Corneal Epithelium Thickness Profile in Normal Adults

doi:10.21203/rs.3.rs-3238472/v1

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Corneal Epithelium Thickness Profile in Normal Adults

https://doi.org/10.21203/rs.3.rs-3238472/v1

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Aim

To characterize the corneal epithelial thickness (ET) and corneal thickness (CT) profiles in normal eyes of Syrian adults, and to investigate associated factors with central epithelial thickness (CET).

Method

ET and CT were measured by Cirrus high-definition optical coherence tomography (HD-OCT) device in 208 eyes of 104 healthy adults aged 18 to 40 years. The average ET and CT were calculated in 25 (9 mm circle) zones and 17 (7 mm circle) zones, respectively. Correlations of CET with age, refractive errors, keratometry, and central corneal thickness (CCT) were calculated.

Results

The average ET was thicker in the central 2 mm than the paracentral, midperipheral and peripheral zones (50.42 ± 3.51 µm, 49.29 ± 3.61 µm, 47.80 ± 3.54 µm, and 46.74 ± 3.47 µm, respectively), whereas the average CT was thinnest in the centre. While Males have thicker ET than females in all zones (p < 0.05, all), CT did not significantly differ (p > 0.05, all). ET was thinner in the superior area than in the inferior, with the highest difference registered in the peripheral zone (-6 ± 5 µm). We found a positive significant correlation between CET and sphere (r = 0.25, p = 0.0022), and a negative significant correlation between CET and flat keratometry (r = -0.148, p = 0.043). CET was not correlated with age, cylinder or steep keratometry.

Conclusion

We present a comprehensive study in healthy, normal eyes using Cirrus HD-OCT to map the corneal epithelium with a 9 mm diameter. The epithelium was thinner centrally than peripherally and superiorly than inferiorly. Myopic eyes tend to have thinner corneal epithelium than hyperopic eyes. This may help in refractive procedures and in the prediction of corneal diseases.

Corneal thickness

epithelial thickness

nomogram

corneal tomography

The human corneal epithelium is the outermost layer of the cornea. It is a multilayered tissue consisting of five to seven layers of nonkeratinized stratified squamous epithelium. This configuration provides a smooth regular surface in normal corneas, providing not only a barrier to exogenous pathogens, chemicals and water, but ensures a smooth optical surface interfacing with the tear film, contributing to the refractive power of the optical system. In the normal corneal epithelium, limbal stem cells maintain regeneration of the tissue every 7–10 days (1).

The epithelium does not have a uniform refractive power, contributing an average of 1.03 D over the central 2-mm zone and 0.85 D at the 3.6-mm zone (2). Corneal epithelial thickness (ET) is not homogenously distributed and it tends to compensate for the irregular stromal surface in order to re-establish a regular and smooth ocular surface (3, 4, 5). These potential epithelial changes have been reported following refractive procedures, contact lenses wear and in numerous pathologies such as dry eye disease and keratoconus (KC) (6, 7, 8, 9). Reinstein and colleagues described the mechanism of epithelial thickness profile remodeling in response to underlying stromal irregularities. One such cause of epithelial remodeling is commonly seen in areas overlying a laser in situ keratomileusis (LASIK) ablation zone (6). Corneal epithelial hyperplasia has also been reported to be a potential cause of post-photorefractive keratectomy (PRK) regression (10). Previous studies have shown that the apex of early KC focal steepening is compensated by corneal epithelial thinning and the degree of potential epithelial remodeling is dependent on the severity of the keratoconus (9, 11, 12). Significant differences in central corneal thicknesses have been described between genders and various populations. The evaluation of corneal epithelium thickness in normal populations may provide references to define any abnormal thinning or thickening, or change of the distribution pattern in pathological eyes.

Numerous diagnostic modalities are available to quantify corneal thickness (CT) and ET such as very high-frequency (VHF) digital ultrasound, confocal microscopy, and anterior segment optical coherence tomography (AS-OCT) (13, 14). AS-OCT is a non-contact, high-resolution imaging technique that allows precise delineation of corneal surfaces (15).

