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ORIGINAL RESEARCH
Effect of Carotid Artery Stenting on Ophthalmic Artery Flow Patterns Namik K. Altinbas, MD, Evren Ustuner, MD, Hasan Ozcan, MD, Sadik Bilgic, MD, Tanzer Sancak, MD, Ebru Dusunceli, MD
Article includes CME test
Objectives—The purpose of this study was to assess the effect of carotid artery stenting on ophthalmic artery blood flow using transorbital color and spectral Doppler sonography and review the changes in relation to cerebral hemodynamics. Methods—Twenty-eight consecutive patients with severe internal carotid artery stenosis (≥70%) who were scheduled for carotid stenting were included. Ophthalmic artery Doppler sonography was performed bilaterally before and after stenting. The flow direction, peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index in the ophthalmic artery were recorded. Results—Twenty male and 8 female patients with 10 right-sided and 18 left-sided stenoses were studied. The mean overall carotid stenosis ratio ± SD was 87.3% ± 9.9%. After stenting in the ophthalmic artery ipsilateral to the stenosis, significant increases in the PSV (–3.87 ± 48.81 to 46.70 ± 25.33 cm/s; P < .001), and EDV (–3.02 ± 16.31 to 11.24 ± 7.37 cm/s; P < .001) were detected, and the increase in the PI approached significance (1.40 ± 0.59 to 1.62 ± 0.52; P = .055). A change in the flow direction from retrograde to antegrade was noted in 11 patients (39%) after stenting, and in 1 patient with no detectable flow, reconstitution of flow was observed. Increases in the PSV and EDV (P = .03 for ΔEDV) were more pronounced in symptomatic patients than asymptomatic patients after stenting.
Received May 13, 2013, from the Department of Radiology, Ankara University School of Medicine, Ankara, Turkey (N.K.A., E.U., H.O., S.B., E.D.); and Radiology Unit, Private Tobb-Etu Hospital, Ankara, Turkey (T.S.). Revision requested June 4, 2013. Revised manuscript accepted for publication August 5, 2013. This study was presented as a oral presentation at the Eighth Interventional Radiology Annual Meeting; March 28–31, 2013; Antalya, Turkey. Address correspondence to Namik K. Altinbas, MD, Department of Radiology, Ankara University School of Medicine, Ibn-i Sina Hospital, 06230 Ankara, Turkey. E-mail: [email protected] Abbreviations
EDV, end-diastolic velocity; PI, pulsatility index; PSV, peak systolic velocity; RI, resistive index doi:10.7863/ultra.33.4.629
Conclusions—Substantially decreased ophthalmic artery velocity and retrograde flow are suggestive of high-grade carotid artery stenosis (≳90%). Stenting improves ophthalmic artery perfusion and positively changes cerebral hemodynamics in high-grade carotid artery stenosis, especially in symptomatic patients, which can be monitored with ophthalmic artery Doppler sonography. Key Words—carotid artery stenosis; color and spectral Doppler sonography; endovascular treatment; ophthalmic artery; ophthalmologic ultrasound; stenting; stroke
C
arotid artery stenosis is a major cause of cerebrovascular disease and causes devastating impacts on health.1–4 Recently, in addition to medication and surgery, endovascular techniques (angioplasty and stenting) have been introduced for treatment of carotid artery stenosis with success.2,3 Endovascular procedures are gaining wide popularity as alternatives and have similar outcomes and periprocedural risks compared to endarterectomy.1–5 Carotid imaging using color Doppler sonography or angiography is highly accurate in revealing carotid artery stenosis of 70% or greater.6–9 Examination of the ophthalmic artery with Doppler sonography also provides valuable information about blood flow
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patterns and hemodynamics of cerebral perfusion.10–17 The ophthalmic artery provides many advantages in this regard, being a downstream intracerebral branch of the internal carotid artery and also being easily accessible by Doppler sonography. In this study, our aim was to investigate the immediate effects of carotid artery stenting on ophthalmic artery flow patterns in patients with internal carotid artery stenosis of 70% or greater. In this way, we could indirectly observe intracerebral hemodynamic changes after stenting. In addition, using this information, we can obtain definite, quantitative, and measurable information about the effects of stenting on the ophthalmic artery, which may help us follow and plan endovascular treatments.
