Color Doppler Imaging of the Ocular Ischemic Syndrome Allen C. Ho, MD,l Wolfgang E. Lieb, MD,2 Patrick M. Flaharty MD 1 ' , Robert C. Sergott, MD, 1 Gary C. Brown, MD, 3 Thomas M. Bosley, MD, 1 Peter]. Savino, MDl Purpose: This study describes hemodynamic characteristics of the ophthalmic, central retinal, and posterior ciliary arteries in 16 eyes of 11 patients with the ocular ischemic syndrome. Understanding the hemodynamic characteristics of the retrobulbar circulation may elucidate the natural history and pathophysiology of the ocular ischemic syndrome and perhaps form the basis for rational treatment of this condition. Methods: Color Doppler imaging, a procedure that permits rapid noninvasive imaging of the ophthalmic, central retinal, and posterior ciliary arteries, was used to quantitate peak systolic blood flow velocities and vascular resistance (pulsatility index) within these vessels in study group eyes and in an age-matched control population. Results: We demonstrated markedly reduced ocular ischemic syndrome central retinal and posterior ciliary artery peak systolic velocities compared with control group eyes. Central retinal and posterior ciliary artery vascular reSistance (pulsatility index) was greater in ocular ischemic eyes versus control group eyes. Reversal of ophthalmic artery blood flow was detected in 12 of 16 ocular ischemic syndrome eyes. Study group eyes with poor vision had no detectable posterior Ciliary arterial blood flow. Conclusion: Color Doppler imaging quantitates hemodynamic characteristics of the retrobulbar circulation in the ocular ischemic syndrome. There is markedly reduced peak systolic velocity and increased vascular resistance in ocular end arteries such as the central retinal and posterior ciliary arteries. Ophthalmic artery reversal of flow seems to represent collateral blood flow to lower resistance vascular beds. Posterior ciliary artery hypoperfusion may correlate with poor vision in the ocular ischemic syndrome. Ophthalmology 1992;99; 1453-1462
Although ocular ischemic syndrome is relatively uncommon in the general population, its ocular sequelae in addition to associated cardiac and cerebrovascular morbidity Originally received: July 5, 1991. Revision accepted: February 17, 1992. I
Neuro-Ophthalmology Service, Wills Eye Hospital, Philadelphia.
Universitets Augenklinik, Johannes Gutenberg Universitat, Mainz, Germany. 3 Retina Vascular Unit, Wills Eye Hospital, Philadelphia. 2
Presented at the American Academy of Ophthalmology Annual Meeting, Anaheim, October 1991, and the Wills Eye Hospital/Pennsylvania Academy of Ophthalmology Annual Meeting, April 1991. The authors have no proprietary interest in the development or marketing of this device. Reprint requests to Robert C. Sergott, MD, Wills Eye Hospital, Ninth and Walnut Sts, Philadelphia, PA 19107.
and mortality underscore its importance. l It is estimated that carotid occlusion occurs in 4% to 18% of patients with ocular ischemic syndrome. 2 Because ocular hypoperfusion is the hallmark of ocular ischemic syndrome, indirect measures of blood flow such as continuous-wave Doppler spectra and duplex ultrasonography of the carotid arteries searching for potentially treatable vascular lesions are important in the evaluation of these patients. These conventional methods, which image blood flow within the larger vessels of the head and neck, are unable to describe the circulation of the smaller caliber vessels within the retrobulbar space, including the op~thalmic, central retinal, and short posterior ciliary artenes. Color Doppler imaging (CDI) facilitates the study of this orbital vasculature by color encoding the Doppler frequency shifts of blood flow, superimposing this color on B-scan anatomic detail, and thereby allowing local-
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Volume 99, Number 9, September 1992
ization and orientation of vessel angles. We examined color Doppler blood flow characteristics of the orbital vasculature in 16 eyes with ocular ischemic syndrome to define the hemodynamics of the ophthalmic, central retinal, and short posterior ciliary arteries.
