Evaluation of Maternal Ophthalmic Artery Doppler Indices and Its Correlation with Mean Arterial Blood Pressure in Pregnant Indian Women: A Cross-Sectional Observational Study

Objective: Evaluation of maternal ophthalmic artery doppler indices and its correlation with mean arterial blood pressure in pregnant Indian women.

Design: Cross-sectional observational study.

Method: This study included 200 pregnant women aged 21 to 35, irrespective of parity. Doppler measurements of the ophthalmic artery, including peak systolic velocity, peak diastolic velocity, end-diastolic velocity, pulsatility index (PI), and peak ratio, were taken using transorbital ultrasound with a 6–13 MHz probe. Patients with chronic hypertension, heart disease, diabetes, or renal disease were excluded. Doppler findings were compared across trimesters and correlated with MAP.

Results: Independent T-tests and Fisher’s exact tests were used for analysis. A decrease in resistivity and pulsatility indices correlated with rising blood pressure, while peak diastolic velocity, end-diastolic velocity, and mean PSV ratio increased. In the second trimester, the mean PSV ratio was lower than in the first and third trimesters. A mean PSV ratio of 0.55 or above indicated a MAP of 100 mmHg or above. A single eye reading with a low PI or RI value correlated with elevated MAP, even if the mean PI or mean RI appeared normal.

Conclusion: Ophthalmic artery Doppler indices start showing changes before the appearance of signs and symptoms due to high BP, suggesting its utility in early detection of preeclampsia. Studies with larger sample sizes are needed to validate these findings.

Introduction

Hypertensive disorders are the most common and serious disorders in pregnancy. Preeclampsia is the leading cause of maternal morbidity and mortality. It affects 3% to 4% of deaths worldwide [1], [2]. Preeclampsia causes intracranial hemorrhage and eclampsia. Because of these complications, preeclampsia kills the pregnant mother [3]. Apart from mortality, preeclampsia also causes significant short-term and long-term morbidity to the mother and foetus [4]. Preeclampsia causes morbidity like visual impairment, permanent neurological deficit, and cognitive impairment in later life.

The role of the placenta in the pathogenesis of preeclampsia is well known. Early onset of the placenta is a 2-stage process. First is deficit remodeling of the spiral artery; second is placental oxidative stress, which leads to inadequate perfusion [5]. Late-onset preeclampsia is often not associated with fetal growth retardation, and deficient placentation is also not seen in these patients [6].

There are drastic changes in maternal haemodynamics in preeclamptic patients. It is necessary to study the maternal haemodynamic and vascular beds outside the uteroplacental area [7]. The neurological impact of preeclampsia is very significant, so there is an increased need for evaluation of cerebrovascular changes associated with preeclampsia [8]. Real-time assessment using computed tomography and magnetic resonance imaging is very challenging. These modalities study the changes in large caliber intracranial vessels like the middle cerebral artery. They do not study the changes in the small vasculature of the brain. Changes due to preeclampsia occur in small caliber intracranial vasculature.

Doppler study of maternal ophthalmic arteries can give rise to intracranial changes due to preeclampsia. Maternal cardiovascular changes can be studied using an ophthalmic artery doppler. The ophthalmic artery is anatomically and embryologically similar to intracranial vessels [9], [10].

Ophthalmic artery doppler is cost-effective and easily available. Patient compliance is good, repeatable, non-invasive and without radiation exposure.

With this concept, this study will study the doppler changes in the ophthalmic artery in pregnancy and its correlation with mean arterial blood pressure.

Objective

The objective of the current study was to study the changes in doppler indices of the ophthalmic artery in pregnancy and its correlation with mean arterial blood pressure in pregnant Indian women.

Materials and Methods

This study was done at Sparsh Hospital Kannauj. The duration of the study is March 2023 to June 2024. This is a cross-sectional observational study. Ethical clearance is obtained from the hospital’s ethical committee. 200 patients were included in this study.