Materials and Methods Patient Selection A total of 28 consecutive patients who had been referred to the interventional radiology department for a carotid artery stenting procedure between June 2007 and August 2009 were included in the study. All patients were confirmed to have carotid artery stenosis of 70% or greater by selective contrast angiography at the time of stenting, and all were thoroughly examined and referred for a stenting procedure by neurologists before admission to the radiology department. Indications for stenting were made according to the guidelines and evidence provided by the North American Symptomatic Carotid Endarterectomy Trial,18 the European Carotid Surgery Trial,19 and the Asymptomatic Carotid Atherosclerosis Study,20 which suggest that symptomatic patients and asymptomatic patients benefit from the procedure if they have severe stenosis (≥70%) and if their complication rates are less than 6% for symptomatic and 3% for asymptomatic patients.18–21 As part of their treatment plan, all patients gave informed written consent before diagnostic angiographic and endovascular treatment (angioplasty and stenting) procedures. The patients also gave informed written consent for ophthalmic artery Doppler sonography before and after the procedure. All of the procedures in this study were done in accordance with the Declaration of Helsinki for human subjects, and the study was approved by our Institutional Review Board. Angiographic Evaluation and Stenting Diagnostic cerebral angiography was performed in all patients before the stenting procedure to assess the intracranial and extracranial cerebral circulation. Stenosis ratios were calculated in accordance with the guidelines
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provided by the North American Symptomatic Carotid Endarterectomy Trial.18 The stenting procedure was performed according to the guidelines and techniques described by Moran et al.22 After definite localization of the stenosis, self-expandable stents (Wallstent; Boston Scientific, Galway, Ireland) were deployed using a protective umbrella device (Emboshield; Abbott Ireland, Galway, Ireland). At the end of the procedure, the carotid artery and intracranial circulation was reevaluated for dissection, vasospasm, and patency using anteroposterior and lateral views. Color and Spectral Doppler Sonographic Examinations Doppler sonography of the ophthalmic artery was performed in accordance with the standard technique described by Belden et al.23 Doppler sonographic examinations of the ophthalmic artery were done on the same day before stenting and 1 to 3 days after the procedure, when the patients became ambulatory and hemodynamically stable, using Aplio SSA-770A/80 Doppler equipment (Toshiba Medical Systems Co, Ltd, Tokyo, Japan) with a 7.5-MHz multifrequency linear transducer. The carotid artery and transorbital ophthalmic artery were evaluated bilaterally by Doppler sonography. To standardize Doppler sonographic measurements, all studies were performed bilaterally by the same radiologist. First, carotid arteries were examined on both sides for lumen and stent patency. Next, Doppler sonography of both ophthalmic arteries was done. The ophthalmic artery peak systolic velocity (PSV), enddiastolic velocity (EDV), pulsatility index (PI), and resistive index (RI) were all recorded. Care was taken not to apply pressure on the globe during measurements by using the correct angles and sample width. During the spectral analysis mode, the spatial-peak temporal-average intensity was always kept below the threshold of 17 mW/cm2, as recommended by the US Food and Drug Administration.16 The ages, sexes, medical histories (hypertension, diabetes mellitus, and atherosclerotic heart disease), and neurologic examination findings of the patients were recorded as well (Table 1). Statistical Analysis Normal distribution of the variables was assessed by the Shapiro-Wilk test. Comparisons of pre- and post-stent ophthalmic artery velocity variables were evaluated by the Wilcoxon signed ranks test. The Mann-Whitney U test was used to test the difference between two groups. Nominal variables were tested by the Fisher exact test. The degree of association between the stenosis ratio and differences between pre- and post-stent ophthalmic artery velocity
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variables were assessed by the Spearman ρ coefficient. P < .05 was considered significant. SPSS version 15.0 software for Windows (IBM Corporation, Armonk, NY) was used for statistical evaluations.
Results The carotid stenting procedure was performed in 20 male and 8 female patients. Stents were placed on the right side in 10 patients and on the left side in 18. None of the patients received bilateral stents during the same procedure or underwent a later contralateral stent placement procedure. The mean age of the study group ± SD was 71 ± 7.9 years (range, 53–87 years). The total mean stenosis ratio was 87.3% ± 9.9% (range, 70%–98%). Stenosis was significantly higher on the left side (P < .05).
