Ocular Immunology & Inflammation, 2014; 22(3): 224–227 ! Informa Healthcare USA, Inc. ISSN: 0927-3948 print / 1744-5078 online DOI: 10.3109/09273948.2013.841957
ORIGINAL ARTICLE
Evaluation of Corneal Biomechanical Properties in Patients with Rheumatoid Arthritis: A Study by Ocular Response Analyzer Mehmet Tas , 1
¨ ner, , Veysi O
1
MD
MD
¨ zkaya, , Erdal O
2
1
MD
, and Mustafa Durmus ,
MD
2
Malatya State Hospital, Malatya, Turkey and 2Department of Ophthalmology, Recep Tayyip Erdog˘an University Medical School, Rize, Turkey
ABSTRACT Purpose: To compare the corneal biomechanical properties of rheumatoid arthritis (RA) patients with those of healthy controls. Methods: Measurements of 39 eyes of 39 RA patients (patient group) were compared with those of 55 eyes of 55 healthy controls (control group). Corneal hysteresis (CH), corneal resistance factor (CRF), intraocular pressure (IOP), and corneal-compensated IOP (IOPcc) were obtained for each subject by the ocular response analyzer (ORA). Corneal thickness (CCT) was measured by ultrasonic pachymeter. Results: CH and CRF were significantly lower in the patient group than in the control group (p1 = 0.002, p2 = 0.019, respectively). The patient group had significantly higher IOPcc values than the control group (p = 0.024). There was no significant differences between the groups concerning CCT and IOP. Conclusions: RA patients had lower CH and CRF, but higher IOPcc values than healthy controls. RA should be considered when the corneal biomechanical properties measured by the ORA are used for diagnoses or therapies. Keywords: Corneal hysteresis; corneal resistance factor; intraocular pressure; ocular response analyzer; rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of unknown etiology characterized by an erosive and symmetric synovitis. It frequently presents with multiregional extraarticular manifestations. The ocular surface is one of the most frequently affected regions by the disease. The most common ocular problem in RA is keratoconjunctivitis sicca.1 In addition, episcleritis, scleritis, and a variety of corneal changes, including keratitis, may also occur.2 A recently produced device, the ocular response analyzer (ORA), allows direct clinical measurement of the biomechanical properties of the cornea.3–5 It provides the measurement of intraocular pressure (IOP), corneal-compensated IOP (IOPcc), corneal
hysteresis (CH), and corneal resistance factor (CRF). CH is associated with the viscoelastic behavior of the corneal tissue. CRF is a parameter that shows the overall resistance of the cornea. IOPcc is a pressure measurement based on data provided by the CH. Corneal biomechanical properties are important for preoperative screening of refractive surgery, preventing misreading of the IOP, and helping the differentiation of the healthy and abnormal corneas.6 Few previous studies have shown that autoimmune connective tissue diseases, such as systemic lupus erythematosus and scleroderma, could affect the corneal biomechanical properties measured by the ORA.6,7 In the present study, we aimed
Received 27 May 2013; revised 29 August 2013; accepted 3 September 2013; published online 16 October 2013 ¨ ner, Department of Ophthalmology, Recep Tayyip Erdog˘an University Medical School, Rize, Turkey. E-mail: Correspondence: Veysi O [email protected]
224
Corneal Biomechanics in Rheumatoid Arthritis to compare the corneal biomechanical properties of RA patients with those of healthy controls by using the ORA.
