|Year : 2022 | Volume
| Issue : 3 | Page : 141-148
Corneal epithelial profile in psoriasis patients with and without dry eye disease
Doaa A Tolba1, Sara M Esmat1, Aya M AlOrbani2, Rana H Amin1
1 Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt
2 Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt
|Date of Submission||24-Jan-2022|
|Date of Decision||16-Feb-2022|
|Date of Acceptance||30-Apr-2022|
|Date of Web Publication||30-Jul-2022|
Sara M Esmat
1183 4th District, 6th of October City, Giza 12573
Source of Support: None, Conflict of Interest: None
Background Psoriasis is an immune-mediated systemic inflammatory disease in which corneal affection takes various forms such as dry eye disease (DED), punctate epithelial keratitis, and sterile corneal infiltrates.
Purpose The aim of this study was to evaluate the corneal epithelial profile of psoriasis patients using anterior segment optical coherence tomography (AS-OCT).
Patients and methods This is a cross-sectional analytic study that included 81 eyes: 39 eyes of 20 psoriasis patients and 42 eyes of 21 healthy age-matched and sex-matched controls. They were divided into three groups: psoriasis patients with dry eye disease (PDED), psoriasis patients without DED (PS), and healthy subjects (HS). AS-OCT was done to study the epithelial profile data of each eye and to correlate any finding with the disease activity evaluated by the Psoriasis Area and Severity Index score and disease extent.
Results The PDED patients showed significantly lower central corneal thickness (CCT), higher central epithelial thickness (CET), and thicker inferior epithelium (P=0.004, 0.002, and 0.005, respectively). A significantly thinner superior epithelium was detected in the PS group compared with the PDED and HS groups (P=0.001 and 0.010, respectively). In addition, the topographic thickness variability (SD) and minimim–maximum were significantly higher in both the PDED and PS groups compared with the HS group (P<0.001). The CCT showed a significantly positive correlation with the tear breakup time (r=0.373, P=0.020), while the CET showed a significantly negative correlation with it (r=−0.331, P=0.040). The CET also had a significant positive correlation with disease duration (r=0.390, P=0.014) and disease extent (r=0.323, P=0.045).
Conclusion AS-OCT has proved to be a valuable method for screening and detecting the corneal whole thickness and epithelial thickness abnormalities in psoriasis patients in the presence or absence of DED. The presence of thicker epithelium and thinner CCT were significant findings in the PDED, while in psoriasis patients without DED, superior epithelial thinning was the significant finding. A statistically significant high topographic thickness variability was detected in both groups compared with the controls.
Keywords: dry eye disease, epithelial thickness, psoriasis, tear breakup time
|How to cite this article:|
Tolba DA, Esmat SM, AlOrbani AM, Amin RH. Corneal epithelial profile in psoriasis patients with and without dry eye disease. Delta J Ophthalmol 2022;23:141-8
|How to cite this URL:|
Tolba DA, Esmat SM, AlOrbani AM, Amin RH. Corneal epithelial profile in psoriasis patients with and without dry eye disease. Delta J Ophthalmol [serial online] 2022 [cited 2022 Dec 3];23:141-8. Available from: http://www.djo.eg.net/text.asp?2022/23/3/141/353040
| Introduction|| |
Psoriasis is an immune-mediated systemic inflammatory disease with a strong genetic predisposition. The pathogenesis of psoriasis involves an initiation phase possibly triggered by infection, trauma, or drugs, and a maintenance phase characterized by chronic inflammation . T-helper (Th) 1 cell and Th17 cells’ overactivation was demonstrated to play a key role through keratinocyte proliferation and production of tumor necrosis factor-α .
Psoriasis approximately affects 2–3% of the people worldwide . The reported prevalence of psoriasis in Egypt ranges from 0.19 to 3% . It can present at any age, however, there is a bimodal peak at the age between 20–30 and 50–60 years . Psoriatic arthritis occurs in ∼30% of psoriatic patients , while ocular involvement occurs in about 10% of the patients; yet it is almost always preceded by skin involvement . Ocular involvement in psoriasis takes various forms. However, ocular-surface disease is by far the most common manifestation . Blepharitis, loss of cilia, psoriatic plaques around the eyelids, chronic nonspecific conjunctivitis, and uveitis were reported in psoriasis patients .