Results of the spectral Doppler sonographic examinations of the ophthalmic artery before and after stenting are presented in Table 2. The PSV in the ophthalmic artery ipsilateral to the stenosis before stenting was –3.87 ± 48.81 cm/s and increased significantly to 46.70 ± 25.33 cm/s after stenting (P < .001). To sum up, statistically significant increases in ophthalmic artery flow values on the stented side (PSV, EDV, and PI) were noted after the stenting procedure (Table 2). A mild to moderate relationship was noted between the changes from the pre- to post-stent PSV and EDV compared to the stenosis ratio (ΔPSV, r = 0.4731; P = .018; ΔEDV, r = 0.0473; P = .001). Scattergrams show the pre- and post-stent changes in ophthalmic artery velocities in relation to the stenosis ratio (Figures 1–3). In 11 patients (39%), retrograde flow was noted in the ophthalmic artery before the procedure. After stenting, spectral analysis showed that the flow direction changed
Table 1. Patient Demographics Patient
Age, y
Sex
ICA Stenosis, % Right Left
Stented Side
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
75 87 85 63 62 67 74 79 65 75 66 58 64 71 69
Male Male Female Female Male Female Male Male Male Male Female Male Male Male Male
80 85 71 92 70 98 74 79 75 96 100 40 60 60 63
30 86 0 100 100 70 100 67 20 0 70 92 92 80 96
Right Right Right Right Right Right Right Right Right Right Left Left Left Left Left
16 17 18 19 20
65 63 76 80 53
Male Male Male Female Male
40 78 50 30 70
95 87 98 95 95
Left Left Left Left Left
21 22 23 24 25 26 27 28
73 77 76 73 65 76 75 76
Male Male Male Male Female Male Female Female
33 50 100 20 30 35 50 100
70 90 98 89 92 95 98 92
Left Left Left Left Left Left Left Left
Symptom Status Mild right MCA infarct Asymptomatic Asymptomatic Right upper extremity paresis Left amaurosis fugax Right amaurosis fugax, TIA TIA Asymptomatic Asymptomatic Left hemiparesis Asymptomatic TIA, syncope, confusion TIA TIA Right lower extremity paresis, left lacunar infarcts Asymptomatic TIA Right arm hemiparesis TIA, right hemiparesis Right upper extremity paresis, left amaurosis fugax Small left MCA infarct Right hemiparesis Asymptomatic Asymptomatic TIA Asymptomatic Motor aphasia, small left MCA infarct Left hemianopsia, right upper extremity paresis
Comorbidities HL, dementia None None HL, HT None DM, HL, HT None None None None None TX HL, COPD, CVD HL, HT, CVD TX, HL, HT, CAD None None None DM, HT None HT None None None None None HL None
CAD indicates coronary artery disease; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; DM, diabetes mellitus; HL, hyperlipidemia; HT, hypertension; ICA, internal carotid artery; MCA, middle cerebral artery; TIA, transient ischemic attack; and TX, thyrotoxicosis.
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Table 2. Pre- and Post-Stent Ophthalmic Artery PSV, EDV, RI, and PI Values Parameter PSV, cm/s EDV, cm/s RI PI
Pre-Stent –3.87 ± 48.81 10.75 (–112.8 to 62.7) –3.02 ± 16.31 1.95 (–49.3 to 20.3) 0.71 ± 0.18 0.74 (0 to 0.98) 1.40 ± 0.59 1.45 (0 to 2.62)
Post-Stent
P
46.70 ± 25.33 44.95 (–16.6 to 95.5) 11.24 ± 7.37 9.8 (–3.4 to 28.5) 0.77 ± 0.09 0.78 (0.59 to 0.9) 1.62 ± 0.52 1.63 (0 to 2.35)
15 cm/s) were noted compared to asymptomatic patients (P = .0108 and .006, respectively). Comorbidities such as hypertension, diabetes, hyperlipidemia, and thyrotoxicosis were detected in 10 patients. Having comorbidities did not correlate with the changes in ophthalmic artery velocities or having negative pre-stent ophthalmic artery flow.
Discussion The ophthalmic artery is an intracranial artery with unique properties. It can reflect hemodynamic changes related to cerebrovascular disease at the intracranial level. The acoustic barrier formed by bone imposes a great problem during examinations of intracranial vessels by Doppler sonography. However, such a barrier does not exist for the ophthalmic artery when a transorbital approach is used. The study can be performed in an easy and reliable manner with linear
Figure 5. Images from a patient with 96% stenosis in the left internal carotid artery. A, No notable flow was in the left ophthalmic artery before stenting. B, After stenting, an antegrade normal flow pattern with a high PSV (71.9 cm/s at end systole) was detected in the left ophthalmic artery. C and D, Left internal carotid artery stent patency was confirmed on grayscale (C) and on color Doppler (D) sonography after the stenting procedure. A
B
C
D
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7.5-MHz probes that are also used in standard Doppler sonographic examinations of the carotid artery. The imager can have a direct view of the ophthalmic artery and thus can examine a major vessel of the intracranial circulation. A decrease in the velocity and pulsatility of the incoming flow is indirect proof of severe upstream stenosis. The ophthalmic artery is located downstream of the internal carotid artery. The inflow artery for the ophthalmic artery is the internal carotid artery, and the ophthalmic artery can reflect changes in the petrous and cavernous portions of the internal carotid artery.16,17 The responses to cerebral ischemia and compensation mechanisms show differences among individuals. Studies have shown that in high-grade stenosis, collateral pathways and circle of Willis collaterals come into play. If circle of Willis collaterals decompensate, alternative mechanisms will become manifest.10–12,24 Absence of collaterals or reversal of normal antegrade flow in the ophthalmic artery is a grave finding suggestive of decompensation from the contralateral internal carotid artery (mainly via the anterior communicating artery).1,3,10,12,14,17 In such a situation, the ophthalmic artery is often filled by collaterals from the ipsilateral external carotid artery but not from the Circle of Willis.10,12,24 The direction of blood flow in the ophthalmic artery is maintained by blood pressure differences between the ipsilateral internal carotid artery and external carotid artery.10 Patients with inadequate collaterals have been reported to benefit most from carotid endarterectomy procedures.1
Figure 6. Scattergram of ophthalmic artery ΔEDV and ΔPSV. Symbols are as in Figure 1.
