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Ophthalmic artery Doppler in the prediction of preeclampsia

Published:April 24, 2021DOI:https://doi.org/10.1016/j.ajog.2020.11.039
      The ophthalmic artery is an easily accessible vessel for Doppler assessment that provides information on the less accessible intracranial circulation. In women with preeclampsia, compared with normotensive pregnant women, there is a decrease in impedance to flow and an increase in velocities in the flow velocity waveforms from the ophthalmic arteries. This study aimed to report the methodology for ophthalmic artery Doppler and summarize findings from the clinical implementation of such assessment in the prediction of preeclampsia. The Embase and MEDLINE were searched from inception to November 2020 to identify studies reporting on the use of ophthalmic artery Doppler in the prediction of preeclampsia. Of note, 2 small studies in high-risk pregnancies, one at 11 to 14 weeks’ gestation and another at 20 to 28 weeks’ gestation, reported differences between women who developed preeclampsia, compared with unaffected pregnancies, in ophthalmic artery Doppler and suggested that this is a useful biomarker for screening for preeclampsia. Another small study in high-risk pregnancies at 18 to 23 weeks’ gestation reported that there was no marked difference in ophthalmic artery Doppler indices between the preeclampsia and unaffected groups. In addition, 2 recent, large observational studies in unselected pregnancies at 19 to 23 and 35 to 37 weeks’ gestation, respectively, reported that, first, it is necessary to record waveforms from both eyes to get reproducible results; second, the waveform from the ophthalmic arteries is characterized by 2 systolic peaks and the ratio of the second to the first peak systolic velocity was increased in women who developed preeclampsia; third, in the study at 19 to 23 weeks’ gestation, the peak systolic velocity ratio was superior to the uterine artery pulsatility index, mean arterial pressure, serum placental growth factor, and soluble fms-like tyrosine kinase-1 as individual biomarkers in the prediction of both preterm and term preeclampsia and the peak systolic velocity ratio improved the prediction of preeclampsia provided by all the other biomarkers; and fourth, in the study at 35 to 37 weeks’ gestation, the peak systolic velocity ratio improved the prediction of subsequent development of preeclampsia provided by maternal factors alone and combinations of maternal factors with mean arterial pressure, uterine artery pulsatility index, placental growth factor, and serum placental growth factor. The ophthalmic artery Doppler provides a useful biomarker for the prediction of preeclampsia.

      Key words

      Introduction

      The ophthalmic artery is the first branch of the internal carotid artery and is an easily accessible vessel for Doppler assessment that provides information on the less accessible intracranial circulation. In the 1990s, cross-sectional studies reported that in women with preeclampsia (PE), compared with normotensive pregnant women, there is a decrease in impedance to flow and an increase in velocities in the flow velocity waveforms from the ophthalmic arteries.
      • Hata T.
      • Hata K.
      • Moritake K.
      Maternal ophthalmic artery Doppler velocimetry in normotensive pregnancies and pregnancies complicated by hypertensive disorders.
      • Belfort M.A.
      • Giannina G.
      • Herd J.A.
      Transcranial and orbital Doppler ultrasound in normal pregnancy and preeclampsia.
      • Ohno Y.
      • Kawai M.
      • Wakahara Y.
      • Kitagawa T.
      • Kakihara M.
      • Arii Y.
      Ophthalmic artery velocimetry in normotensive and preeclamptic women with or without photophobia.
      The objectives of this article were to report the methodology for ophthalmic artery Doppler and summarize findings from the clinical implementation of such assessment in the prediction of PE.

      Description of the Method

      The mother is placed in the supine position and placed to rest for 5 minutes. A 7.5-MHz linear transducer is then placed transversely and gently over her closed upper eyelid after application of conduction gel. Color flow Doppler is used to identify the ophthalmic artery, which is found superior and medially to the hypoechoic band representing the optic nerve (Figure).
      • Erickson S.J.
      • Hendrix L.E.
      • Massaro B.M.
      • et al.
      Color Doppler flow imaging of the normal and abnormal orbit.
      Pulsed-wave Doppler is then used to record 3 to 5 similar waveforms. The angle of insonation should be kept at <20°, the sample gate is set at 2 mm to cover the whole vessel, the depth is 3.0 to 4.5 cm, the high-pass filter is 50 Hz, and the pulse repetition frequency is set at 125 kHz. To minimize any potential adverse effects on the eyes, the duration of the examination of each eye is a few seconds, and a special preset should be used with a marked reduction in output power and maximum mechanical index of 0.4.
      Figure thumbnail gr1
      FigureColor flow demonstration of the left ophthalmic artery
      At the bottom is the flow velocity waveform from the ophthalmic artery obtained by pulsed-wave Doppler illustrating the first PSV, second PSV, and EDV.
      EDV, end-diastolic velocity; PSV, peak systolic velocity.
      Nicolaides. Ophthalmic artery Doppler and preeclampsia. Am J Obstet Gynecol 2022.
      The waveform from the ophthalmic artery is characterized by 2 peaks in systole (Figure). The following 4 indices are used for analysis: first peak systolic velocity (PSV), second PSV, pulsatility index (PI), and ratio of second to first PSV. The first PSV and PI are automatically obtained by the machine, the second PSV is measured manually, and the ratio of the second to first PSV is calculated.
      A study in which waveforms were obtained in sequence from the right eye, left eye, and again right eye and then left eye found that there was good correlation between the first and second measurements from the same eye but poorer correlation in the first and second measurements between the 2 eyes.
      • Sarno M.
      • Wright A.
      • Vieira N.
      • Sapantzoglou I.
      • Charakida M.
      • Nicolaides K.H.
      Ophthalmic artery Doppler in prediction of pre-eclampsia at 35-37 weeks’ gestation.
      It was estimated that the best performance of screening for PE was achieved by taking the average of 4 measurements (2 from each eye); satisfactory results were also achieved by taking the average of 1 measurement from each eye.

