Contact Lens & Anterior Eye 38 (2015) 181–184
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Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Corneal biomechanics in steroid induced ocular hypertension Fatma Yülek a,∗ , Sıdıka Gerc¸eker b , Emine Akc¸ay a , Özge Sarac¸ a , Nurullah C¸a˘gıl a a b
Yıldırım Beyazıt University, Medical Faculty, Ankara Atatürk Education and Research Hospital, Ophthalmology Department, Bilkent, Ankara, Turkey Nevs¸ehir State Hospital, Ophthalmology Department, Nevs¸ehir, Turkey
a r t i c l e
i n f o
Article history: Received 25 July 2014 Received in revised form 26 January 2015 Accepted 26 January 2015 Keywords: Steroid induced ocular hypertension Corneal hysteresis Ocular response analyser Corneal resistance factor Glaucoma
a b s t r a c t Aim: This study aims to investigate the corneal biomechanical properties of steroid sensitive refractive surgery patients and to compare these with those patients that did not have steroid induced ocular hypertension after refractive surgery. Material and methods: This retrospective study in a tertiary care center involved 48 eyes with steroid induced ocular hypertension (Group I) and 61 eyes of age and sex matched refractive patients who used topical steroids for the same duration as group I without developing ocular hypertension (group II). All patients had preoperative ophthalmological examination, pachymetry and postoperative corneal hysteresis (CH) and resistance factor (CRF) measurements by ocular response analyser. The preoperative CH and CRF measurements of the two groups were compared. Results: The mean CH was statistically lower in group I (6.89 ± 1.62) as compared to group II (7.80 ± 1.30) (p = 0.001). The CRF was higher in group I (7.68 ± 2.26) as compared to group II (7.66 ± 1.72) but the difference was not statistically significant (p = 0.96). The preoperative spherical refractive error (r = 0.43, p = 0.00) and postoperative corneal thickness (r = 0.58, p = 0.001) were moderately correlated with CH. Conclusions: A statistically significant decrease in CH in subjects with steroid induced ocular hypertension is found. Previous studies have revealed an association of low CH with risk of glaucomatous damage of optic nerve. This may imply risk of optic disc damage in this ocular hypertension group if not recognized and treated properly. However the results should be confirmed with larger sample sizes. © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Glucocorticoid (GC) therapy (e.g. topical, injected, oral, or inhalants) may cause elevated intraocular pressure (IOP) in susceptible individuals. These individuals often are referred to as “steroid responders” [1]. Topical ocular administration of a GC for 4–6 weeks can produce an elevated IOP in approximately 40% of the general population [2,3]. Interestingly, steroid responders are more likely to develop primary open angle glaucoma (POAG) as compared to non-responders [4,5]. The exact mechanisms responsible for this steroid-induced ocular hypertension have been intensely studied. The GCs inhibit trabecular meshwork (TM) cell functions and alter TM cell gene and protein expression [6,7]. In addition, GCs alter the TM cytoskeleton and increased extracellular matrix deposition [8,9]. However there is still paucity of data regarding properties of cornea and lamina cribrosa in these patients who are susceptible to steroid induced glaucoma.
The Ocular Response Analyzer [ORA] (Reichert Ophthalmic Instruments, Depew, NY, USA) measures non-contact IOP, CH and CRF. The CH is believed to be a reflection of the viscoelastic properties of the cornea and the CRF, a derived parameter, which is dominated by the elastic properties of the cornea and appears to be an indicator of the overall ‘resistance’ of the cornea [10]. It has been hypothesized that the corneal properties like central corneal thickness (CCT) and corneal biomechanical properties may constitute a pressure independent risk factor for glaucoma related to the composition of the eye wall itself [11]. The corneal biomechanical properties have been studied in several glaucoma types [12,13]. On the other hand the corneal biomechanical properties have not been previously reported in steroid responders. This study has been planned to investigate the corneal biomechanical properties of steroid sensitive refractive surgery patients and to compare these with those patients that did not have steroid induced ocular hypertension after refractive surgery. 2. Methods
∗ Corresponding author at: Gülden Sokak, No. 13/1, Kavaklıdere, Ankara, Turkey. Tel.: +90 312 4676550; fax: +90 312 4677532. E-mail address: [email protected] (F. Yülek).
This study was carried out in accordance with the Declaration of Helsinki after approval by the institutional review board. Informed consent was obtained from all of the patients. The refractive
http://dx.doi.org/10.1016/j.clae.2015.01.011 1367-0484/© 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
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F. Yülek et al. / Contact Lens & Anterior Eye 38 (2015) 181–184
Table 1 Some baseline and postoperative characteristics of patients.