In the current study, we used spectral domain AS-OCT to evaluate ET and CT and corresponding distributions across the 9-mm central cornea in healthy eyes of an adult Syrian population. To our knowledge, no previous studies have investigated the normative parameters for both ET and CT in the Syrian population.

This is a single center, prospective observational study that included healthy adults between 18 and 40 years of age. All participants were recruited from the out-patient clinics at the Eye Surgical Hospital (the largest ophthalmology hospital in Syria), Ministry of Health, Damascus, Syria. Inclusion criteria were absence of corneal pathology, previous ocular surgery or trauma, no history of contact lens wear in the past 3 months, corrected distance visual acuity (CDVA) of 20/20 or better, absence of family history of KC, and normal topography and tomographic parameters using Sirius (normal class soft wear indicator and Symmetry Index back (SIb) of < 0.12 D) (16). Study participants underwent comprehensive ocular assessment including: uncorrected distance visual acuity (UDVA), CDVA, auto-refracto-keratometry (SEIKO CO., GR-3500KA, Tokyo, Japan), slit-lamp examination to detect the presence or absence of clinical signs of KC (apical scar or thinning, Fleischer rings and Vogt’s striae), Goldmann applanation tonometry, and fundoscopy.

ET and CT were acquired with the anterior segment spectral-domain Cirrus 5000 HD-OCT (Carl Zeiss Meditec, Germany). In line with the method described previously (17), the cornea lens attachment was used for the pachymetry map and HD cornea scans. The subjects were positioned on the headrest looking to the fixation light and the image was centered on the pupil center. Two scans were obtained for each eye by a single examiner with 60-second rest periods to optimize the tear film rest, and average values were registered. ET and CT mapping was obtained at a certain time (from 10:00 to 14:00 and at least 2 hours after awakening) and by the same operator to avoid operator variability.

The pachymetry map scans include 8 radial scans (1024 axial scans each) repeated 5 times covering a 9 mm central corneal diameter area. The software algorithm measures ET as the distance between the middle of the first (tear film) and second (anterior surface of the Bowman layer) hyperreflective lines on the B-scan. CT was measured as the distance between the air-tear and cornea-aqueous interfaces. The pachymetry analysis tool provided automated cornea thickness measurement in seventeen sectors. Images were captured after the horizontal single scan line was placed on the corneal apex where the hyper-reflective corneal reflex was visible. Repeat scans were taken if the initial scan was decentered or had a poor corneal apex reflection.

Automated data export and processing with Cirrus HD-OCT review software (version 10.0) provided ET of four concentric ring-shaped zones centered on the center of the cornea: 0–2 mm central, 2–5 mm para central, 5–7 mm midperipheral and 7–9 mm peripheral (Fig. 1), and CT from three concentric zones: 0–2 mm central, 2–5 mm paracentral, and 5–7mm midperipheral (Fig. 2). ET and CT were also presented for specific octants of the cornea: superior (S), inferior (I), temporal (T), nasal (N), superior nasal (SN), superior temporal (ST), inferior temporal (IT) and inferior nasal (IN) within the paracentral, midperipheral and peripheral zones for ET map, and within the paracentral and midperipheral zones for CT map.

The study was approved by the research committee of Eye Surgical Hospital (approval number: HM-2401-2293) in accordance with the ethical standards stated in the 1964 Declaration of Helsinki, with the informed consent of all participants.

Statistical Analysis

Statistical analysis was performed using SPSS software (version, 17, SPSS Inc, Chicago, IL, USA). The data was checked for normality using the Kolmogorov-Smirnov test. Descriptive statistics including mean, range, and standard deviations were calculated. The analysis of variance (ANOVA) with post-hoc Bonferroni was used to compare more than two means. Student t tests were performed to determine whether there was a difference in CT and CET between females and males, and between right and left eye. Pearson correlation test was used to evaluate the correlation between CET and age, flat keratometry (K1), steep keratometry (K2), sphere, cylinder and CCT. A p-value of less than 0.05 was considered statistically significant.

