Corneal biomechanics in connective tissue disorders

Divya Kesarwani; Vaibhav Kumar Jain; Rachna Agarwal; Jaya Kaushik; Kumudini Sharma

doi:10.4103/jcor.jcor_74_20

ORIGINAL ARTICLE

Year : 2021 | Volume : 9 | Issue : 2 | Page : 64-66

Corneal biomechanics in connective tissue disorders

Divya Kesarwani¹, Vaibhav Kumar Jain¹, Rachna Agarwal¹, Jaya Kaushik², Kumudini Sharma¹
¹ Department of Ophthalmology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
² Department of Ophthalmology, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission	04-Jun-2020
Date of Decision	07-Dec-2020
Date of Acceptance	25-May-2021
Date of Web Publication	31-Jul-2021

Correspondence Address:
Vaibhav Kumar Jain
Department of Ophthalmology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

Check

DOI: 10.4103/jcor.jcor_74_20

Abstract

Purpose: The purpose of this study is to determine the corneal biomechanical properties in patients with connective tissue disorders (CTDs) and compare them with age-matched healthy control. Materials and Methods: In this cross-sectional study, 62 patients (study group) with CTDs and 44 healthy patients (control) were analyzed by Ocular Response Analyzer (Reichert Inc., Depew, N. Y., USA) and Corneal Pachymetry (SP-2000, Tomey, Nagoya, Japan). The right eye of all patients was assessed for corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPc), and Goldmann-correlated intraocular pressure (IOPg), and central corneal thickness (CCT). Results: Mean CH (9.54 ± 1.66 mm Hg [study group] and 10.62 ± 1.21 mm Hg [control]; P = 0.013) and mean CRF (9.95 ± 1.47 mm Hg [study group] and 10.76 ± 1.25 mm Hg [control]; P = 0.040) were significantly different between groups. Mean IOPc, IOPg, and CCT were not significantly different between groups. In the subgroup analysis of study cases (oral steroid versus nonsteroid therapy) of CTDs, CRF which was significantly lower in steroid (9.25 mm Hg) compared nonsteroid therapy (10.20 mm Hg) (P = 0.045), whereas, other parameters such as CCT, CH, IOPc, and IOPg were comparable between the two groups (P ≥ 0.05). Conclusion: CH is altered in CTDs which may be an independent risk factor for glaucoma and might underestimate intraocular pressure so CH is an important consideration in patients with CTDs.s

Keywords: Connective tissue disorders, corneal biomechanics, corneal hysteresis, intraocular pressure, rheumatoid

How to cite this article:
Kesarwani D, Jain VK, Agarwal R, Kaushik J, Sharma K. Corneal biomechanics in connective tissue disorders. J Clin Ophthalmol Res 2021;9:64-6

How to cite this URL:
Kesarwani D, Jain VK, Agarwal R, Kaushik J, Sharma K. Corneal biomechanics in connective tissue disorders. J Clin Ophthalmol Res [serial online] 2021 [cited 2023 Mar 24];9:64-6. Available from: https://www.jcor.in/text.asp?2021/9/2/64/322795

Introduction

Connective tissue disorder (CTD) is a multisystem disease characterized by chronic inflammation of organs rich in connective tissues such as skin, joints, and eyes, usually due to the altered immune response including production of autoantibodies and abnormal cell-mediated immunity. It includes a wide array of disorders such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, dermatomyositis, systemic sclerosis, and others.^[1]

Collagen is a part of connective tissue abundantly found in the eyes, particularly in the cornea. It is hypothesized that corneal stroma might be affected in CTDs ultrastructurally without clinical manifestation as it is rich in collagen. Corneal biomechanical properties have been shown to be affected in patients with glaucoma and are important to consider while measuring intraocular pressure (IOP).^[2],[3] The ocular response analyzer (ORA, Reichert Inc., Depew, N. Y., USA) measures intraocular pressure and various corneal biomechanical properties such as corneal hysteresis (CH) that is a measure of viscous dampening of the cornea, and corneal resistance factor (CRF) which is a resistance factor for deformation of cornea.^[4]

Earlier studies have evaluated the corneal biomechanical properties using ORA in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and collagen vascular diseases with conflicting results.^[5],[6],[7] This is a cross-sectional study in participants with CTDs in which corneal biomechanical properties have been studied and compared with controls.

Materials and Methods

In this study, 62 eyes of 62 patients with CTD were assessed for corneal biomechanical properties using ORA in a tertiary care referral hospital from January 2017 to July 2018. The study was carried out according to the Declaration of Helsinki and ethical committee clearance was obtained for the same. Informed consent was obtained from all the patients.