Age (years) Preoperative IOP (mmHg) Anterior chamber depth (mm) Sim K1 Sim K2 Preoperative spherical equivalent (D) Preoperative cylindrical error (D) Preoperative pachymetry (microns) Post operative 21st day cIOP (mmHg) Postoperative pachymetry (microns) Change in spherical equivalent with surgery (D) *
Group I: patients with steroid induced ocular hypertension
Group II: control
Mean
SD
Mean
SD
p
29.91 14.67 3.47 42.54 44.11 −3.88 −1.73 532.88 22.28 439.75 −4.68
6.12 2.74 0.38 1.23 1.38 3.00 1.32 26.23 6.58 62.66 3.12
31.34 14.36 3.40 42.10 43.98 −1.58 −1.93 535.84 16.61 470.23 −2.31
6.86 2.84 0.41 1.39 1.39 2.96 1.69 25.93 3.51 37.46 2.99
0.26 0.57 0.38 0.09 0.65 0.001* 0.45 0.56 0.001* 0.002* 0.001*
Statistically significant.
surgery patients who had photorefractive keratectomy (PRK) for myopia were retrospectively evaluated. Topical dexamethasone (qid, Maxidex, Alcon, USA), lomefloxacin (qid, Okacin, Novartis), preservative free artificial eye drops and oral nonsteroidal antiinflammatory agents were used postoperatively in all patients to prevent corneal haze. The IOP was measured on postoperative 21st day with Goldmann applanation tonometry. Patients with corrected IOP (cIOP) above 21 mmHg according to new pachymetry values and elevation of more than 5 mmHg after treatment with steroids were involved in the group of steroid responders (group I). After detection of ocular hypertension topical fluorometholone replaced dexamethasone in this group and antiglaucomatous drops were added. The cIOP was calculated according to the Ehler’s method [14] involved in Sirius 3D Rotating Scheimpflug CameraTopography System (Costruzione Strumenti Oftalmici, Florence, Italy) by taking into account the IOP measured by Goldmann applanation tonometry and the postoperative pachymetry. The refractive surgery patients who did not develop ocular hypertension on topical steroid therapy (group II) were included as control patients Table 1. All patients had preoperative ophthalmological examination, postoperative pachymetry (measured by ultrasonic pachymetry: model 200P, Sonomed, New York, USA), CH and CRF measurements by ORA (Reichert Ophthalmic Instruments Inc., Depew, NY, USA) The age, sex, ocular or systemic disease, glaucoma history in the family were noted. The postoperative CH and CRF, pre and postoperative refractive spherical equivalents, pachymetry, IOP with Goldmann applanation tonometry, cIOP after laser (at third week after PRK) were recorded from files of patients. The ORA measurements of patients with steroid induced ocular hypertension (group I, n = 24) were compared with those of age and sex matched refractive surgery patients who used topical steroids for the same duration without developing ocular hypertension (group 2, n = 31). The software package used for statistical analysis was SPSS Version 15.0 for Windows (SPSS Inc., Chicago, IL). The difference of two groups was evaluated with Students’ t test for CH and CRF. Values were presented as mean with SD. A two-tailed probability of 0.05 was considered statistically significant. The data evaluated was normally distributed. 3. Results All of the patients had PRK for myopic refractive error. The distribution of sex (15 female in group I, 14 female patients in group II, p = 0.06) and mean age (29.92 ± 6.12 years in group I vs 31.34 ± 6.86 years in group II, p = 0.26) were not significantly different between groups. The preoperative refractive and anterior chamber properties and the mean correction achieved with PRK
in each group are demonstrated in Table 1. The mean IOP corrected according to new corneal thickness was 22.28 ± 6.58 mmHg in group I and 16.61 ± 3.51 in group II. The mean CH was statistically lower in group I (6.89 ± 1.62) as compared to group II (7.80 ± 1.30) (p = 0.001). The CRF was higher in group I (7.68 ± 2.26) as compared to group II (7.66 ± 1.72) but the difference was not statistically significant (p = 0.96). The postoperative corneal thickness was significantly higher in the group II (470.23 ± 37.46) as compared to group I (439.75 ± 62.66) (p = 0.002). There was more myopia in the ocular hypertension group as compared to the control (−3.88 D vs −1.58, p = 0.001). The correlation of CH and CRF with preoperative spherical and cylindrical refractive error, Sim K values, anterior chamber depth and pachymetry were evaluated (Table 2). The moderate correlation of CH (r = 0.43, p = 0.001) and CRF (r = 0.46, p = 0.001) with preoperative spherical refractive error were statistically significant. The postoperative corneal thickness was moderately correlated with CH (p = 0.58, r = 0.001) and CRF (p = 0.56, r = 0.001). 