A total of 116 adults participated in the study. One hundred and four subjects were included in the analyses, 50 (48.08%) females and 54 (51.92%) males. Reasons for exclusion were recent contact lenses wear (6 subjects), history of laser in situ keratomileusis (LASIK) surgery (2 subjects), and suspicion of KC (4 subjects); 3 as evidenced by a positive Sirius software indicator and 1 with negative software indicator but SIb of > 0.12 D.

The mean age was 27.30 ± 5.32 years (18–40 years) and there was no significant difference between female and male, 26.70 ± 6.07 years vs 27.85 ± 4.50 years, respectively (p = 0.27). One hundred-four right eyes (50%) and one hundred-four left eyes (50%) were selected after randomization. Of the 208 eyes, 73 (35.09%) eyes were emmetropic, 36 (17.30%) eyes were hypermetropic, and 99 (47.59%) eyes were myopic. Mean refraction was − 0.29 ± 1.63 dioptres (D) sphere (range: -6.5 to + 3.5 D), and − 0.74 ± 1.13 D (range: -5.5 to + 3.75 D) cylinder. Although the refraction was biased toward myopes, all eyes were considered normal as they were free of ocular pathology other than refractive error. Mean K1 and K2 were 42.55 ± 1.36 D and 43.69 ± 1.28 D, respectively.

Corneal Epithelial Thickness in the corneal center, central [0–2 mm], paracentral [2–5 mm], midperipheral [5–7 mm], and peripheral [7–9 mm] zones, in male and female and in right and left eyes is presented in Table 1. Mean ET in the centre (CET), central (0–2 mm), paracentral (2–5 mm), midperipheral (5–7 mm), and peripheral (7–9 mm) was 50.70 ± 3.56 µm (range: 43–67 µm), 50.42 ± 3.51 µm (range: 42–67 µm), 49.29 ± 3.61 µm (41–66 µm), 47.80 ± 3.54 µm (40–63 µm), and 46.74 ± 3.47 µm (39–62 µm), respectively, with no statistically significant differences between right and left eyes (P > 0.05, all). All ET values were significantly higher in males compared to females (P < 0.05, all), except minimum ET in the peripheral area did not show a significant difference (P = 0.464).

Table 1

Corneal Epithelial Thickness in the corneal center, central [0–2 mm], paracentral [2–5 mm], midperipheral [5–7 mm], and peripheral [7–9 mm] zones, in male and female and in right and left eyes.
	All Eyes (n = 208)	Female (n = 50)	Male (n = 54)	P value	Right eye (n = 104)	Left eye (n = 104)	P value
	Mean ± SD [range]	Mean ± SD	Mean ± SD	P value	Mean ± SD	Mean ± SD	P value
ET 0–2 mm (µm)
CET	50.70 ± 3.56 [43–67]	50 ± 3	52 ± 4	< 0.0001*	51 ± 4	51 ± 4	0.9473
Min a	48.59 ± 3.54 [39–60]	48 ± 3	49 ± 4	0.0012*	49 ± 3	49 ± 4	0.8281
ET a	50.42 ± 3.51 [42–67]	49 ± 3	51 ± 4	0.0001*	50 ± 4	50 ± 3	0.9975
Max a	51.99 ± 3.85 [45–73]	51 ± 3	53 ± 4	0.0001*	52 ± 4	52 ± 4	0.7537
ET 2–5 mm (µm)
Min b	45.14 ± 3.36 [37–53]	44 ± 3	46 ± 3	0.0001*	45 ± 3	45 ± 3	0.6456
ET b	49.29 ± 3.61 [41–66]	48 ± 3	50 ± 4	0.0001*	49 ± 4	49 ± 4	0.9437
Max b	52.82 ± 4.44 [45–73]	52 ± 4	54 ± 5	0.0001*	53 ± 4	53 ± 5	0.7166
ET 5–7 mm (µm)
Min c	41.48 ± 3.58 [32–51]	41 ± 3	42 ± 4	0.0014*	42 ± 4	41 ± 3	0.537
ET c	47.80 ± 3.54 [40–63]	47 ± 3	49 ± 4	0.0001*	48 ± 4	48 ± 4	0.6638
Max c	53.20 ± 5.04 [44–74]	52 ± 4	55 ± 6	0.003*	53 ± 5	54 ± 5	0.3774
ET 7–9 mm (µm)
Min d	36.54 ± 4.18 [25–47]	36 ± 4	37 ± 4	0.4641	37 ± 4	37 ± 4	0.9604
ET d	46.74 ± 3.47 [39–62]	46 ± 3	48 ± 3	0.0004*	47 ± 4	47 ± 3	0.5866
Max d	55.91 ± 7.32 [44–87]	55 ± 6	57 ± 8	0.038*	55 ± 7	56 ± 8	0.3104
ET: epithelial thickness, µm: micron, CET: central epithelial thickness, Min: minimum, a: 0–2 mm zone, Max: maximum, b: 2–5 mm zone, c: 5–7 mm zone, d: 7–9 mm zone, n: number, SD: standard deviation. Student's t-test was used to compare the difference between means of each two samples. *Reached statistical significance (P < 0.05) .

