DOI: 10.5301/ejo.5000378
Eur J Ophthalmol 2014; 24 ( 3 ): 314-319
ORIGINAL ARTICLE
Corneal biomechanical parameters during pregnancy Emine Sen1, Yüksel Onaran2, Pinar Nalcacioglu-Yuksekkaya1, Ufuk Elgin1, Faruk Ozturk1 1 2
Ulucanlar Eye Research Hospital, Ankara - Turkey Department of Obstetrics and Gynecology, Fatih University of Medical School, Ankara - Turkey
Purpose: To evaluate the variation in biomechanical properties and central corneal thickness (CCT) for each trimester during pregnancy and to compare the values with those in nonpregnant women. Methods: We prospectively studied the eyes of 32 pregnant and 34 age-matched non-pregnant women. The parameters included corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOP), and corneal-compensated IOP measured by the Ocular Response Analyzer (ORA). The CCT was also measured with an ultrasonic pachymeter attached to the ORA. Results: The mean age was 27.0 ± 3.8 years in the study group and 28.0 ± 4.1 years in the control group. The mean CH measurement was 10.6 ± 1.4 mmHg in the study group and 10.1 ± 1.3 mmHg in the control group. The mean CRF value was 9.6 ± 1.7 mmHg in the study group and 10.0 ± 1.4 mmHg in the control group. The mean CCT value was 541.1 ± 22.4 µm in the study group and 536.5 ± 27.1 µm in the control group. No statistically significant differences were found regarding CH, CRF, or CCT values between the 2 groups (independent t test, p = 0.160, p = 0.355, p = 0.450, respectively). Conclusions: Hormonal changes during pregnancy may not affect corneal biomechanics. This may be due to the balanced effect of the various hormones on the cornea during pregnancy. Keywords: Central corneal thickness, Corneal biomechanics, Hormonal changes, Pregnancy Accepted: September 16, 2013
INTRODUCTION Pregnancy is associated with changes involving multiple organ systems, including the eyes. Ocular physiologic changes including decreased intraocular pressure (IOP), increased facility of outflow, decreased corneal sensitivity (1), increased central corneal thickness (CCT) (2) and curvature (3), and temporary refractive changes and contact lens intolerance (3) have been reported previously. Estrogen, progesterone, and androgen receptors have been shown in the nuclei of human corneal epithelial, stromal, and endothelial cells (4-6). Goldich et al (7) reported variations in corneal biomechanical properties during the menstrual cycle. These changes probably occur due to these receptors in the cornea (4-7). It is therefore possible that the increased 314
estrogen and progesterone levels during pregnancy may lead to changes in corneal biomechanical properties. The Ocular Response Analyzer (ORA, Reichert Inc.; Depew, New York, USA) is used to measure in vivo corneal biomechanical properties, which are presented by 2 parameters: corneal hysteresis (CH) and the corneal resistance factor (CRF). It also measures Goldmann-correlated IOP (IOPg) and corneal compensated IOP (IOPcc), which is independent from the influence of corneal biomechanical properties. To our knowledge, ORA parameters during pregnancy have not been described. We hypothesized that there would be some changes in corneal biomechanics during pregnancy. The aim of this study was to investigate the changes of the biomechanical properties of the cornea and CCT value in
© 2013 Wichtig Editore - ISSN 1120-6721
Sen et al
pregnant women and to compare them with age-matched nonpregnant subjects.
