Current Eye Research, 2014; 39(6): 642–647 ! Informa Healthcare USA, Inc. ISSN: 0271-3683 print / 1460-2202 online DOI: 10.3109/02713683.2013.855236
ORIGINAL ARTICLE
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Evaluation of Subfoveal Choroidal Thickness in Pregnant Women Using Enhanced Depth Imaging Optical Coherence Tomography Necip Kara1, Nihat Sayin2, Dilara Pirhan2, Asli Deger Vural2, Hatice Bilge ArazErsan2, Ali Ismet Tekirdag3, Gonca Yetkin Yildirim3, Bekir Gulac3 and Gokce Yilmaz3 1
Department of Ophthalmology, Sehitkamil State Hospital, Gaziantep, Istanbul, 2Department of Ophthalmology, and 3Department of Obstetrics and Gynaecology, Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey
ABSTRACT Purpose: To evaluate the subfoveal choroidal thickness (SFCT) measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in pregnant women. Methods: In this prospective and cross-sectional study, 100 pregnant women and 100 age-matched nonpregnant women were enrolled. The SFCT was measured by EDI-OCT. The refractive error, intraocular pressure (IOP), axial length (AL), central corneal thickness (CCT), systolic and diastolic blood pressure, and ocular perfusion pressure (OPP) were also measured. Pregnancy-related factors including gestational age, maternal weight gain, and fetal weight were noted. Results: Mean SFCT was 371.1 61.8 mm in the study group and 337.2 62.4 mm in the control group (p50.001). No significant correlation was found between SFCT and spherical refraction, IOP, AL, CCT, OPP, gestational age, maternal weight gain, or fetal weight. Conclusion: Our results suggest that subfoveal choroidal thickness increases in pregnant women compared with age-matched nonpregnant women. Keywords: Choroidal thickness, enhanced depth imaging optical coherence tomography, pregnancy
INTRODUCTION
coherence tomography technique, called enhanced depth imaging optical coherence tomography (EDIOCT), allows in vivo examination and quantification of the choroid. The choroid accounts for most ocular blood flow,6 and several previous studies have shown ocular blood circulation to be altered in pregnant women. Many previous studies have focused on measuring subfoveal choroidal thickness (SFCT) in healthy participants as well as those with several pathologies.7–13 The choroid is thickened in central serous chorioretinopathy (CSC) likely due to the choroidal vascular alteration. It has been shown that pregnancy is an important risk factor for CSC.14 Also, pregnancy complicated by preeclampsia may lead to dysfunction choroidal circulation. Based on these findings,
Pregnancy may lead to three types of ocular changes, including physiological and pathological changes, as well as those that aggravate pre-existing diseases. Previous studies have reported various pregnancyrelated ocular changes, including a decrease in corneal sensitivity, an increase in central corneal thickness (CCT) and curvature, a decrease in intraocular pressure (IOP), and changes in vision and ocular blood flow.1–5 Recent advances in ophthalmic imaging devices have enhanced the understanding of ocular pathophysiology. Until recently, choroidal thickness could not be accurately measured by any imaging modality. A recent modification to the standard optical
Received 7 June 2013; revised 16 August 2013; accepted 5 October 2013; published online 8 January 2014 Correspondence: Necip Kara, Department of Ophthalmology, Sehitkamil State Hospital, Pancarli Mh. 580015 nolu Sk. No.: 9, Gaziantep, Turkey. E-mail: [email protected]
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Subfoveal Choroidal Thickness in Pregnancy we thought that pregnancy may cause choroidal changes. The purpose of this study is to evaluate SFCT measured by EDI-OCT in pregnant women.
METHODS
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Study Population and Design This prospective and comparative study was performed at the Obstetrics and Gynecology and Ophthalmology Departments of Istanbul Kanuni Sultan Suleyman Education and Research Hospital. The study followed the tenets of the Declaration of Helsinki and was approved by the local ethics committee. All participants received oral and written information about the study, and each participant provided written informed consent. One hundred healthy pregnant women were recruited from the Division of Obstetrics for the study (Study group). One hundred healthy nonpregnant volunteers were included as a control group for comparison purposes. These volunteers included employees and visitors of the hospital. Ocular exclusion criteria included the following: a best corrected visual acuity worse than 20/20, glaucomatous optic disc changes such as excavation, notching, or focal thinning of the neuroretinal rim, peripapillary hemorrhage, glaucomatous visual field defects, IOP readings greater than 22 mmHg, more than 2 diopters of cylindrical and/or 4 diopters of spherical refractive error, poor image quality, any history of ocular diseases, and history of previous intraocular surgery or laser therapy. Extraocular exclusion criteria included a history of systemic disease such as hypertension or diabetes mellitus, and the development of complications such as preeclampsia and pregnancyinduced hypertension in pregnant women.