Mean CT values in the centre (CCT), central (0–2 mm), paracentral (2–5 mm), and midperipheral (5–7 mm) were 538.48 ± 34.02 µm (460–652 µm), 541.37 ± 34.12 µm (466–655 µm), 559.37 ± 34.15 µm (483–671 µm), and 593.91 ± 34.67 µm (515–697 µm), respectively. Although these values were higher in female than in male, the differences were not statistically significant (P > 0.05, all). When CT values were compared between right and left eyes, no statistically significant differences were noted ( P > 0.05, all) (Table 2).

Table 2

Corneal Thickness in the corneal center, 0–2 mm central Zone, 2–5 mm paracentral zone, and 5–7 mm midperipheral zone in male and female and in right and left eyes.
	All Eyes [n = 208]	Female [n = 50]	Male [n = 54]	P value	Right eye [n = 104]	Left eye [n = 104]	P value
	Mean ± SD [range]	Mean ± SD	Mean ± SD	P value	Mean ± SD	Mean ± SD	P value
CT 0–2 mm (µm)
CCT	538.48 ± 34.02 [460–652]	543 ± 37	536 ± 32	0.1843	540 ± 33	537 ± 35	0.4589
Min CT a	534.40 ± 34.16 [446–645]	538 ± 37	532 ± 32	0.2594	534 ± 33	534 ± 35	0.9713
CT a	541.37 ± 34.12 [466–655]	545 ± 37	540 ± 32	0.3059	542 ± 33	541 ± 35	0.7864
Max CT a	552.92 ± 34.34 [480–671]	556 ± 38	552 ± 32	0.5057	554 ± 34	552 ± 35	0.6055
CT 2–5 mm (µm)
Min CT b	534.75 ± 34.19 [449–644]	539 ± 37	533 ± 32	0.2706	535 ± 34	535 ± 35	0.9775
CT b	559.37 ± 34.15 [483–671]	563 ± 37	558 ± 32	0.3647	560 ± 34	559 ± 35	0.7882
Max CT b	600.92 ± 36.55 [515–718]	604 ± 39	600 ± 35	0.4919	602 ± 36	600 ± 38	0.6751
CT 5–7 mm (µm)
Min CT c	546.65 ± 39.28 [305–651]	550 ± 47	544 ± 34	0.402	545 ± 41	549 ± 37	0.9775
CT c	593.91 ± 34.67 [515–697]	598 ± 37	593 ± 32	0.3478	594 ± 34	593 ± 36	0.7882
Max CT c	651.13 ± 39.89 [497–761]	653 ± 40	652 ± 38	0.8292	651 ± 40	651 ± 40	0.6751
CT: corneal thickness, µm: micron, CCT: central corneal thickness, Min: minimum, a: 0–2 mm zone, Max: maximum, b: 2–5 mm zone, c: 5–7 mm zone, n: number, SD: standard deviation, Student's t-test was used to compare the difference between means of each two samples. *Reached statistical significance (P < 0.05).