MATERIALS AND METHODS The current study was a retrospective medical records investigation comparing the ORA measurements, including CH, CRF, IOP, and IOPcc, of 39 eyes of 39 RA patients (patient group) with those of 55 eyes of 55 healthy controls (control group). The right eye of each subject was enrolled in the study. The patient group included patients with a diagnosis of RA referred to Department of Ophthalmology for ocular consultations from the Department of Physical Medicine and Rehabilitation. The control subjects were chosen from the ophthalmology outpatient clinic. The study followed the tenets of the Declaration of Helsinki. Each patient underwent a complete ophthalmic evaluation, including assessment of visual acuity, slitlamp biomicroscopic examination, and funduscopy. Exclusion criteria included any ocular disease other than dry eye and cataract, a history of ocular inflammatory disease or ocular surgery, use of any topical medication other than artificial tears, diabetes, and pregnancy. The ORA (Reichert Ophthalmic Instruments, Depew, NY, USA) was used to determine the biomechanical properties and IOP. The measurements were performed by a single experienced clinician. CH, CRF, IOP, and IOPcc were obtained for each subject. The ORA uses a rapid air impulse to deform the cornea, and the shape alterations are monitored by an electro-optical system. The air impulse induces inward and outward applanations of the cornea. CH is assessed as the difference between the two pressures caused by the inward and outward applanations. The IOP is measured as the average of two pressures. CRF and IOPcc are also determined as the combinations of the ORA-induced inward and outward applanation measurements. The details of the methodology of the ORA has been described elsewhere.4,8 Central corneal thickness (CCT) was measured by ultrasonic pachymeter (Micropach Model 200P, Sonomed, Lake Success, NY, USA).
Statistical Analysis Statistical analysis was performed using SPSS version 16.0. The distributions of variables were checked with Kolmogorov-Smirnov test. Gender was compared using the chi-square test. The Student t-test was used to compare the study groups. Pearson correlation coefficients were used for correlation analyses. Statistical significance was set at p50.05. !
2014 Informa Healthcare USA, Inc.
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RESULTS The mean age was 58.9 14.2 (ranging from 27 to 87) years in the patient group and 56.9 17.8 (ranging from 19 to 89) years in the control group. There were 19 females and 20 males in the patient group and 28 females and 27 males in the control group. There were no significant differences between the groups regarding age and gender (p1 = 0.564, p2 = 0.500, respectively). No patient had an ocular pathology other than dry eye and cataract. All patients had visual acuities of 0.6 or better (by Snellen charts). Thirty out of 39 (76.9%) RA patients had a history of dry eye requiring use of artificial teardrops. In addition, 2 patients had a history of peripheral marginal keratitis (5.1%) and 5 patients (12.8%) had a history of episcleritis. The clinical characteristics of the subjects are given in Table 1. CH and CRF were significantly lower in the patient group than in the control group (p1 = 0.002, p2 = 0.019, respectively). In addition, the patient group had significantly higher IOPcc values than the control group (p = 0.024). On the other hand, there were no significant differences between the groups concerning IOP (p = .837) and CCT (p = .339). After correcting IOP according to CCT there was still a significant difference between the groups regarding IOPcc (p = 0.013). The groups were similar concerning corrected IOP. Correlations analyses among the corneal biomechanical properties of the study population showed that there were significantly positive correlations between CH and CRF (r = 0.921, p50.001), CRF and IOP (r = 0.522, p50.001), and IOP and IOPcc (r = 0.666, p50.001). Additionally, there was a significantly negative correlation between CH and IOPcc (r = 0.746, p50.001). Further, CCT had significantly positive correlations with CH (r = 0.552, p50.001), CRF (r = 0.650, p50.001), and IOP (r = 416, p50.001). However, there was no correlation between CCT and IOPcc. TABLE 1. Clinical characteristics of the groups (mean SD). Characteristic CH (mmHg) CRF (mmHg) IOP (mmHg) Corrected IOP IOPcc (mmHg) Corrected IOPcc CCT (m)
Patient group (n = 39)
Control group (n = 55)
p Value
9.3 2.3 10.0 2.4 16.6 4.2 16.6 4.1 17.5 4.3 17.6 4.7 537.2 27.6
11.1 2.9 11.3 2.9 16.5 3.2 16.0 2.6 15.7 3.2 15.4 3.6 541.6 15.6
0.002 0.019 0.837 0.454 0.024 0.013 0.339
CCT, central corneal thickness; CH, corneal hysteresis; CRF, corneal resistance factor; IOP, non-contact tonometer intraocular pressure; IOPcc, corneal-compensated intraocular pressure. Patient group: patients with rheumatoid arthritis. Statistically significant p values are given in bold. IOP corrections were performed according to CCT.
