Hemodynamic Insights into Preeclampsia: Comparing Ophthalmic and Uterine Artery Resistive Indices

Introduction

Preeclampsia is a severe, progressive, and unpredictable cardiovascular disorder characterized by the onset of hypertension with or without proteinuria, affecting approximately 2% to 8% of pregnancies worldwide [1–3]. The condition accounts for an estimated 46 000 maternal deaths and 500 000 fetal and neonatal deaths annually. Most cases of preeclampsia occur at term and present with mild, transient symptoms that typically resolve postpartum. However, 5% to 20% of women, particularly those experiencing preeclampsia preterm, can develop life-threatening complications [1].

The underlying pathophysiology of preeclampsia remains incompletely defined and is likely heterogeneous. Substantial evidence suggests that endothelial dysfunction and impaired placentation contribute to its pathogenesis in some patients, with effects of persisting postpartum complications [4,5]. Moreover, visual disturbances occur in up to 40% of patients with preeclampsia and can affect various parts of the visual pathway due to retinal changes, serous retinal detachment, and cortical visual impairment [4,5]. Identifying women at risk of developing preeclampsia is critical due to the lack of effective treatments for this condition. Early prediction efforts focus on detecting early signs, such as hypertension, proteinuria, edema, excessive weight gain, and mean arterial pressure [4,5]. This approach is not sufficiently accurate in predicting preeclampsia, with a detection rate of approximately 20% to 40% [6,7].

Recently, studies have focused on biochemical markers, especially those indicating endothelial dysfunction [4]. Several biochemical markers have been proposed to identify women at risk of preeclampsia [8–11]. Most are based on specific pathophysiological mechanisms linked to preeclampsia, such as placentation disorders, endothelial dysfunction, coagulation activation, and systemic inflammation [4]. Among these, measuring serum levels of angiogenic and anti-angiogenic markers, including placental growth factor (PlGF) and soluble Fms-like tyrosine kinase-1, has shown promise [8,12]. Low PlGF concentrations early in pregnancy are associated with increased risk of preeclampsia, particularly early-onset preeclampsia. Systematic reviews and meta-analyses indicate that PlGF concentration alone can detect 40% of preeclampsia cases, with a 10% false-positive rate [8,12]. Markers such as vascular cell adhesion protein, indicating leukocyte activation and endothelial damage, show high specificity (100%) but low sensitivity (41%). These markers are useful in predicting high-risk preeclampsia cases but are costly and inaccessible in developing countries [12–16].

In preeclampsia, failed invasion of spiral arteries by trophoblasts results in persistent high-resistance, low-volume vessels instead of the expected low-resistance, high-volume vessels [13]. This leads to uteroplacental blood flow resistance and placental hypoxia or ischemia, detectable via Doppler ultrasound. Abnormal Doppler waveforms in the uterine arteries, such as increased pulsatility and resistance indices and persistent notching after 18 weeks [17], are indicative of preeclampsia risk. Expanding diagnostic tools to assess maternal hemodynamic blood flow abnormalities caused by endothelial dysfunction – such as cardiovascular and cerebral compartments – is promising [18]. Doppler imaging of uterine and maternal arteries, including the ophthalmic artery, is increasingly being explored as a screening tool for preeclampsia risk. Doppler evaluation of uterine and spiral arteries helps predict significant vascular events in pregnancy [18]. In the first trimester, uterine artery Doppler alone shows low predictive accuracy (30%) for preeclampsia but achieves excellent prediction (up to 90%) for early-onset preeclampsia when combined with maternal parameters and biomarkers. In the second trimester, Doppler evaluation predicts 50% of preeclampsia cases and placental diseases [15,16,18,19]. Ophthalmic artery Doppler assessment has been proposed as a predictor for preeclampsia severity, cerebral hemorrhage risk, and maternal hemodynamic changes. However, the accuracy of uterine artery Doppler measurements in the first and second trimesters is limited due to challenges in standardization and quality control. Furthermore, the high costs of these diagnostic modalities restrict their accessibility, particularly in low-income settings [16,18,19].

The ophthalmic artery, a direct branch of the internal carotid artery, shares embryological, anatomical, and functional similarities with small-caliber intracranial arteries [14]. Doppler ultrasonography of the ophthalmic artery represents a non-invasive technique for evaluating cerebral vascular regions. Maternal hemodynamic changes assessed via ophthalmic artery Doppler parameters have gained attention for their potential role in diagnosing preeclampsia [18]. Recent studies have proposed ophthalmic artery Doppler assessment as a promising predictor for both early- and late-onset preeclampsia and for evaluating disease severity. This procedure is considered safe and enables continuous monitoring of maternal cerebral vascular hemodynamics during the progression of preeclampsia [16,18,19–23].