Many studies reported dry eye disease (DED) as a common manifestation in psoriasis patients as evidenced by poor tear-function tests in the form of short tear breakup time (TBUT) and low Schirmer’s test results with evidence of Meibomian gland More Details dysfunction . The cornea can be affected in various ways such as punctate epithelial keratitis, sterile corneal infiltrates, and corneal melting . Not only were epithelial changes reported in psoriasis patients but also changes in the corneal biochemical properties were reported in the form of decreased corneal hysteresis and corneal resistance factor ,. The presence of a relationship between keratoconus and psoriasis was investigated by Akcam et al.  who detected tomographic changes in the form of central thinning and posterior steepening in some patients.
The corneal epithelium is a field of interest in many studies. Anterior segment optical coherence tomography (AS-OCT) is a noncontact, noninvasive imaging technique that allows for assessment of the ocular surface and measurement of whole corneal and epithelial thickness . Several studies showed that the corneal epithelium can alter its thickness profile as a compensatory mechanism to reestablish a smooth optical surface , such as the donut pattern suggestive of keratoconus and the increased epithelial thickness in dry eye patients that may precede the abnormalities in traditional dry eye tests such as TBUT and Schirmer’s test .
The aim of this study was to evaluate the corneal epithelial profile of psoriasis patients using AS-OCT.
| Patients and methods|| |
This is a cross-sectional case–control study of psoriasis patients, which was approved by the Scientific Committee of the Ophthalmology Department (5/7/2020-1), Cairo University, Cairo, Egypt. All participants signed a written informed consent to participate in the study and for publication of data before enrollment in the study. The study included 81 eyes: 39 eyes of 20 psoriasis patients and 42 eyes of 21 healthy age-matched and sex-matched controls. One eye was excluded from the psoriasis patients due to corneal opacity after trauma since childhood. The patients included in the study were divided into three groups: psoriasis patients with dry eye disease (PDED), psoriasis patients without dry eye (PS), and healthy subjects (HS). The psoriasis patients were recruited from Kasr Alainy Psoriasis Unit, Cairo University, Cairo, Egypt.
All psoriasis patients were subjected to full history taking and a complete dermatological examination. The rule of nine was applied to detect the extent of the disease , as well as disease severity using the Psoriasis Area and Severity Index (PASI) score .
All candidates were subjected to a complete ophthalmological examination, including full history taking, refraction, best-corrected visual acuity measurement, slit-lamp examination, fundus examination, and intraocular pressure measurement by Goldmann applanation tonometry (Haag-Streit AT 900, Switzerland).
The diagnosis of DED was based on self-reporting of ocular discomfort and an abnormal result of TBUT.
The controls were taken as patients without DED by any of the previously mentioned methods.
Patients with corneal opacities, recurrent epithelial erosions, corneal dystrophies, glaucoma, ocular hypertension, history of use of systemic steroids or contact lenses, previous surgery, or trauma were excluded from the study.
Anterior segment optical coherence tomography
AS-OCT scans were performed using the Optovue RTVue model (RT100; Optovue Inc., Fremont, California, USA), which is a Fourier-domain OCT that can capture 26 000 axial scans per second using a wavelength of 830 nm, a depth resolution of 5 μm, and a frame rate from 256 to 1024 A-scans per second.
After ensuring accurate fixation and centration of the patient’s eye, each eye was scanned three times during a single visit with an acquisition time of a few seconds per scan. The corneal thickness and corneal epithelial thickness profile were recorded over a 6-mm-diameter corneal area, which was further divided into three zones: central zone, 2 mm; inner ring, 2–5 mm (mid-zone); and outer ring, 5–6 mm (peripheral zone). The inner and outer rings were further subdivided into eight sectors, making the thinnest epithelial location for each eye easy to be detected. Indicators (*) and (+) were used to refer to the thinnest and thickest epithelial locations, respectively.