Examination Protocol and Study Measurements Each participant underwent a comprehensive ophthalmologic examination, including a review of the patient’s medical history, corrected distance visual acuity, visual field test, slit-lamp microscopy, and funduscopic examination. A complete medical history including gestational age, fetal weight, and maternal weight gain was recorded. Study participants underwent central corneal thickness (CCT) and axial length (AL) measurements using ultrasonic scans. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were measured before the choroidal thickness measurement. Mean blood pressure (mBP) was calculated as the dBP plus onethird of the difference between sBP and dBP. The ocular perfusion pressure (OPP) was calculated by !
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measuring the difference between two of the three mBP and the IOP values.15,16 EDI-OCT Measurement All participants with undilated pupils were examined with the Cirrus HD-OCT 4000 (Carl Zeiss Meditec, Inc., Dublin, CA). The scan pattern used in the Zeiss Cirrus, HD 5-line raster, is a 6-mm line consisting of 4096 A-scans. EDI-OCT measurement has been previously described.10 The images were not inverted to bring the choroid into closer proximity to the zerodelay line because image inversion using Cirrus software results in a low-resolution, pixelated image. To be included in this study, images had to be taken as close to the fovea as possible, by choosing to image the thinnest point of the macula. One eye per patient was selected for measurements. SFCT was determined as the vertical distance from the hyperreflective line of the hyperreflective RPE to the line of the inner surface of the sclera centered on the fovea using a measuring tool with built-in linear measuring (Figure 1). The thickness of the horizontal scan centered on the fovea was referred as subfoveal choroidal thickness. The best image that both inner and outer borders of the choroid of the image were clearly distinguishable was deemed acceptable and used for the following analysis. The images were taken by one experienced clinician (N.S.), and the images were assessed by two ophthalmologists (N.K. and D.P.), who masked in terms of groups. The measurements from the two observers were then averaged for analysis.
Statistical Analyses One eye per patient was selected for analyses. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS, Chicago, IL) version 16. The normality of the data was confirmed using the Shapiro–Wilk test (p40.05). A t-test was used to compare variables between groups. Pearson’s correlation was used to examine the relationships among the measured variables. A p value of less than 0.05 was considered significant.
RESULTS One hundred volunteer pregnant and 100 nonpregnant healthy women were evaluated. All subjects were free of ocular or systemic diseases, had no pregnancy-induced complications such as preeclampsia, were not taking any medication, and had good health. The mean age, mean AL, and mean spherical refraction of the two groups did not differ significantly. The demographic and clinical characteristics of the subjects are summarized in Table 1.
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644 N. Kara et al.
FIGURE 1 Enhanced depth ımaging. Optical coherence tomography scans showing subfoveal choroidal thicknesses of a nonpregnant women (A) and a pregnant women (B). TABLE 1. Demographic and clinical characteristics for the study (pregnant) and control (nonpregnant) groups. Study group Number of eyes/patients Age (yr) Spherical refraction, D Gestational age (weeks) Maternal weight gain (kg) Fetal weight (g)
Control group
100/100 28.6 6.3 (19–41) 0.04 0.9 ( 3.75 to 2.25) 27.3 6.6 (15-38) 6.6 4.5 (2–15) 1624 1134 (185–5500)
100/100 30.5 6.2 (18–42) 0.27 0.8 ( 3.50 to 1.25)
pa 0.069 0.130
Data are expressed as the mean SD. SD: Standard deviation. Independent student t test.
a
TABLE 2. Subfoveal choroidal thickness and other clinical measurements in the study (pregnant) and control (nonpregnant) groups.