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In a study by Fujioka et al,10 6 different ophthalmic artery flow patterns in carotid artery stenosis were described, depending on the collateral flow, grade of stenosis, and blood pressure. Retrograde flow in the ophthalmic artery was correlated with high-grade stenosis and ipsilateral external carotid artery collateralization of the ophthalmic artery with absence of a Circle of Willis contribution. The same abnormal flow patterns were also observed in our study. We detected retrograde flow, absence of flow, and changes in the shapes of systolic and diastolic peaks in correlation with a decrease in the flow velocity and resistance. In a study by Schneider et al,17 transorbital and transcranial color Doppler sonographic findings for 25 internal carotid artery occlusions and 10 normal internal carotid arteries were examined. In cases with retrograde ophthalmic artery flow, a decrease in the middle cerebral artery flow velocity was noted, which was presumed to be related to inadequate intracranial collateral flow. The ophthalmic artery PSV (38 ± 10.2 cm/s) and PI in internal carotid artery occlusions decreased on the occluded side compared to the nonoccluded side and the control group.17 Another study by Fujioka13 suggested that a decrease in the PSV of less than 10 cm/s and the presence of retrograde flow (90%) seem to support this evidence. An interesting relationship that emerged from our study was that symptomatic patients with high-grade stenosis (≥85%) had a marked ophthalmic artery flow increase after stenting compared to asymptomatic patients. In all of our patients, Circle of Willis arteries were complete, but in 6 patients, complete occlusion of the contralateral internal carotid artery was present, and in 4 patients, severe stenosis of 70% or greater in the contralateral internal carotid artery was present. Statistical analysis showed that the ophthalmic artery flow changes after stenting were not statistically different in this group of patients compared to patients with a patent contralateral internal carotid artery. In the study by Gee et al,28 which studied pre- and postocular blood flow in 701 carotid endarterectomy cases using ocular pneumoplethysmography, 27% and 47% improvements on the side of the repaired carotid artery were detected when there was severe stenosis (>70%) and total occlusion of the contralateral carotid artery, respectively. This increase was only 16% when the contralateral side was functionally patent.28 Although a similar increase was present in our study, it was not statistically significant, perhaps because our study group was small or somehow well compensated due to having patent Circle of Willis arteries, or because ophthalmic artery flow is subject to autoregulation, whereas ocular blood flow is not. In our study, ophthalmic artery flow appeared to be driven more by the ipsilateral internal carotid artery stenosis rather than the contralateral internal carotid artery. Having comorbidities did not influence ophthalmic artery flow changes. Both angiography and color Doppler sonography have high accuracy for detection of stenosis of greater than 70% and follow-up after intervention. Color Doppler sonography is widely used to assess stent patency after the procedure.6–9 Ophthalmic artery Doppler sonography can be effectively incorporated into the routine carotid artery sonographic protocol and may prove useful in decision making when unequivocal carotid artery stenosis cases are encountered. There is always a possibility of stenosis beyond the extracranial segment of the carotid artery, which may affect the success of the stenting procedure. Such stenosis may interfere with ophthalmic artery flow patterns after stenting as well. The ophthalmic artery PSV was noted to decrease in response to siphon stenosis and a tortuous common
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carotid artery.24 Intracranial atherosclerotic disease may be present in 20% to 50% of patients with extracranial carotid artery stenosis.9,32 Fortunately, endarterectomy studies have shown that the presence of such substantial intracranial stenosis greater than 50% is quite low and does not affect surgical success, the prognosis, or stroke ratios after endarterectomy.32 The prognosis is much better in intracranial vascular stenosis than internal carotid artery stenosis and does not change the mortality and morbidity ratios. Also, the degree of calcification in the carotid siphon is not used as a prognostic factor in cerebral stroke.32 Patients with mild to moderate intracranial atherosclerotic disease and severe carotid artery stenosis are considered ideal candidates who can benefit the most from carotid endarterectomy.1 Such severe intracranial stenosis was not detected in any of our patients, but in patients with no apparent extracranial carotid artery stenosis presenting with findings suggestive of intracranial arterial occlusive disease, substantially decreased ophthalmic artery flow or retrograde flow may prompt further investigation for intracranial atherosclerotic disease. In conclusion, transorbital Doppler sonography can provide information about early cerebral hemodynamic changes after angioplasty and stent placement in carotid artery stenosis. Even indirect information about internal carotid artery stent patency can be inferred. Simultaneous use of ophthalmic artery Doppler sonography with carotid Doppler sonography during the same scan session can yield more diagnostic information. Retrograde flow or substantially decreased flow (