MATERIALS AND METHODS We examined 32 pregnant women with uncompleted singleton pregnancies and no history of an ocular problem who were consecutively referred to our clinic from the Obstetrics and Gynecology Clinic of Fatih University School of Medicine. The control group consisted of 34 age- and sex-matched subjects and they underwent concurrent ophthalmic examination in this prospective study. All the study procedures were conducted in accordance with the Declaration of Helsinki, and informed consent was obtained from each participant. This study was approved by the Ethical Committee of the Ankara University School of Medicine. Inclusion criteria were age over 18 years and uncomplicated pregnancy for the study group. Exclusion criteria were known systemic disease, ophthalmic disorders, contact lenses wear, refractive error exceeding ± 3.00 D, or any type of previous eye surgery. Healthy subjects using contraceptive medications were also excluded. The subjects in both the study and the control groups underwent complete ophthalmologic examination including best-corrected visual acuity with Snellen chart, refraction, and anterior segment and fundus examination (without mydriatics). To avoid possible diurnal variations, corneal biomechanical parameters including CH, CRF, IOPg, and IOPcc were measured between 9:00 and 11:00 AM by the same experienced physician (E. S.) according to normal clinical practice and the manufacturer’s guidelines. Three readings of good-quality images were included for each patient. Good quality was defined as readings having a waveform with 2 distinct peaks. The mean values of each parameter were used for statistical evaluation. A dynamic bidirectional applanation process is used to measure the corneal biomechanical properties and IOP with the ORA. The device is based on noncontact tonometry where the air pressure required to applanate the central cornea is used to determine IOP (8). Rapid air deforms the cornea, measured by an electro-optical system. The air pushes the cornea into a slightly concave position and corneal indentation. Afterwards the cornea returns to its normal convex curvature. The system measures 2 pressure
values: the force at which the cornea flattens as the air pressure rises (force-in applanation) and the force at which the cornea flattens again as the pressure falls (force-out applanation). A hand-held ultrasonic pachymeter that was attached to the ORA was used for CCT measurement. The CCT measurements were performed at the same time of the day after the ORA measurement. Repeated sets of 5 readings were taken at the center of the cornea after administration of topical anesthesia (proparacaine hydrochloride 0.5%, Alcaine ophthalmic solution, Alcon, Turkey). The Kolmogorov-Smirnov test was used to evaluate the normal distribution for all groups. The correlation between the right and left eye was evaluated with the Pearson correlation test. The differences between the 2 groups were evaluated by the independent t test. The Kruskal-Wallis test was used to compare each parameter between trimesters in the study group. A p value 0.05).
DISCUSSION Corneal hysteresis and CRF are new parameters that assess corneal biomechanical properties (9). Previous studies have shown the influence of the hormone status on the cornea (2, 10, 11). Changes in corneal curvature (2) and corneal thickness (12) and regression of keratoconus have been reported during pregnancy (13). β-human chorionic gonadotropin, progesterone (14), and estrogen (12) levels are markedly elevated during pregnancy. The progesterone level begins to increase at about 20 weeks of gestation, at the end of the third trimester (14). The effect of progesterone appears during the latter half of pregnancy. Estrogen is first detected at 9 weeks and peaks at 31-35 weeks of gestation (15). Studies have reported the presence of estrogen, progesterone, and androgen receptors in the nuclei of human corneal epithelial, stromal, and endothelial cells (4-6). We therefore hypothesized that there may be some changes in corneal biomechanics due to pregnancy-associated hormones. The stroma makes up 90% of the corneal thickness and is the most important corneal layer from the biomechanical point of view. The extracellular matrix in the stroma mainly consists of collagens, proteoglycans, and glycosaminoglycans and defines the elasticity and viscoelastic structure of the cornea (12). The CH reflects the viscous damping of the cornea that may define the corneal response to applanation forces during ocular tonometry (16), whereas the CRF has been strongly associated with corneal stiffness (8). During pregnancy, progesterone (14) and estrogen (12) levels are markedly elevated. Progesterone prevents the production of prostaglandins that cause activation of collagenases, therefore leading to collagenase activation (17). Progesterone also affects proteinase inhibitors through the production of tissue inhibitor of metalloproteinases (TIMP) (18). Sato et al (18) found that progesterone increased the production of TIMP in their experimental study and reported progesterone to be more effective than 17-β estradiol in rabbit uterine cervical cells (18). Estradiol stimulates the production of matrix metalloproteinase (19) and the production or activation of collagenolytic enzymes (20). Estrogen also induces prostaglandin