SFCT (mm) AL (mm) CCT (mm) IOP (mmHg) OPP (mmHg)
Study group
Control group
pa
371.1 61.8 (223–517) 23.0 0.7 (20.9–25.7) 588.8 46.0 (488–724) 14.1 1.9 (10–20) 37.9 5.0 (28.6–48.2)
337.2 62.4 (197–436) 23.1 0.8 (21.0–25.4) 555.5 48.7 (473–677) 15.2 2.1 (8–21) 38.5 6.4 (25.6–50.6)
p50.001 0.378 p50.001 0.002 0.466
Data are expressed as the mean SD. SFCT: subfoveal choroidal thickness, AL:axial lenght, CCT: central corneal thickness, IOP: ıntraocular pressure, OPP: ocular perfusion pressure, SD: standard deviation. a Independent student t test.
Table 2 shows the results of clinical measurements. Mean SFCT was measured as 371.1 61.8 mm in the study group and 337.2 62.4 mm in the control group (p50.001) (Figure 2). The mean CCT of the study and control groups were 588.8 46.0 mm and 555.5 48.7 mm, respectively (p50.001). The mean IOP of the study group and controls was 14.1 1.9 mmHg and 15.2 2.1 mmHg, respectively (p = 0.002). The mean AL and mean OPP between the groups were not significantly different (p = 0.378 and p = 0.466, respectively). Table 3 shows the correlation analysis between SFCT and CCT, AL, IOP, OPP, age, spherical
refraction, gestational age, maternal weight gain, and fetal weight in pregnant women. There was no significant correlation between the choroidal thickness and these measurements.
DISCUSSION The choroidal circulation displays one of the highest rates of blood flow in the body.17 The choroid performs several important functions such as supplying oxygen and nutrients to the retinal pigment epithelium and the retina up to the inner nuclear Current Eye Research
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Subfoveal Choroidal Thickness in Pregnancy
FIGURE 2 Mean subfoveal choroidal thickness in the pregnant women and in the controls. The mean thickness is significantly (p = 0.001) greater in the pregnant women.
TABLE 3. Correlation analyses between subfoveal choroidal thickness and other clinical and demographic factors in pregnant women. Pear Corr SFCT AL CCT IOP OPP Age Spherical refraction Gestational age Maternal weight gain Fetal weight
0.226 0.117 0.124 0.092 0.173 0.271 0.116 0.030 0.306
pa 0.135 0.461 0.432 0.582 0.279 0.110 0.454 0.857 0.094
SFCT: subfoveal choroidal thickness, AL: axial lenght, CCT: central corneal thickness, IOP: ıntraocular pressure, OPP: ocular perfusion pressure. a Pearson correlation test.
layer, temperature regulation, and waste product removal.18 Thus, a structurally and functionally normal choroidal vasculature is essential for the function of the retina. Abnormal choroidal blood volume or compromised flow or both can result in photoreceptor dysfunction and death.19 Pregnancy is a period of enormous physiological changes in the human body. On average, there is a 40% increase in cardiac output resulting from increases in heart rate, cardiac contractility, and circulating volume, combined with decreased peripheral vascular resistance.20 During pregnancy, blood flow has been demonstrated to be increased in many organs, such as the cerebral cortex,21 skin,22 and kidneys.23 Previous studies have also reported that ocular blood flow increases throughout gestation.24–26 Pregnancy is also a risk factor of CSC. Several hypotheses have been offered regarding the pathogenesis of CSR in pregnancy, but none have been !