ORIGINAL RESEARCH
Effect of Carotid Artery Stenting on Ophthalmic Artery Flow Patterns Namik K. Altinbas, MD, Evren Ustuner, MD, Hasan Ozcan, MD, Sadik Bilgic, MD, Tanzer Sancak, MD, Ebru Dusunceli, MD
Article includes CME test
Objectives—The purpose of this study was to assess the effect of carotid artery stenting on ophthalmic artery blood flow using transorbital color and spectral Doppler sonography and review the changes in relation to cerebral hemodynamics. Methods—Twenty-eight consecutive patients with severe internal carotid artery stenosis (≥70%) who were scheduled for carotid stenting were included. Ophthalmic artery Doppler sonography was performed bilaterally before and after stenting. The flow direction, peak systolic velocity (PSV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index in the ophthalmic artery were recorded. Results—Twenty male and 8 female patients with 10 right-sided and 18 left-sided stenoses were studied. The mean overall carotid stenosis ratio ± SD was 87.3% ± 9.9%. After stenting in the ophthalmic artery ipsilateral to the stenosis, significant increases in the PSV (–3.87 ± 48.81 to 46.70 ± 25.33 cm/s; P < .001), and EDV (–3.02 ± 16.31 to 11.24 ± 7.37 cm/s; P < .001) were detected, and the increase in the PI approached significance (1.40 ± 0.59 to 1.62 ± 0.52; P = .055). A change in the flow direction from retrograde to antegrade was noted in 11 patients (39%) after stenting, and in 1 patient with no detectable flow, reconstitution of flow was observed. Increases in the PSV and EDV (P = .03 for ΔEDV) were more pronounced in symptomatic patients than asymptomatic patients after stenting.
Received May 13, 2013, from the Department of Radiology, Ankara University School of Medicine, Ankara, Turkey (N.K.A., E.U., H.O., S.B., E.D.); and Radiology Unit, Private Tobb-Etu Hospital, Ankara, Turkey (T.S.). Revision requested June 4, 2013. Revised manuscript accepted for publication August 5, 2013. This study was presented as a oral presentation at the Eighth Interventional Radiology Annual Meeting; March 28–31, 2013; Antalya, Turkey. Address correspondence to Namik K. Altinbas, MD, Department of Radiology, Ankara University School of Medicine, Ibn-i Sina Hospital, 06230 Ankara, Turkey. E-mail: [email protected] Abbreviations
EDV, end-diastolic velocity; PI, pulsatility index; PSV, peak systolic velocity; RI, resistive index doi:10.7863/ultra.33.4.629
Conclusions—Substantially decreased ophthalmic artery velocity and retrograde flow are suggestive of high-grade carotid artery stenosis (≳90%). Stenting improves ophthalmic artery perfusion and positively changes cerebral hemodynamics in high-grade carotid artery stenosis, especially in symptomatic patients, which can be monitored with ophthalmic artery Doppler sonography. Key Words—carotid artery stenosis; color and spectral Doppler sonography; endovascular treatment; ophthalmic artery; ophthalmologic ultrasound; stenting; stroke
C
arotid artery stenosis is a major cause of cerebrovascular disease and causes devastating impacts on health.1–4 Recently, in addition to medication and surgery, endovascular techniques (angioplasty and stenting) have been introduced for treatment of carotid artery stenosis with success.2,3 Endovascular procedures are gaining wide popularity as alternatives and have similar outcomes and periprocedural risks compared to endarterectomy.1–5 Carotid imaging using color Doppler sonography or angiography is highly accurate in revealing carotid artery stenosis of 70% or greater.6–9 Examination of the ophthalmic artery with Doppler sonography also provides valuable information about blood flow
©2014 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2014; 33:629–638 | 0278-4297 | www.aium.org
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patterns and hemodynamics of cerebral perfusion.10–17 The ophthalmic artery provides many advantages in this regard, being a downstream intracerebral branch of the internal carotid artery and also being easily accessible by Doppler sonography. In this study, our aim was to investigate the immediate effects of carotid artery stenting on ophthalmic artery flow patterns in patients with internal carotid artery stenosis of 70% or greater. In this way, we could indirectly observe intracerebral hemodynamic changes after stenting. In addition, using this information, we can obtain definite, quantitative, and measurable information about the effects of stenting on the ophthalmic artery, which may help us follow and plan endovascular treatments.