© 2013 Wichtig Editore - ISSN 1120-6721
Sen et al
production, causing collagenase activation (12). The increased collagenolytic activities may predispose the cornea to keratoconus development (21-25). This is encountered as a biomechanically weakened cornea in the clinic. Estrogen-induced changes in corneal biomechanical properties have been reported by Spoerl et al (12). They suggested that the estrogen hormone is a potentially modulating factor for the biomechanical properties of the cornea (12). In their experimental study, they showed significantly reduced stiffness as determined with stressstrain curves in porcine eyes that were incubated with high levels of estrogen as in pregnancy (12). Goldich et al (7) observed a significant variation in corneal thickness and biomechanical parameters during the normal menstrual cycle. Estrogen has 2 peaks during the menstrual cycle, with one during the ovulation period and the other at the end of the cycle. In their study, the CH and CRF were significantly decreased at ovulation and CCT increased at both peaks of estrogen in a way that was closely related to the changes in the estrogen level (7). We report the corneal biomechanical properties of uncomplicated pregnant women in this study. We observed no changes in corneal biomechanical parameters during pregnancy when compared with nonpregnant subjects. There was also no difference in biomechanical parameters among the 3 trimesters of pregnancy. Sato et al (18) state that the collagenase activation decreasing activity of progesterone is more effective than the effect of estrogen in rabbit uterine cells, which may have led to stabilization of the corneal biomechanical framework. The negative effect of estrogen on the corneal biomechanical structure of pregnant women may therefore have been balanced by progesterone, leading to unchanged corneal structure when pregnant women were compared with nonpregnant subjects in our study. We also measured CCT and IOP in addition to corneal biomechanical features with the ORA in our study. The mean CCT value is higher in pregnant women than in nonpregnant women but this was not statistically significant. A recent study by Efe et al (2) reported a significant decrease in IOP during the second and third trimester of pregnancy, accompanied by a reciprocal increase in CCT during the same period. Weinreb et al (26) compared the CCT in 89 pregnant women with the control eyes of 18 nongravida and 17 postpartum women and reported that the cornea was significantly thicker in the pregnant women. They hypothesized that pregnancy-associated fluid retention may
cause higher corneal thickness (26). Pregnancy may also result in changes in corneal biomechanics. Similar to this result, recent studies have reported that increased CCT due to postoperative corneal edema after phacoemulsification surgery leads to a change in corneal biomechanical properties (27, 28). The increase in CCT after phacoemulsification was followed by a reduction in CRF and CH, while decreased IOPcc and IOPg were also reported by de Freitas Valbon et al (28). Previous experimental studies have reported the relationship between corneal hydration degree and biomechanical properties (29, 30). A study showed a reduction of shearing strength with increasing hydration (29). Hjortdal (30) suggested a significantly increased distensibility of the cornea at a higher hydration level. In our study, decreased IOPg and IOPcc values were observed in pregnant women. Previous studies have reported IOP decreases and CCT increases during pregnancy (2, 26, 31-34). The main mechanism underlying the decreased IOP during pregnancy is the relationship between female hormones and increased outflow (2). Treister and Mannor (35) showed decreased IOP with the use of progesterone or the combination of progesterone and estrogen at pharmacologic doses. A statistically significant increase in aqueous outflow associated with progesterone levels has been shown in pregnancy (36, 37). Ziai et al (14) hypothesized that progesterone acts as a glucocorticoid antagonist in the outflow apparatus and prevents the ocular hypertensive effect of endogenous steroids. Another hypothesis suggests decreased episcleral venous pressure in pregnant women (38). In summary, there was no difference in corneal biomechanical features between pregnant and nonpregnant subjects, indicating no effect of hormonal changes during pregnancy on these features. This may be due to balancing of hormonal effects on the cornea during pregnancy. Financial Support: No financial support was received for this submission. Conflict of Interest Statement: None of the authors has conflict of interest with this submission. Address for correspondence: Emine Sen, MD Ulucanlar Eye Research Hospital Ulucanlar Street No: 59 (06240) Altındag/Ankara Turkey [email protected]
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REFERENCES 1.