The associations of ET between opposite octants are presented in Table 3. The superior epithelium was thinner than the inferior epithelium in the paracentral, midperipheral and peripheral arears (-2 ± 22 µm, -4 ± 3 µm and − 6 ± 5 µm, respectively), with statistically significant differences between the three zones (P < 0.05, all). The difference between T and N epithelium was − 1 ± 2 µm, -1 ± 2 µm, and − 2 ± 3 µm, respectively, with a statistically significant difference between paracentral and peripheral areas ( P = 0.004) only. The difference between ST and IN was − 1 ± 2 µm, -2 ± 3 µm, and − 4 ± 4 µm, respectively with statistically significant differences between the midperipheral and peripheral areas and between the paracentral and peripheral areas (P < 0.0001, both). The lowest ET difference − 0 ± 3 µm was registered between SN and IT octants at the paracentral zone, with statistically differences between the three zones (P < 0.05, all).

Table 3

The Differences of corneal epithelial thickness and corneal thickness between the opposite Octans.
	Paracentral(b)	Midperipheral(c)	Peripheral(d)	P value
	Mean ± SD	Mean ± SD	Mean ± SD	a-b	b-c	a-c
ET
S-I	-2 ± 22	-4 ± 3	-6 ± 5	< 0.0001*	< 0.0001*	< 0.0001*
T-N	-1 ± 2	-1 ± 2	-2 ± 3	1	0.059	0.004*
ST-IN	-1 ± 2	-2 ± 3	-4 ± 4	0.199	< 0.0001*	< 0.0001*
SN-IT	-0 ± 3	-1 ± 3	-3 ± 4	0.006*	< 0.0001*	< 0.0001*
CT
S-I	18 ± 14	27 ± 26		0.0002*
T-N	-15 ± 20	-25 ± 34		< 0.0001*
ST-IN	1 ± 13	1 ± 22		0.157
SN-IT	24 ± 19	37 ± 33		< 0.0001*
ET: epithelial thickness, S: superior, I: inferior, T: temporal, N: nasal, ST: superior temporal, IN: inferior nasal, SN: superior nasal, IT: inferior temporal, ET: epithelial thickness,, b: 2–5 mm zone, c: 5–7 mm zone, n: number, SD: standard deviation, *Reached statistical significance (P < 0.05)

Epithelial thickness distribution is presented in Fig. 3. ET decreases from the centre to the periphery. ET values in the ST, S, and SN octants in the paracentral, midperipheral and peripheral areas were thinner than those in their corresponding radially opposite octants(IT, I, and IT, respectively). Furthermore, ET in the temporal octants in the three concentric areas was thinner than ET in the nasal octants.

Corneal thickness distribution is presented in Fig. 4. CT increases from the centre to the periphery. The highest value was seen at the superior octants of the midperipheral zone (614.68 ± 38.91µm), while the lowest value was seen in the central zone (538.48 ± 34.02 µm).

Spearman correlation between CET and age, flat keratometry, steep keratometry, sphere, cylinder and CCT is presented in Table 4. No statistically significant correlation, as tested by Pearson correlation test, between central epithelial thickness and age (p = 0.87, r = 0.015) was noted, nor between central epithelial thickness and astigmatism (p = 0.52, r = 0.053), nor between corneal epithelial thickness and steep keratometry (p = 0.20, r = -0.094). Furthermore, no statistically significant correlation between CET and CCT (p = 0.11, r = 0.11) was seen. A statistically significant trend for the CET to become thicker with increasing sphere (p = 0.002, r = 0.250), and thicker with decreasing flat keratometry (p = 0.043, r = -0.149) was seen.

Table 4

Spearman correlation between CET and age, flat keratometry, steep keratometry, sphere, cylinder and CCT.
		CET	CCT
Age	r	0.0156	0.1254
	P value	0.8791	0.2186
Sphere	r	0.2502	0.0488
	P value	0.0022*	0.5586
Cylinder	r	0.0537	0.0197
	P value	0.5225	0.8157
Flat K	r	-0.1489	-0.1819
	P value	0.0436*	0.0135*
Steep K	r	-0.0942	-0.1777
	P value	0.2046	0.0161*
CCT	r		0.11
	P value		0.11
CET: central epithelial thickness, CCT: central corneal thickness,
K: keratometry, r: correlation coefficient, *Reached statistical significance (P < 0.05).