4. Discussion Steroid-induced ocular hypertension after photorefractive keratectomy has been reported in several studies with effects on visual acuity [15]. Several risk factors have been proposed for steroid induced ocular hypertension like increased age, history of glaucoma suspect, connective tissue disease, type I diabetes, a first-degree relative with POAG, or high myopia [2]. Morphological changes like thickened trabecular beams, decreased intertrabecular spaces, thickened juxtacanalicular tissues and increased amounts of amorphous granular extracellular material have been shown in these eyes [7–9]. On the other hand the cause of steroid induced glaucoma is still obscure with some genetic, structural factors reported [2]. The ORA is a device that measures corneal biomechanical properties in vivo [16]. In addition to calculating corrected IOP from CH, the ORA may also enable ocular rigidity to be estimated from CH measurements. One theory proposed for the mechanism of glaucoma pathogenesis is that a rise in IOP causes posterior bowing of the lamina cribrosa associated with weakening of the tissues, exerting mechanical pressure on optic nerve fibres that pass through the centre and causing atrophy of the optic nerve [17]. The sclera and cornea are tissues that together form the external membrane of the eyeball, possessing thick, tough connective tissue that consists mainly of an extracellular matrix containing collagen fibres and other components. As both the sclera and the cornea are formed from continuous extracellular matrix [18], weakening of the lamina cribrosa in glaucomatous eyes may be estimable by measuring CH. Low CH is reportedly associated with glaucomatous damage [19]. Association of glaucoma and low corneal hysteresis has been
F. Yülek et al. / Contact Lens & Anterior Eye 38 (2015) 181–184
183
Table 2 Correlation of CH and CRF with baseline characteristics of patients.
Anterior chamber depth Sim K1 Sim K2 Preoperative spherical error Preoperative cylindrical error Preoperative pachymetry Postoperative pachymetry *
Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed)
CH
CRF
−0.10 0.29 0.04 0.68 −0.08 0.42 0.43* 0.001 0.16 0.10 0.17 0.08 0.58* 0.001
0.004 0.96 0.05 0.63 −0.17 0.09 0.46* 0.001 0.26* 0.007 0.14 0.14 0.56* 0.001
Statistically significant.
indicated in several glaucoma types with normotensive glaucoma eyes having the lowest CH value among glaucomatous eyes [13]. Previously a study in patients with steroid induced ocular hypertension evaluating CH and CRF has not been observed. In a study of Indian subjects the CH of normal subjects, OHT and POAG patients were 9.5 ± 0.4 mmHg, 9.2 ± 1.9 mmHg and 7.9 ± 2.8 mmHg respectively [20]. Pseudoexfoliative glaucoma patients were reported to have mean CH values of 6.9 ± 2.1 mmHg [10]. In this study population the CH values of subjects with steroid induced ocular hypertension and control group were 6.89 ± 1.62 mmHg and 7.80 ± 1.30 mmHg respectively. The difference was significant. The CH values of study patients also seem to be lower as compared to the above studies with normal subjects, OHT and POAG. The study with pseudoexfoliation patients involves a population similar to present study in ethnicity with CH of normal subjects as 9.4 ± 1.4 mmHg [10]. They also report lower CRF in pseudoexfoliative glaucoma patients. Opposingly an increase (though insignificant) in CRF in steroid induced ocular hypertension patients is found in this study. The properties related to the age, ethnics of subjects and refractive error may be important regarding the inconsistencies of results. In a Chinese study the non myopic subjects had mean CH of 11.13 ± 1.45 mmHg while those with moderate and high myopia had mean CH of 10.49 ± 0.89 mmHg and 10.05 ± 1.66 mmHg respectively [23]. This study suggests that CH is positively correlated with refractive error though there are controversial reports on subjects with lower levels of myopia (2.35 ± 2.49 D [24], 2.20 ± 1.60 D [25]) than this study (5.85 ± 7.84 D [23]). They report higher CRF in patients with low myopia (8.88 ± 1.74 mmHg) as compared to the non myopia (8.56 ± 1.60 mmHg) and moderate myopia group (8.40 ± 1.48 mmHg). Similarly the present study revealed decreased CH as opposed to increased CRF in patients with steroid induced ocular hypertension. The mean preoperative spherical refractive errors were −3.88 ± 3.00 D and −1.58 ± 2.96 D in steroid induced ocular hypertension and control groups respectively (p = 0.001). Also a moderate correlation of CH and CRF with preoperative spherical refractive error is noted. These findings are in agreement with other studies [24] and supporting the hypothesis of Schmid et al. [26] that myopia increases IOP by an elevated stress of the global wall and a declined ocular rigidity. Since refractive surgery patients with myopia may have lower CH values, this may seem to pose another risk for glaucomatous damage. The central corneal thickness was significantly lower in the ocular hypertension group similar to other studies [19]. The intraocular pressure was higher after correction for central corneal thickness. The CH which is also correlated with central corneal thickness was lower in the ocular hypertension group.