The study group comprised 62 diagnosed cases of CTDs who were already on treatment and were in inactive phase of disease under the immunology department. Forty-four patients formed the age-matched healthy control group without CTDs. All participants in control group were >18 years of age and were free from any ophthalmic and systemic disorders. Exclusion criteria comprised patients with ophthalmic disease such as corneal disorders, refractive error of 3Diopters (D) sphere or more and cylinder of 1 D or more, glaucoma, cataract, retinal disorders, patients with diabetes mellitus, previous intraocular surgery, ocular trauma, previous refractive surgery, corneal crosslinking treatment, corneal ectasia, keratitis, corneal dystrophy or degeneration or vascularization, and anterior segment morphologic anomaly and IOP (>21 mmHg).

All participants underwent comprehensive ophthalmic examination which included best-corrected visual acuity, slit-lamp examination, and fundus examination with + 90 D biomicroscopy. For corneal biomechanical properties measurements, ORA and corneal pachymetry measurements (SP-2000, Tomey, Nagoya, Japan) were performed. Only one eye (right) of a patient was enrolled in the study. All patients were assessed for CH, CRF, corneal-compensated intraocular pressure (IOPc), and Goldmann-correlated intraocular pressure (IOPg), and central corneal thickness (CCT). Four or five measurements were obtained for each eye, and the average of these measurements was taken as a final reading.

Sample sizes of 40 and 40 achieve 90% power to detect a mean difference of 1.8 mmHg in IOPg between the cases and controls groups, where mean ± standard deviations of the cases and controls group (Emre Sinan et al. 2010) were 15.9 ± 2.5 and 14.1 ± 2.4 (observed effect size = 0.735) with significance level (alpha) of 0.05 using a two-sided two-sample t-test. Sample size was estimated using software G Power version-3.1.9.2 (Düsseldorf University, Germany).

Normality of the continuous variable was tested and a variable was considered normally distributed when standard normal variate (Z value) of the skewness was ± 3.29. Continuous variables were presented in mean ± standard deviation and compared between two groups (cases and controls) using independent samples t-test. Categorical variables were presented in frequency (percentage). To compare the proportions between two groups (cases and controls), Chi-square test was used. The Statistical package for the social sciences, version 23 (SPSS-23, IBM, Chicago, Illinois, USA) was used to analyze the data. P <0.05 was considered statistically significant.

Results

In this study, a total of 106 individuals was included with 62 in cases (diseases) and 44 in controls. Mean age (years) of the study participants was 36.87 ± 14.26 with range of 16–65 years and almost equal proportion of males (n = 33, 53.22%) and females (n = 29, 46.77%). The mean age of control group was 36.45 ± 13.39 years (P 0.915). The sex ratio (male/female) in the control group was 23/21 which was comparable to the study group (P = 0.947). Sixteen (25.8%) patients were treated with steroid in study group and none in the control group.

The various clinical diagnoses of CTDs are mentioned below. The most common disorder noticed was rheumatoid arthritis (29.03%), followed by systemic lupus erythematosus (19.35%) and sarcoidosis (19.35%), spondyloarthropathies (6.45%), fibromyalgia (6.45%), ankylosing spondylitis (6.45%), juvenile idiopathic arthritis (6.45%), and Behcet disease (6.45%).

Mean CH of study group patients with CTD was 9.54 ± 1.66 mm Hg which was statistically significantly lower compared to the control group having mean CH of 10.62 ± 1.21 mm Hg (P = 0.013). Furthermore, a statistically significantly lower CRF was found in the study group (9.95 ± 1.47 mm Hg) compared to the control group (10.76 ± 1.25 mm Hg) with P= 0.040. Mean IOPc in study group was 14.45 ± 2.77 mm Hg which was slightly lower compared to the mean IOPc in the control group (16.0 ± 4.08 mm Hg) but not statistically significant (P = 0.132). Both the study group and control group had comparable mean IOPg (16.35 ± 2.93 mm Hg in the study group; 15.80 ± 4.36 mm Hg in the control group; P = 0.612). The difference in CCT was also not significant between the two groups, though it was slightly higher in the study group (544.61 ± 29.94) than the control group (528.81 ± 32.43) (P = 0.073). This line need to be deleted as figures have been removed as suggested by reviewer.

In study cases, patients who were on steroid treatment (n = 16) and those who were not (n = 46), were compared to assess the effect of steroid on corneal biomechanical properties. CRF was statistically significantly lower in patients with steroid (9.25 mm Hg) as compared to nonsteroid study cases (10.20 mm Hg). Whereas other parameters such as CH, IOPg, IOPc, and CCT were comparable between the steroid and nonsteroid cases [Table 1].