Materials and Methods The QAD 1 color Dopplerimaging unit (Quantum Medical Systems, Inc, Issaquah, WA) with 5.0 or 7.5 MHz linear phased transducers was used to examine all patients according to the method of Lieb and co-workers. 3 The estimated in situ peak temporal average intensity in the color imaging mode is 2 to 3 mW/cm 2 for the 7.5 MHz transducer. During spectral analysis, the in situ peak temporal average intensity is approximately 50 to 100 m W/ cm 2 , exceeding the currently approved Food and Drug
Administration upper guidelines of 17 m W/cm 2 • For specific use of this higher in situ peak temporal average intensity, we obtained approval from the Institutional Review Board of Wills Eye Hospital. Informed consent was received from all patients. Depending on the direction of flow with respect to the transducer, flow is displayed either in red or blue. The colors may be arbitrarily assigned but by convention, and, in this study, flow toward the transducer is depicted as red and away from the transducer as blue. Therefore, most arterial flow is red and venous flow is blue. When examining the eye and orbit through the eyelids, we attempted to align the ultrasound beam parallel to the vessel of regard and its stream of blood flow. In the imaging mode, arteries can usually be distinguished from veins by their pulsatility. Spectral analysis distinguishes between the usually pulsatile arterial and nonpulsatile venous flow and allows for quantification of Doppler shifts of moving acoustic reflectors such as red Table 1. Patient
Patient No./ Age (yrs)/Sex
Medical History
1/58/M
Myocardial infarction
2/76jM
Hypertension, stroke
3/76jM
Diabetes mellitus, hypertension, stroke Transient ischemic attacks
4/53/M
5/76/F
Diabetes mellitus, chronic obstructive pulmonary disease
6/75/M
Stroke
7/74jM
Diabetes mellitus
8/71jM
Hypertension, stroke, myocardial infarction, diabetes mellitus
9/81jM
Hypertension, hypercholesterolemia
1O/62/M
Cervical radiculopathy, paresthesias
11/57/M
Diabetes mellitus, myocardial infarction, hypercholesterolemia
Eye
Ocular History
Visual Acuity
lOP (mmHg)
OD OS OD OS OD OS OD
Graying of vision, colored lights None None None Intermittent dimming, ocular ache Loss of vision, ocular ache Loss of vision
20/40 20/30 20/30 20/30 20/50 HM NLP
8 13 7 12 12 10 4
OS OD
None Intraocular lens
20/30 20/40
19 14
OS
Central retinal vein occlusion
NLP
38
OD OS OD OS OD OS
None None Intraocular lens Intraocular lens Loss of vision Loss of vision
20/30 20/30 20/40 20/30 20/50 LP
17 17 11 13 11 10
OD OS OD OS
None None None Flickering lights
20/50 20/25 20/20 20/20
19 17 18 16
OD
Loss of vision
20/40
20
OS
Loss of vision
20/30
22
lOP = intraocular pressure; OA = ophthalmic artery peak systolic velocity cm/sec; CRA = central retinal artery peak systolic velocity cm/sec; PCAN = nasal short posterior ciliary artery peak systolic velocity cm/sec; PCAT = temporal short posterior ciliary artery peak systolic velOcity cm/sec; OD = right eye; OS = left eye; NFD = no flow detected; HM = hand motions; NLP = no light perception. • Denotes eyes with clinical ocular ischemic syndrome. t Percent stenosis of internal carotid artery via duplex scan ultrasound.
1454
Ho et al . Color Doppler Imaging blood cells. When the Doppler ultrasound beam is at an angle of 90° in relation to the flow stream, or the vessel of interest exhibits very low flow velocity, no frequency shift is recorded and therefore no color flow information is generated. In these instances, vessels are depicted in gray scale only. The study group comprised II patients, 9 men and 2 women, ranging in age from 53 to 81 years with a mean age of 67 years (Table I). Patients were examined in the supine position after applying a contact gel, sterile ophthalmic methylcellulose, to closed eyelids. Transverse (axial) scans through the eye and orbit were performed using the 7.5 MHz probe. Color-encoded blood flow of the central retinal artery is identified within the B-scan gray scale image of the optic nerve, while short posterior ciliary arterial flow is depicted just adjacent to the optic nerve within the retrobulbar space. Right ophthalmic artery blood flow is most easily imaged with patient left gaze and right gaze for the left ophthalmic artery. With