Inclusion and Exclusion Criteria

The inclusion criteria for this study comprised all singleton pregnant patients in any trimester, with ages ranging from 21 to 35 years. The exclusion criteria, on the other hand, involved individuals who were known to have chronic hypertension, or those with a history of diabetes, heart disease, epilepsy, or glaucoma, as these patients were not included in the study.

Procedure

General details of patients, like name, age, occupation and social status, are noted. A detailed history is taken, especially regarding headache, pedal oedema, blurred vision, sleep pattern, and increased or decreased urine output. A detailed obstetric history of every patient is taken. BP is taken in the brachial artery in both arms and mean arterial BP is recorded.

The patient lies down in a supine position. USG jelly is applied over the closed eyelid, and the patient is instructed to keep the eye closed and the eyeball fixed during the examination. Both eyes were examined one by one, first right, then left. Single readings from both eyes are taken, and the mean is taken for data calculation. During the examination, the eye angle of intonation was kept below 20, and the doppler sample volume was 2 mm. For USG, a linear probe with 6 to 13 -MHz is used.

The ophthalmic artery is identified on the medial side of the optic nerve using colour Doppler flow imaging and measured flow imaging and measured the flow velocity of approximately 15 mm from the optic disc. Depth is 3 to 4.5 cm, high pass filter is 50 HZ and high repetition frequency is 125 KHz. The duration of examination in each eye is a few seconds, and a special preset in the machine is used with a maximum mechanical index of 0.4. At the same time, obstetric USG is also done.

The waveform of the ophthalmic artery shows two peaks in systole. The plurality index, resistance index, and the second-to-first peak systolic velocity ratio are used for analysis.

Data Analysis

Qualitative data has been presented as frequency and percentages. Quantitative data (measurable) were first checked for normality in distribution through Shapiro-Wilk, and the q-q plot was visually inspected. If normally distributed quantitative variables across two categories, an independent t-test has been used.

The waveform from the ophthalmic artery is characterized by 2 peaks in systole (Fig. 1). The following 4 indices are used for analysis: first peak systolic velocity (PSV), second PSV, pulsatility index (PI), and the ratio of second to first PSV. The machine automatically obtains the first PSV and PI, the second PSV is measured manually, and the second-to-first PSV ratio is calculated.

Fig. 1. The waveform of ophthalmic artery.

Results

The patients included in this study were between 21 and 35 years old. The average BMI in non-pregnant patients was 22, and in pregnant patients was 25.

The independent sample t-test showed no statistically significant change in the mean PSV ratio, mean PI, and mean RI in first-trimester normotensive patients (Table II).

Table I. Comparison of the Mean Ophthalmic Artery PI of First Trimester Patients with Mean Artery PI of Non-Pregnant Women

	Trimester	Average	Mean RI	Mean PI
N	0	28	28	28
	1	28	28	28
Missing	0	0	0	0
	1	0	0	0
Mean	0	0.427	0.788	2.28
	1	0.425	0.750	2.32
Median	0	0.435	0.740	2.24
	1	0.425	0.760	2.31
Standard deviation	0	0.0451	0.234	0.252
	1	0.0574	0.0441	0.303
Minimum	0	0.330	0.670	1.89
	1	0.290	0.670	1.86
Maximum	0	0.500	1.96	2.92
	1	0.530	0.850	3.03

Table II. Independent Samples t-test Results

		Statistic	df	p
Mean PSV ratio	Student’s t	0.155	54	0.877
Mean RI	Student’s t	0.850	54	0.399
Mean PI	Student’s t	−0.494	54	0.624

The results in Table III show that the RI of hypertensive patients in the first trimester is decreased as compared to non-pregnant patients, but this change is not statistically significant.

Table III. Comparison of the PI, RI and PSV of Hypertensive Patients of First Trimester and Non-Pregnant Women

		statistic	df	p
Mean ophthalmic artery RI	Student’s t test	1.83	36.0	0.075
Mean ophthalmic artery PI	Student’s test	5.35	36.0	<0.001
Mean ophthalmic artery PSV	Student’s test	7.27	36.0	<0.001

PI of hypertensive patients in the first trimester is decreased, and mean PSV is increased; this change is statistically significant. The p-value is below 0.001 for both PI and PSV.