There are some limitations in this study. Axial length was not measured and only subjects with myopia were involved. The effect of refractive error can be investigated thoroughly by including also hyperopic patients. The study was retrospective. The myopic patients were more numerous in the study population. On the other hand the steroid induced ocular hypertension may seem to be more prevalent in myopic refractive patients leading to the bias of involving mostly myopic subjects. This question remains to be answered by extensive review of increased number of cases with different types of refractive errors. Conclusively a relatively decreased CH in subjects with steroid induced ocular hypertension and a moderate correlation of CH with spherical refractive error and central corneal thickness is found. This study points out the complex association between spherical refractive error, ocular hypertension, corneal thickness and corneal hysteresis. However the results should be confirmed with larger sample sizes. Funding There is no source of funding for this study. Conflict of interest There is no conflict of interest in this study. References [1] Armaly A. Effect of corticosteroids on intraocular pressure and fluid dynamics. Arch Ophthalmol 1963;70:482–91. [2] Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye 2006;20:407–16. [3] Jones 3rd R, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol 2006;7:163–7. [4] Kitazawa Y, Horie T. The prognosis of corticosteroid-responsive individuals. Arch Ophthalmol 1981;99:819–23. [5] Lewis JM, Priddy T. Intraocular pressure response to topical dexamethasone as a predictor for the development of primary open-angle glaucoma. Am J Ophthalmol 1988;106:607–12. [6] Ishibashi T, Takagi Y. cDNA microarray analysis of gene expression changes induced by dexamethasone in cultured human trabecular meshwork cells. Investig Ophthalmol Vis Sci 2002;43:3691–7. [7] Matsumoto Y, Johnson DH. Dexamethasone decreases phagocytosis by human trabecular meshwork cells in situ. Investig Ophthalmol Vis Sci 1997;38:1902–7. [8] Johnson D, Gottanka J. Ultrastructural changes in the trabecular meshwork of human eyes treated with corticosteroids. Arch Ophthalmol 1997;115:375–83. [9] Engelbrecht-Schnur S, Siegner A. Dexamethasone treatment decreases hyaluronan-formation by primate trabecular meshwork cells in vitro. Exp Eye Res 1997;64:539–43. [10] Cankaya AB, Anayol A, Özcelik D, Demirdogen E, Yilmazbas P. Ocular response analyzer to assess corneal biomechanical properties in exfoliation syndrome and exfoliative glaucoma. Graefes Arch Clin Exp Ophthalmol 2012;250:255–60.
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[11] Congdon NG, Broman AT, Bandeen-Roche K, Grover D, Quigley HA. Central corneal thickness and corneal hysteresis associated with glaucoma damage. Am J Ophthalmol 2006;141:868–75. [12] Hager A, Loge K, Schroeder B, Fullhas MO, Wiegand W. Effect of central corneal thickness and corneal hysteresis on tonometry as measured by dynamic contour tonometry, ocular response analyzer, and Goldmann tonometry in glaucomatous eyes. J Glaucoma 2008;17:361–5. [13] Shah S, Laiquzzaman M, Mantry S, Cunliffe I. Ocular response analyser to assess hysteresis and corneal resistance factor in low tension, open angle glaucoma and ocular hypertension. Clin Exp Ophthalmol 2008;36:508–13. [14] Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal thickness. Acta Ophthalmol (Copenh) 1975;53:34–43. [15] Yamaguchi T, Murat D, Kimura I, Negishi K, Yuki K, Tsubota K, et al. Diagnosis of steroid-induced glaucoma after photorefractive keratectomy. J Refract Surg 2008 Apr;24:413–5. [16] Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005;31:156–62. [17] Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR. Morpho-logic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol 1983;95:673–91. [18] McBrien NA, Gentle A. Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res 2003;22:307–38.