      Prediction of Preeclampsia

      Traditional methods

      Effective prediction of preeclampsia can be achieved in screening by a combination of maternal demographic characteristics and medical history with biomarkers
      • Wright D.
      • Wright A.
      • Nicolaides K.H.
      The competing risk approach for prediction of preeclampsia.
      ; useful biomarkers at 11 to 13 weeks’ gestation are uterine artery PI (UtA-PI), mean arterial pressure (MAP), and serum placental growth factor (PlGF)
      • O’Gorman N.
      • Wright D.
      • Syngelaki A.
      • et al.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation.
      ; useful biomarkers at 19 to 24 weeks’ gestation are UtA-PI, MAP, PlGF, and serum soluble fms-like tyrosine kinase-1 (sFlt-1)
      • Gallo D.M.
      • Wright D.
      • Casanova C.
      • Campanero M.
      • Nicolaides K.H.
      Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19-24 weeks’ gestation.
      ; and useful biomarkers at 35 to 37 weeks’ gestation are MAP, PlGF, and sFlt-1.
      • Ciobanu A.
      • Wright A.
      • Panaitescu A.
      • Syngelaki A.
      • Wright D.
      • Nicolaides K.H.
      Prediction of imminent preeclampsia at 35-37 weeks gestation.

      Ophthalmic artery Doppler

      The 3 small studies in high-risk pregnancies examined the potential value of the ophthalmic artery Doppler in screening for subsequent development of PE.
      • Gurgel Alves J.A.
      • Praciano de Sousa P.C.
      • Bezerra Maia E Holanda Moura S.
      • Kane S.C.
      • da Silva Costa F.
      First-trimester maternal ophthalmic artery Doppler analysis for prediction of pre-eclampsia.
      • Matias D.S.
      • Costa R.F.
      • Matias B.S.
      • Gordiano L.
      • Correia L.C.
      Predictive value of ophthalmic artery Doppler velocimetry in relation to development of pre-eclampsia.
      • Praciano de Souza P.C.
      • Gurgel Alves J.A.
      • Bezerra Maia E Holanda Moura S.
      • Araujo Júnior E.
      • Martins W.P.
      • Da Silva Costa F.
      Second trimester screening of preeclampsia using maternal characteristics and uterine and ophthalmic artery Doppler.
      In these studies, only the right ophthalmic artery was examined. In the first study, 440 pregnancies were examined at 11 to 14 weeks’ gestation, and the authors reported that in the group that developed PE, compared with unaffected pregnancies, the second PSV was increased; all other indices were not markedly different.
      • Gurgel Alves J.A.
      • Praciano de Sousa P.C.
      • Bezerra Maia E Holanda Moura S.
      • Kane S.C.
      • da Silva Costa F.
      First-trimester maternal ophthalmic artery Doppler analysis for prediction of pre-eclampsia.
      Screening by maternal demographic characteristics and medical history identified 45% of cases of PE, at 10% false positive rate (FPR); addition of ophthalmic artery second PSV was associated with a small improvement in the detection rate (DR) to 48%. In the second study, 347 pregnancies were examined at 20 to 28 weeks’ gestation, and the authors reported that in the group that developed PE, compared with unaffected pregnancies, the second PSV was increased and, in screening by this marker, the DR for PE was 70% at an FPR of 25%.
      • Matias D.S.
      • Costa R.F.
      • Matias B.S.
      • Gordiano L.
      • Correia L.C.
      Predictive value of ophthalmic artery Doppler velocimetry in relation to development of pre-eclampsia.
      In the third study, 372 pregnancies were examined at 18 to 23 weeks’ gestation, and the authors reported that in the group that developed PE, compared with unaffected pregnancies, there was no marked difference in second PSV, second to first PSV ratio, or PI.
      • Praciano de Souza P.C.
      • Gurgel Alves J.A.
      • Bezerra Maia E Holanda Moura S.
      • Araujo Júnior E.
      • Martins W.P.
      • Da Silva Costa F.
      Second trimester screening of preeclampsia using maternal characteristics and uterine and ophthalmic artery Doppler.