these maneuvers, the ophthalmic artery is typically identified as a larger caliber pulsatile vessel adjacent to the optic nerve. Doppler frequency shifts (Hz) within the ophthalmic, central retinal, and posterior ciliary arteries were measured to determine peak systolic, end diastolic, and mean blood flow velocities (cm/sec). For all orbital vessels with detectable blood flow, vascular resistance was calculated by the formula of Gosling and King (Gosling's pulsatility index = [peak systolic velocity minus end diastolic velocity divided by mean velocity in cm/sec]).4 Velocity measurements are dependent on and can vary with the angle of Doppler insonation, but pulsatility is angle independent. We determined these angles by aligning the angle cursor with color pixels that identified blood flow within the vessel of regard. When examining carotid and vertebral arteries, a 7.5 MHz probe using an 18° wedge or a 5.0 MHz probe using a 14 °wedge is used, depending on the depth of the vessels
Characteristics Clinical Findings
Internal Carotidst
OA
CRA
PCAN
PCAT
Dilated retinal veins, midperipheral intraretinal hemorrhage· Normal Midperipheral intraretinal hemorrhage, dilated retinal veins· Normal Dilated retinal veins, midperipheral intraretinal hemorrhage" Iris neovascularization, optic disc pallor, dilated retinal veins· Optic disc and iris neovascularization, dilated retinal veins, midperipheral intraretinal hemorrhages· Minimally dilated retinal veins Anterior chamber cell and flare, dilated retinal veins, midperipheral intraretinal hemorrhages· Relative afferent pupillary defect, attenuated arterioles, chorioretinal laser photocoagulation scars Normal Dilated retinal veins, midperipheral intraretinal hemorrhage· Dilated retinal veins, midperipheral intraretinal hemorrhage" Dilated retinal veins, midperipheral intraretinal hemorrhage" Dilated retinal veins, midperipheral intraretinal hemorrhage· Dilated retinal veins, optic disc pallor, midperipheral intraretinal hemorrhage" Dilated retinal veins, midperipheral intraretinal hemorrhages· Dilated retinal veins, midperipheral intraretinal hemorrhages· Normal Macular edema, dilated retinal veins, midperipheral intraretinal hemorrhages· Iris neovascularization, dilated retinal veins, midperipheral intraretinal hemorrhages· Iris neovascularization, dilated retinal veins, midperipheral intraretinal hemorrhages"
90% RICA 4O%LICA 100% RICA 90%LICA 100% RICA 100% LICA 100% RICA 20%LICA
19.6 28.2 (-60.2) 34.1 (-40.3) (-47.0) (-23.3) 15.8
5 .1 7.8 4.9 5.1 2.8 4.2 4.5
3 12.1 8.1 5.8 6.1 NFD NFD 9.1
3.6 11.9 5.9 NFD 8.3 NFD NFD 11
100% RICA
40.5
5.4
5.4
6.7
100% LICA
27.3
2.4
7.9
5.4
100% RICA 100% LICA 100% RICA 98%LICA 90% RICA
27.8 (-8.9) (-66.1) (-40.7) (-55.8)
6.3 2.6 1.5 2.1 2.9
9.9 5 8.2 4 3.2
7 4.1 8.4 4.8 4.3
100%LICA 70% RICA 100% LICA 30% RICA
(-32.3) (-15.4) (-20.3) 44.2
1.3 5.6 4.8 9.7
NFD NFD 6.5 4.7
NFD 6.8 NFD 7.7
100% LICA 90% RICA
(-40.0) 17.8
4 6
3.8 8.6
3.3 NFD
90%LICA
21
3.4
7.7
NFD
1.7
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Table 2. Study Group Controls (n = 21 Patients, 27 Eyes) Artery
Peak Systolic Velocity em/sec Mean ± 1 SD
Pulsatility Index Mean ± 1 SD
30.6 ± 8.9 10.5 ± 2.4 9.1 ± 2.6
1.5 ± 0.5 1.5 ± 0.5 1.2 ± 0.4
OA CRA PCA
Gosling's pulsatility index = peak systolic velocity minus end diastolic velocity divided by average velocity in cm/ sec. SD = standard deviation; OA = ophthalmic artery; CRA = central retinal artery; PCA = short posterior ciliary artery.
as determined by individual body habitus. A probe wedge facilitates study of vessels that course parallel to the skin surface. Doppler spectra were obtained in several locations within the vessels of interest. The study control group comprised 21 patients, 16 men and 5 women, ranging in age from 54 to 85 years with a mean age of 67 years and no known history of carotid occlusive disease. Peak systolic velocities and pulsatility indices were determined for ophthalmic, central retinal, and posterior ciliary arteries (Table 2).
