Pregnancy related hormonal, hemodynamic and cardiovascular changes can affect the ocular structures . The complex vascular structure of the choroid makes it vulnerable to pregnancy related alterations, either the physiologic or pathologic events. Choroidal thickness changes can be expected due to the increased blood volume and water retention during pregnancy [18, 19]. Certain ocular conditions such as central serous chorioretinopathy (CSC), serous retinal detachment and retinal vascular events have an increased prevalence during pregnancy [20, 21].
There is no definite consensus on whether pregnancy can change choroidal structure and thickness and whether these changes are reversible. Previous studies have shown controversial results regarding choroidal thickness in pregnant women. Studies by Rothwell et al., Kara et al., Atas et al., Sayin et al. and Acmez et al. have shown increased choroidal thickness in the third trimester of pregnancy compared to controls [14, 22–25]. Whilst Takahashi et al., Benfica et al., Su et al. and Kim et al. found no significant difference between choroidal thickness of healthy pregnant women in the third trimester and the control group [26–29]. A recent meta-analysis concluded that choroidal thickness is significantly higher in healthy pregnant patients over 24 weeks of GA compared to controls .
The case-control and cross-sectional design of most of these previous studies has limited the achievement of definite results due to individual bias. The choroidal thickness is affected by various factors including age, sex, systemic or local diseases, diurnal variation, IOP, axial length, menstrual cycle and pregnancy trimester [31–33]. In our study, we considered these confounding variables and their effect was eliminated to a great extent. Other factors such as previous pregnancy was regarded in our study. We only included nulligravid women (no prior pregnancy) for the control group and primigravid women for our pregnant group. Whereas, most aforementioned studies have not accounted for this factor [26, 23, 24, 34].
To date, very few studies have investigated choroid thickness changes in different trimesters and post-partum. Goktas et al. investigated choroidal thickness in the three trimesters but in different sets of pregnant patients at 3 points (subfoveal and 3mm nasal and temporal to the fovea) . Their results showed significantly greater choroidal thickness in the 2nd trimester group in comparison with the 1st and 3rd trimester and control groups. They did not find any statistical difference between the 2nd and 3rd trimester groups and the control. Green et al. also conducted a study with a similar design but used the average measurement of subfoveal, 500µm nasal and temporal choroidal thickness . The choroidal thickness was significantly lower in the 3rd trimester compared to the 1st and 2nd trimester and also compared to the control group. They did not find any statistical difference between the 1nd and 2rd trimester groups and the control. In our study, on the other hand, we observed significantly thicker choroids in all three pregnancy trimesters compared to control. We also demonstrated increasing choroidal thickness from the first trimester into the second and third trimesters. The fact that Goktas et al. and Green et al. included different patients for each trimester may have caused the dissimilar results [35, 15]. Moreover, as choroidal thickness is affected by the menstrual cycle, we measured the choroidal thickness of the control group in the follicular phase. This issue was not addressed in neither of the two mentioned studies.
Dadaci et al. compared choroidal thickness of pregnant women in the first trimester (6–8 GA weeks) with the third trimester (32–37 GA weeks) . Similar to our findings, they reported thicker choroids during pregnancy compared to control. However, choroidal thickness decreased significantly in the third trimester compared to the first trimester. As we noted in our study, the choroidal thickness in the 3rd trimester was similar to that of the 2nd trimester and greater than the 1st trimester. We believe different sampling time points in the 3rd trimester may have caused this disagreement, as our measurements were taken between 28-34 weeks GA and theirs was between 32-37 GA weeks. Reasons for this finding may be that towards the end of pregnancy, blood flow is redistributed to vital organs and increase in adrenoreceptor activity leads to vasoconstriction [37, 38].
It has been proposed that increased blood flow, enhanced arterial compliance, and decreased vascular resistance during pregnancy leads to an increase in choroidal thickness . Also, fluid retention in the choroidal layer may affect the thickness . Kim et al., Benfica et al. and Sharudin etal. noted significantly greater choroidal thickness in patients with pre-eclampsia compared to the healthy pregnancy group [40, 41, 27]. This may suggest a correlation between choroidal thickness and ocular perfusion pressure; rather than pregnancy itself. However, other studies in line with ours did not find a correlation between OPP and choroidal thickness [35, 23, 34]. This issue may highlight the influence of hormones, particularly estrogen, progesterone and cortisol, on choroidal thickness [5, 33].
In the present longitudinal study, we also measured choroidal thickness after delivery. Previous studies on choroidal thickness before and after delivery have displayed conflicting results. Ulusoy et al. examined subfoveal choroidal thickness in third trimester (36 weeks GA) pregnant woman and prospectively 3 months after delivery . They reported significant decrease in the thickness 3 months after delivery. In contrast Taradaj et al., which assessed choroidal thickness at 36 weeks GA and at 6th week after delivery, reported greater choroidal thickness at 6th week postpartum compared to 36 weeks GA . Additionally, they evaluated choroidal thickness changes depending on mode of delivery and reported more noticeable changes in the cesarean section group compared to normal labour. Therefore, mode of delivery is presumed to affect the choroidal thickness post-partum. As mentioned, all our participants had normal vaginal delivery.
Takahashi et al. were the first to evaluate choroidal thickness from early pregnancy until after delivery in the same group of patients . They measured the subfoveal CT of 25 eyes of pregnant women in the 1st and 3rd trimesters, shortly after delivery, and 1 month postpartum. Their results indicated that the choroidal thickness increases in the first trimester and decreases in the third trimester and remains subsequently unchanged until the first month after delivery. In comparison to our study, in which we measured choroidal thickness in seven locations, Takahashi et al. only measured the subfoveal choroidal thickness; moreover, their study did not include measurements at the 2nd trimester of pregnancy .
In contrast to Takahashi et al., we showed that the choroidal thickness changed significantly during pregnancy and post-partum, with increased thickness until the 3rd trimester and subsequent reduction at 6 weeks post-partum in all seven measured locations. Takahashi et al. post-partum measurements was done at 4 weeks after delivery, this issue is of clinical relevance as the regression of pregnancy-related physiological changes takes place at 6-7 weeks post-partum . In our study we also noted that post-partum choroidal thickness was still greater than control, Takahashi et al. however, did not include a control group.
To the best of our knowledge, the present study is the first longitudinal design to evaluate the changes in choroidal thickness at several locations throughout pregnancy and post-partum and in comparison with non-pregnant healthy women. As there are considerable choroidal thickness variations between individuals, the longitudinal design of our study is of great value. To add to the strength of our study we included a group of healthy non-pregnant women, to compensate for the absent pre-pregnancy measurements. Although a study including pre-pregnancy choroidal measurements of the same group of patients would be the ideal and optimal design. Another advantage of our study was that all pregnant participants were primigravid, as it is debated whether previous pregnancy-related choroidal changes are reversible, this matter may act as a confounding factor .
Our study also had some limitation. The first was the relatively small number of subjects and also the drop-outs. Although previous studies also had similar sample size and drop-out is an inevitable part of longitudinal studies of this kind. Another limitation was the lack of patients’ pre-pregnancy choroidal measurements and data. Further studies including pre-pregnancy choroidal thickness and longer post-partum follow-up measurements are needed to determine precise choroidal changes and reversal. Moreover, evaluating choroidal thickness in patients with pregnancy-related ocular complications can provide guidance for clinical practice.
In conclusion, our study showed significant change in choroidal thickness at seven locations measured with EDI-OCT throughout pregnancy and 6 weeks after delivery. We showed that 6 weeks after delivery, choroidal thickness remains significantly higher than non-pregnant subjects.