Comparison of PI, RI and PSV of nonpregnant women and second-trimester normotensive patients shows that changes in these doppler indices of the ophthalmic artery are not statistically significant.

Results in Table IV show that changes in RI of the hypertensive second trimester are not statistically significant. The mean PI of second-trimester hypertensive patients are decreased, and the mean PSV ratio is increased; these changes are statistically significant values of 0.002 and below 0.001, respectively.

Table IV. Comparison of the PI, RI, and PSV between Non-Pregnant Women and Hypertensive Second Trimester Patients

		Statistic	df	p
Ophthalmic artery RI	Student’s t test	1.27	33	0.213
Ophthalmic artery PI	Student’s t test	3.14	33	0.002
Ophthalmic artery PSV	Student’s t test	4.88	33	<0.001

Table V. Comparison of the Mean PI and PSV of First and Second Trimester Patients

		Statistic	df	p
Average PI	Student’s t	−2.89	93.0	0.005
Mean PSV ratio	Student’s t	2.94	94.0	0.004

Comparison of PI, RI and PSV of first-trimester patients and second-trimester patients shows an increase in the mean PI of second-trimester patients, which is statistically significant; the p-value is 0.005. RI also increases in second-trimester patients but is not statistically significant.

This result shows a decrease in the mean PSV of second-trimester patients compared to first-trimester patients. This change is statistically significant; the value is 0.004.

In second-trimester patients, a mean PSV ratio of 0.5 or more is associated with a mean arterial BP of 90 mmHg or more. Increased PSV in one eye is also associated with an increased mean arterial BP. This shows that an increase in PSV in a single eye of 0.5 or more should be taken seriously in the second trimester. This also indicates that we should take reading from both eyes. Single eye reading sometimes may result in missed changes in second eye reading.

Table VI shows that 7 patients in our study had mean arterial PSV of 0.55 or more; all of these patients had increased mean arterial BP of 100 or more. The mean PI of these patients is 1.94 compared to the mean PI of normotensive patients, 2.41. The mean RI of hypertensive patients is 0.67 as compared to normotensive patients in the second trimester, which is 0.757. This result shows that RI and PI are inversely proportional to the mean arterial blood pressure increase, and the mean PSV ratio is directly proportional to the increase in mean arterial blood pressure in the second trimester.

Table VI. Comparison of Hypertensive Third–Trimester Patients with Second Trimester Patients

	Trimester	Mean RI	Mean PI	Mean PSV ratio
N	2	57	57	57
	3	24	24	24
Missing	2	0	0	0
	3	0	0	0
Mean	2	0.757	2.41	0.416
	3	0.664	1.85	0.515
Median	2	0.70	2.34	0.410
	3	0.67	1.92	0.515
Standard deviation	2	0.0552	0.345	0.0611
	3	0.0484	0.408	0.0443
Minimum	2	0.600	1.75	0.250
	3	0.560	0.860	0.430
Maximum	2	0.910	3.29	0.550
	3	0.780	2.37	0.590

The results shown in Table VII reveal a decrease in mean PI and RI of third-trimester hypertensive patients compared to normotensive patients of third-trimester patients. PSV of hypertensive patients is increased. These changes are statistically significant compared to normotensive patients in the second trimester. The p-value is less than 0.001 for each index. The mean RI is 0.664, and the mean PI is 1.85 in hypertensive patients in the third–trimester. The mean PSV of hypertensive patients in the third–trimester is 0.515. at or above this value corresponds to a mean arterial BP of 90 mmHg or more. The mean RI and PI of normotensive patients in the third–trimester are 0.711 and 2.16, respectively. The mean PSV of normotensive patients in the third–trimester is 0.459.