There were no correlations between CCT and age (p = 0.21, r = 0.125), nor between CCT and sphere (p = 0.55, r = 0.048), nor between CCT and astigmatism (p = 0.18, r = 0.019). Statistically significant negative correlations between CCT and flat keratometry (p = 0.013, r = -0.181), and between CCT and steep keratometry (p = 0.01, r = -0.177), were noted (Table 4).

In our study, we investigated the corneal epithelial thickness profile over a 9-mm diameter zone in a population with normal eyes. To the best of our knowledge, no study has yet reported the corneal epithelial thickness in the Syrian population.

In previous studies, central corneal epithelial thickness values for normal eyes were between 48.0 ± 5 and 59.9 ± 5.9 µm in adults (18, 19, 20, 21, 22). The differences between central epithelial thickness values reported in different studies may be partially affected by the differences in the image acquisition modalities used to quantify the epithelial thickness, such as anterior segment optical coherence tomography, confocal microscopy and very high frequency (VHF) digital ultrasound. The advantage of contact measurement devices is that they exclude the variable thickness of the tear film, which is reported to be between 3 and 5 µm in thickness (23). On the other hand, AS-OCT is a fast, non-invasive technique, mitigating any risk of corneal abrasions or infection transfer between subjects (24). We found an average central epithelial thickness of 50.70 ± 3.56 µm, which agrees with a study conducted in Egypt, where the author reported CET of 49.57 ± 2.11 µm using the same instrument (Zeiss, Cirrus 5000-OST) (25). In contrast, our study showed lower CET values to those reported in Jordan, an ethnically similar population, by Mohammad Abusamak reporting CET values of 53.7 ± 4.0 µm using Optovue Avanti spectral-domain OCT (5).

Consistent with previous data (3, 4, 5, 13, 14, 17, 25, 26), our findings demonstrated that the corneal epithelium was nonuniform. The superior epithelium was thinner than the inferior one. This difference was higher in the peripheral area (-6 ± 5 µm) than the paracentral and midperipheral areas (-4 ± 3 µm, both). Reinstein et al. justified this phenomenon by the mechanical chaffing and abrasion caused by the accelerated movement of the upper tarsus with larger force being applied on the superior epithelium (26). In keeping with previous studies (17, 25, 26, 27), we found that the nasal epithelium was thicker than the temporal epithelium, with the highest difference reported in the peripheral area (2 ± 3 µm). It has been postulated that the nasal cornea is more protected from tarsus rubbing than the nasal cornea due to the outer canthus laying higher than the inner canthus (26).

Mean epithelial thickness was significantly higher in male than female in all three zones (central, paracentral, and peripheral, p < 0.05, all). This is consistent with previous studies (4, 5, 17, 28). It has been postulated that males have thicker CET than females because the total corneal thickness was reported to be thicker in males than in females (29, 30). Our results demonstrated that ET was significantly higher in males. Interestingly, central corneal thickness was higher in female than in males, but this was not statistically significant (p = 0.184).

Colakoglu and Cosar found that the mean CET for right eyes, although not statistically significant, was higher than the thickness for the left eyes (31). Wu and Wang reported a statistically insignificant thinner epithelial thickness of right eyes compared to left eyes in myopic subjects (4). In the current study, the mean CET for the right eye was the same thickness for the left eye.

With regards to age, Wu and Wang reported a negative correlation between corneal epithelial thickness and age (4). Conversely, Abusamak found a positive and significant correlation between age and CET (5). In this study, we did not observe a significant association between the CET and age (p = 0.87).

Reinstein and colleagues found a non-significant correlation between vertex CET and refraction in 56 subjects (26). However, the sample size was too small to conclusively establish any possible correlations. In our study which included 208 normal eyes, we found that the ET was positively correlated with sphere.

In their study, Ma et al. found that thicker para-central and peripheral ETs were positively associated with a larger corneal curvature radius (28). This finding, to some extent, is consistent with ours. We found that decreasing flat keratometry (increasing corneal curvature radius) was significantly associated with increasing central epithelial thickness.

In agreement with previously reported studies (4, 17, 28), the distribution of corneal epithelial thickness was different from that of corneal thickness. While the ET decreased from the centre towards the periphery, the corneal thickness increased gradually from the centre to the periphery. However, no significant correlation between CET and CCT was observed (p = 0.11).

