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Changes in choroidal thickness during pregnancy detected by enhanced depth imaging optical coherence tomography
  1. Zeynep Dadaci1,
  2. Husnu Alptekin2,
  3. Nursen Oncel Acir1,
  4. Mehmet Borazan1
  1. 1Department of Ophthalmology, Mevlana University School of Medicine, Konya, Turkey
  2. 2Department of Obstetrics and Gynecology, Mevlana University School of Medicine, Konya, Turkey
  1. Correspondence to Dr Zeynep Dadaci, Department of Ophthalmology, Mevlana University School of Medicine, Aksinne M., Esmetas S., No: 16, Meram, Konya 42040, Turkey; zdadaci{at}hotmail.com

Abstract

Aim To compare the choroidal thickness measurements of healthy pregnant women obtained in the first trimester with measurements obtained in the third trimester using enhanced depth imaging optical coherence tomography (OCT).

Methods 54 eyes of 27 healthy pregnant women and 50 eyes of 25 age matched healthy women were enrolled in this observational, cross-sectional study. The pregnant women underwent two OCT scans, one in the first trimester at gestational weeks 6–8, and the other during the third trimester at gestational weeks 32–37; the control group had OCT scanning during the follicular phase of the menstrual cycle, using the enhanced depth imaging mode. Choroidal thicknesses were measured at the fovea, at three locations nasal, and at three locations temporal to the fovea at 500 μm intervals.

Results The choroidal thickness measurements obtained in the third trimester were significantly decreased in all measured points in both eyes compared to the measurements obtained in the first trimester (p<0.05). At the fovea, the mean (±SD) choroidal thickness measured in the first trimester was 349.22±82.11 μm in the right eyes and 341.30±85.22 μm in the left eyes, which decreased to 333.56±76.61 μm in the right eyes (p=0.014) and 326.93±75.84 μm in the left eyes (p=0.024) in the third trimester. Although not statistically significant, choroidal thicknesses of the control group were less than the choroidal thicknesses of the pregnant women (p>0.05).

Conclusions Choroidal thickness was found to be significantly decreased in healthy pregnant women during the third trimester compared to the first trimester. This finding can provide valuable information when interpreting pregnancy related ocular disorders.

  • Choroid
  • Imaging
  • Physiology

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Introduction

Women's physiology changes markedly during normal pregnancy. The most distinct alterations occur in the hormonal and cardiovascular systems. There is a dramatic increase in the concentrations of both oestradiol and progesterone.1 Oestradiol is known to induce nitric oxide synthases and increased concentrations of nitric oxide, which is a potent vasodilator, lead to a decrease vascular tone both in the luteal phase of the menstrual cycle and in pregnancy.2 Blood volume starts to increase in the first gestational weeks and reaches a peak in the third trimester. Consequently, peripheral vascular resistance decreases throughout the pregnancy, preventing a rise in the mean arterial blood pressure (MAP).1 The blood flow is redistributed and the perfusion of certain organs, such as the uterus, breasts, and kidneys, increases.3

Besides the normal physiological adaptations, pregnancy is also a period of various pathologies, some of which are unique to pregnancy. From an ophthalmological point of view, various ocular conditions may occur uniquely during pregnancy and some ocular diseases, such as diabetic retinopathy, may worsen.4 Previous studies have reported increased central corneal thickness,5 changes in corneal curvature, and intraocular pressure (IOP)6 during pregnancy. Pre-eclampsia or eclampsia associated retinopathy and amniotic fluid embolism are unique to pregnancy.4 Also, it is known that pregnancy is a major risk factor for some ocular pathologies such as central serous chorioretinopathy (CSC).7

Choroid is the vascular structure of the eye supplying blood to vital ocular structures. It has some unique characteristics; in contrast to the retina, autoregulation of the blood flow is limited in the choroid and it has intense autonomic innervation.8 Also, increased sympathetic activity and decreased parasympathetic activity occurs in patients with CSC,9 which is one of the most common ocular pathologies encountered in pregnant women. The choroid can also change its thickness to compensate for various ocular conditions, as in response to retinal defocus,10 and its thickness is reported to change in various ocular pathologies, such as central retinal vein occlusion and CSC.11 ,12 The enhanced depth mode of optical coherence tomography (OCT) allows us to investigate the changes in the choroidal layer of the eye in vivo. Using this method, high resolution cross sectional images of the posterior segment of the eye can be obtained. In particular, OCT devices with enhanced depth imaging programmes can effectively evaluate the choroidal thickness.13

To understand the pathogenesis of pregnancy related ocular disorders, it is important to know the normal ocular adaptations that occur during pregnancy. Therefore, in this study we aimed to investigate the changes in the choroidal thickness during normal pregnancy using enhanced depth imaging spectral domain OCT and to compare these changes with healthy non-pregnant women. To the best of our knowledge, there have been no previous studies reported in the literature demonstrating choroidal thickness changes of the same women throughout their pregnancy.