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definitively proved. The changes in the choroidal circulation such as choroidal vasodilation and choroidal vascular hyperpermeability may lead to serous retinal detachment.27 Moreover, pregnancy complicated by preeclampsia may cause to dysfunction of both retinal and choroidal circulation.28,29 It has been speculated that preeclampsia may lead to intense spasm of the choroidal arterioles, resulting in choroidal ischemia and increased vascular permeability, and ultimately, accumulation of serous fluid in the subretinal space.30 As mentioned above, many previous studies have reported that the choroid accounts for a large portion of ocular blood flow, and many other studies have reported that pregnancy increases ocular blood flow. However, there are limited information on choroidal changes in pregnant women. In this comparative study, pregnant women demonstrated significantly thicker SFCT than did age-matched nonpregnant controls. In normal pregnancy, cardiac output and arterial compliance increase, and blood pressure remains stable, while total vascular resistance, plasma protein concentrations, and total plasma osmolality decrease.31,32 In addition, an increase in choroidal blood flow and a decrease in IOP are observed during pregnancy.33,34 We thought that the choroidal thickness changes might be associated with these hemodynamic changes in pregnant women. Many physiological factors may influence choroidal thickness. Aging is one factor associated with changes in choroidal thickness, and older patients are reported to have thinner choroids.8,10,11,35–38 Similarly, increased myopia and axial length were demonstrated to be associated with a significantly thinner choroid.8,9–13,35,37,38 In our study, no significant correlation was found between the SFCT and age, refractive error, or AL. These results may be related to two factors. The study subjects had a relatively narrower range in terms of age, refractive error, and AL. However, other studies have had a wider range for these parameters. Pregnancy is a distinct period in the life of a woman, which causes many physiological changes in the eye. Therefore, many ocular factors that have been associated with choroidal thickness in nonpregnant healthy subjects may not be associated with pregnant. A recent study investigated the association between choroidal thickness and IOP and OPP values, and no significant correlation was found in healthy subjects.39 Similarly, our study showed no correlation between SFCT and IOP and OPP in pregnant women. Also, the study found no significant association between SFCT and pregnancy-related factors such as gestational age, maternal weight gain, and fetal weight. In addition to physiological causes, there are several diseases in which choroidal thickness has been reported to be significantly different from that of normal subjects.40 For example, choroid thickness has
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646 N. Kara et al. been found to be thinner in cases of age-related macular degeneration. In patients with central serous chorioretinopathy, it is believed that the choroid is hyperpermeable, and thus there is an increase in choroidal thickness compared with that of healthy subjects.41 However, diabetic patients with retinopathy have thinner choroids and show a decrease in mean subfoveal choroidal blood flow, as measured by laser Doppler flowmetry.42 Further studies using EDIOCT are required to evaluate the choroidal changes in pregnancy-related chorioretinal disorders such as serous retinal detachment. To the best of our knowledge, our study is the first work that has assessed choroidal thickness in pregnant women and its association with ocular parameters and pregnancy-related factors. Strengths of the study include its prospective design and large study population. Also, all measurements were performed within a limited time (9:00 am to 12:00 pm), which minimized the possibility of choroidal thickness change caused by diurnal variations that have been reported in many previous studies.9,43,44 On the other hand, this study had several limitations. The optical coherence tomography used in this study did not include an eye tracking system and thus may be inhibited from obtaining images of the highest possible contrast. The images of the EDI-OCT were obtained in a single line, and the choroidal thickness measurement did not cover the overall macular area. We determined the SFCT by measuring from the outer border of the RPE to the inner border of the sclera on the display, using the planimetric scale software in the device. Therefore, our subfoveal thickness measurements may contain slight errors. Moreover, the reproducibility of choroidal thickness measurements using OCT is still debatable. However, others found high interobserver correlation,7 high repeatability,45 and high intersystem, interexaminer, and intervisit reproducibility46 in choroidal thickness measurements. In summary, SFCT in pregnant women was significantly thicker than in nonpregnant healthy controls. This result should be taken into consideration when choroidal thickness is evaluated for pregnancy-related disease or clinical research. SFCT was not correlated with age, axial length, refractive error, IOP, OPP, or pregnancy-related factors including gestational age, maternal weight gain, or fetal weight. Improved in vivo visualization of the choroid and measurement of choroidal thickness using EDI-OCT could improve our understanding of a variety of pregnancy-related disorders such as serous retinal detachment in the future.