Sunness JS. The pregnant woman’s eye. Surv Ophthalmol 1988;32:219-38. 2. Efe YK, Ugurbas SC, Alpay A, Ugurbas SH. The course of corneal and intraocular pressure changes during pregnancy. Can J Ophthalmol 2012;47:150-4. 3. Park SB, Lindahl KJ, Temnycky GO, Aquavella JV. The effect of pregnancy on corneal curvature. CLAO J 1992;18: 256-9. 4. Gupta PD, Johar K Sr, Nagpal K, Vasavada AR. Sex hormone receptors in the human eye. Surv Ophthalmol 2005;50: 274-84. 5. Suzuki T, Kinoshita Y, Tachibana M, et al. Expression of sex steroid hormone receptors in human cornea. Curr Eye Res 2001;22:28-33. 6. Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA. Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand 2000;78:146-53. 7. 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: 1507-11. 8. Kotecha A. What biomechanical properties of the cornea are relevant for the clinician? Surv Ophthalmol 2007;52 (Suppl 2):109-14. 9. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg 2005;31:156-62. 10. Kiely PM, Carney LG, Smith G. Menstrual cycle variations of corneal topography and thickness. Am J Optom Physiol Opt 1983;60:822-9. 11. Giuffrè G, Di Rosa L, Fiorino F, Bubella DM, Lodato G. Variations in central corneal thickness during the menstrual cycle in women. Cornea 2007;26:144-6. 12. Spoerl E, Zubaty V, Raiskup-Wolf F, Pillunat LE. Oestrogeninduced changes in biomechanics in the cornea as a possible reason for keratectasia. Br J Ophthalmol 2007;91: 1547-50. 13. Bilgihan K, Hondur A, Sul S, Ozturk S. Pregnancy-induced progression of keratoconus. Cornea 2011;30:991-4. 14. Ziai N, Ory SJ, Khan AR, Brubaker RF. Beta-human chorionic gonadotropin, progesterone, and aqueous dynamics during pregnancy. Arch Ophthalmol 1994;112:801-6. 15. Yaron Y, Cherry M, Kramer RL, et al. Second-trimester maternal serum marker screening: maternal serum alphafetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome. Am J Obstet Gynecol 1999;181:968-74. 16. Broman AT, Congdon NG, Bandeen-Roche K, Quigley
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HA. Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure. J Glaucoma 2007;16:581-8. 17. Koob TJ, Jeffrey JJ, Eisen AZ, Bauer EA. Hormonal interactions in mammalian collagenase regulation. Comparative studies in human skin and rat uterus. Biochim Biophys Acta 1980;629:13-23. 18. Sato T, Ito A, Mori Y, Yamashita K, Hayakawa T, Nagase H. Hormonal regulation of collagenolysis in uterine cervical fibroblasts. Modulation of synthesis of procollagenase, prostromelysin and tissue inhibitor of metalloproteinases (TIMP) by progesterone and oestradiol-17 beta. Biochem J 1991;275:645-50. 19. Suzuki T, Sullivan DA. Estrogen stimulation of proinflammatory cytokine and matrix metalloproteinase gene expression in human corneal epithelial cells. Cornea 2005;24:1004-9. 20. Harris ED Jr, Krane SM. Collagenases (third of three parts). N Engl J Med 1974;291:652-61. 21. Kao WW, Vergnes JP, Ebert J, Sundar-Raj CV, Brown SI. Increased collagenase and gelatinase activities in keratoconus. Biochem Biophys Res Commun 1982;107:929-36. 22. Rehany U, Lahav M, Shoshan S. Collagenolytic activity in keratoconus. Ann Ophthalmol 1982;14:751-4. 23. Kenney MC, Chwa M, Escobar M, Brown D. Altered gelatinolytic activity by keratoconus corneal cells. Biochem Biophys Res Commun 1989;161:353-7. 24. Mackiewicz Z, Määttä M, Stenman M, Konttinen L, Tervo T, Konttinen YT. Collagenolytic proteinases in keratoconus. Cornea 2006;25:603-10. 25. Zhou L, Sawaguchi S, Twining SS, Sugar J, Feder RS, Yue BY. Expression of degradative enzymes and protease inhibitors in corneas with keratoconus. Invest Ophthalmol Vis Sci 1998;39:1117-24. 26. Weinreb RN, Lu A, Beeson C. Maternal corneal thickness during pregnancy. Am J Ophthalmol 1988;105:258-60. 27. Hager A, Loge K, Füllhas MO, Schroeder B, Grossherr M, Wiegand W. Changes in corneal hysteresis after clear corneal cataract surgery. Am J Ophthalmol 2007;144:341-6. 28. de Freitas Valbon B, Ventura MP, da Silva RS, Canedo AL, Velarde GC, Ambrósio R Jr. Central corneal thickness and biomechanical changes after clear corneal phacoemulsification. J Refract Surg 2012;28:215-9. 29. Soergel F, Jean B, Seiler T, et al. Dynamic mechanical spectroscopy of the cornea for measurement of its viscoelastic properties in vitro. Ger J Ophthalmol 1995;4:151-6. 30. Hjortdal JO. Biomechanical studies of the human cornea. Development and application of a method for experimental studies of the extensibility of the intact human cornea. Acta Ophthalmol Scand 1995;73:364-5.