226 M. Tas et al.
DISCUSSION Our results displayed that the patients with RA had significantly lower CH and CRF and higher IOPcc values than the healthy controls. In addition, we found that there were significantly positive correlations between CH and CRF, CRF and IOP, and IOP and IOPcc. Further, there was a significantly negative correlation between CH and IOPcc. Recently, there has been an increasing interest in corneal biomechanical properties for management of glaucoma. Corneal biomechanical properties measured by the ORA have been found to have clinical significance in assuming visual damage in patients with glaucoma.3 A rising attention has also developed on corneal biomechanical properties concerning diagnosis and therapy, such as keratoconus and corneal refractive surgery. The ORA has proven its capability to identify the biomechanical properties of keratoconus and post-refractive surgery corneas.4 RA is a chronic autoimmune inflammatory multisystem connective tissue disorder that is generally accompanied by joint involvements. The main ocular involvement is tear deficiency; however, scleral and corneal involvements may result in potentially blinding disorders. Corneal changes can range from mild punctate keratitis to severe sterile stromal ulcerations.9,10 Corneal morphological changes such as corneal thinning, lower density of superficial epithelial cells, fewer subbasal nerves and greater nerve tortuosity have been shown in RA patients.11 In addition, it has been demonstrated that corneal peripheral and central epithelium apoptosis were seen in dry eye.12 Elsheikh et al.13 displayed that an intact corneal epithelium has a very important function over the corneal biomechanics. In the present study, most of the RA patients had a history of dry eye and 7 had a history of corneal or episcleral inflammation. Consequently, we can speculate that lower CH and CRF values in our patient group might be caused by corneal changes or dry eye in RA patients. Previous studies have shown that autoimmune disorders were significantly associated with corneal ectasias.14,15 In this regard, Nemet et al.14 found that there were significant associations between keratoconus and several autoimmune disorders, including rheumatoid, ulcerative colitis, autoimmune chronic active hepatitis, Hashimoto thyroiditis, arthropathy, asthma, environmental allergy, and irritable bowel syndrome. Ferna´ndez-Barboza et al.15 have reported a relation between pellucid marginal degeneration and Sjo¨gren syndrome, which is an autoimmune disease. Previous studies have found that corneal biomechanical properties were affected by numerous corneal diseases, such as keratoconus, Fuch’s endothelial dystrophy, and corneal edema and some systemic factors, including diabetes and menstruation.16–21 To our best knowledge, there is only one previous
study investigating the corneal biomechanical properties of RA patients.22 Prata et al.22 compared the biomechanical properties of 20 eyes of 11 women RA patients with those of 36 eyes of 20 women healthy controls. In accordance with our results, CH was significantly lower in the RA patients than in the controls. In addition, they found no significant difference between the RA patients and controls concerning IOP. However, there was no information about the CRF and IOPcc values of the groups. Yaz|c| et al.6 compared the corneal biomechanical properties and IOP of patients with systemic lupus erythematosis with age-matched controls. Patients with systemic lupus erythematosis had lower CH, CRF, and IOP values compared with age-matched controls. Emre et al.7 evaluated the influence of scleroderma on corneal biomechanical properties. CRF and IOP values were significantly higher in patients with scleroderma than in age-matched healthy controls. Further, lower CH and CRF values have been seen in advanced stages of Marfan syndrome, which is a genetic