Materials and Methods Patient Selection A total of 28 consecutive patients who had been referred to the interventional radiology department for a carotid artery stenting procedure between June 2007 and August 2009 were included in the study. All patients were confirmed to have carotid artery stenosis of 70% or greater by selective contrast angiography at the time of stenting, and all were thoroughly examined and referred for a stenting procedure by neurologists before admission to the radiology department. Indications for stenting were made according to the guidelines and evidence provided by the North American Symptomatic Carotid Endarterectomy Trial,18 the European Carotid Surgery Trial,19 and the Asymptomatic Carotid Atherosclerosis Study,20 which suggest that symptomatic patients and asymptomatic patients benefit from the procedure if they have severe stenosis (≥70%) and if their complication rates are less than 6% for symptomatic and 3% for asymptomatic patients.18–21 As part of their treatment plan, all patients gave informed written consent before diagnostic angiographic and endovascular treatment (angioplasty and stenting) procedures. The patients also gave informed written consent for ophthalmic artery Doppler sonography before and after the procedure. All of the procedures in this study were done in accordance with the Declaration of Helsinki for human subjects, and the study was approved by our Institutional Review Board. Angiographic Evaluation and Stenting Diagnostic cerebral angiography was performed in all patients before the stenting procedure to assess the intracranial and extracranial cerebral circulation. Stenosis ratios were calculated in accordance with the guidelines
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provided by the North American Symptomatic Carotid Endarterectomy Trial.18 The stenting procedure was performed according to the guidelines and techniques described by Moran et al.22 After definite localization of the stenosis, self-expandable stents (Wallstent; Boston Scientific, Galway, Ireland) were deployed using a protective umbrella device (Emboshield; Abbott Ireland, Galway, Ireland). At the end of the procedure, the carotid artery and intracranial circulation was reevaluated for dissection, vasospasm, and patency using anteroposterior and lateral views. Color and Spectral Doppler Sonographic Examinations Doppler sonography of the ophthalmic artery was performed in accordance with the standard technique described by Belden et al.23 Doppler sonographic examinations of the ophthalmic artery were done on the same day before stenting and 1 to 3 days after the procedure, when the patients became ambulatory and hemodynamically stable, using Aplio SSA-770A/80 Doppler equipment (Toshiba Medical Systems Co, Ltd, Tokyo, Japan) with a 7.5-MHz multifrequency linear transducer. The carotid artery and transorbital ophthalmic artery were evaluated bilaterally by Doppler sonography. To standardize Doppler sonographic measurements, all studies were performed bilaterally by the same radiologist. First, carotid arteries were examined on both sides for lumen and stent patency. Next, Doppler sonography of both ophthalmic arteries was done. The ophthalmic artery peak systolic velocity (PSV), enddiastolic velocity (EDV), pulsatility index (PI), and resistive index (RI) were all recorded. Care was taken not to apply pressure on the globe during measurements by using the correct angles and sample width. During the spectral analysis mode, the spatial-peak temporal-average intensity was always kept below the threshold of 17 mW/cm2, as recommended by the US Food and Drug Administration.16 The ages, sexes, medical histories (hypertension, diabetes mellitus, and atherosclerotic heart disease), and neurologic examination findings of the patients were recorded as well (Table 1). Statistical Analysis Normal distribution of the variables was assessed by the Shapiro-Wilk test. Comparisons of pre- and post-stent ophthalmic artery velocity variables were evaluated by the Wilcoxon signed ranks test. The Mann-Whitney U test was used to test the difference between two groups. Nominal variables were tested by the Fisher exact test. The degree of association between the stenosis ratio and differences between pre- and post-stent ophthalmic artery velocity
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variables were assessed by the Spearman ρ coefficient. P < .05 was considered significant. SPSS version 15.0 software for Windows (IBM Corporation, Armonk, NY) was used for statistical evaluations.
Results The carotid stenting procedure was performed in 20 male and 8 female patients. Stents were placed on the right side in 10 patients and on the left side in 18. None of the patients received bilateral stents during the same procedure or underwent a later contralateral stent placement procedure. The mean age of the study group ± SD was 71 ± 7.9 years (range, 53–87 years). The total mean stenosis ratio was 87.3% ± 9.9% (range, 70%–98%). Stenosis was significantly higher on the left side (P < .05).