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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36. Hirata M, Tsujikawa A, Matsumoto A, Hangai M, Ooto S, Yamashiro K, et al. Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography. Investig Ophthalmol Vis Sci 2011;52:4971–4978. 37. Maul EA, Friedman DS, Chang DS, Boland MV, Ramulu PY, Jampel HD, et al. Choroidal thickness measured by spectral domain optical coherence tomography. Factors affecting thickness in glaucoma patients. Ophthalmology 2011;118:1571–1579. 38. Mwanza JC, Hochberg JT, Banitt MR, Feuer WJ, Budenz DL. Lack of association between glaucoma and macular choroidal thickness measured with enhanced depth-imaging optical coherence tomography. Investig Ophthalmol Vis Sci 2011;52:3430–3343. 39. Wei WB, Xu L, Jonas JB, Shao L, Du KF, Wang S, et al. Subfoveal choroidal thickness: The Beijing Eye Study. Ophthalmology 2013;120:175-180. 40. Manjunath V, Goren J, Fujimoto JG, Duker JS. Analysis of choroidal thickness in age-related macular degeneration using spectral-domain optical coherence tomography. Am J Ophthalmol 2011;152:663–668. 41. Kim SW, Oh J, Kwon SS, Huh K. Comparison of choroidal thickness among patients with healthy eyes, early agerelated maculopathy, neovascular age-related macular degeneration, central serous chorioretinopathy, and polypoidal choroidal vasculopathy. Retina 2011;31:1904–1911. 42. Nagaoka T, Kitaya N, Sugawara R, Yokota H, Mori F, Hikichi T, et al. Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes. Br J Ophthalmol 2004;88:1060–1063. 43. Chakraborty R, Read SA, Collins MJ. Diurnal variations in axial length, choroidal thickness, intraocular pressure, and ocular biometrics. Invest Ophthalmol Vis Sci 2011;52: 5121–5129. 44. Tan CS, Ouyang Y, Ruiz H, Sadda SR. Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 2012;53:261–266. 45. Rahman W, Chen FK, Yeoh J, Patel P, Tufail A, Da Cruz L. Repeatability of manual subfoveal choroidal thickness measurements in healthy subjects using the technique of enhanced depth imaging optical coherence tomography. Invest Ophthalmol Vis Sci 2011;52:2267–2271. 46. Ikuno Y, Maruko I, Yasuno Y, Miura M, Sekiryu T, Nishida K, et al. Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and highpenetration optical coherence tomography. Invest Ophthalmol Vis Sci 2011;52:5536–5540.
ORIGINAL ARTICLE
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Evaluation of Subfoveal Choroidal Thickness in Pregnant Women Using Enhanced Depth Imaging Optical Coherence Tomography Necip Kara1, Nihat Sayin2, Dilara Pirhan2, Asli Deger Vural2, Hatice Bilge ArazErsan2, Ali Ismet Tekirdag3, Gonca Yetkin Yildirim3, Bekir Gulac3 and Gokce Yilmaz3 1
Department of Ophthalmology, Sehitkamil State Hospital, Gaziantep, Istanbul, 2Department of Ophthalmology, and 3Department of Obstetrics and Gynaecology, Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey
ABSTRACT Purpose: To evaluate the subfoveal choroidal thickness (SFCT) measured by enhanced depth imaging optical coherence tomography (EDI-OCT) in pregnant women. Methods: In this prospective and cross-sectional study, 100 pregnant women and 100 age-matched nonpregnant women were enrolled. The SFCT was measured by EDI-OCT. The refractive error, intraocular pressure (IOP), axial length (AL), central corneal thickness (CCT), systolic and diastolic blood pressure, and ocular perfusion pressure (OPP) were also measured. Pregnancy-related factors including gestational age, maternal weight gain, and fetal weight were noted. Results: Mean SFCT was 371.1 61.8 mm in the study group and 337.2 62.4 mm in the control group (p50.001). No significant correlation was found between SFCT and spherical refraction, IOP, AL, CCT, OPP, gestational age, maternal weight gain, or fetal weight. Conclusion: Our results suggest that subfoveal choroidal thickness increases in pregnant women compared with age-matched nonpregnant women. Keywords: Choroidal thickness, enhanced depth imaging optical coherence tomography, pregnancy
INTRODUCTION
coherence tomography technique, called enhanced depth imaging optical coherence tomography (EDIOCT), allows in vivo examination and quantification of the choroid. The choroid accounts for most ocular blood flow,6 and several previous studies have shown ocular blood circulation to be altered in pregnant women. Many previous studies have focused on measuring subfoveal choroidal thickness (SFCT) in healthy participants as well as those with several pathologies.7–13 The choroid is thickened in central serous chorioretinopathy (CSC) likely due to the choroidal vascular alteration. It has been shown that pregnancy is an important risk factor for CSC.14 Also, pregnancy complicated by preeclampsia may lead to dysfunction choroidal circulation. Based on these findings,
Pregnancy may lead to three types of ocular changes, including physiological and pathological changes, as well as those that aggravate pre-existing diseases. Previous studies have reported various pregnancyrelated ocular changes, including a decrease in corneal sensitivity, an increase in central corneal thickness (CCT) and curvature, a decrease in intraocular pressure (IOP), and changes in vision and ocular blood flow.1–5 Recent advances in ophthalmic imaging devices have enhanced the understanding of ocular pathophysiology. Until recently, choroidal thickness could not be accurately measured by any imaging modality. A recent modification to the standard optical
Received 7 June 2013; revised 16 August 2013; accepted 5 October 2013; published online 8 January 2014 Correspondence: Necip Kara, Department of Ophthalmology, Sehitkamil State Hospital, Pancarli Mh. 580015 nolu Sk. No.: 9, Gaziantep, Turkey. E-mail: [email protected]
642
Subfoveal Choroidal Thickness in Pregnancy we thought that pregnancy may cause choroidal changes. The purpose of this study is to evaluate SFCT measured by EDI-OCT in pregnant women.