[19] Wells AP, Garway-Heath DF, Poostchi A, Wong T, Chan KC, Sachdev N. Corneal hysteresis but not corneal thickness correlates with optic nerve surface compliance in glaucoma patients. Investig Ophthalmol Vis Sci 2008;49: 3262–8. [20] 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 May;153:840–9. [23] Jiang Z, Shen M, Mao G, Chen D, Wang J, Qu J, et al. Association between corneal biomechanical properties and myopia in Chinese subjects. Eye 2011;25:1083–9. [24] Lim L, Gazzard G, Chan YH, Fong A, Kotecha A, Sim EL, et al. Cornea biomechanical characteristics and their correlates with refractive error in Singaporean children. Investig Ophthalmol Vis Sci 2008;49:3852–7. [25] Song Y, Congdon N, Li L, Zhou Z, Choi K, Lam DS, et al. Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4. Am J Ophthalmol 2008;145:819–26. [26] Schmid KL, Li RW, Edwards MH, Lew JK. The expandability of the eye in childhood myopia. Curr Eye Res 2003;26:65–71.
Contents lists available at ScienceDirect
Contact Lens & Anterior Eye journal homepage: www.elsevier.com/locate/clae
Corneal biomechanics in steroid induced ocular hypertension Fatma Yülek a,∗ , Sıdıka Gerc¸eker b , Emine Akc¸ay a , Özge Sarac¸ a , Nurullah C¸a˘gıl a a b
Yıldırım Beyazıt University, Medical Faculty, Ankara Atatürk Education and Research Hospital, Ophthalmology Department, Bilkent, Ankara, Turkey Nevs¸ehir State Hospital, Ophthalmology Department, Nevs¸ehir, Turkey
a r t i c l e
i n f o
Article history: Received 25 July 2014 Received in revised form 26 January 2015 Accepted 26 January 2015 Keywords: Steroid induced ocular hypertension Corneal hysteresis Ocular response analyser Corneal resistance factor Glaucoma
a b s t r a c t Aim: This study aims to investigate the corneal biomechanical properties of steroid sensitive refractive surgery patients and to compare these with those patients that did not have steroid induced ocular hypertension after refractive surgery. Material and methods: This retrospective study in a tertiary care center involved 48 eyes with steroid induced ocular hypertension (Group I) and 61 eyes of age and sex matched refractive patients who used topical steroids for the same duration as group I without developing ocular hypertension (group II). All patients had preoperative ophthalmological examination, pachymetry and postoperative corneal hysteresis (CH) and resistance factor (CRF) measurements by ocular response analyser. The preoperative CH and CRF measurements of the two groups were compared. Results: The mean CH was statistically lower in group I (6.89 ± 1.62) as compared to group II (7.80 ± 1.30) (p = 0.001). The CRF was higher in group I (7.68 ± 2.26) as compared to group II (7.66 ± 1.72) but the difference was not statistically significant (p = 0.96). The preoperative spherical refractive error (r = 0.43, p = 0.00) and postoperative corneal thickness (r = 0.58, p = 0.001) were moderately correlated with CH. Conclusions: A statistically significant decrease in CH in subjects with steroid induced ocular hypertension is found. Previous studies have revealed an association of low CH with risk of glaucomatous damage of optic nerve. This may imply risk of optic disc damage in this ocular hypertension group if not recognized and treated properly. However the results should be confirmed with larger sample sizes. © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
1. Introduction Glucocorticoid (GC) therapy (e.g. topical, injected, oral, or inhalants) may cause elevated intraocular pressure (IOP) in susceptible individuals. These individuals often are referred to as “steroid responders” [1]. Topical ocular administration of a GC for 4–6 weeks can produce an elevated IOP in approximately 40% of the general population [2,3]. Interestingly, steroid responders are more likely to develop primary open angle glaucoma (POAG) as compared to non-responders [4,5]. The exact mechanisms responsible for this steroid-induced ocular hypertension have been intensely studied. The GCs inhibit trabecular meshwork (TM) cell functions and alter TM cell gene and protein expression [6,7]. In addition, GCs alter the TM cytoskeleton and increased extracellular matrix deposition [8,9]. However there is still paucity of data regarding properties of cornea and lamina cribrosa in these patients who are susceptible to steroid induced glaucoma.