disorder of connective tissue.23 In our study, RA patients had higher IOPcc values than the healthy controls. It has been shown that there were significant alterations in autoantibody profiles of glaucoma patients, indicating an autoimmune involvement in glaucoma.24 In addition, it has been found that there was a potential pathogenic role for autoimmunity in facilitating neuronal loss in glaucomatous optic neuropathy.25 In the present study, IOP measurements were significantly correlated with CCT and the association between these 2 variables was similar to the previous studies.26,27 On the other hand, IOPcc measurements were not significantly correlated with CCT, showing that the IOPcc values provided by the ORA do not seem to be affected by corneal thickness. Similarly, in our study, although IOP measurements were significantly correlated with CRF, ORA IOPcc values were not influenced by CRF, suggesting that the ORA IOPcc measurements were not influenced by the corneal properties. In this regard, Medeiros et al.28 have found similar results to ours. Therefore, it can be speculated that IOPcc may be more reliable than IOP values for evaluation of IOP. The limitation of the present study was the absence of the measurements evaluating the presence and severity of dry eye. Although the most of our patients had a history of dry eye, we did not have objective dry eye test results of the patients (such as Schirmer or break-up time tests). The changes occurring in the corneas of RA patients might be caused by dry eye. The objective dry eye tests may be used in further studies. In conclusion, the present study revealed that RA influenced biomechanical properties measured by the ORA. The patients with RA had lower CH and CRF, but higher IOPcc values than healthy controls. Ocular Immunology & Inflammation
Corneal Biomechanics in Rheumatoid Arthritis RA should be considered when the corneal biomechanical properties measured by the ORA are used for diagnoses or therapies.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Lemp MA. Dry eye (keratoconjunctivitis sicca), rheumatoid arthritis, and Sjo¨gren’s syndrome. Am J Ophthalmol. 2005:140:898–899. 2. Harper SL, Foster CS. The ocular manifestations of rheumatoid disease. Int Ophthalmol Clin. 1998:38:1–19. 3. Congdon NG, Broman AT, Bandeen-Roche K, et al. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol. 2006:141:868–875. 4. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg. 2005:31:156–162. 5. Kotecha A, Elsheikh A, Roberts CR, et al. Corneal thickness- and age-related biomechanical properties of the cornea measured with the ocular response analyzer. Invest Ophthalmol Vis Sci. 2006:47:5337–5347. 6. Yazici AT, Kara N, Yu¨ksel K, et al. The biomechanical properties of the cornea in patients with systemic lupus erythematosus. Eye (Lond). 2011:25:1005–1009. 7. Emre S, Kayikcioglu O, Ates H, et al. Corneal hysteresis, corneal resistance factor, and intraocular pressure measurement in patients with scleroderma using the reichert ocular response analyzer. Cornea. 2010:29:628–631. 8. Grossniklaus HE, Hutchinson AK, Capone Jr A, et al. Clinicopathologic features of surgically excised choroidal neovascular membranes. Ophthalmology. 1994:101:1099–1111. 9. Bernauer WQ, Ficker LA, Watson PG, et al. The management of corneal perforations associated with rheumatoid arthritis: an analysis of 32 eyes. Ophthalmology. 1995:102:1325–1337. 10. Kervick GN, Pflugfelder SC, Haimovici R, et al. Paracentral rheumatoid corneal ulceration: clinical features and cyclosporine therapy. Ophthalmology. 1992:99:80–88. 11. Villani E, Galimberti D, Viola F, et al. Corneal involvement in rheumatoid artritis: an in vivo confocal study. Invest Ohpthalmol Vis Sci. 2008:49:560–564. 12. Yeh S, Song XJ, Farley W, et al. Apoptosis of ocular surface cells in experimentally induced dry eye. Invest Ophthalmol Vis Sci. 2003:44:124–129.