METHODS
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Study Population and Design This prospective and comparative study was performed at the Obstetrics and Gynecology and Ophthalmology Departments of Istanbul Kanuni Sultan Suleyman Education and Research Hospital. The study followed the tenets of the Declaration of Helsinki and was approved by the local ethics committee. All participants received oral and written information about the study, and each participant provided written informed consent. One hundred healthy pregnant women were recruited from the Division of Obstetrics for the study (Study group). One hundred healthy nonpregnant volunteers were included as a control group for comparison purposes. These volunteers included employees and visitors of the hospital. Ocular exclusion criteria included the following: a best corrected visual acuity worse than 20/20, glaucomatous optic disc changes such as excavation, notching, or focal thinning of the neuroretinal rim, peripapillary hemorrhage, glaucomatous visual field defects, IOP readings greater than 22 mmHg, more than 2 diopters of cylindrical and/or 4 diopters of spherical refractive error, poor image quality, any history of ocular diseases, and history of previous intraocular surgery or laser therapy. Extraocular exclusion criteria included a history of systemic disease such as hypertension or diabetes mellitus, and the development of complications such as preeclampsia and pregnancyinduced hypertension in pregnant women.
Examination Protocol and Study Measurements Each participant underwent a comprehensive ophthalmologic examination, including a review of the patient’s medical history, corrected distance visual acuity, visual field test, slit-lamp microscopy, and funduscopic examination. A complete medical history including gestational age, fetal weight, and maternal weight gain was recorded. Study participants underwent central corneal thickness (CCT) and axial length (AL) measurements using ultrasonic scans. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were measured before the choroidal thickness measurement. Mean blood pressure (mBP) was calculated as the dBP plus onethird of the difference between sBP and dBP. The ocular perfusion pressure (OPP) was calculated by !
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measuring the difference between two of the three mBP and the IOP values.15,16 EDI-OCT Measurement All participants with undilated pupils were examined with the Cirrus HD-OCT 4000 (Carl Zeiss Meditec, Inc., Dublin, CA). The scan pattern used in the Zeiss Cirrus, HD 5-line raster, is a 6-mm line consisting of 4096 A-scans. EDI-OCT measurement has been previously described.10 The images were not inverted to bring the choroid into closer proximity to the zerodelay line because image inversion using Cirrus software results in a low-resolution, pixelated image. To be included in this study, images had to be taken as close to the fovea as possible, by choosing to image the thinnest point of the macula. One eye per patient was selected for measurements. SFCT was determined as the vertical distance from the hyperreflective line of the hyperreflective RPE to the line of the inner surface of the sclera centered on the fovea using a measuring tool with built-in linear measuring (Figure 1). The thickness of the horizontal scan centered on the fovea was referred as subfoveal choroidal thickness. The best image that both inner and outer borders of the choroid of the image were clearly distinguishable was deemed acceptable and used for the following analysis. The images were taken by one experienced clinician (N.S.), and the images were assessed by two ophthalmologists (N.K. and D.P.), who masked in terms of groups. The measurements from the two observers were then averaged for analysis.
Statistical Analyses One eye per patient was selected for analyses. All statistical analyses were performed using Statistical Package for the Social Sciences (SPSS, Chicago, IL) version 16. The normality of the data was confirmed using the Shapiro–Wilk test (p40.05). A t-test was used to compare variables between groups. Pearson’s correlation was used to examine the relationships among the measured variables. A p value of less than 0.05 was considered significant.
RESULTS One hundred volunteer pregnant and 100 nonpregnant healthy women were evaluated. All subjects were free of ocular or systemic diseases, had no pregnancy-induced complications such as preeclampsia, were not taking any medication, and had good health. The mean age, mean AL, and mean spherical refraction of the two groups did not differ significantly. The demographic and clinical characteristics of the subjects are summarized in Table 1.
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644 N. Kara et al.