The epithelial profile data for each eye included the central epithelial thickness (CET), average superior, inferior epithelial thickness, minimum and maximum epithelial thickness locations, and topographic-thickness variability as reported by the SD of all reported sectors.
The outcome parameter(s) included:
- Detection of any structural abnormalities in the ocular surface and cornea of psoriasis patients by AS-OCT.
- Detection of any changes or abnormal patterns in the whole corneal thickness and epithelial thickness profiles of psoriasis patients.
- Correlation between any AS-OCT changes and TBUT, psoriasis-disease activity score, extent, and duration.
The data were coded and entered using the Statistical Package for Social Sciences (SPSS), version 26 (IBM Corp., Armonk, New York, USA). Data were summarized using median and interquartile range (IQR) in quantitative data and using frequency (count) and relative frequency (percentage) for categorical data. Comparisons between quantitative variables were done using the nonparametric Kruskal–Wallis and Mann–Whitney tests . For comparing categorical data, χ2 test was performed. Exact test was used instead when the expected frequency was less than 5 . Correlations between quantitative variables were done using Spearman correlation coefficient . P values less than 0.05 were considered statistically significant.
| Results|| |
The study included 39 eyes of 20 psoriasis patients: 15 eyes of eight patients with psoriasis only (PS) and 24 eyes of 12 patients with PDED, and 42 eyes of 21 HS. All groups were age-matched and sex-matched. There were no statistically significant differences in intraocular pressure or refraction between patients and controls. All participants had normal fundus examination. The median duration of the disease was 5.5 years with an IQR of 2.5–12 years in the PS group and 10 years (IQR=7–15 years) in the PDED group. The median PASI score was 10.5 (IQR=5.45–17.10) in the PS group and 10.2 (IQR=9–28.5) in the PDED group, while the median disease extent was in 12.5 (IQR=22.5–55) in the PS group and 50 (IQR=30–75) in the PDED group. There were no statistically significant differences in PASI score, disease extent, or disease duration between the PS and the PDED groups ([Table 1]).
The median central corneal thickness (CCT) was 499 μm (IQR=480–531 μm) in the PDED group, 525.5 μm (IQR=513.5–563 μm) in the PS group, and 540 μm (IQR=522–554 μm) in the HS group with statistically significantly lower CCT in the PDED group than in the controls (P=0.004, [Table 2] and [Figure 1][Figure 2][Figure 3]).
|Figure 1 Total corneal (left) and epithelial (right) three-dimensional pachymetry maps in a healthy control.|
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|Figure 2 Total corneal (left) and epithelial (right) three-dimensional pachymetry maps in a psoriasis patient with dry eye disease.|
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|Figure 3 Total corneal (left) and epithelial (right) three-dimensional pachymetry maps in a psoriasis patient without dry eye disease.|
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The median CET was 56 μm (IQR=54–58 μm) in PDED group, 54 μm (IQR=53–55 μm) in the PS group, and 54 μm (IQR=52–55 μm) in the HS group, with statistically significantly higher CET in the PDED group than in the controls (P=0.002, [Table 2] and [Figure 1][Figure 2][Figure 3]).
The median superior epithelium thickness was 54 μm (IQR=50–56 μm) in the PDED group, 49 μm (IQR=47–51.5 μm) in the PS group, and 52 μm (IQR=51–54 μm) in the HS group, with statistically significantly thinner superior epithelium in the PS group than the PDED and the HS groups (P=0.001 and 0.010, respectively, [Table 2]).
The median inferior epithelium thickness was 57 μm (IQR=55–57 μm) in the PDED group, 54 μm (IQR=52–56 μm) in the PS group, and 54 μm (IQR=52–55 μm) in the HS group, with significantly thicker inferior epithelium in the PDED group than in the controls (P=0.005, [Table 2]). In addition, the topographic-thickness variability (SD) and minimum–maximum were significantly higher in both PDED and PS groups than in the HS groups (P<0.001, [Table 2]).