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31. Qureshi IA, Xi XR, Yaqob T. The ocular hypotensive effect of late pregnancy is higher in multigravidae than in primigravidae. Graefes Arch Clin Exp Ophthalmol 2000;238:64-7. 32. Horven I, Gjonnaess H. Corneal indentation pulse and intraocular pressure in pregnancy. Arch Ophthalmol 1974;91:92-8. 33. Phillips CI, Gore SM. Ocular hypotensive effect of late pregnancy with and without high blood pressure. Br J Ophthalmol 1985;69:117-9. 34. Horven I, Gjonnaess H. Corneal indentation pulse reduc-
tion in pregnancy. Acta Ophthalmol 1972;50:375-84. 35. Treister G, Mannor S. Intraocular pressure and outflow facility. Effect of estrogen and combined estrogen-progestin treatment in normal human eyes. Arch Ophthalmol 1970; 83:311-8. 36. Paterson GD, Miller SJ. Hormonal influence in simple glaucoma. Br J Ophthalmol 1963;47:129-37. 37. Becker B, Friedenwald JS. Clinical aqueous outflow. Arch Ophthalmol 1953;50:557-71. 38. Wilke K. Episcleral venous pressure and pregnancy [proceedings]. Acta Ophthalmol Suppl 1975;125:40-1.
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Eur J Ophthalmol 2014; 24 ( 3 ): 314-319
ORIGINAL ARTICLE
Corneal biomechanical parameters during pregnancy Emine Sen1, Yüksel Onaran2, Pinar Nalcacioglu-Yuksekkaya1, Ufuk Elgin1, Faruk Ozturk1 1 2
Ulucanlar Eye Research Hospital, Ankara - Turkey Department of Obstetrics and Gynecology, Fatih University of Medical School, Ankara - Turkey
Purpose: To evaluate the variation in biomechanical properties and central corneal thickness (CCT) for each trimester during pregnancy and to compare the values with those in nonpregnant women. Methods: We prospectively studied the eyes of 32 pregnant and 34 age-matched non-pregnant women. The parameters included corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOP), and corneal-compensated IOP measured by the Ocular Response Analyzer (ORA). The CCT was also measured with an ultrasonic pachymeter attached to the ORA. Results: The mean age was 27.0 ± 3.8 years in the study group and 28.0 ± 4.1 years in the control group. The mean CH measurement was 10.6 ± 1.4 mmHg in the study group and 10.1 ± 1.3 mmHg in the control group. The mean CRF value was 9.6 ± 1.7 mmHg in the study group and 10.0 ± 1.4 mmHg in the control group. The mean CCT value was 541.1 ± 22.4 µm in the study group and 536.5 ± 27.1 µm in the control group. No statistically significant differences were found regarding CH, CRF, or CCT values between the 2 groups (independent t test, p = 0.160, p = 0.355, p = 0.450, respectively). Conclusions: Hormonal changes during pregnancy may not affect corneal biomechanics. This may be due to the balanced effect of the various hormones on the cornea during pregnancy. Keywords: Central corneal thickness, Corneal biomechanics, Hormonal changes, Pregnancy Accepted: September 16, 2013
INTRODUCTION Pregnancy is associated with changes involving multiple organ systems, including the eyes. Ocular physiologic changes including decreased intraocular pressure (IOP), increased facility of outflow, decreased corneal sensitivity (1), increased central corneal thickness (CCT) (2) and curvature (3), and temporary refractive changes and contact lens intolerance (3) have been reported previously. Estrogen, progesterone, and androgen receptors have been shown in the nuclei of human corneal epithelial, stromal, and endothelial cells (4-6). Goldich et al (7) reported variations in corneal biomechanical properties during the menstrual cycle. These changes probably occur due to these receptors in the cornea (4-7). It is therefore possible that the increased 314
estrogen and progesterone levels during pregnancy may lead to changes in corneal biomechanical properties. The Ocular Response Analyzer (ORA, Reichert Inc.; Depew, New York, USA) is used to measure in vivo corneal biomechanical properties, which are presented by 2 parameters: corneal hysteresis (CH) and the corneal resistance factor (CRF). It also measures Goldmann-correlated IOP (IOPg) and corneal compensated IOP (IOPcc), which is independent from the influence of corneal biomechanical properties. To our knowledge, ORA parameters during pregnancy have not been described. We hypothesized that there would be some changes in corneal biomechanics during pregnancy. The aim of this study was to investigate the changes of the biomechanical properties of the cornea and CCT value in
© 2013 Wichtig Editore - ISSN 1120-6721
Sen et al
pregnant women and to compare them with age-matched nonpregnant subjects.