The Ocular Response Analyzer [ORA] (Reichert Ophthalmic Instruments, Depew, NY, USA) measures non-contact IOP, CH and CRF. The CH is believed to be a reflection of the viscoelastic properties of the cornea and the CRF, a derived parameter, which is dominated by the elastic properties of the cornea and appears to be an indicator of the overall ‘resistance’ of the cornea [10]. It has been hypothesized that the corneal properties like central corneal thickness (CCT) and corneal biomechanical properties may constitute a pressure independent risk factor for glaucoma related to the composition of the eye wall itself [11]. The corneal biomechanical properties have been studied in several glaucoma types [12,13]. On the other hand the corneal biomechanical properties have not been previously reported in steroid responders. This study has been planned to investigate the corneal biomechanical properties of steroid sensitive refractive surgery patients and to compare these with those patients that did not have steroid induced ocular hypertension after refractive surgery. 2. Methods
∗ Corresponding author at: Gülden Sokak, No. 13/1, Kavaklıdere, Ankara, Turkey. Tel.: +90 312 4676550; fax: +90 312 4677532. E-mail address: [email protected] (F. Yülek).
This study was carried out in accordance with the Declaration of Helsinki after approval by the institutional review board. Informed consent was obtained from all of the patients. The refractive
http://dx.doi.org/10.1016/j.clae.2015.01.011 1367-0484/© 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
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F. Yülek et al. / Contact Lens & Anterior Eye 38 (2015) 181–184
Table 1 Some baseline and postoperative characteristics of patients.
Age (years) Preoperative IOP (mmHg) Anterior chamber depth (mm) Sim K1 Sim K2 Preoperative spherical equivalent (D) Preoperative cylindrical error (D) Preoperative pachymetry (microns) Post operative 21st day cIOP (mmHg) Postoperative pachymetry (microns) Change in spherical equivalent with surgery (D) *
Group I: patients with steroid induced ocular hypertension
Group II: control
Mean
SD
Mean
SD
p
29.91 14.67 3.47 42.54 44.11 −3.88 −1.73 532.88 22.28 439.75 −4.68
6.12 2.74 0.38 1.23 1.38 3.00 1.32 26.23 6.58 62.66 3.12
31.34 14.36 3.40 42.10 43.98 −1.58 −1.93 535.84 16.61 470.23 −2.31
6.86 2.84 0.41 1.39 1.39 2.96 1.69 25.93 3.51 37.46 2.99
0.26 0.57 0.38 0.09 0.65 0.001* 0.45 0.56 0.001* 0.002* 0.001*
Statistically significant.
surgery patients who had photorefractive keratectomy (PRK) for myopia were retrospectively evaluated. Topical dexamethasone (qid, Maxidex, Alcon, USA), lomefloxacin (qid, Okacin, Novartis), preservative free artificial eye drops and oral nonsteroidal antiinflammatory agents were used postoperatively in all patients to prevent corneal haze. The IOP was measured on postoperative 21st day with Goldmann applanation tonometry. Patients with corrected IOP (cIOP) above 21 mmHg according to new pachymetry values and elevation of more than 5 mmHg after treatment with steroids were involved in the group of steroid responders (group I). After detection of ocular hypertension topical fluorometholone replaced dexamethasone in this group and antiglaucomatous drops were added. The cIOP was calculated according to the Ehler’s method [14] involved in Sirius 3D Rotating Scheimpflug CameraTopography System (Costruzione Strumenti Oftalmici, Florence, Italy) by taking into account the IOP measured by Goldmann applanation tonometry and the postoperative pachymetry. The refractive surgery patients who did not develop ocular hypertension on topical steroid therapy (group II) were included as control patients Table 1. All patients had preoperative ophthalmological examination, postoperative pachymetry (measured by ultrasonic pachymetry: model 200P, Sonomed, New York, USA), CH and CRF measurements by ORA (Reichert Ophthalmic Instruments Inc., Depew, NY, USA) The age, sex, ocular or systemic disease, glaucoma history in the family were noted. The postoperative CH and CRF, pre and postoperative refractive spherical equivalents, pachymetry, IOP with Goldmann applanation tonometry, cIOP after laser (at third week after PRK) were recorded from files of patients. The ORA measurements of patients with steroid induced ocular hypertension (group I, n = 24) were compared with those of age and sex matched refractive surgery patients who used topical steroids for the same duration without developing ocular hypertension (group 2, n = 31). The software package used for statistical analysis was SPSS Version 15.0 for Windows (SPSS Inc., Chicago, IL). The difference of two groups was evaluated with Students’ t test for CH and CRF. Values were presented as mean with SD. A two-tailed probability of 0.05 was considered statistically significant. The data evaluated was normally distributed. 