schlegel Z, Hoang-Xuan T, Gatinel D. Comparison of and correlation between anterior and posterior corneal elevation maps in normal eyes and keratoconus-suspect eyes. J Cataract Refract Surg 2008; 34:789–795.  Back to cited text no. 12
    
13.
Reinstein DZ, Gobbe M, Archer TJ, Couch D. Epithelial thickness profile as a method to evaluate the effectiveness of collagen cross-linking treatment after corneal ectasia. J Refract Surg 2011; 27:356–363.  Back to cited text no. 13
    


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