We investigated the relationship between AS-OCT parameters and TBUT, PASI score, and disease extent and duration. The CCT showed a significantly positive correlation with TBUT (r=0.373, P=0.020), while the CET showed a significantly negative correlation with it (r=−0.331, P=0.040, [Figure 4]). The CET also showed a significantly positive correlation with the disease duration (r=0.390, P=0.014) and disease extent (r=0.323, P=0.045, [Figure 5]). The topographic-thickness variability (SD) had significantly positive correlation with PASI score (r=0.465, P=0.003) and disease extent (r=0.515, P=0.001).
|Figure 4 Correlation between tear breakup time (TBUT) and central epithelial thickness (CET) (left) and central corneal thickness (CCT) (right).|
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|Figure 5 Correlation between central epithelial thickness (CET) and disease extent (left) and disease duration (right).|
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Color-coded map analysis
The thin crescent of superior thinning in PS patients appearing blue on the epithelial thickness color-coded map resulted in a particular pattern of diffuse, round green area similar to normal, yet it was slightly decentered inferiorly ([Figure 3]). The PDED seemed to have diffuse green maps similar to HSs in addition to irregular foci of thickened epithelium over the central and superior cornea ([Figure 2]).
| Discussion|| |
Psoriasis is an immune-mediated inflammatory disease characterized by an abnormal cellular immune reaction with hyperplasia of epidermal keratinocytes and infiltration of inflammatory cells . Ocular-surface disease occurs in some of the patients in the form of blepharitis, dryness, punctate keratitis, and even peripheral ulcerative keratitis ,,. Because of this, several studies focused on studying the cornea and conjunctiva clinically and microscopically in psoriasis patients in an attempt to understand the mechanism behind the structural changes seen in affected individuals ,. To date, the corneal epithelial maps in psoriasis patients have never been studied in depth for any abnormalities or particular pattern when compared with healthy individuals.
When compared with controls, the PDED patients, in the current study, were found to have significantly thinner corneas. Thinning of the central cornea, mainly the corneal stroma, can be explained by the release of inflammatory cytokines and metalloproteinases with tear-film evaporation that induced apoptosis of stromal keratocytes. This is in agreement with the findings reported by Liu and Pflugfelder . On the other hand, the PS patients’ CCT did not differ significantly from HSs, and this was similar to what was reported by Celik et al.  in their study of corneal biomechanics of psoriasis patients. Even though, they did report lower corneal hysteresis and corneal-resistance factors among psoriasis patients with a possible link to keratoconus susceptibility. Therefore, it seems that the presence of dry eye in psoriasis patients denotes a more severe disease and poses an additional risk in affecting the corneal thickness in such patients. This was further supported by the significant positive correlation we found between the CCT and TBUT. Candidates with shorter TBUT, and hence more severe DED, tended to have thinner corneas.
Regarding the CET, the significantly higher value in the PDED group, reported in the present study, agrees with what was previously reported by Kanellopoulos and Asimellis , who have found increased epithelial thickness in cases with positive dry eye tests such as TBUT and Schirmer’s tests. The tear-film dysfunction, osmotic stress, and inflammatory cytokines in DED are believed to be responsible for accelerated turnover of the apical epithelium that happens to make up for the increased loss of dead and detaching epithelial cells . In addition, impression cytology of the cornea and conjunctiva revealed epithelial dysfunction and mild surface squamous metaplasia in psoriasis patients ,. Whether or not the hyperplastic changes that happen in the epidermis of dermatologic psoriatic plaques also take place in the corneal epithelium is yet to be determined. However, there are opposite reports where dry eyes tend to have thinner epithelium due to the loss of limbal stem cells and less cellular regeneration . However, the study of Cui et al.  showed no significant difference between the CET of DED patients and healthy controls. They concluded that this might be due to longer distance of the central cornea from the limbus and that the peripheral cornea is more susceptible to damage from inflammatory cells in limbal and conjunctival blood vessels.