FIGURE 1 Enhanced depth ımaging. Optical coherence tomography scans showing subfoveal choroidal thicknesses of a nonpregnant women (A) and a pregnant women (B). TABLE 1. Demographic and clinical characteristics for the study (pregnant) and control (nonpregnant) groups. Study group Number of eyes/patients Age (yr) Spherical refraction, D Gestational age (weeks) Maternal weight gain (kg) Fetal weight (g)
Control group
100/100 28.6 6.3 (19–41) 0.04 0.9 ( 3.75 to 2.25) 27.3 6.6 (15-38) 6.6 4.5 (2–15) 1624 1134 (185–5500)
100/100 30.5 6.2 (18–42) 0.27 0.8 ( 3.50 to 1.25)
pa 0.069 0.130
Data are expressed as the mean SD. SD: Standard deviation. Independent student t test.
a
TABLE 2. Subfoveal choroidal thickness and other clinical measurements in the study (pregnant) and control (nonpregnant) groups.
SFCT (mm) AL (mm) CCT (mm) IOP (mmHg) OPP (mmHg)
Study group
Control group
pa
371.1 61.8 (223–517) 23.0 0.7 (20.9–25.7) 588.8 46.0 (488–724) 14.1 1.9 (10–20) 37.9 5.0 (28.6–48.2)
337.2 62.4 (197–436) 23.1 0.8 (21.0–25.4) 555.5 48.7 (473–677) 15.2 2.1 (8–21) 38.5 6.4 (25.6–50.6)
p50.001 0.378 p50.001 0.002 0.466
Data are expressed as the mean SD. SFCT: subfoveal choroidal thickness, AL:axial lenght, CCT: central corneal thickness, IOP: ıntraocular pressure, OPP: ocular perfusion pressure, SD: standard deviation. a Independent student t test.
Table 2 shows the results of clinical measurements. Mean SFCT was measured as 371.1 61.8 mm in the study group and 337.2 62.4 mm in the control group (p50.001) (Figure 2). The mean CCT of the study and control groups were 588.8 46.0 mm and 555.5 48.7 mm, respectively (p50.001). The mean IOP of the study group and controls was 14.1 1.9 mmHg and 15.2 2.1 mmHg, respectively (p = 0.002). The mean AL and mean OPP between the groups were not significantly different (p = 0.378 and p = 0.466, respectively). Table 3 shows the correlation analysis between SFCT and CCT, AL, IOP, OPP, age, spherical
refraction, gestational age, maternal weight gain, and fetal weight in pregnant women. There was no significant correlation between the choroidal thickness and these measurements.
DISCUSSION The choroidal circulation displays one of the highest rates of blood flow in the body.17 The choroid performs several important functions such as supplying oxygen and nutrients to the retinal pigment epithelium and the retina up to the inner nuclear Current Eye Research
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Subfoveal Choroidal Thickness in Pregnancy
FIGURE 2 Mean subfoveal choroidal thickness in the pregnant women and in the controls. The mean thickness is significantly (p = 0.001) greater in the pregnant women.
TABLE 3. Correlation analyses between subfoveal choroidal thickness and other clinical and demographic factors in pregnant women. Pear Corr SFCT AL CCT IOP OPP Age Spherical refraction Gestational age Maternal weight gain Fetal weight
0.226 0.117 0.124 0.092 0.173 0.271 0.116 0.030 0.306
pa 0.135 0.461 0.432 0.582 0.279 0.110 0.454 0.857 0.094
SFCT: subfoveal choroidal thickness, AL: axial lenght, CCT: central corneal thickness, IOP: ıntraocular pressure, OPP: ocular perfusion pressure. a Pearson correlation test.
layer, temperature regulation, and waste product removal.18 Thus, a structurally and functionally normal choroidal vasculature is essential for the function of the retina. Abnormal choroidal blood volume or compromised flow or both can result in photoreceptor dysfunction and death.19 Pregnancy is a period of enormous physiological changes in the human body. On average, there is a 40% increase in cardiac output resulting from increases in heart rate, cardiac contractility, and circulating volume, combined with decreased peripheral vascular resistance.20 During pregnancy, blood flow has been demonstrated to be increased in many organs, such as the cerebral cortex,21 skin,22 and kidneys.23 Previous studies have also reported that ocular blood flow increases throughout gestation.24–26 Pregnancy is also a risk factor of CSC. Several hypotheses have been offered regarding the pathogenesis of CSR in pregnancy, but none have been !