Table VII. Independent Samples t-test Comparing the PI, RI and PSV between Second Trimester and Hypertensive Patients of Third–Trimester

Ophthalmic artery		Statistic	df	p
Mean RI	Student’s t	7.17	79.0	<0.001
Mean PI	Student’s t	6.20	79.0	<0.001
Mean PSV	Student’s t	−7.23	79.0	<0.001

Decreases in PI and RI are inversely proportional to an increase in mean arterial BP, and an increase in PSV is directly related to an increase in mean arterial BP. The mean PSV of 0.55 corresponds to mean arterial BP of 100 mmHg.

Table VIII shows that the RI of hypertensive patients is decreased in comparison to non-pregnant patients, but this decrease is not statistically significant. A decrease in PI and an increase in mean PSV are significant statistically (p < 0.001).

Table VIII. Comparison of the Non-Pregnant Women with Hypertensive Patients of Third–Trimester

Ophthalmic artery		Statistic	df	p
Mean RI	Student’s t	2.56	50	0.014
Mean PI	Student’s t	4.81	50	<0.001
Mean PSV	Student’s t	−7.09	50	<0.001

Table IX shows that the best predictor for the rise in mean arterial BP is the mean PSV ratio; the p-value is less than 0.05, and the Pearson coefficient (r) is 0.402, suggesting a linear relationship. It has a low correlation since the correlation coefficient is between 0.3 and 0.5.

Table IX. Correlation Matrix

		Average ophthalmic artery PI	Average ophthalmic arteryRI	Mean BP	PSV ratio
Average ophthalmic artery PI	Pearson’s r
	P value
Average ophthalmic artery RI	Pearson’s r	0.459
	P value	<0.001
Mean arterial BP	Pearson’s r	−0.393	−0.267
	P value	<0.001	<0.001
Mean PSV ratio	Pearson’s r	−0.864	−0.446	0.402
	P value	<0.001	<0.001	<0.001

Discussion

Principal Findings of This Study

The result of this study done in different gestational ages shows changes in ophthalmic artery doppler indices occurring throughout the pregnancy. These changes also correlate with changes in mean arterial pressure. This study investigated changes in RI, PI, and mean PSV ratio of ophthalmic arteries.

In first-trimester normotensive patients, mean PI, PSV ratio and RI changes are not statistically significant in comparison to non-pregnant patients.

Changes in PI and PSV ratio of hypertensive patients in the first trimester are statistically significant as compared to non-pregnant patients. The p-values are 0.001 and 0.001, respectively.

Changes in RI, PI and PSV of normotensive patients of the second trimester are not significant when compared with non-pregnant patients.

The results of this group show that changes in RI of the hypertensive second trimester are not statistically significant. The mean PI of second-trimester hypertensive patients are decreased, and the mean PSV ratio is increased; these changes are statistically significant values of 0.002 and <0.001, respectively.

Comparison of PI, RI and PSV of first-trimester patients and second-trimester patients shows an increase in the mean PI of second-trimester patients, which is statistically significant; the p-value is 0.005. RI also increases in second-trimester patients but is not statistically significant.

This result shows a decrease in the mean PSV ratio of second-trimester normotensive patients compared to first-trimester patients; this change is statistically significant, and the p-value is 0.004.

These changes may be due to relative hypotension or haemodynamic changes in the second trimester.

In second-trimester hypertensive patients, a mean PSV ratio of 0.55 or more is associated with a mean arterial BP of more than 100 mmHg.

There is an increase in the mean PSV ratio of hypertensive patients in the third–trimester and a decrease in RI and PI values of hypertensive values; these changes are statistically significant. The p-value is less than 0.001 for each index. The mean RI is 0.664, and the mean PI is 1.85 in hypertensive patients in the third–trimester. The mean PSV of hypertensive patients in the third–trimester is 0.515.

The result of the study shows that the mean PSV ratio is the best predictor in all doppler indices of the ophthalmic artery for predicting a rise in mean arterial blood pressure in all trimesters.