We were puzzled by the consistent blue crescent of superior thinning in the CET seen in the scans of PS patients, resulting in a green round pattern slightly decentered inferiorly. In normal eyes, the superior corneal epithelium was found to be naturally thinner than the inferior epithelium possibly due to the mechanical ‹trauma’ or ‹friction’ induced by blinking . Yet, we cannot explain the exaggeration of this finding in the PS group. One can assume that it may alert an early sign of peripheral ulcerative keratitis. Although it is not common to have ulcerative keratitis with psoriasis, yet it has been reported before ,, a hypothesis that needs to be proven on a larger sample of patients. The dry eye patients, in an attempt to lubricate their corneas and to overcome the sensation of irritation, discomfort, and foreign body sensation, tend to have more frequent and more forcible eye blinking , inducing more damage to the superior corneal epithelium, as reported by Cui et al.  study. According to this theory, we were expected to find superior thinning in the corneal epithelium of the PDED group. On the contrary, the PDED patients had thicker epithelial thickness throughout the cornea, including the superior quadrants, possibly due to the effect of desiccation. Another possible cause would be the small number of PDED patients enrolled in the current study.
During the past decade, corneal epithelial topographic asymmetry has been reported and was used as a sensitive tool for diagnosis of early and advancing keratoconus . The results of the current study showed a statistically significant difference between psoriasis and healthy controls. This parameter may support the presence of a possible link between psoriasis and keratoconus, and perhaps should be taken into consideration prior to refractive surgery in such patients. A large study evaluating the topographic-thickness variability, corneal topography, and corneal biomechanics together is needed for stronger evidence.
| Conclusion|| |
The ophthalmological examination in psoriasis patients must include dry eye tests due to the additional corneal structural changes that are present secondary to DED. AS-OCT has proved to be a valuable method for screening and detecting epithelial and corneal thickness abnormalities in psoriasis patients that may warrant the need for special treatment related to DED. The presence of thicker epithelium, thinner CCT, and high topographic-thickness variability may point toward a more severe disease. Further work enrolling a larger number of psoriasis patients (categorized into groups according to the presence of dry eye and disease severity and duration) with longer periods of follow-up is needed to elucidate the long-term corneal structural changes in psoriasis patients.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Rendon A, Schäkel K. Psoriasis pathogenesis and treatment. Int J Mol Sci 2019; 20:1475.
Ogawa E, Sato Y, Minagawa A, Okuyama R. Pathogenesis of psoriasis and development of treatment. J Dermatol 2018; 45:264–272.
Abdel-Hafez K, Abdel-Aty MA, Hofny ERM. Prevalence of skin diseases in rural areas of Assiut Governorate, Upper Egypt. Int J Dermatol 2003; 42:887–892.
Bandoli G, Johnson DL, Jones KL, Lopez Jiminez J, Salas E, Mirrasoul N. Potentially modifiable risk factors for adverse pregnancy outcomes in women with psoriasis. Br J Dermatol 2010; 163:334–339.
Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med 2017; 376:957–970.
Constantin MM, Ciurduc MD, Bucur S, Olteanu R, Ionescu RA, Constantin T, Furtunescu F. Psoriasis beyond the skin: ophthalmological changes. Exp Therap Med 2021; 22:1–4.
Queiro R, Torre JC, Belzunegui J, González C, De Dios JR, Unanue F, Figueroa M. Clinical features and predictive factors in psoriatic arthritis-related uveitis. Semin Arthritis Rheum 2002; 31:264–270.
Her Y, Lim JW, Han SH. Dry eye and tear film functions in patients with psoriasis. Jpn J Ophthalmol 2013; 57:341–346.
Au S-C, Yaniv S, Gottlieb AB. Psoriatic eye manifestations. Psoriasis Forum 2011; 17:169–179.