Case Reports Case 1. A 58-year-old man experienced intermittent graying
of vision in his right eye, lasting between 5 and 10 minutes and associated with colored lights. He denied headache or ocular pain. Medical history was significant for a myocardial infarction, but there was no history of diabetes mellitus or systemic hypertension. Best-corrected visual acuities were 20/40 in the right eye and 20/30 in the left, and applanation tonometry intraocular tensions
were 8 mmHg in the right eye and 13 in the left. No iris neovascularization was observed. The right fundus demonstrated dilated nontortuous retinal veins and dot and blot intraretinal hemorrhages in the midperipheral retina and a normal optic nerve. There were no spontaneous retinal arterial pulsations. The left fundus was normal. Duplex scan (Biosound 2000SA, Indianapolis, IN) ultrasonography showed 90% stenosis of the right internal carotid artery, 40% stenosis ofthe left internal carotid artery, and 20% stenosis in the left and right external carotid vessels. Ocular pneumoplethysmography (Electro-Diagnostics Instruments, Burbank, CA) using the Gee technique 5 was markedly abnormal on the right with an ophthalmic artery systolic pressure of 60 mmHg versus 107 mmHg on the left. Westergren erythrocyte sedimentation rate was 19 mm/hr. With a supine pulse rate of 55/min and a brachial blood pressure of 110/50 mmHg, CDI showed marked reductions of peak systolic blood flow velocity within the retrobulbar arterial circulation of the right eye. Peak systolic flow velocity of the right ophthalmic artery was 19.6 cm/sec compared with the left ophthalmic artery velocity of28.2 cm/sec. The right ophthalmic artery peak systolic velocity was much less than control group ophthalmic artery peak systolic velocity of 30.6 ± 8.9 cm/sec, mean ± I standard deviation. The right central retinal artery showed a peak systolic flow velocity of 5.1 cm/sec compared with 7.8 cm/sec for the left central retinal artery (Fig I), and both were below control group central retinal artery peak systolic flow velocity of 10.5 ± 2.4 cm/sec, mean ± I standard deviation. Peak systolic blood flow velocity of a representative short right nasal and short right temporal posterior ciliary artery was 3.0 and 3.6 cm/sec, respectively. These slow velocities were markedly less than corresponding nasal 12.1 cm/sec and temporal 11.9 cm/sec short left posterior ciliary arteries. Control group peak systolic velocity for the short posterior ciliary arteries is 9.1 ± 2.6 cm/sec, mean ± I standard deviation. Intravenous fluorescein angiography of the affected eye showed delayed choroidal filling, delayed retinal arterial filling (30 seconds), slow arteriovenous transit time (45 seconds), and late staining of retinal vessels, all consistent with ocular ischemic syndrome (Fig 2).
Figure 1. COl of the right central retinal artery (CRA) in patient 1 with ocular ischemic syndrome (left). Notice the reduced systolic peaks of the time-velocity waveform (graph below color image) in contrast to the normal pattern of the uninvolved side (right). Adjacent central retinal venous flow is below the baseline.
1456
Ho et al . Color Doppler Imaging
Figure 2. Red-free Ulumination shows dilated retinal veins and intraretinal hemorrhages of the right eye, patient 1 (A). Intravenous fluorescein angiography of the right eye, patient 1, demonstrates patchy peripapillary choroidal filling worse temporal to the optic disc than nasal as well as delayed retinal arterial filling (30 seconds) (B). Late phase of the angiogram reveals staining of the retinal arterioles (C).