The evaluation of epithelial thickness profiles may help in many areas of ophthalmology. The aspheric profile, used in trans-epithelial photorefractive keratectomy (Trans-PRK), is calculated according to data from the literature, estimating that the normal corneal epithelial thickness is 55 µm centrally and 65 peripherally at 4 mm radially from the centre (32). Since standardised epithelial ablation algorithms are used for all eyes in tPRK, regardless of the actual epithelial thickness, more stroma tissue may be ablated than intended in eyes with a thin corneal epithelium leading to overcorrection. In addition, in eyes with thick epithelium the refractive part of the ablation may include some of the deep epithelial cell layer leading to under correction (33). This is of immense significance, and our data demonstrated that these standardised thickness algorithms do not apply to our population. The central ET and peripheral ET values were different from those used in standardised epithelial ablation algorithms. We found that the average ET was highest (50.42 ± 3.51 µm) in the 0–2 mm central zone and lowest (46.74 ± 3.47 µm) in the 7–9 mm peripheral zone. Accurate measurement of corneal epithelial thickness of the centre and the more peripheral zones may help refractive surgeons to maintain accurate refractive results and avoid refractive surprise.

ET measurement and distribution analysis has proven to be a useful tool in the diagnosis of early corneal ectatic diseases in adults. Due to the epithelium’s ability to compensate for changes in stromal structure by thinning over the cone, resulting in a seemingly normal front surface topography (34). Moreover, keratoconic protrusion most frequently occurs in the inferotemporal cornea and the CET in keratoconic eyes were consequently reported to be thinner inferotemporally and thicker supranasally compared with normal eyes, where the reverse is true (35). Within the region of the cone, the epithelial doughnut pattern consists of a localized zone of thinning surrounded by an annulus of thickened epithelium (Fig. 5).

The study has several limitations. The relatively small sample size, and the limited age range of the participants, may limit the extent of extrapolating the results to a wider population. In addition, OCT, CT and ET acquisition in our study included the thickness of the precorneal tear film. Tear film thickness values are comprised between 3–5 µm. CET measurements including the tear film thickness may influence the possible correlated factors of CET (36).

In conclusion, the present study provided corneal epithelial and total corneal thickness distribution in healthy adults aged 18 to 40 years by Cirrus HD-OCT. The average central epithelial thickness was 50.70 ± 3.56 µm, with higher value in males than in females. This is the first study in Syria to present the characteristics of corneal epithelial thickness in normal subjects. This will be a valuable addition to the literature, and highlights differences to nomograms, in a non-Caucasian population. It provides a useful guide for corneal refractive surgeons to develop a customized corneal epithelial thickness-based diagnostic or therapeutic algorithms in non-Caucasian populations. We recommend use of evidence-based customised ablation profiles, according to patient characteristics, to optimise refractive outcomes and mitigate the risk of refractive surprise, particularly in Trans-PRK treatments.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the research ethics committee of Eye Surgical Hospital in accordance with tents of the Declaration of Helsinki. Informed consent to participate in this study was obtained from all participants.

Consent of publication

Not applicable.

Availability of data and materials

The datasets generated and analysed during the current study are not publicly available due their containing information that could compromise the privacy of research participants but are available from the corresponding author (AS) on reasonable request.

Competing interests

The authors declare that they have no conflicting interests.

Funding

None.

Author’s contributions

AS: Conceptualization, Methodology, Formal analysis, Project administration. A.S and O.K: Writing and editing. R.O and B.K: Interpretation of data and Revision. M.G, R.S, and T.D: Analysis and revision. Z.B, F,D. H.I, and T.H: acquisition, prepared tables and figures. All authors have read and agreed to the published version of the manuscript.

Acknowledgement

We would like to express our heartfelt gratitude to Minister of Health Dr. Hassan Al-Ghabash for his unwavering support throughout the research process. His insights, and encouragement were invaluable in helping us to complete this work.

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No competing interests reported.

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Corneal Epithelium Thickness Profile in Normal Adults

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