Methods

Study population

This observational, cross-sectional study involved 54 eyes of 27 otherwise healthy pregnant women and 50 eyes of 25 age matched healthy non-pregnant women. All the pregnant women were recruited between November 2013 and February 2014 and evaluated at the Mevlana University Eye Clinic. The research protocol was approved by the Mevlana University Ethics Committee and followed the tenets of the Declaration of Helsinki. Written informed consent was obtained from each subject before enrolment in the study.

Study measurements

Healthy pregnant women at gestational weeks 6–8 and healthy non-pregnant women in the follicular phase of the menstrual cycle were included in the study. Subjects with any ocular pathology including refractive disorders greater than ±1.0 dioptres, best corrected visual acuity <20/20 (Snellen chart), or previous ocular surgery were excluded. Subjects with a history of systemic diseases, such as diabetes, hypertension, collagen vascular disease, and smokers (both current and previous) were not included in the study. Also pregnant women who developed gestational diseases, such as diabetes, pre-eclampsia or eclampsia, were excluded. All subjects underwent full ophthalmological examinations, including best-corrected visual acuity obtained with a Snellen projection chart, refraction, slit-lamp biomicroscopy, IOP measured by Goldmann applanation tonometry and corrected for central corneal thickness (measured with ultrasound pachymetry; AccuPach VI, Accutome Inc, Malvern, USA), and fundus examination. We did not perform axial length measurements to evaluate its effect on choroidal thickness because we excluded subjects with refractive disorders greater than ±1.0 dioptres to keep the axial length in a small range, and it was reported that this parameter does not change during pregnancy.6

Enhanced depth imaging OCT scans

All OCT scans were performed by the same experienced technician. Before the scan, it was verified that none of the patients had consumed drinks containing caffeine or had taken medications including analgesics for at least 24 h previously. Two scans were undertaken for each pregnant woman, one in the first trimester at gestational weeks 6–8, and the other during the third trimester at gestational weeks 32–37. Both scans were performed at the same time of the day, in the morning, to avoid diurnal fluctuations. The control group underwent OCT scanning during the follicular phase of the menstrual cycle and all scans were performed in the morning.

OCT was performed with a spectral-domain OCT machine (Cirrus HD-OCT, model 4000; Carl Zeiss Meditec, Dublin, California, USA) with the enhanced depth imaging mode. Cirrus HD-OCT has a light source with an 840 nm wavelength that can obtain 27 000 A-scans/s with an axial resolution of 5 μm in tissue. The scan pattern used the Zeiss Cirrus HD-OCT instrument software V.6.5; this is an HD 1-line raster, which is a 6 mm line consisting of 4096 A-scans. A high definition 1-line raster image is generated from 20 B-scans taken at a single location.

Choroidal thickness measurements

Choroidal thickness, defined as the distance between the outer portion of the hyperreflective line that corresponds to the retinal pigment epithelium and the inner surface of the sclera, was measured using the manual calliper function of the Cirrus HD-OCT software. Seven measurements perpendicular to the retina pigment epithelial layer were obtained for each scan: one at the fovea; three located at, respectively, 500, 1000, and 1500 μm nasal; and three located at, respectively, 500, 1000, and 1500 μm temporal to the fovea. All measurements were made by two observers who were not involved in data analysis, and were then averaged for analysis.

Statistical analysis

Statistical analyses were performed using SPSS V.15.0 (SPSS Science, Chicago, Illinois, USA). Quantitative variables were presented as mean (±SD). Normality was checked by the Kolmogorov-Smirnov and Shapiro-Wilk tests and by histograms for each variable. The data were analysed separately for the right and the left eyes. The Wilcoxon signed-rank test was used to test the differences in mean refractive error, IOP, and choroidal thicknesses between the first and the third trimesters of the pregnant women. Mean age, refractive error, IOP, and choroidal thicknesses of the pregnant women and the control group were compared with the Mann-Whitney U test. Values of p<0.05 were considered statistically significant.