The same CDI unit used for orbital imaging was used to characterize the structure and flow characteristics within the carotid arterial system. Color Doppler imaging showed greater than 90% stenosis of the right internal carotid artery (Fig 3). The left
internal carotid artery revealed only mild stenosis and normal arterial wave forms. Before this patient could be completely evaluated for possible carotid endarterectomy, he experienced a stroke with residual left sided hemiparesis. His ophthalmic status remains unchanged. Case 2. A 76-year-old hypertensive man with a medical history of a "mild stroke" in 1987 was seen for a routine eye examination and had no ocular complaints. Best-corrected visual acuity was 20/30 in both eyes. Applanation tonometry intraocular tensions were 7 mmHg in the right eye and 12 mmHg in the left. No iris neovascularization was present. Funduscopic examination of the right eye showed dilated nontortuous retinal veins as well as midperipheral intraretinal dot hemorrhages. The left fundus was unremarkable. Duplex scan evaluation of the carotid vessels showed an occlusion of the right internal carotid artery, 90% stenosis of the left internal carotid artery, and mild stenoses of the external carotid arteries right greater than left. With a supine pulse rate of 70/min and a brachial blood pressure of 137/96, CDI documented reversal of ophthalmic artery blood flow in the right eye (-60.2 cm/sec) and antegrade ophthalmic artery peak systolic blood flow in the left (34.1 cm/ sec) (Fig 4). Peak systolic blood flow velocity of the right central retinal artery (4.9 cm/sec) and the left central retinal artery (5.1 cm/sec) were less than the control group (10.5 ± 2.4 cm/sec). Peak systolic blood flow velocity of a right nasal short posterior ciliary artery (8.1 cm/sec), a right temporal short posterior ciliary artery (5.9 cm/sec), and a left nasal short posterior ciliary artery (5.8 cm/sec) all were low compared with the control group (9.1 ± 2.6 cm/sec). There was no detectable blood flow in the left temporal short posterior ciliary arteries. This patient's clinical status has remained stable for 8 months after his orbital CD!. Case 3. A 58-year-old diabetic, hypertensive woman whose medical history was significant for a stroke and mild residual right-sided hemiparesis, presented with progressive loss of vision in her left eye during the last year as well as intermittent dimming of vision in her right eye and dull ocular aching in both eyes. Best-corrected visual acuity was 20/50 in the right eye and hand motions in the left. Applanation tonometry intraocular tensions were 12 mmHg in the right eye and 10 mmHg in the left. Bilateral iris neovascularization was present. The right anterior chamber angle was normal. The angle on the left was closed for 360 0 with haphazard new vessel growth crossing Schwalbe's line. Results of funduscopic examination of the right eye showed retinal venous dilation with midperipheral intraretinal hemorrhages. There was no evidence of posterior segment neovascularization in the right eye. The left fundus showed moderate pallor of the optic disc with retinal venous dilation and attenuated retinal arterioles. Duplex scan evaluation of the carotid vessels showed occlusions of both internal carotid arteries and normal left and right common and external carotid vessels. With a supine pulse rate of 80/min and a brachial blood pressure of 140/94 mmHg, CDI documented reversal of blood flow with turbulence in both right (-40.3 cm/sec) and left ophthalmic arteries (-47.0 cm/sec). Peak systolic blood flow velocity in the left central retinal artery (1.7 cm/sec) was less than the right central retinal artery (2.8 cm/sec) and these values were less than control (10.5 ± 2.4 cm/sec). Peak systolic blood flow velocity ofthe right nasal and temporal short posterior ciliary arteries of 6.1 cm/sec and 8.3 cm/sec, respectively, were less than control (9.1 ± 2.6 cm/sec). No short posterior ciliary artery flow was detected in the left orbit (Fig 5).
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Volume 99, Number 9, September 1992
Top, Figure 3. COl of the right internal carotid artery of patient 1 demonstrates a greater than 90% stenosis (left). The time-frequency display (graph, below color image) shows high Doppler frequency shifts and therefore high flow velocity (>250 em/sec) at the filiform stenosis. High velocity blood flow is also indicated by the white color in the lumen of the poststenotic vessel. The left internal carotid artery demonstrates a more normal color image and time-velocity waveform (right). Center, Figure 4. Reversal of ophthalmic artery (OA) blood flow in the right eye in patient 2 (left) as shown by the blue color and pulsatile waveform demonstrating arterial not venous hemodynamics. In contrast, the flow of blood in the unaffected left eye is red and toward the globe with an arterial pulsatile waveform (right). Bottom, Figure 5. Red anterograde short posterior ciliary artery (PCA) flow in the right eye, patient 3 (left). In contrast, note the relative absence of Doppler signal in the region of the temporal and nasal short posterior ciliary arteries of the left eye with hand motion visual acuity (right). The cursor is placed on the Doppler signals of the central retinal artery (CRA) and central retinal vein (CRV) in the left eye within the B-scan shadow of the optic nerve. COl demonstrates severe impairment of short posterior ciliary arterial blood flow in this eye.
1458
Ho et al . Color Doppler Imaging Intravenous fluorescein angiography in the left eye showed profoundly delayed, patchy choroidal filling, a retinal arteriovenous transit time of greater than 45 seconds, and multiple sites ofleading edges of fluorescein dye within retinal arterioles, all indicative of severely compromised ocular perfusion. Her clinical status has remained unchanged for 6 months.