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13. Elsheikh A, Alhasso D, Rama P. Assessment of the epithelium’s contribution to corneal biomechanics. Exp Eye Res. 2008:86:445–451. 14. Nemet AY, Vinker S, Bahar I, et al. The association of keratoconus with immune disorders. Cornea. 2010:29:1261– 1264. 15. Ferna´ndez-Barboza F, Verdiguel-Sotelo K, Herna´ndezLo´pez A. [Pellucid marginal degeneration and corneal ulceration, associated with Sjo¨gren syndrome]. Rev Med Inst Mex Seguro Soc. 2009:47:77–82. 16. Shah S, Laiquzzaman M, Bhojwani R, et al. Assessment of the biomechanical properties of the cornea with the ocular response analyzer in normal and keratoconic eyes. Invest Ophthalmol Vis Sci. 2007:48:3026–3031. 17. Johnson RD, Nguyen MT, Lee N, et al. Corneal biomechanical properties in normal, forme fruste keratoconus, and manifest keratoconus after statistical correction for potentially confounding factors. Cornea. 2011:30:516–523. 18. del Buey MA, Cristobal JA, Ascaso FJ, et al. Biomechanical properties of the cornea in Fuchs’ corneal dystrophy. Invest Ophthalmol Vis Sci. 2009:50:3199–3202. 19. Hager A, Loge K, Fullhas MO, et al. Changes in corneal hysteresis after clear corneal cataract surgery. Am J Ophthalmol. 2007:144:341–346. 20. Goldich Y, Barkana Y, Gerber Y, et al. Effect of diabetes mellitus on biomechanical parameters of the cornea. J Cataract Refract Surg. 2009:35:715–719. 21. Goldich Y, Barkana Y, Pras E, et al. Variations in corneal biomechanical parameters and central corneal thickness during the menstrual cycle. J Cataract Refract Surg. 2011:37:1507–1511. 22. Prata TS, Sousa AK, Garcia Filho CA, et al. Assessment of corneal biomechanical properties and intraocular pressure in patients with rheumatoid arthritis. Can J Ophthalmol. 2009:44:602. 23. Kara N, Bozkurt E, Baz O, et al. Corneal biomechanical properties and intraocular pressure measurement in Marfan patients. J Cataract Refract Surg. 2012:38:309–314. 24. Gramlich OW, Beck S, von Thun Und Hohenstein-Blaul N, et al. Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina. PLoS One. 2013:8:57557. 25. Grus FH, Joachim SC, Wuenschig D, et al. Autoimmunity and glaucoma. J Glaucoma. 2008:17:79–84. 26. Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv Ophthalmol. 2000:44:367–408. 27. Wolfs RC, Klaver CC, Vingerling JR, et al. Distribution of central corneal thickness and its association with intraocular pressure: the Rotterdam Study. Am J Ophthalmol. 1997:123:767–772. 28. Medeiros FA, Weinreb RN. Evaluation of the influence of corneal biomechanical properties on intraocular pressure measurements using the ocular response analyzer. J Glaucoma. 2006:15:364–370.
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ORIGINAL ARTICLE
Evaluation of Corneal Biomechanical Properties in Patients with Rheumatoid Arthritis: A Study by Ocular Response Analyzer Mehmet Tas , 1
¨ ner, , Veysi O
1
MD
MD
¨ zkaya, , Erdal O
2
1
MD
, and Mustafa Durmus ,
MD
2
Malatya State Hospital, Malatya, Turkey and 2Department of Ophthalmology, Recep Tayyip Erdog˘an University Medical School, Rize, Turkey
ABSTRACT Purpose: To compare the corneal biomechanical properties of rheumatoid arthritis (RA) patients with those of healthy controls. Methods: Measurements of 39 eyes of 39 RA patients (patient group) were compared with those of 55 eyes of 55 healthy controls (control group). Corneal hysteresis (CH), corneal resistance factor (CRF), intraocular pressure (IOP), and corneal-compensated IOP (IOPcc) were obtained for each subject by the ocular response analyzer (ORA). Corneal thickness (CCT) was measured by ultrasonic pachymeter. Results: CH and CRF were significantly lower in the patient group than in the control group (p1 = 0.002, p2 = 0.019, respectively). The patient group had significantly higher IOPcc values than the control group (p = 0.024). There was no significant differences between the groups concerning CCT and IOP. Conclusions: RA patients had lower CH and CRF, but higher IOPcc values than healthy controls. RA should be considered when the corneal biomechanical properties measured by the ORA are used for diagnoses or therapies. Keywords: Corneal hysteresis; corneal