Results of the spectral Doppler sonographic examinations of the ophthalmic artery before and after stenting are presented in Table 2. The PSV in the ophthalmic artery ipsilateral to the stenosis before stenting was –3.87 ± 48.81 cm/s and increased significantly to 46.70 ± 25.33 cm/s after stenting (P < .001). To sum up, statistically significant increases in ophthalmic artery flow values on the stented side (PSV, EDV, and PI) were noted after the stenting procedure (Table 2). A mild to moderate relationship was noted between the changes from the pre- to post-stent PSV and EDV compared to the stenosis ratio (ΔPSV, r = 0.4731; P = .018; ΔEDV, r = 0.0473; P = .001). Scattergrams show the pre- and post-stent changes in ophthalmic artery velocities in relation to the stenosis ratio (Figures 1–3). In 11 patients (39%), retrograde flow was noted in the ophthalmic artery before the procedure. After stenting, spectral analysis showed that the flow direction changed
Table 1. Patient Demographics Patient
Age, y
Sex
ICA Stenosis, % Right Left
Stented Side
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
75 87 85 63 62 67 74 79 65 75 66 58 64 71 69
Male Male Female Female Male Female Male Male Male Male Female Male Male Male Male
80 85 71 92 70 98 74 79 75 96 100 40 60 60 63
30 86 0 100 100 70 100 67 20 0 70 92 92 80 96
Right Right Right Right Right Right Right Right Right Right Left Left Left Left Left
16 17 18 19 20
65 63 76 80 53
Male Male Male Female Male
40 78 50 30 70
95 87 98 95 95
Left Left Left Left Left
21 22 23 24 25 26 27 28
73 77 76 73 65 76 75 76
Male Male Male Male Female Male Female Female
33 50 100 20 30 35 50 100
70 90 98 89 92 95 98 92
Left Left Left Left Left Left Left Left
Symptom Status Mild right MCA infarct Asymptomatic Asymptomatic Right upper extremity paresis Left amaurosis fugax Right amaurosis fugax, TIA TIA Asymptomatic Asymptomatic Left hemiparesis Asymptomatic TIA, syncope, confusion TIA TIA Right lower extremity paresis, left lacunar infarcts Asymptomatic TIA Right arm hemiparesis TIA, right hemiparesis Right upper extremity paresis, left amaurosis fugax Small left MCA infarct Right hemiparesis Asymptomatic Asymptomatic TIA Asymptomatic Motor aphasia, small left MCA infarct Left hemianopsia, right upper extremity paresis
Comorbidities HL, dementia None None HL, HT None DM, HL, HT None None None None None TX HL, COPD, CVD HL, HT, CVD TX, HL, HT, CAD None None None DM, HT None HT None None None None None HL None
CAD indicates coronary artery disease; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; DM, diabetes mellitus; HL, hyperlipidemia; HT, hypertension; ICA, internal carotid artery; MCA, middle cerebral artery; TIA, transient ischemic attack; and TX, thyrotoxicosis.
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Table 2. Pre- and Post-Stent Ophthalmic Artery PSV, EDV, RI, and PI Values Parameter PSV, cm/s EDV, cm/s RI PI
Pre-Stent –3.87 ± 48.81 10.75 (–112.8 to 62.7) –3.02 ± 16.31 1.95 (–49.3 to 20.3) 0.71 ± 0.18 0.74 (0 to 0.98) 1.40 ± 0.59 1.45 (0 to 2.62)
Post-Stent
P
46.70 ± 25.33 44.95 (–16.6 to 95.5) 11.24 ± 7.37 9.8 (–3.4 to 28.5) 0.77 ± 0.09 0.78 (0.59 to 0.9) 1.62 ± 0.52 1.63 (0 to 2.35)
15 cm/s) were noted compared to asymptomatic patients (P = .0108 and .006, respectively). Comorbidities such as hypertension, diabetes, hyperlipidemia, and thyrotoxicosis were detected in 10 patients. Having comorbidities did not correlate with the changes in ophthalmic artery velocities or having negative pre-stent ophthalmic artery flow.
Discussion The ophthalmic artery is an intracranial artery with unique properties. It can reflect hemodynamic changes related to cerebrovascular disease at the intracranial level. The acoustic barrier formed by bone imposes a great problem during examinations of intracranial vessels by Doppler sonography. However, such a barrier does not exist for the ophthalmic artery when a transorbital approach is used. The study can be performed in an easy and reliable manner with linear
Figure 5. Images from a patient with 96% stenosis in the left internal carotid artery. A, No notable flow was in the left ophthalmic artery before stenting. B, After stenting, an antegrade normal flow pattern with a high PSV (71.9 cm/s at end systole) was detected in the left ophthalmic artery. C and D, Left internal carotid artery stent patency was confirmed on grayscale (C) and on color Doppler (D) sonography after the stenting procedure. A
B
C
D
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7.5-MHz probes that are also used in standard Doppler sonographic examinations of the carotid artery. The imager can have a direct view of the ophthalmic artery and thus can examine a major vessel of the intracranial circulation. A decrease in the velocity and pulsatility of the incoming flow is indirect proof of severe upstream stenosis. The ophthalmic artery is located downstream of the internal carotid artery. The inflow artery for the ophthalmic artery is the internal carotid artery, and the ophthalmic artery can reflect changes in the petrous and cavernous portions of the internal carotid artery.16,17 The responses to cerebral ischemia and compensation mechanisms show differences among individuals. Studies have shown that in high-grade stenosis, collateral pathways and circle of Willis collaterals come into play. If circle of Willis collaterals decompensate, alternative mechanisms will become manifest.10–12,24 Absence of collaterals or reversal of normal antegrade flow in the ophthalmic artery is a grave finding suggestive of decompensation from the contralateral internal carotid artery (mainly via the anterior communicating artery).1,3,10,12,14,17 In such a situation, the ophthalmic artery is often filled by collaterals from the ipsilateral external carotid artery but not from the Circle of Willis.10,12,24 The direction of blood flow in the ophthalmic artery is maintained by blood pressure differences between the ipsilateral internal carotid artery and external carotid artery.10 Patients with inadequate collaterals have been reported to benefit most from carotid endarterectomy procedures.1
Figure 6. Scattergram of ophthalmic artery ΔEDV and ΔPSV. Symbols are as in Figure 1.