OA PEAK SYSTOLIC . VELOCITY 60 40
20
Results
OA PSV 0
.J4-JH...I~:r=ir=iir==.=t-'=r"ir'iT'rnii=in=in=i:r=iL...f:lJ;j
CM/SEC
A total of22 eyes were studied with CDI, and 16 of these eyes had clinical signs of ocular ischemic syndrome; five patients (patients 3, 7, 8, 9, and 11) had bilateral disease. Vasculopathic diseases such as diabetes mellitus, hypertension, or prior myocardial infarction were present in nearly all patients. Visual acuity of ocular ischemic syndrome eyes ranged from 20/20 to no light perception. Five of 11 ocular ischemic patients (patients 2, 5, 6, 7, and 9) did not present with any new ocular or visual complaint (patient 5 had longstanding poor vision in the left eye from a prior central retinal vein obstruction). However, five patients (patients 1, 3, 4, 8, and 11) experienced diminished visual acuity. One patient (patient 3) with bilateral ocular ischemia experienced ocular aching in both eyes and two patients (patients 1 and 10) noted flickering lights. All 16 affected eyes presented with dilated nontortuous retinal veins and 15 affected eyes had midperipheral intraretinal hemorrhages. Four affected eyes (patients 3, 4, 11) had iris neovascularization and 1 affected eye (patient 4) had optic disc neovascularization. Duplex ultrasonographic evaluation of the carotid arteries revealed that all 16 eyes with the ocular ischemic syndrome were associated with high grade ipsilateral internal carotid artery lesions ranging from 70% stenosis to CRA PEAK SYSTOLIC VELOCITY 12~------------------------------'
10 8
CRA PSV CM/SEC
6 4
N 12345678910111213141516
OIS EYES
Figure 6. Central retinal artery peak systolic velocity in normal eyes (mean ± SD = 10.5 ± 2.4 em/sec) and in eyes with ocular ischemic syndrome (3.5 ± 1.5 em/sec). Note the significantly reduced values of ocular ischemic syndrome eyes. CRA = central retinal artery; PSV = mean peak systolic velocity; OIS = ocular ischemic syndrome; N = normal eyes.
·20 ·40
·60
N 12345678910111213141516
OIS EYES
Figure 7. Ophthalmic artery peak systolic velocity in normal eyes (mean ± SD = 30.6 ± 8.9 em/sec) and in eyes with ocular ischemic syndrome (mean ± SD, -21.9 ± 32.2 em/sec). Reversal of flow within the ophthalmic artery is depicted below the horizontal. Twelve of 16 eyes with OIS demonstrated ophthalmic artery reversal of flow. OA = ophthalmic artery; PSV = mean peak systolic velocity; N = normal eyes; OIS = ocular ischemic syndrome.
total occlusion. Ten of 16 ocular ischemic syndrome eyes were associated with ipsilateral occlusion of the internal carotid artery. Two of 10 eyes with internal carotid artery occlusion had no signs of the syndrome. Only 1 of 3 patients with bilateral internal carotid artery occlusion had bilateral signs of ocular ischemic syndrome. Color Doppler imaging demonstrated markedly reduced central retinal artery peak systolic blood flow velocity in all eyes with ocular ischemic syndrome versus control subjects (Fig 6). The ocular ischemic syndrome central retinal artery peak systolic blood flow velocity ranged from 1.3 to 6.0 cm/sec with a mean of 3.5 cm/ sec, while control group central retinal artery peak systolic blood flow velocity is 10.3 ± 2.1 cm/sec. Color Doppler imaging documented reversal of ophthalmic artery blood flow in 12 of 16 eyes with ocular ischemic syndrome. Ophthalmic artery peak systolic blood flow velocity ranged from -66.1 to 40.5 cm/sec with a mean of - 21.9 cm/sec (Fig 7). The ocular ischemic syndrome mean peak systolic blood flow velocity was significantly less than control group ophthalmic artery peak systolic flow velocity of 30.6 cm/sec ± 8.9 cm/sec. Ocular ischemic syndrome short posterior ciliary artery peak systolic blood flow velocity ranged from no detectable flow to 8.6 cm/sec with a mean of 3.9 em/sec (Fig 8). This mean peak systolic flow velocity was significantly less than control group short posterior ciliary artery peak systolic flow velocity of 9.1 ± 2.6 em/sec. Table 3 compares mean pulsatility indices of this vasculopathic study group with study group control values for the ophthalmic, central retinal, and short posterior ciliary arteries. Mean ophthalmic artery pulsatility index
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Volume 99, Number 9, September 1992
Ophthalmology
of 2.0 ± 0.5 was greater than control ophthalmic .artery pulsatility index of 1.5 ± 0.5; the mean ophthalmic artery pulsatility index of those vessels with reversal of flow of 1.2 ± 0.4, however, was less than control. The central retinal artery mean pulsatility index of 2.2 ± 0.7 was greater than the control group central retinal artery pulsatility index of 1.5 ± 0.5. The mean pulsatility index of the short posterior ciliary arteries of 2.0 ± 0.5 also was greater than the control group posterior ciliary artery pulsatility index of 1.2 ± 0.4.