Emerging evidence highlights a decrease in resistance and hyper-perfusion of orbital blood flow in preeclamptic patients, prompting interest in investigating the correlation between uterine artery resistance indices and ophthalmic artery resistance indices in preeclampsia cases. This relationship may provide new insights into the pathophysiology and clinical management of the disorder. Therefore, this study aimed to compare the Doppler ultrasound pulsatility index (PI) and resistive index (RI) in the ophthalmic artery and uterine artery in 60 pregnant women with and without preeclampsia.

Material and Methods

STUDY DESIGN RESEARCH PARTICIPANTS:

This study was a descriptive analytical study conducted using a cross-sectional method on pregnant women at risk of developing preeclampsia (gestational age 26 to 36 weeks) who meet the protocols of Dr. Hasan Sadikin General Hospital and its affiliated hospitals from July to September 2024. Only those who met the inclusion criteria and agreed to participate in the study by completing and signing the informed consent form were included.

INCLUSION AND EXCLUSION CRITERIA:

The study included groups of women with normal pregnancies and pregnancies with preeclampsia, with or without complications based on American College of Obstetrician and Gynecologist criteria [24], meeting the following conditions: (1) gestational age between 26 and 36 weeks, determined based on the last menstrual period or crown-rump length measurement at 11 to 14 weeks of pregnancy, (2) singleton live pregnancy, (3) parity ≤4, (4) maternal age between 16 and 35 years, and (5) no vascular diseases in the orbital region. The exclusion criteria were as follows: pregnant women who met inclusion criteria but had history of chronic hypertension, hyperthyroidism, hypothyroidism, diabetes mellitus, systemic lupus erythematosus, renal dysfunction, or other chronic diseases confirmed through diagnostic investigations by the relevant departments, pregnancy complicated by congenital abnormalities in the fetus, confirmed definitively through supporting examinations (eg, ultrasound), intrauterine fetal death confirmed definitively through clinical and supporting examinations (eg, ultrasound), multiple pregnancies, and history of vascular disorders in the orbital region.

DATA COLLECTION METHODS:

A total of 60 women who gave vaginal birth that met the study criteria were divided into 2 groups: n=30 in preeclampsia group and n=30 in non-preeclampsia group. All samples were collected using consecutive samplings. This study used primary data to measure Doppler parameters of the uterine artery and ophthalmic artery in patients with normal pregnancies and pregnancies with preeclampsia at gestational ages of 26 to 36 weeks. The ultrasound machine used in this study was the Voluson GE S8 BT-19 (high resolution, Austria), equipped with a 7.5 MHz linear transducer; it was operated by a single maternal-fetal medicine trainee. An experienced ophthalmologist, skilled in performing Doppler imaging of the ophthalmic artery, participated in the study by supervising the acquisition of Doppler ultrasound images of the ophthalmic artery.

After providing informed consents to patients, clinical data were recorded from medical records. For obtaining Doppler indices of the uterine artery, patients were positioned supine and rested for 5 min. The examination was performed transabdominally. The transducer was placed laterally to the uterus and tilted medially until the uterine artery was identified at the point where it crosses the external iliac artery. The sample gate was set to cover the entire diameter of the artery, and pulsatile Doppler waveforms were recorded for 3 consecutive cycles. The measured parameters were the PI and RI. To obtain Doppler indices of ophthalmic artery, the patients were positioned supine and rested for 5 min. The transducer was carefully placed transversely on the closed upper eyelid after applying conductive gel. Color Doppler flow was used to identify the ophthalmic artery, located superiorly and medially relative to the “hypoechoic band”, representing the optic nerve. Pulse-wave Doppler was used to record 3 to 5 identical waveforms. The insonation angle was maintained at <20°, the sample gate was set to 2 mm to cover the entire canal at a depth of 3.0 to 4.5 cm, the high-pass filter was set to 50 Hz, and the pulse repetition frequency was set to 125 kHz. Only the right eye was examined, as prior studies have shown no statistically significant difference in blood flow between eyes. The maximum mechanical index allowed was 0.4. The ophthalmic artery waveform was characterized by 2 systolic peaks. The measured indices, including the first and second peak systolic velocity (PSV), RI, PI, and PSV1, were recorded for each of the 3 waveforms, and the average values were calculated for each parameter. PSV represented the highest blood flow velocity during systole, while end-diastolic velocity represented the lowest velocity during diastole. All indices were either automatically calculated by the ultrasound equipment or manually estimated by tracing the spectral waveform. Care was taken to avoid excessive pressure on the eyelid with the transducer during the examination.