Table 1: Comparison of corneal biomechanical properties between steroid and nonsteroid cases in study participants with connective tissue disorders

Click here to view

Discussion

Corneal biomechanical properties are being increasingly considered as a tool for glaucoma evaluation and are shown to be affected in various systemic immune-mediated diseases.^[5],[6],[7] As the CTDs require prolonged immunosuppressive therapy in the form of oral steroid, so corneal biomechanics play an important role as these patients may be at the risk of development of steroid-induced glaucoma. We assessed the corneal biomechanical properties in CTDs as it might affect collagen-rich corneal stroma with no clinical finding. Consideration of biomechanical properties is highly important when patient is planned for refractive surgery and measuring intraocular pressure.

There are limited studies that have analysed corneal biomechanical properties in these patients with no conclusive result. Yazici, et al. studied corneal biomechanical properties in thirty patients with systemic lupus erythematosus and found that the mean CH, mean CRF and Goldmann correlated IOP were statistically significantly lower compared to control.^[5] Whereas another study of 29 patients with scleroderma showed higher CRF and Goldmann correlated IOP but comparable CH.^[7] In another study by Colaco, et al. 23 patients of collagen vascular disease had no significant difference in mean CH and CRF.^[8] We reported significantly lower CH and CRF in our patients with CTDs with comparable Goldmann correlated IOP and corneal compensated IOP.

To assess the possible effect of oral steroids on corneal biomechanical properties, we have compared the patients who were on steroids and those who were not, among CTD cases. Except CRF which was found to be statistically significant lower in steroid group, other factors were comparable between the two groups. Therefore, the lower CH could be a possible manifestation of CTD itself. The exact mechanism of CH alteration in CTDs is not clear. However, it is possible that it may affect through structural alteration of proteoglycans and glycosaminoglycans responsible for elasticity and rigidity of corneal stroma.^[9] The lower CH has been reported in steroid-induced ocular hypertension in a retrospective study involving 48 eyes.^[10] However, our both groups had patients with normal IOP.

Lower CH is associated with various types of glaucoma including primary open-angle glaucoma, primary angle-closure glaucoma, normal-tension glaucoma, and pseudoexfoliative glaucoma.^[9] Low CH is also associated with glaucomatous visual field and optic nerve progression, and greater reduction of IOP following glaucoma treatment including prostaglandin and selective laser trabeculoplasty.^[11],[12] Lower CH found in our patients with CTDs may be an independent risk factor for glaucoma and may underestimate IOP that may have clinical implications in the diagnosis and management of glaucoma.

The major limitation of this study was the small sample size. Furthermore, there was a heterogeneous group of CTDs with different pathophysiology and varied treatment. Although, this study shows an interesting observation of lower CH in patients with CTDs, a larger study with high number of participants is required to validate these findings. It definitely opens up a horizon for further research in this field.

This study highlights the importance of corneal biomechanics in patients with CTDs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Yanoff M, Duker JS. Ophthalmology: Expert Consult. China: Mosby Elsevier; 2009. p. 838-43.
2.	Kaushik S, Pandav SS, Banger A, Aggarwal K, Gupta A. Relationship between corneal biomechanical properties, central corneal thickness, and intraocular pressure across the spectrum of glaucoma. Am J Ophthalmol 2012;153:840-9.
3.	Liu J, Roberts CJ. Influence of corneal biomechanical properties on intraocular pressure measurement: Quantitative analysis. J Cataract Refract Surg 2005;31:146-55.
4.	Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005;31:156-62.
5.	Yazici AT, Kara N, Yuksel K, Altinkaynak H, Baz O, Bozkurt E, et al. The biomechanical properties of the cornea in patients with systemic lupus erythematosus. Eye (Lond) 2011;25:1005-9.
6.	Can ME, Erten S, Can GD, Cakmak HB, Sarac O, Cagil N. Corneal biomechanical properties in rheumatoid arthritis. Eye Contact Lens 2015;41:382-5.
7.	Emre S, Kayikçioğlu O, Ateş H, Cinar E, Inceoğlu N, Yargucu F, et al. Corneal hysteresis, corneal resistance factor, and intraocular pressure measurement in patients with scleroderma using the reichert ocular response analyzer. Cornea 2010;29:628-31.
8.	Colaco ML, Franco M, Pinto R, Seco JM. Corneal structure and biomechanics in collagen vascular diseases. Oftalmologia 2014;38:243-7.
9.	Kotecha A. What biomechanical properties of the cornea are relevant for the clinician? Surv Ophthalmol 2007;52 Suppl 2:S109-14.
10.	Yülek F, Gerçeker S, Akçay E, Saraç Á 3^rd, Çağıl N. Corneal biomechanics in steroid induced ocular hypertension. Cont Lens Anterior Eye 2015;38:181-4.
11.	Deol M, Taylor DA, Radcliffe NM. Corneal hysteresis and its relevance to glaucoma. Curr Opin Ophthalmol 2015;26:96-102.
12.	Liang L, Zhang R, He LY. Corneal hysteresis and glaucoma. Int Ophthalmol 2019;39:1909-16. [doi: 10.1007/s10792-018-1011-2].