resistance factor; intraocular pressure; ocular response analyzer; rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of unknown etiology characterized by an erosive and symmetric synovitis. It frequently presents with multiregional extraarticular manifestations. The ocular surface is one of the most frequently affected regions by the disease. The most common ocular problem in RA is keratoconjunctivitis sicca.1 In addition, episcleritis, scleritis, and a variety of corneal changes, including keratitis, may also occur.2 A recently produced device, the ocular response analyzer (ORA), allows direct clinical measurement of the biomechanical properties of the cornea.3–5 It provides the measurement of intraocular pressure (IOP), corneal-compensated IOP (IOPcc), corneal
hysteresis (CH), and corneal resistance factor (CRF). CH is associated with the viscoelastic behavior of the corneal tissue. CRF is a parameter that shows the overall resistance of the cornea. IOPcc is a pressure measurement based on data provided by the CH. Corneal biomechanical properties are important for preoperative screening of refractive surgery, preventing misreading of the IOP, and helping the differentiation of the healthy and abnormal corneas.6 Few previous studies have shown that autoimmune connective tissue diseases, such as systemic lupus erythematosus and scleroderma, could affect the corneal biomechanical properties measured by the ORA.6,7 In the present study, we aimed
Received 27 May 2013; revised 29 August 2013; accepted 3 September 2013; published online 16 October 2013 ¨ ner, Department of Ophthalmology, Recep Tayyip Erdog˘an University Medical School, Rize, Turkey. E-mail: Correspondence: Veysi O [email protected]
224
Corneal Biomechanics in Rheumatoid Arthritis to compare the corneal biomechanical properties of RA patients with those of healthy controls by using the ORA.
MATERIALS AND METHODS The current study was a retrospective medical records investigation comparing the ORA measurements, including CH, CRF, IOP, and IOPcc, of 39 eyes of 39 RA patients (patient group) with those of 55 eyes of 55 healthy controls (control group). The right eye of each subject was enrolled in the study. The patient group included patients with a diagnosis of RA referred to Department of Ophthalmology for ocular consultations from the Department of Physical Medicine and Rehabilitation. The control subjects were chosen from the ophthalmology outpatient clinic. The study followed the tenets of the Declaration of Helsinki. Each patient underwent a complete ophthalmic evaluation, including assessment of visual acuity, slitlamp biomicroscopic examination, and funduscopy. Exclusion criteria included any ocular disease other than dry eye and cataract, a history of ocular inflammatory disease or ocular surgery, use of any topical medication other than artificial tears, diabetes, and pregnancy. The ORA (Reichert Ophthalmic Instruments, Depew, NY, USA) was used to determine the biomechanical properties and IOP. The measurements were performed by a single experienced clinician. CH, CRF, IOP, and IOPcc were obtained for each subject. The ORA uses a rapid air impulse to deform the cornea, and the shape alterations are monitored by an electro-optical system. The air impulse induces inward and outward applanations of the cornea. CH is assessed as the difference between the two pressures caused by the inward and outward applanations. The IOP is measured as the average of two pressures. CRF and IOPcc are also determined as the combinations of the ORA-induced inward and outward applanation measurements. The details of the methodology of the ORA has been described elsewhere.4,8 Central corneal thickness (CCT) was measured by ultrasonic pachymeter (Micropach Model 200P, Sonomed, Lake Success, NY, USA).
Statistical Analysis Statistical analysis was performed using SPSS version 16.0. The distributions of variables were checked with Kolmogorov-Smirnov test. Gender was compared using the chi-square test. The Student t-test was used to compare the study groups. Pearson correlation coefficients were used for correlation analyses. Statistical significance was set at p50.05. !