The ocular ischemic syndrome is a relatively uncommon condition with a rather broad presentation. Patients may complain of visual loss, photopsia, eye pain, or may be asymptomatic. Visual acuity can range from 20/20 to no light perception. The diagnosis is made from a constellation of signs including but not limited to anterior chamber cell and flare, iris neovascularization, retinal venous dilation retinal arteriolar attenuation or pulsation, midperiphe;al retinal hemorrhages, macular edema, and optic disc neovascularization. Most eyes are associated with ipsilateral carotid arterial occlusive disease and most patients have multiple vasculopathic risk factors such as hypertension and diabetes mellitus. Vascular hypoperfusion has been recognized for many years as the major cause of the ocular ischemic syndrome. 6 ,7 It is unclear, however, why certain eyes with carotid arterial occlusive disease manifest ocular ischemic syndrome and maintain good visual acuity, others dete-
PCA PEAK SYSTOLIC VELOCITY 10
-
8
CM/SEC
6
4
2
-
Il-
e---
~
I----
o N 12345678910111213141516
015 EYES
Figure 8. Short posterior ciliary artery peak systolic velocity in normal eyes (mean ± SD = 9.1 ± 2.6 em/sec) and in eyes with ocular ischemic syndrome (3.9 ± 3.2 em/ sec). Note the reduced values of ocular ischemic syndrome eyes and that three OIS eyes with marked visual loss had no detectable nasal or temporal short posterior ciliary artery blood flow. PCA = short posterior ciliary artery; PSV = mean peak systolic velocity; N = normal eyes; OIS = ocular ischemic syndrome. Solid white bar represents nasal PCA; other bar represents temporal PCA.
1460
Subject Eyes
Artery
OA ROA CRA
PCA
Mean ± 1 SD
2.0 ± 0.5 (n 1.2 ± 0.4 (n 2.2 ± 0.7 (n 2.0 ± 0.5 (n
= 4) 12) = 16) = 22) =
Control Eyes
Mean ± 1 SD
1.5 ± 0.5 (n 1.5 ± 0.5 (n 1.5 ± 0.5 (n
=
1.2 ± 0.4 (n
=
=
=
27) 27) 27) 27)
Gosling's pulsatility index = peak systolic velocity minus end diastolic velocity divided by average velocity in em/ sec.
Discussion
PCA PSV
Table 3. Pulsatility Index in Subject Eyes Versus Control Eyes
SD = standard deviation; OA = ophthalmic artery; ROA = ophthalmic artery with reversal of flow; CRA = central retinal artery; PCA = short posterior ciliary artery; n = number of eyes.