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In a study by Fujioka et al,10 6 different ophthalmic artery flow patterns in carotid artery stenosis were described, depending on the collateral flow, grade of stenosis, and blood pressure. Retrograde flow in the ophthalmic artery was correlated with high-grade stenosis and ipsilateral external carotid artery collateralization of the ophthalmic artery with absence of a Circle of Willis contribution. The same abnormal flow patterns were also observed in our study. We detected retrograde flow, absence of flow, and changes in the shapes of systolic and diastolic peaks in correlation with a decrease in the flow velocity and resistance. In a study by Schneider et al,17 transorbital and transcranial color Doppler sonographic findings for 25 internal carotid artery occlusions and 10 normal internal carotid arteries were examined. In cases with retrograde ophthalmic artery flow, a decrease in the middle cerebral artery flow velocity was noted, which was presumed to be related to inadequate intracranial collateral flow. The ophthalmic artery PSV (38 ± 10.2 cm/s) and PI in internal carotid artery occlusions decreased on the occluded side compared to the nonoccluded side and the control group.17 Another study by Fujioka13 suggested that a decrease in the PSV of less than 10 cm/s and the presence of retrograde flow (90%) seem to support this evidence. An interesting relationship that emerged from our study was that symptomatic patients with high-grade stenosis (≥85%) had a marked ophthalmic artery flow increase after stenting compared to asymptomatic patients. In all of our patients, Circle of Willis arteries were complete, but in 6 patients, complete occlusion of the contralateral internal carotid artery was present, and in 4 patients, severe stenosis of 70% or greater in the contralateral internal carotid artery was present. Statistical analysis showed that the ophthalmic artery flow changes after stenting were not statistically different in this group of patients compared to patients with a patent contralateral internal carotid artery. In the study by Gee et al,28 which studied pre- and postocular blood flow in 701 carotid endarterectomy cases using ocular pneumoplethysmography, 27% and 47% improvements on the side of the repaired carotid artery were detected when there was severe stenosis (>70%) and total occlusion of the contralateral carotid artery, respectively. This increase was only 16% when the contralateral side was functionally patent.28 Although a similar increase was present in our study, it was not statistically significant, perhaps because our study group was small or somehow well compensated due to having patent Circle of Willis arteries, or because ophthalmic artery flow is subject to autoregulation, whereas ocular blood flow is not. In our study, ophthalmic artery flow appeared to be driven more by the ipsilateral internal carotid artery stenosis rather than the contralateral internal carotid artery. Having comorbidities did not influence ophthalmic artery flow changes. Both angiography and color Doppler sonography have high accuracy for detection of stenosis of greater than 70% and follow-up after intervention. Color Doppler sonography is widely used to assess stent patency after the procedure.6–9 Ophthalmic artery Doppler sonography can be effectively incorporated into the routine carotid artery sonographic protocol and may prove useful in decision making when unequivocal carotid artery stenosis cases are encountered. There is always a possibility of stenosis beyond the extracranial segment of the carotid artery, which may affect the success of the stenting procedure. Such stenosis may interfere with ophthalmic artery flow patterns after stenting as well. The ophthalmic artery PSV was noted to decrease in response to siphon stenosis and a tortuous common
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carotid artery.24 Intracranial atherosclerotic disease may be present in 20% to 50% of patients with extracranial carotid artery stenosis.9,32 Fortunately, endarterectomy studies have shown that the presence of such substantial intracranial stenosis greater than 50% is quite low and does not affect surgical success, the prognosis, or stroke ratios after endarterectomy.32 The prognosis is much better in intracranial vascular stenosis than internal carotid artery stenosis and does not change the mortality and morbidity ratios. Also, the degree of calcification in the carotid siphon is not used as a prognostic factor in cerebral stroke.32 Patients with mild to moderate intracranial atherosclerotic disease and severe carotid artery stenosis are considered ideal candidates who can benefit the most from carotid endarterectomy.1 Such severe intracranial stenosis was not detected in any of our patients, but in patients with no apparent extracranial carotid artery stenosis presenting with findings suggestive of intracranial arterial occlusive disease, substantially decreased ophthalmic artery flow or retrograde flow may prompt further investigation for intracranial atherosclerotic disease. In conclusion, transorbital Doppler sonography can provide information about early cerebral hemodynamic changes after angioplasty and stent placement in carotid artery stenosis. Even indirect information about internal carotid artery stent patency can be inferred. Simultaneous use of ophthalmic artery Doppler sonography with carotid Doppler sonography during the same scan session can yield more diagnostic information. Retrograde flow or substantially decreased flow (