2014 Informa Healthcare USA, Inc.
225
RESULTS The mean age was 58.9 14.2 (ranging from 27 to 87) years in the patient group and 56.9 17.8 (ranging from 19 to 89) years in the control group. There were 19 females and 20 males in the patient group and 28 females and 27 males in the control group. There were no significant differences between the groups regarding age and gender (p1 = 0.564, p2 = 0.500, respectively). No patient had an ocular pathology other than dry eye and cataract. All patients had visual acuities of 0.6 or better (by Snellen charts). Thirty out of 39 (76.9%) RA patients had a history of dry eye requiring use of artificial teardrops. In addition, 2 patients had a history of peripheral marginal keratitis (5.1%) and 5 patients (12.8%) had a history of episcleritis. The clinical characteristics of the subjects are given in Table 1. CH and CRF were significantly lower in the patient group than in the control group (p1 = 0.002, p2 = 0.019, respectively). In addition, the patient group had significantly higher IOPcc values than the control group (p = 0.024). On the other hand, there were no significant differences between the groups concerning IOP (p = .837) and CCT (p = .339). After correcting IOP according to CCT there was still a significant difference between the groups regarding IOPcc (p = 0.013). The groups were similar concerning corrected IOP. Correlations analyses among the corneal biomechanical properties of the study population showed that there were significantly positive correlations between CH and CRF (r = 0.921, p50.001), CRF and IOP (r = 0.522, p50.001), and IOP and IOPcc (r = 0.666, p50.001). Additionally, there was a significantly negative correlation between CH and IOPcc (r = 0.746, p50.001). Further, CCT had significantly positive correlations with CH (r = 0.552, p50.001), CRF (r = 0.650, p50.001), and IOP (r = 416, p50.001). However, there was no correlation between CCT and IOPcc. TABLE 1. Clinical characteristics of the groups (mean SD). Characteristic CH (mmHg) CRF (mmHg) IOP (mmHg) Corrected IOP IOPcc (mmHg) Corrected IOPcc CCT (m)
Patient group (n = 39)
Control group (n = 55)
p Value
9.3 2.3 10.0 2.4 16.6 4.2 16.6 4.1 17.5 4.3 17.6 4.7 537.2 27.6
11.1 2.9 11.3 2.9 16.5 3.2 16.0 2.6 15.7 3.2 15.4 3.6 541.6 15.6
0.002 0.019 0.837 0.454 0.024 0.013 0.339
CCT, central corneal thickness; CH, corneal hysteresis; CRF, corneal resistance factor; IOP, non-contact tonometer intraocular pressure; IOPcc, corneal-compensated intraocular pressure. Patient group: patients with rheumatoid arthritis. Statistically significant p values are given in bold. IOP corrections were performed according to CCT.