      In 2 recent prospective observational studies, we examined 2853 unselected pregnancies at 19 to 23 weeks’ gestation and 2287 unselected pregnancies at 35 to 37 weeks’ gestation.
      • Sapantzoglou I.
      • Wright A.
      • Gallardo Arozena M.
      • Vallenas Campos R.
      • Charakida M.
      • Nicolaides K.H.
      Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 19-23 weeks’ gestation.
      ,
      • Sarno M.
      • Wright A.
      • Vieira N.
      • Sapantzoglou I.
      • Charakida M.
      • Nicolaides K.H.
      Ophthalmic artery Doppler in combination with other biomarkers in the prediction of pre-eclampsia at 35-37 weeks’ gestation.
      We conducted Doppler studies twice in each eye and used the average of the 4 measurements for analysis. In both study groups, we found that the second to first PSV ratio was the only ophthalmic artery index that provided useful prediction of PE; the PSV ratio was increased in PE pregnancies, and the deviation from normal was greater for earlier PE than later PE. In the study at 19 to 23 weeks’ gestation, the PSV ratio was superior to MAP, UtA-PI, PlGF, or sFlt-1 as individual biomarkers in the prediction of both preterm and term PE (Table 1).
      • Sapantzoglou I.
      • Wright A.
      • Gallardo Arozena M.
      • Vallenas Campos R.
      • Charakida M.
      • Nicolaides K.H.
      Ophthalmic artery Doppler in combination with other biomarkers in prediction of pre-eclampsia at 19-23 weeks’ gestation.
      The PSV ratio improved the prediction of both preterm and term PE provided by MAP, UtA-PI, PlGF, and sFlt-1, both individually and in various combinations between each other. In the study at 35 to 37 weeks’ gestation, the PSV ratio improved the prediction of PE with delivery at any stage after assessment provided by maternal factors alone and combinations of maternal factors with MAP, UtA-PI, PlGF, and sFlt-1 (Table 2).
      • Sarno M.
      • Wright A.
      • Vieira N.
      • Sapantzoglou I.
      • Charakida M.
      • Nicolaides K.H.
      Ophthalmic artery Doppler in combination with other biomarkers in the prediction of pre-eclampsia at 35-37 weeks’ gestation.
      The PSV ratio also improved the prediction of PE with delivery at <3 weeks from assessment.
      Table 1DR, at 10% false positive rate, of delivery with PE at <37 and ≥37 weeks’ gestation in screening at 19 to 23 weeks’ gestation by maternal factors, ophthalmic artery second to first PSV ratio, and combinations with MAP, UtA-PI, serum PlGF, and sFlt
      Method of screeningDR of PE at <37 wk

      PSV ratio
      DR of PE at ≥37 wk

      PSV ratio
      NoYesNoYes
      Maternal factors56803446
      +MAP69834251
      +UtA-PI75864151
      +PlGF76863144
      +sFLT60813145
      +MAP+UtA-PI81884754
      +MAP+UtA-PI+PlGF86904553
      +MAP+UtA-PI+PlGF+sFLT85904351
      DR, detection rate; MAP, mean arterial pressure; PE, preeclampsia; PlGF, placental growth factor; PSV, peak systolic velocity; sFlt, soluble fms-like tyrosine kinase-1; UtA-PI, uterine artery pulsatility index.
      Nicolaides. Ophthalmic artery Doppler and preeclampsia. Am J Obstet Gynecol 2022.
      Table 2DR, at 10% false positive rate, of delivery with PE within 3 weeks and at any time after assessment at 35 to 37 weeks’ gestation by maternal factors, ophthalmic artery second to first PSV ratio, and combinations with MAP, UtA-PI, serum PlGF, and sFlt
      Method of screeningDR of PE at <3 wk

      PSV ratio
      DR of PE at any time

      PSV ratio
      NoYesNoYes
      Maternal factors31692551
      +MAP74835463
      +UtA-PI43713153
      +PlGF73816066
      +sFLT84886771
      +MAP+PlGF85896871
      +MAP+sFLT91937374
      +MAP+PlGF+sFLT93937677
      DR, detection rate; MAP, mean arterial pressure; PE, preeclampsia; PlGF, placental growth factor; PSV, peak systolic velocity; sFLT, soluble fms-like tyrosine kinase-1; UtA-PI, uterine artery pulsatility index.
      Nicolaides. Ophthalmic artery Doppler and preeclampsia. Am J Obstet Gynecol 2022.

      Conclusion

      Ophthalmic artery Doppler provides a useful biomarker for the prediction of PE.

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