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definitively proved. The changes in the choroidal circulation such as choroidal vasodilation and choroidal vascular hyperpermeability may lead to serous retinal detachment.27 Moreover, pregnancy complicated by preeclampsia may cause to dysfunction of both retinal and choroidal circulation.28,29 It has been speculated that preeclampsia may lead to intense spasm of the choroidal arterioles, resulting in choroidal ischemia and increased vascular permeability, and ultimately, accumulation of serous fluid in the subretinal space.30 As mentioned above, many previous studies have reported that the choroid accounts for a large portion of ocular blood flow, and many other studies have reported that pregnancy increases ocular blood flow. However, there are limited information on choroidal changes in pregnant women. In this comparative study, pregnant women demonstrated significantly thicker SFCT than did age-matched nonpregnant controls. In normal pregnancy, cardiac output and arterial compliance increase, and blood pressure remains stable, while total vascular resistance, plasma protein concentrations, and total plasma osmolality decrease.31,32 In addition, an increase in choroidal blood flow and a decrease in IOP are observed during pregnancy.33,34 We thought that the choroidal thickness changes might be associated with these hemodynamic changes in pregnant women. Many physiological factors may influence choroidal thickness. Aging is one factor associated with changes in choroidal thickness, and older patients are reported to have thinner choroids.8,10,11,35–38 Similarly, increased myopia and axial length were demonstrated to be associated with a significantly thinner choroid.8,9–13,35,37,38 In our study, no significant correlation was found between the SFCT and age, refractive error, or AL. These results may be related to two factors. The study subjects had a relatively narrower range in terms of age, refractive error, and AL. However, other studies have had a wider range for these parameters. Pregnancy is a distinct period in the life of a woman, which causes many physiological changes in the eye. Therefore, many ocular factors that have been associated with choroidal thickness in nonpregnant healthy subjects may not be associated with pregnant. A recent study investigated the association between choroidal thickness and IOP and OPP values, and no significant correlation was found in healthy subjects.39 Similarly, our study showed no correlation between SFCT and IOP and OPP in pregnant women. Also, the study found no significant association between SFCT and pregnancy-related factors such as gestational age, maternal weight gain, and fetal weight. In addition to physiological causes, there are several diseases in which choroidal thickness has been reported to be significantly different from that of normal subjects.40 For example, choroid thickness has
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646 N. Kara et al. been found to be thinner in cases of age-related macular degeneration. In patients with central serous chorioretinopathy, it is believed that the choroid is hyperpermeable, and thus there is an increase in choroidal thickness compared with that of healthy subjects.41 However, diabetic patients with retinopathy have thinner choroids and show a decrease in mean subfoveal choroidal blood flow, as measured by laser Doppler flowmetry.42 Further studies using EDIOCT are required to evaluate the choroidal changes in pregnancy-related chorioretinal disorders such as serous retinal detachment. To the best of our knowledge, our study is the first work that has assessed choroidal thickness in pregnant women and its association with ocular parameters and pregnancy-related factors. Strengths of the study include its prospective design and large study population. Also, all measurements were performed within a limited time (9:00 am to 12:00 pm), which minimized the possibility of choroidal thickness change caused by diurnal variations that have been reported in many previous studies.9,43,44 On the other hand, this study had several limitations. The optical coherence tomography used in this study did not include an eye tracking system and thus may be inhibited from obtaining images of the highest possible contrast. The images of the EDI-OCT were obtained in a single line, and the choroidal thickness measurement did not cover the overall macular area. We determined the SFCT by measuring from the outer border of the RPE to the inner border of the sclera on the display, using the planimetric scale software in the device. Therefore, our subfoveal thickness measurements may contain slight errors. Moreover, the reproducibility of choroidal thickness measurements using OCT is still debatable. However, others found high interobserver correlation,7 high repeatability,45 and high intersystem, interexaminer, and intervisit reproducibility46 in choroidal thickness measurements. In summary, SFCT in pregnant women was significantly thicker than in nonpregnant healthy controls. This result should be taken into consideration when choroidal thickness is evaluated for pregnancy-related disease or clinical research. SFCT was not correlated with age, axial length, refractive error, IOP, OPP, or pregnancy-related factors including gestational age, maternal weight gain, or fetal weight. Improved in vivo visualization of the choroid and measurement of choroidal thickness using EDI-OCT could improve our understanding of a variety of pregnancy-related disorders such as serous retinal detachment in the future.
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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