MATERIALS AND METHODS We examined 32 pregnant women with uncompleted singleton pregnancies and no history of an ocular problem who were consecutively referred to our clinic from the Obstetrics and Gynecology Clinic of Fatih University School of Medicine. The control group consisted of 34 age- and sex-matched subjects and they underwent concurrent ophthalmic examination in this prospective study. All the study procedures were conducted in accordance with the Declaration of Helsinki, and informed consent was obtained from each participant. This study was approved by the Ethical Committee of the Ankara University School of Medicine. Inclusion criteria were age over 18 years and uncomplicated pregnancy for the study group. Exclusion criteria were known systemic disease, ophthalmic disorders, contact lenses wear, refractive error exceeding ± 3.00 D, or any type of previous eye surgery. Healthy subjects using contraceptive medications were also excluded. The subjects in both the study and the control groups underwent complete ophthalmologic examination including best-corrected visual acuity with Snellen chart, refraction, and anterior segment and fundus examination (without mydriatics). To avoid possible diurnal variations, corneal biomechanical parameters including CH, CRF, IOPg, and IOPcc were measured between 9:00 and 11:00 AM by the same experienced physician (E. S.) according to normal clinical practice and the manufacturer’s guidelines. Three readings of good-quality images were included for each patient. Good quality was defined as readings having a waveform with 2 distinct peaks. The mean values of each parameter were used for statistical evaluation. A dynamic bidirectional applanation process is used to measure the corneal biomechanical properties and IOP with the ORA. The device is based on noncontact tonometry where the air pressure required to applanate the central cornea is used to determine IOP (8). Rapid air deforms the cornea, measured by an electro-optical system. The air pushes the cornea into a slightly concave position and corneal indentation. Afterwards the cornea returns to its normal convex curvature. The system measures 2 pressure
values: the force at which the cornea flattens as the air pressure rises (force-in applanation) and the force at which the cornea flattens again as the pressure falls (force-out applanation). A hand-held ultrasonic pachymeter that was attached to the ORA was used for CCT measurement. The CCT measurements were performed at the same time of the day after the ORA measurement. Repeated sets of 5 readings were taken at the center of the cornea after administration of topical anesthesia (proparacaine hydrochloride 0.5%, Alcaine ophthalmic solution, Alcon, Turkey). The Kolmogorov-Smirnov test was used to evaluate the normal distribution for all groups. The correlation between the right and left eye was evaluated with the Pearson correlation test. The differences between the 2 groups were evaluated by the independent t test. The Kruskal-Wallis test was used to compare each parameter between trimesters in the study group. A p value 0.05).
DISCUSSION Corneal hysteresis and CRF are new parameters that assess corneal biomechanical properties (9). Previous studies have shown the influence of the hormone status on the cornea (2, 10, 11). Changes in corneal curvature (2) and corneal thickness (12) and regression of keratoconus have been reported during pregnancy (13). β-human chorionic gonadotropin, progesterone (14), and estrogen (12) levels are markedly elevated during pregnancy. The progesterone level begins to increase at about 20 weeks of gestation, at the end of the third trimester (14). The effect of progesterone appears during the latter half of pregnancy. Estrogen is first detected at 9 weeks and peaks at 31-35 weeks of gestation (15). Studies have reported the presence of estrogen, progesterone, and androgen receptors in the nuclei of human corneal epithelial, stromal, and endothelial cells (4-6). We therefore hypothesized that there may be some changes in corneal biomechanics due to pregnancy-associated hormones. The stroma makes up 90% of the corneal thickness and is the most important corneal layer from the biomechanical point of view. The extracellular matrix in the stroma mainly consists of collagens, proteoglycans, and glycosaminoglycans and defines the elasticity and viscoelastic structure of the cornea (12). The CH reflects the viscous damping of the cornea that may define the corneal response to applanation forces during ocular tonometry (16), whereas the CRF has been strongly associated with corneal stiffness (8). During pregnancy, progesterone (14) and estrogen (12) levels are markedly elevated. Progesterone prevents the production of prostaglandins that cause activation of collagenases, therefore leading to collagenase activation (17). Progesterone also affects proteinase inhibitors through the production of tissue inhibitor of metalloproteinases (TIMP) (18). Sato et al (18) found that progesterone increased the production of TIMP in their experimental study and reported progesterone to be more effective than 17-β estradiol in rabbit uterine cervical cells (18). Estradiol stimulates the production of matrix metalloproteinase (19) and the production or activation of collagenolytic enzymes (20). Estrogen also induces prostaglandin