Results

Of the 52 pregnant women who agreed to take part and had their OCT scans in the first trimester, 27 completed the second scans in the third trimester and were included in the study. The control group comprised 25 healthy non-pregnant women. The mean (±SD) ages of the pregnant women and the control group were 28.9±5.5 years (range 18–43) and 29.2±7.0 years (range 18–42) (p=0.86), respectively. The mean gestational age was 6.8±0.8 and 35.1±1.9 weeks in the first and the third trimesters, respectively. There were no significant differences between the mean refractive errors obtained in the first and the third trimesters (p>0.05). However, there was a statistically significant decrease in the mean IOP in the third trimester, in both eyes (p=0.03 and p=0.019, in right and left eyes, respectively). There were no significant differences between the mean refractive errors and the mean IOP obtained in the first and the third trimesters of the pregnant women and the control group (p>0.05). There were no twin gestations. The clinical data of the subjects are presented in table 1.

Table 1

Clinical data (presented as mean±SD) of the pregnant women in the first and the third trimesters (n=27) and the control group (n=25)

Compared to the measurements obtained in the first trimester, the choroidal thickness measurements obtained in the third trimester were significantly decreased at all measured points, in both eyes of the pregnant women. At the fovea, the mean (±SD) choroidal thickness measured in the first trimester was 349.22±82.11 μm in the right eyes and 341.30±85.22 μm in the left eyes, which decreased to 333.56±76.61 μm in the right eyes (p=0.014) and 326.93±75.84 μm in the left eyes (p=0.024) in the third trimester (table 2). Enhanced depth imaging OCT scans obtained in the first and third trimesters of the same pregnant woman is shown in figure 1.

Table 2

Choroidal thickness measurements (mean±SD in μm) of healthy pregnant women in the first and the third trimesters (n=27) and the control group (n=25)

Figure 1

Choroidal thickness measurements of a pregnant woman using enhanced depth imaging optical coherence tomography. (A) Measurements obtained at gestational week 7. (B) Measurements obtained at gestational week 36.

The choroidal thickness measurements of the control group were less than the measurements of the pregnant women obtained in the first and the third trimesters, but the difference was not statistically significant (p>0.05). At the fovea, the mean choroidal thickness of the control group was 318.88±53.13 μm in the right eyes and 310.60±51.09 μm in the left eyes (table 2).

Discussion

Pregnancy is a special period in a woman's life with marked hormonal, haemodynamic, cardiovascular, metabolic, and immunologic changes, which exert an influence on most systems including the eyes. To date, mainly anterior segment changes of the eye related to pregnancy have been investigated.5 ,14 However, most ocular pathologies associated with pregnancy, such as CSC, serous retinal detachment, worsening of diabetic retinopathy, and vascular changes in pre-eclampsia/eclampsia, occur in the posterior segment of the eye.4 In the current study, we found a statistically significant decrease in choroidal thickness in the third trimester. This finding can be valuable in understanding the pathophysiology of ocular disorders associated with pregnancy.

Most physiologic changes begin in early gestation. Peripheral vascular resistance decreases significantly in the first trimester (peak decrease at 6–8 weeks of pregnancy) and continues to be low throughout the pregnancy. Similarly, MAP decreases significantly between the sixth and eighth gestational weeks, remains low during the second trimester, and begins to increase again in the third trimester.1 Also, primary peripheral vasodilatation was reported to occur early in the first trimester and decrease towards the end of the third trimester.15 Plasma volume expansion and blood volume increase starts in the first trimester and reaches maximum levels in the third trimester. Also, there is a striking increase in the concentration of both oestradiol and progesterone, reaching more than a 10-fold increase at gestational week 36 compared to gestational week 6.1 ,3 Besides these physiologic alterations, ocular pathologies associated with pregnancy, such as CSC and serous retinal detachment, are most frequently encountered in the third trimester.4 ,16 So in the current study we compared the choroidal thicknesses between the first and the third trimesters to establish the changes in choroidal physiology during normal pregnancy and compared them with healthy non-pregnant women.

We detected a statistically significant decrease in the choroidal thickness at gestational weeks 32–37 when compared to gestational weeks 6–8. Although total blood volume increases by about 40% by the end of the third trimester,17 the concurrent decrease in the choroidal thickness may be explained by the redistribution of blood flow to certain vital organs such as the uterus and kidneys, and to the skin for temperature regulation.3 Another explanation may be that choroid thickening at gestational weeks 6–8 is related to the peak decrease in peripheral vascular resistance and MAP during this period.1 ,3 The following decrease of choroidal thickness in the third trimester may be related to the peak increase of oestrogen and progesterone concentrations in this period. A significant increase in α 1-adrenoceptor concentrations has been reported in weeks 37–39 of pregnancy, associated with increased oestrogen and progesterone concentrations,18 and vasoconstriction related to the increased adrenoceptor activity in this period can potentially explain the decrease in choroidal thickness detected in our study.