226 M. Tas et al.
DISCUSSION Our results displayed that the patients with RA had significantly lower CH and CRF and higher IOPcc values than the healthy controls. In addition, we found that there were significantly positive correlations between CH and CRF, CRF and IOP, and IOP and IOPcc. Further, there was a significantly negative correlation between CH and IOPcc. Recently, there has been an increasing interest in corneal biomechanical properties for management of glaucoma. Corneal biomechanical properties measured by the ORA have been found to have clinical significance in assuming visual damage in patients with glaucoma.3 A rising attention has also developed on corneal biomechanical properties concerning diagnosis and therapy, such as keratoconus and corneal refractive surgery. The ORA has proven its capability to identify the biomechanical properties of keratoconus and post-refractive surgery corneas.4 RA is a chronic autoimmune inflammatory multisystem connective tissue disorder that is generally accompanied by joint involvements. The main ocular involvement is tear deficiency; however, scleral and corneal involvements may result in potentially blinding disorders. Corneal changes can range from mild punctate keratitis to severe sterile stromal ulcerations.9,10 Corneal morphological changes such as corneal thinning, lower density of superficial epithelial cells, fewer subbasal nerves and greater nerve tortuosity have been shown in RA patients.11 In addition, it has been demonstrated that corneal peripheral and central epithelium apoptosis were seen in dry eye.12 Elsheikh et al.13 displayed that an intact corneal epithelium has a very important function over the corneal biomechanics. In the present study, most of the RA patients had a history of dry eye and 7 had a history of corneal or episcleral inflammation. Consequently, we can speculate that lower CH and CRF values in our patient group might be caused by corneal changes or dry eye in RA patients. Previous studies have shown that autoimmune disorders were significantly associated with corneal ectasias.14,15 In this regard, Nemet et al.14 found that there were significant associations between keratoconus and several autoimmune disorders, including rheumatoid, ulcerative colitis, autoimmune chronic active hepatitis, Hashimoto thyroiditis, arthropathy, asthma, environmental allergy, and irritable bowel syndrome. Ferna´ndez-Barboza et al.15 have reported a relation between pellucid marginal degeneration and Sjo¨gren syndrome, which is an autoimmune disease. Previous studies have found that corneal biomechanical properties were affected by numerous corneal diseases, such as keratoconus, Fuch’s endothelial dystrophy, and corneal edema and some systemic factors, including diabetes and menstruation.16–21 To our best knowledge, there is only one previous
study investigating the corneal biomechanical properties of RA patients.22 Prata et al.22 compared the biomechanical properties of 20 eyes of 11 women RA patients with those of 36 eyes of 20 women healthy controls. In accordance with our results, CH was significantly lower in the RA patients than in the controls. In addition, they found no significant difference between the RA patients and controls concerning IOP. However, there was no information about the CRF and IOPcc values of the groups. Yaz|c| et al.6 compared the corneal biomechanical properties and IOP of patients with systemic lupus erythematosis with age-matched controls. Patients with systemic lupus erythematosis had lower CH, CRF, and IOP values compared with age-matched controls. Emre et al.7 evaluated the influence of scleroderma on corneal biomechanical properties. CRF and IOP values were significantly higher in patients with scleroderma than in age-matched healthy controls. Further, lower CH and CRF values have been seen in advanced stages of Marfan syndrome, which is a genetic disorder of connective tissue.23 In our study, RA patients had higher IOPcc values than the healthy controls. It has been shown that there were significant alterations in autoantibody profiles of glaucoma patients, indicating an autoimmune involvement in glaucoma.24 In addition, it has been found that there was a potential pathogenic role for autoimmunity in facilitating neuronal loss in glaucomatous optic neuropathy.25 In the present study, IOP measurements were significantly correlated with CCT and the association between these 2 variables was similar to the previous studies.26,27 On the other hand, IOPcc measurements were not significantly correlated with CCT, showing that the IOPcc values provided by the ORA do not seem to be affected by corneal thickness. Similarly, in our study, although IOP measurements were significantly correlated with CRF, ORA IOPcc values were not influenced by CRF, suggesting that the ORA IOPcc measurements were not influenced by the corneal properties. In this regard, Medeiros et al.28 have found similar results to ours. Therefore, it can be speculated that IOPcc may be more reliable than IOP values for evaluation of IOP. The limitation of the present study was the absence of the measurements evaluating the presence and severity of dry eye. Although the most of our patients had a history of dry eye, we did not have objective dry eye test results of the patients (such as Schirmer or break-up time tests). The changes occurring in the corneas of RA patients might be caused by dry eye. The objective dry eye tests may be used in further studies. In conclusion, the present study revealed that RA influenced biomechanical properties measured by the ORA. The patients with RA had lower CH and CRF, but higher IOPcc values than healthy controls. Ocular Immunology & Inflammation
Corneal Biomechanics in Rheumatoid Arthritis RA should be considered when the corneal biomechanical properties measured by the ORA are used for diagnoses or therapies.
DECLARATION OF INTEREST The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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