© 2013 Wichtig Editore - ISSN 1120-6721
Sen et al
production, causing collagenase activation (12). The increased collagenolytic activities may predispose the cornea to keratoconus development (21-25). This is encountered as a biomechanically weakened cornea in the clinic. Estrogen-induced changes in corneal biomechanical properties have been reported by Spoerl et al (12). They suggested that the estrogen hormone is a potentially modulating factor for the biomechanical properties of the cornea (12). In their experimental study, they showed significantly reduced stiffness as determined with stressstrain curves in porcine eyes that were incubated with high levels of estrogen as in pregnancy (12). Goldich et al (7) observed a significant variation in corneal thickness and biomechanical parameters during the normal menstrual cycle. Estrogen has 2 peaks during the menstrual cycle, with one during the ovulation period and the other at the end of the cycle. In their study, the CH and CRF were significantly decreased at ovulation and CCT increased at both peaks of estrogen in a way that was closely related to the changes in the estrogen level (7). We report the corneal biomechanical properties of uncomplicated pregnant women in this study. We observed no changes in corneal biomechanical parameters during pregnancy when compared with nonpregnant subjects. There was also no difference in biomechanical parameters among the 3 trimesters of pregnancy. Sato et al (18) state that the collagenase activation decreasing activity of progesterone is more effective than the effect of estrogen in rabbit uterine cells, which may have led to stabilization of the corneal biomechanical framework. The negative effect of estrogen on the corneal biomechanical structure of pregnant women may therefore have been balanced by progesterone, leading to unchanged corneal structure when pregnant women were compared with nonpregnant subjects in our study. We also measured CCT and IOP in addition to corneal biomechanical features with the ORA in our study. The mean CCT value is higher in pregnant women than in nonpregnant women but this was not statistically significant. A recent study by Efe et al (2) reported a significant decrease in IOP during the second and third trimester of pregnancy, accompanied by a reciprocal increase in CCT during the same period. Weinreb et al (26) compared the CCT in 89 pregnant women with the control eyes of 18 nongravida and 17 postpartum women and reported that the cornea was significantly thicker in the pregnant women. They hypothesized that pregnancy-associated fluid retention may
cause higher corneal thickness (26). Pregnancy may also result in changes in corneal biomechanics. Similar to this result, recent studies have reported that increased CCT due to postoperative corneal edema after phacoemulsification surgery leads to a change in corneal biomechanical properties (27, 28). The increase in CCT after phacoemulsification was followed by a reduction in CRF and CH, while decreased IOPcc and IOPg were also reported by de Freitas Valbon et al (28). Previous experimental studies have reported the relationship between corneal hydration degree and biomechanical properties (29, 30). A study showed a reduction of shearing strength with increasing hydration (29). Hjortdal (30) suggested a significantly increased distensibility of the cornea at a higher hydration level. In our study, decreased IOPg and IOPcc values were observed in pregnant women. Previous studies have reported IOP decreases and CCT increases during pregnancy (2, 26, 31-34). The main mechanism underlying the decreased IOP during pregnancy is the relationship between female hormones and increased outflow (2). Treister and Mannor (35) showed decreased IOP with the use of progesterone or the combination of progesterone and estrogen at pharmacologic doses. A statistically significant increase in aqueous outflow associated with progesterone levels has been shown in pregnancy (36, 37). Ziai et al (14) hypothesized that progesterone acts as a glucocorticoid antagonist in the outflow apparatus and prevents the ocular hypertensive effect of endogenous steroids. Another hypothesis suggests decreased episcleral venous pressure in pregnant women (38). In summary, there was no difference in corneal biomechanical features between pregnant and nonpregnant subjects, indicating no effect of hormonal changes during pregnancy on these features. This may be due to balancing of hormonal effects on the cornea during pregnancy. Financial Support: No financial support was received for this submission. Conflict of Interest Statement: None of the authors has conflict of interest with this submission. Address for correspondence: Emine Sen, MD Ulucanlar Eye Research Hospital Ulucanlar Street No: 59 (06240) Altındag/Ankara Turkey [email protected]
© 2013 Wichtig Editore - ISSN 1120-6721
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Corneal biomechanics and pregnancy
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