In this study, using OCT and OCTA, we determined an increase in the FAZ area of SCP and VD of SCP, DCP and choriocapillaris during the pregnancy period when compared to the first trimester. The FAZ area significantly increased in the third trimester when compared with the first trimester. A significant decrease was detected in central SCP and DCP VD in the third trimester. As the gestational week progressed, there was a significant increase in SCP VD in the 2nd trimester, except for the nasal quadrant, and a significant decrease in the 3rd trimester. The VD measurement in nearly all quadrants of SCP and DCP was found to be higher than the control in all trimesters. Choriocapillaris VD was found to be significantly lower in the first and second trimesters and higher in the third trimester compared to the control group. We observed an increase in CT and OPP during pregnancy however this increase was not statistically significant.
The most important feature that makes this study different from other studies is that, the measurements were taken from the same individuals during the pregnancy period. In other studies, measurements were generally taken from different individuals, in different trimesters. In this study, healthy pregnant women with a gestational age of less than 14 weeks were included, and their follow-up was continued in the second and third trimesters. In addition, this is the first study conducted with Topcon DRI Triton device in healthy pregnant women.
As it is well known, cardiovascular, hematological, and hormonal changes during pregnancy affect many systems. While cardiac output, blood volume, and heart rate increase; peripheral vascular resistance decreases and vasodilation occurs [4]. Peripheral vasodilation is seen in the early stages of the first trimester and decreases towards the third trimester. Plasma and blood volume starts to increase in the first trimester and reaches the maximum level in the third trimester. Changes in retinal and choroidal thickness and blood flow are observed due to changes in ocular blood flow and microcirculation [4]. Since OCTA is a non-invasive method that doesn’t require the use of fluorescein, it can easily visualize the retinal and choroidal circulation during pregnancy.In recent years, the use of OCTA has enabled the examination of retinal findings in pregnant women.
It is seen that progesterone and estrogen increase during pregnancy, and blood levels at 36 weeks of gestation are 10 times higher when compared to blood levels at 6 weeks [5, 6] Estrogen, which causes vasodilation in an endothelium-dependent and independent manner, regulates ocular blood flow [7]. Depending on estrogen, the synthesis of Endothelin-1 decreases, and the synthesis of nitric oxide increases. This leads to vasodilation and a reduction in vascular resistance [8].All these changes suggest that this may lead to changes in choroidal thickness and retinal blood flow. We consider that the vascular changes seen in our study may also be related to these hormonal changes.
In the previous years, many studies have been conducted on choroidal thickness in pregnant women. In previous studies comparing choroidal thicknesses, Takahashi et al. [9] and Rothwell et al. [10] observed no statistically significant difference, unlike this study. However, Kara et al. [11] observed significant difference in pregnancy compared to the control group, similar to our study. Dadaci et al. [12] demonstrated a decrease in choroidal thickness in the last trimester compared to the first trimester measurement. Goktas et al. [13] observed a significant choroidal thickness difference between the second trimester and control groups. Demir et al. [14] observed a statistically significant increase in retinal thickness only in the superior, temporal, and inferior parafoveal quadrants. The differences in these studies may be due to the difference in the number of patients included in the study, patients’ age, race, week of gestation, time of measurement, and included refraction intervals. In addition, the usage of the different devices may have had an effect.
It has been shown that choroidal thickness shows diurnal variation, in previous studies [15]. In our study, choroidal thickness measurements of the participants were performed between 2 p.m. and 4 p.m. to avoid diurnal variation in retinal and choroidal thickness. Apart from diurnal variation, values such as ocular perfusion pressure that may affect choroidal thickness were evaluated and no significant difference was found between the groups. Similar to our study, Goktaş et al. [13] did not find a significant difference in OPP when they compared the pregnant and control groups.
In previous OCTA studies, Yildirim et al. [16] observed no statistical difference in SCP VD, unlike our study. VD in DCP was found to be statistically significantly higher only in the parafoveal region. As a result, VD in the parafovea region, FAZ area of SCP, and foveal density in SCP in pregnant women were found to be higher than the control group, similar to our study. They didn’t observe a significant difference in SFCT between pregnant women and the control group also similar to our study. Chanwimol et al. [17] observed a statistically significant decrease in the mean of the whole area of SCP and the perfusion density in the nasal quadrant in pregnant women compared to the control group. A statistically significant increase was found in the perfusion density in the parafoveal area, inferior and temporal areas in DCP in pregnant women compared to controls. They consider that this difference in SCP and DCP could be due to the compensatory vascular changes during pregnancy and could be affected differently because of the structural and functional differences in SCP and DCP [17]. They didn’t observe a statistically significant difference between the two groups in the FAZ area. Kiziltunc et al. [18] found the parafoveal and perifoveal SCP VD in all areas statistically significantly higher in the pregnant group than the control group, similar to our study; however, foveal VD was found to be significantly lower in contrast to our study. There was no significant difference in VD between the trimester, unlike our study. Hepokur et al. [19] didn’t observe any difference in the VD of SCP, DCP, and peripapillary capillaries between trimesters and compared with the control group. Su et al. [20] didn’t observe a statistically significant difference between pregnant women in the last trimester and healthy controls. As we mentioned before, the inclusion of different individuals in the study and the lack of prospective studies may have caused the differences in the OCTA results. The reason for these changes has not been clearly explained in these studies. To reveal this difference, further molecular and structural studies are needed.
Our study has certain limitations. Estrogen and progesterone levels in the blood were not measured in pregnant and control groups. Therefore, we don’t have any information about whether there is a relationship between hormonal and vascular changes. The other one is the follow-up period is longer compared to the other studies. Postpartum measurements could not be taken due to difficulties in follow-up.
One of the difficulties we encountered in our study was the exclusion of patients who could not be measured in the third trimester due to the termination of pregnancy (such as abortion or premature birth) during their follow-up and developed a systemic disease related to pregnancy (gestational diabetes and preeclampsia) during pregnancy. Despite all these difficulties and limitations, it was concluded that there are significant changes in retinal and choroidal vascular structures during pregnancy.
In conclusion, to the best of our knowledge, our study is the first study examining retinal and choroidal thickness and microvasculature changes with OCT and OCTA prospectively in all trimesters in the same pregnant woman; and it supports the opinion that there are changes in all vascular structures. An important contribution of our study is the evaluation of OCTA parameters, especially GCL thickness and choriocapillaris vessel density prospectively in the same pregnant women during pregnancy.