Celik U, Aykut V, Celik B, Tas M, Yazgan S, Kaldrm H, Erdur SK. A comparison of corneal biomechanical properties in patients with psoriasis and healthy subjects. Eye Contact Lens 2015; 41:127–129.
Edris NA, Arfeen SA, Mosaad R, Nassar GA. Evaluation of corneal biomechanical parameters in psoriasis patients: a controlled study. Clin Ophthalmol 2020; 14:1833–1837.
Akcam HT, Karagun E, Iritas I, Eyup Y. Keratoconus could be associated with psoriasis: novel findings from a comparative study. Cornea 2019; 38:1524–1530.
Venkateswaran N, Galor A, Wang J, Karp CL. Optical coherence tomography for ocular surface and corneal diseases: a review. Eye Vis 2018; 5:1–11.
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.
Kanellopoulos AJ, Asimellis G. In vivo 3-dimensional corneal epithelial thickness mapping as an indicator of dry eye: preliminary clinical assessment. Am J Ophthalmol 2014; 157:63–68.
Ramsay B, Lawrence CM. Measurement of involved surface area in patients with psoriasis. Br J Dermatol 1991; 124:565–570.
Wittkowski KM, Leonardi C, Gottlieb A, Menter A, Krueger GG, Tebbey PW et al.
Clinical symptoms of skin, nails, and joints manifest independently in patients with concomitant psoriasis and psoriatic arthritis. PLoS ONE 2011; 6:e20279.
Chan YH. Biostatistics 102: quantitative data – parametric & non-parametric tests. Singapore Med J 2003; 44:391–396.
Chan YH. Biostatistics 103: qualitative data – tests of independence. Singapore Med J 2003; 44:498–503.
Chan YH. Biostatistics 104: correlational analysis. Singapore Med J 2003; 44:614–619.
Paroli MP, Pinca M, Speranza S, Marino M, Pivetti-Pezzi P. Paracentral corneal melting in a patient with Vogt-Koyanagi-Harada’s syndrome, psoriasis, and Hashimoto’s thyroiditis. Ocul Immunol Inflamm 2003; 11:309–313.
Restrepo JP, Medina LF, Molina Mdel P. Peripheral corneal melting syndrome in psoriatic arthritis treated with adalimumab. Rev Bras Reumatol 2015; 55:387–389.
Aragona E, Rania L, Postorino EI, Interdonato A, Giuffrida R, Cannavò SP et al.
Tear film and ocular surface assessment in psoriasis. Br J Ophthalmol 2018; 102:302–308.
Liu Z, Pflugfelder SC. Corneal thickness is reduced in dry eye. Cornea 1999; 18:403–407.
Shousha MA, Karp CL, Perez VL, Hoffmann R, Ventura R, Chang V et al.
Diagnosis and management of conjunctival and corneal intraepithelial neoplasia using ultra high-resolution optical coherence tomography. Ophthalmology 2011; 118:1531–1537.
Pflugfelder SC. Tear dysfunction and the cornea: LXVIII Edward Jackson Memorial Lecture. Am J Ophthalmol 2011; 152:900–909.
Karabulut AA, Yalvac IS, Vahaboglu H, Nurozler AB, Duman S. Conjunctival impression cytology and tear-film changes in patients with psoriasis. Cornea 1999; 18:544–548.
Erdelyi B, Kraak R, Zhivov A, Guthoff R, Nemeth J. In vivo confocal laser scanning microscopy of the cornea in dry eye. Graefes Arch Clin Exp Ophthalmol 2007; 245:39–44.
Cui X, Hong J, Wang F, Deng S, Yang Y, Zhu X, Xu J. Assessment of corneal epithelial thickness in dry eye patients. Optom Vis Sci 2014; 91:1446–1454.
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.
Evinger C, Bao JB, Powers AS, Kassem IS, Schicatano EJ, Henriquez VM, Peshori KR. Dry eye, blinking, and blepharospasm. Mov Disord 2002; 17 (Suppl 2):S75–S78.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]