3. Results All of the patients had PRK for myopic refractive error. The distribution of sex (15 female in group I, 14 female patients in group II, p = 0.06) and mean age (29.92 ± 6.12 years in group I vs 31.34 ± 6.86 years in group II, p = 0.26) were not significantly different between groups. The preoperative refractive and anterior chamber properties and the mean correction achieved with PRK
in each group are demonstrated in Table 1. The mean IOP corrected according to new corneal thickness was 22.28 ± 6.58 mmHg in group I and 16.61 ± 3.51 in group II. The mean CH was statistically lower in group I (6.89 ± 1.62) as compared to group II (7.80 ± 1.30) (p = 0.001). The CRF was higher in group I (7.68 ± 2.26) as compared to group II (7.66 ± 1.72) but the difference was not statistically significant (p = 0.96). The postoperative corneal thickness was significantly higher in the group II (470.23 ± 37.46) as compared to group I (439.75 ± 62.66) (p = 0.002). There was more myopia in the ocular hypertension group as compared to the control (−3.88 D vs −1.58, p = 0.001). The correlation of CH and CRF with preoperative spherical and cylindrical refractive error, Sim K values, anterior chamber depth and pachymetry were evaluated (Table 2). The moderate correlation of CH (r = 0.43, p = 0.001) and CRF (r = 0.46, p = 0.001) with preoperative spherical refractive error were statistically significant. The postoperative corneal thickness was moderately correlated with CH (p = 0.58, r = 0.001) and CRF (p = 0.56, r = 0.001). 4. Discussion Steroid-induced ocular hypertension after photorefractive keratectomy has been reported in several studies with effects on visual acuity [15]. Several risk factors have been proposed for steroid induced ocular hypertension like increased age, history of glaucoma suspect, connective tissue disease, type I diabetes, a first-degree relative with POAG, or high myopia [2]. Morphological changes like thickened trabecular beams, decreased intertrabecular spaces, thickened juxtacanalicular tissues and increased amounts of amorphous granular extracellular material have been shown in these eyes [7–9]. On the other hand the cause of steroid induced glaucoma is still obscure with some genetic, structural factors reported [2]. The ORA is a device that measures corneal biomechanical properties in vivo [16]. In addition to calculating corrected IOP from CH, the ORA may also enable ocular rigidity to be estimated from CH measurements. One theory proposed for the mechanism of glaucoma pathogenesis is that a rise in IOP causes posterior bowing of the lamina cribrosa associated with weakening of the tissues, exerting mechanical pressure on optic nerve fibres that pass through the centre and causing atrophy of the optic nerve [17]. The sclera and cornea are tissues that together form the external membrane of the eyeball, possessing thick, tough connective tissue that consists mainly of an extracellular matrix containing collagen fibres and other components. As both the sclera and the cornea are formed from continuous extracellular matrix [18], weakening of the lamina cribrosa in glaucomatous eyes may be estimable by measuring CH. Low CH is reportedly associated with glaucomatous damage [19]. Association of glaucoma and low corneal hysteresis has been
F. Yülek et al. / Contact Lens & Anterior Eye 38 (2015) 181–184
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Table 2 Correlation of CH and CRF with baseline characteristics of patients.
Anterior chamber depth Sim K1 Sim K2 Preoperative spherical error Preoperative cylindrical error Preoperative pachymetry Postoperative pachymetry *
Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed) Pearson correlation Sig. (2-tailed)
CH
CRF
−0.10 0.29 0.04 0.68 −0.08 0.42 0.43* 0.001 0.16 0.10 0.17 0.08 0.58* 0.001
0.004 0.96 0.05 0.63 −0.17 0.09 0.46* 0.001 0.26* 0.007 0.14 0.14 0.56* 0.001
Statistically significant.