Our findings may have implications for the pathophysiology of certain pregnancy related ocular diseases, such as CSC which usually occurs in the third trimester.16 Although the exact aetiopathogenesis of CSC is unknown, there are several reports demonstrating increased choroidal thickness in patients with CSC.12 ,19 Vascular alterations, such as decreased choroidal blood flow and areas of choroidal non-perfusion, have also been reported in patients with CSC.20 Considering that CSC in pregnancy is almost always encountered in the third trimester,16 our finding of decreased choroidal thickness during this period may indicate that vascular factors, such as ischaemia resulting from decreased choroidal perfusion, play an inciting role in CSC, and the increase in choroidal thickness found in patients with CSC19 may be secondary to increased permeability and/or dilatation of choroidal vasculature. Furthermore, diabetic retinopathy can worsen during pregnancy.4 Our observation of changes in choroidal thickness during pregnancy may reflect an alteration of ocular circulation, which may explain the worsening of diabetic retinopathy during pregnancy.

Previous studies in the literature comparing choroidal thicknesses of pregnant women with age matched healthy non-pregnant women report conflicting results. Sayin et al21 reported increased choroidal thickness in the healthy pregnant group, while Takahashi et al22 found no difference. However, these studies involved pregnant women at different gestational ages which would affect the consistency of the results. Nevertheless, Sayin et al21 reported a negative correlation between the choroidal thickness and gestational age in the healthy pregnant group (gestational ages between 17–37 weeks), which is consistent with our results. Also, none of these studies reported the phase of the menstrual cycle in which the choroidal thickness measurements were obtained in the healthy non-pregnant group; this should be taken into consideration as it was reported that choroidal thickness can vary significantly during the menstrual cycle.23 In our study, the choroidal thicknesses of the non-pregnant women in the follicular phase of the menstrual cycle were less than the measurements obtained in the pregnant women in the first trimester, but similar to the measurements obtained in the third trimester in some of the measured points (table 2). However, the results did not reach statistical significance, probably because of the small number of participants in the study.

In our study, we found a statistically significant decrease in IOP in the third trimester compared to the first trimester. Lower IOP has been consistently reported in pregnant women in previous studies, and is assumed to be related to increased uveoscleral outflow and decreased episcleral venous pressure.6 ,24 Worsening of myopia during pregnancy has also been reported in the literature.25 Although we found a slight myopic shift in the third trimester in the current study the difference was not statistically significant, probably due to the limited refraction range (±1.0 dioptres) and the small number of the study participants. It would be interesting to hypothesise whether decreased choroidal thickness in the third trimester is associated with the increased myopia observed during pregnancy, as thinner choroids have been demonstrated in subjects with myopia.26

To the best of our knowledge, our study is the first report assessing the changes in choroidal thicknesses of the same women throughout their pregnancy. Comparing the choroidal thicknesses of the same women between the first and third trimesters is a particular strength of our study, as it is known that there are considerable interindividual differences in choroidal thicknesses of healthy subjects, especially related to refractive error.27 Also, we performed all the measurements at the same time of the day to avoid diurnal variations. On the other hand, our study also had some limitations. We did not know the pre-pregnancy choroidal thickness measurements of our patients. However, we included a control group of healthy non-pregnant women in the follicular phase of the menstrual cycle for comparison. Further studies are necessary to evaluate the changes in the choroidal thickness after delivery, as both the time necessary for reversal of previous changes and the effect of lactation on choroidal thickness are unknown. Another limitation was the low number of study participants. Although we enrolled 52 healthy women in the first trimester of gestation, only 27 were followed through to the third trimester and included in the study. The long time period between the measurements was probably the reason for this loss.

In conclusion, we found that the choroidal thickness was significantly decreased in healthy pregnant women during the third trimester when compared to the first trimester. Our results provide valuable information in regard to interpreting pregnancy associated ocular disorders and constitute the basis for future studies.

References

Footnotes

  • Contributors All the authors have made substantial contribution to conception and design, or analysis and interpretation of data; drafting the article or revising it critically for important intellectual content; and final approval of the article.

  • Competing interests None.

  • Ethics approval This study was approved by the Mevlana University Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent Obtained.

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