STATISTICAL ANALYSIS:

Statistical analysis was conducted using independent t tests to compare the Doppler indices between the preeclampsia and normal pregnancy groups, based on the data distribution assessed through the Shapiro-Wilk test. For normally distributed variables, the independent t test was applied, while the Mann-Whitney U test was used for non-normally distributed data. Correlation analysis between the RI and PI of the uterine and ophthalmic arteries was performed using the Pearson correlation test for normally distributed data and Spearman rank correlation test for non-normally distributed data. A P value of <0.05 was considered statistically significant, and all analyses were conducted using Graphpad Prism 9.

Results

PATIENT CHARACTERISTICS:

Table 1 shows that there was no significant difference between the demographic data variables of the patients in the preeclampsia group and the normal group, with all P values >0.05. These findings indicated that the distribution of patient characteristics in this study were homogeneous.

COMPARISON OF PI AND RI OF THE UTERINE ARTERY IN THE NORMAL PREGNANCY AND PREECLAMPSIA GROUPS:

As shown in Table 2, the mean PI and RI of the uterine artery in the normal pregnancy group were 0.75±0.17 and 0.49±0.08, respectively. The mean PI and RI of the uterine artery in the preeclampsia group were 1.4±0.44 and 0.71±0.08, respectively. The statistical test results for both study groups show that the PI of the uterine artery was significantly higher in the preeclampsia group than in the normal group, with P<0.0001 (95% CI 0.52–0.86). Additionally, the RI of the uterine artery was significantly higher in the preeclampsia group than in the normal group, with P<0.0001 (95% CI 0.18–0.26).

COMPARISON OF PI AND RI OF THE OPHTHALMIC ARTERY IN THE NORMAL PREGNANCY AND PREECLAMPSIA GROUPS:

Table 3 shows the results of the independent t test. It was found that the PI of the ophthalmic artery in the preeclampsia group was significantly lower than that in the normal group, with P<0.0001 (95% CI −0.75-0.37). The RI of the ophthalmic artery was also significantly lower in the preeclampsia group than in the normal group, with P<0.0001 (95% CI −0.23 to −0.14). The mean RI of the ophthalmic artery in the normal group was 0.79±0.08, while in the preeclampsia group, it was 0.60±0.08. The table also shows that the peak ratio in the preeclampsia group was significantly higher than that in the normal group, with P<0.0001 (95% CI 0.17–0.30).

CORRELATION OF RI OF THE UTERINE AND OPHTHALMIC ARTERY IN THE NORMAL PREGNANCY AND PREECLAMPSIA GROUPS:

Table 4 and Figure 1 show a negative correlation with a weak strength of correlation (r=−0.19) that was statistically significant between the RI of the uterine artery and the RI of the ophthalmic artery, with P=0.01 (95% CI −0.51 to −0.18) in the preeclampsia group. In the normal group, there was also a negative correlation between these 2 variables, but it was not statistically significant (P=0.36; 95% CI −0.50 to 0.20).

Discussion

LIMITATIONS OF THE STUDY:

In this study, we did not calculate cut-off values, due to time constraints, which is a limitation of this research. The study did not determine the relationship between ophthalmic artery parameters and the severity of neurological symptoms in patients with preeclampsia, as this was not the objective at the start of the study, and time limitations played a role. Nevertheless, Doppler indices can be affected by maternal factors, such as hydration status, stress, and measurement conditions, potentially introducing variability in the results. Doppler ultrasound is highly operator-dependent, and slight variations in probe placement or angle correction can lead to inconsistencies in measurements. Experienced sonographers and standardization and are essential to minimize errors. This represents limitations and is an area for future research. However, the findings from this study add to the growing body of evidence suggesting significant ocular changes in women with preeclampsia.

Conclusions

This study showed that PI and RI changes and a significant correlation between uterine and ophthalmic artery RI values reflect systemic endothelial dysfunction in preeclampsia. Therefore, the examination of ophthalmic artery index parameters could be easily and quickly applied as a tool for early detection of preeclampsia, in addition to the uterine artery. However, further research with a larger scale is needed to determine the benefits of applying Doppler of the ophthalmic artery, particularly in assessing the severity of the disease and its complications, rather than just predicting the risk of preeclampsia.