indicated in several glaucoma types with normotensive glaucoma eyes having the lowest CH value among glaucomatous eyes [13]. Previously a study in patients with steroid induced ocular hypertension evaluating CH and CRF has not been observed. In a study of Indian subjects the CH of normal subjects, OHT and POAG patients were 9.5 ± 0.4 mmHg, 9.2 ± 1.9 mmHg and 7.9 ± 2.8 mmHg respectively [20]. Pseudoexfoliative glaucoma patients were reported to have mean CH values of 6.9 ± 2.1 mmHg [10]. In this study population the CH values of subjects with steroid induced ocular hypertension and control group were 6.89 ± 1.62 mmHg and 7.80 ± 1.30 mmHg respectively. The difference was significant. The CH values of study patients also seem to be lower as compared to the above studies with normal subjects, OHT and POAG. The study with pseudoexfoliation patients involves a population similar to present study in ethnicity with CH of normal subjects as 9.4 ± 1.4 mmHg [10]. They also report lower CRF in pseudoexfoliative glaucoma patients. Opposingly an increase (though insignificant) in CRF in steroid induced ocular hypertension patients is found in this study. The properties related to the age, ethnics of subjects and refractive error may be important regarding the inconsistencies of results. In a Chinese study the non myopic subjects had mean CH of 11.13 ± 1.45 mmHg while those with moderate and high myopia had mean CH of 10.49 ± 0.89 mmHg and 10.05 ± 1.66 mmHg respectively [23]. This study suggests that CH is positively correlated with refractive error though there are controversial reports on subjects with lower levels of myopia (2.35 ± 2.49 D [24], 2.20 ± 1.60 D [25]) than this study (5.85 ± 7.84 D [23]). They report higher CRF in patients with low myopia (8.88 ± 1.74 mmHg) as compared to the non myopia (8.56 ± 1.60 mmHg) and moderate myopia group (8.40 ± 1.48 mmHg). Similarly the present study revealed decreased CH as opposed to increased CRF in patients with steroid induced ocular hypertension. The mean preoperative spherical refractive errors were −3.88 ± 3.00 D and −1.58 ± 2.96 D in steroid induced ocular hypertension and control groups respectively (p = 0.001). Also a moderate correlation of CH and CRF with preoperative spherical refractive error is noted. These findings are in agreement with other studies [24] and supporting the hypothesis of Schmid et al. [26] that myopia increases IOP by an elevated stress of the global wall and a declined ocular rigidity. Since refractive surgery patients with myopia may have lower CH values, this may seem to pose another risk for glaucomatous damage. The central corneal thickness was significantly lower in the ocular hypertension group similar to other studies [19]. The intraocular pressure was higher after correction for central corneal thickness. The CH which is also correlated with central corneal thickness was lower in the ocular hypertension group.
There are some limitations in this study. Axial length was not measured and only subjects with myopia were involved. The effect of refractive error can be investigated thoroughly by including also hyperopic patients. The study was retrospective. The myopic patients were more numerous in the study population. On the other hand the steroid induced ocular hypertension may seem to be more prevalent in myopic refractive patients leading to the bias of involving mostly myopic subjects. This question remains to be answered by extensive review of increased number of cases with different types of refractive errors. Conclusively a relatively decreased CH in subjects with steroid induced ocular hypertension and a moderate correlation of CH with spherical refractive error and central corneal thickness is found. This study points out the complex association between spherical refractive error, ocular hypertension, corneal thickness and corneal hysteresis. However the results should be confirmed with larger sample sizes. Funding There is no source of funding for this study. Conflict of interest There is no conflict of interest in this study. References [1] Armaly A. Effect of corticosteroids on intraocular pressure and fluid dynamics. Arch Ophthalmol 1963;70:482–91. [2] Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye 2006;20:407–16. [3] Jones 3rd R, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol 2006;7:163–7. [4] Kitazawa Y, Horie T. The prognosis of corticosteroid-responsive individuals. Arch Ophthalmol 1981;99:819–23. [5] Lewis JM, Priddy T. Intraocular pressure response to topical dexamethasone as a predictor for the development of primary open-angle glaucoma. Am J Ophthalmol 1988;106:607–12. [6] Ishibashi T, Takagi Y. cDNA microarray analysis of gene expression changes induced by dexamethasone in cultured human trabecular meshwork cells. Investig Ophthalmol Vis Sci 2002;43:3691–7. [7] Matsumoto Y, Johnson DH. Dexamethasone decreases phagocytosis by human trabecular meshwork cells in situ. Investig Ophthalmol Vis Sci 1997;38:1902–7. [8] Johnson D, Gottanka J. Ultrastructural changes in the trabecular meshwork of human eyes treated with corticosteroids. Arch Ophthalmol 1997;115:375–83. [9] Engelbrecht-Schnur S, Siegner A. Dexamethasone treatment decreases hyaluronan-formation by primate trabecular meshwork cells in vitro. Exp Eye Res 1997;64:539–43. [10] Cankaya AB, Anayol A, Özcelik D, Demirdogen E, Yilmazbas P. Ocular response analyzer to assess corneal biomechanical properties in exfoliation syndrome and exfoliative glaucoma. Graefes Arch Clin Exp Ophthalmol 2012;250:255–60.
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