Changes in doppler indices of the ophthalmic artery start quite early before the signs and symptoms appear clinically due to rise in BP. Identifying these changes gives us a window to pick up these patents quite early. Moreover, start treatment to prevent morbidity due to pre-eclampsia in the mother and baby.

Comparison with Other Studies

In a study by Kumari et al. [11], the mean ophthalmic artery decreases as the gestation age increases. It is also inversely related to an increase in BP. Our study shows a decrease in mean PI and RI of ophthalmic A, but this is not statistically significant in normotensive patients. In hypertensive patients of the first trimester, an increase in PI and a decrease in the mean PSV ratio are statistically significant in our study. The increase in the mean PSV ratio in the second and third–trimesters is also significant and correlated with an increase in BP in all three trimesters.

A previous study done by Diniz et al. [12] showed that there is an increase in EDV in pre-eclamptic women than in normotensive women. Our study result shows that the mean PSV ratio is increased in pre-eclamptic patients more than in normotensive patients, which is statistically significant. This increase is directly proportional to the increase in mean arterial BP.

Three studies from the literature [13]–[15] done the ophthalmic artery doppler study in pregnant women in indifferent trimesters. In a study done by Gurgel Alves et al. [13], they studied between 11 to 14 weeks and found that patients who develop PET have an increased second PSV. The rest of the other markers did not change significantly. Our study shows a statistically significant change in PI and PSV ratio in all trimesters in patients who developed raised mean arterial blood pressure.

Matias et al. [14] studied the ophthalmic artery Doppler between 20 to 28 weeks gestation and found that the first and second PSV and the ratio of PSV are increased in patients who develop PET.

The result of our study in this gestational age patients shows that PI is decreased and mean PSV ratio is increased in patients with raised mean arterial BP.

The results of a study done by Praciano de Souza et al. [15] show no statistically significant change in PI and mean PSV ratio between normotensive patients and patients who develop PET. They studied second-trimester patients between 18 and 23 weeks of gestational age.

Conclusion

During pregnancy, there are continuous changes in doppler indices of the ophthalmic artery. Some changes are statistically significant, and some are not. Changes in mean PSV ratio are the most reliable marker. Changes in this are directly related to changes in pregnant women’s mean arterial blood pressure. An increase in the mean PSV ratio corresponds to an increase in mean arterial blood pressure in each trimester. This study’s mean PSV ratio of 0.55 corresponds to a mean arterial blood pressure of 100 mmHg or more. The ophthalmic artery doppler changes start early before the patient develops signs and symptoms due to raised blood pressure. Approximately three weeks prior. These changes give us a wide window to interfere with disease. Raised single-eye mean PSV ratio also corresponds to raised mean arterial blood pressure, so single raised mean PSV value should be taken seriously for further evaluation.

According to this study, both eyes should be studied. Single eye studies can miss changes in the other eye. Last, the ophthalmic artery doppler mean PSV ratio can be used as a screening method for the detection of PET.

Limitations and Strengths

This is a single-centre study. Patients are only of Indian origin. The sample size is small in each trimester. Doppler findings of the ophthalmic artery were not compared with a biochemical marker of the patient at that particular time. Multiple gestational patients were not included in the study.

The study’s strength is that we have included all patients coming for antenatal care in all trimesters and compared the PI, RI, and mean PSV ratio of each trimester patient with non-pregnant patients. We also compared findings in inter-trimester patients.

Our study had a few limitations, including a small sample size based on a survey by Hata et al. [16]. A larger sample size may have produced more precise results. Additionally, the normotensive and preeclamptic women were not matched based on maternal age, gestational age, or other factors that could affect the result. Matching patients could have reduced potential unknown biases. We performed a cross-sectional study; however, a longitudinal study tracking ophthalmic artery changes from early gestation to term might have provided more temporality. Nevertheless, we opted for a cross-sectional design to avoid dropout rates often accompanying longitudinal studies.