riorate rapidly, and others do not manifest signs of ocular ischemia at all. Previous methods including carotid and cerebral angiography, transcranial Doppler analysis, and intravenous fluorescein angiography have been unable to assess directly the microcirculation of the retrobulbar space,3,8 Color Doppler imaging adds a new rapidly performed, noninvasive dimension to the understanding of ocular ischemic syndrome by providing a quantitative analysis of blood flow within the ophthalmic, central retinal, and posterior ciliary arteries. Although current CDI technology cannot determine volumetric flow within the relatively small caliber retroorbital vessels because of limitations in color Doppler spatial resolution, it does provide a method of measuring blood flow velocity as well as vascular resistance. In most physiologic circumstances, peak systolic blood flow velocity may be a gauge of systolic blood flow and vascular resistance as calculated by the pulsatility index may be an index of diastolic blood flow.4, lo Moreover, CDI data correlate well with intravenous fluorescein angiography and digital subtraction carotid arteriography as illustrated by a case of ophthalmic artery obstruction associated with occlusive carotid artery disease. 9 In summary, CDI provides quantitative data about retrobulbar blood flow characteristics in a rapid, noninvasive, and reproducible fashion . Color Doppler imaging documented reversal of ophthalmic artery flow in 12 of 16 eyes with ocular ischemic syndrome and decreased central retinal artery peak systolic flow velocity in all eyes with the syndrome. Previous reports note the association of ophthalmic artery flow reversal with internal carotid occlusion I 1-13; 9 of 12 eyes with ophthalmic artery blood flow reversal were associated with internal carotid artery occlusion while 3 eyes were associated with ipsilateral internal carotid artery stenosis. Flow reversal within the ophthalmic artery represents collateralization through the external carotid artery system in response to obstructions within the internal carotid and/or intracranial arterial systems. In our experience with over 400 CDI studies of the retrobulbar micro-
Ho et al . Color Doppler Imaging circulation, reversal of flow within the ophthalmic artery has been observed only in ocular ischemic syndrome with associated internal carotid artery stenosis, 1 case of giant cell arteritis and as a late development in ophthalmic artery occlusion. 9 Mean pulsatility indices of the ophthalmic, central retinal, and posterior ciliary arteries of all ocular ischemic syndrome eyes were greater than those of normal control eyes (Table 2). In an animal model, Evans et al 14 showed that for a proximal stenosis, pulsatility index was directly dependent on the vascular resistance of the distal vascular bed. IS Multiple vasculopathic risk factors, such as hypertension, diabetes mellitus, and atherosclerosis appear to account for the higher pulsatility indices of ocular ischemic syndrome eyes as compared to normal eyes. Differences in the pulsatility index of ocular end arteries such as the central retinal artery or the short posterior ciliary arteries may reflect asymmetric distal stenosis within these vessels and/or dynamic variations of distal retinal or choroidal arterial resistance. The mean pulsatility index of ocular ischemic syndrome eyes with ophthalmic artery reversal of flow (1.2 ± 0.4), however, was less than normal control eyes (1.5 ± 0.5). Reversed ophthalmic artery flow in the setting of high-grade internal carotid artery stenosis or occlusion results in a reduced pulsatility index as the ophthalmic artery now supplies the low resistance intracranial circulation rather than the somewhat higher resistance orbital circulation. Because ophthalmic artery flow reversal was observed in the majority of ocular ischemic syndrome eyes (12 of 16), we believe that this lower distal vascular resistance accounts for the lower mean pulsatility index of this group. Although ipsilateral high-grade carotid stenosis, reversal of ophthalmic artery flow, decreased central retinal artery flow, and higher pulsatility indices in ocular end arteries are very often associated with ocular ischemic syndrome, this combination was not sufficient to produce decreased vision. In 3 eyes (left eye of patient 3, right eye of patient 4, left eye of patient 8) in which ocular ischemic syndrome and its sequelae were responsible for markedly decreased visual acuity (hand motions or worse), severe impairment of flow in both the nasal and temporal posterior ciliary arteries was demonstrated with COL Although we recognize that only a small number of patients were studied, the COl data suggest that posterior ciliary artery hypoperfusion and therefore secondary ischemia of the optic nerve, choroid, retinal pigment epithelium, and outer segments of the photoreceptors may be responsible for visual loss in ocular ischemic syndrome. Furthermore, the lower rise of the electro-oculogram as described by Ross Russell and Ikeda I 6 and the experimental blood flow studies of McFadzean and co-workers l ? corroborate our COl findings in strongly suggesting posterior ciliary arterial hypoperfusion as a cause of visual loss in the ocular ischemic syndrome. The specific finding of posterior ciliary artery hypoperfusion may explain why patients with the ocular ischemic syndrome and similar degrees of carotid
stenosis and retinal findings can have very different levels of visual function. Therefore, in managing the ocular ischemic syndrome patient, one should consider monitoring for (1) decreased posterior ciliary artery flow by COl; (2) visual field defects consistent with optic neuropathy; and (3) peripapillary hypoperfusion as assessed by fluorescein angiography. The development of these findings may herald significant loss of vision and prompt consideration of medical therapies to attempt to improve blood flow or more aggressive management of the underlying high grade carotid occlusive disease. In contrast, patients retain excellent vision with ocular ischemic syndrome when the short posterior ciliary arterial circulation is maintained. Therefore, in patients with preserved short posterior ciliary artery perfusion, decisions concerning carotid surgery should be based only on the risk of cerebral infarction and not upon the theory that carotid surgery is necessary to prevent visual loss. Whether successful carotid endarterectomy will improve diminished posterior ciliary artery perfusion is not yet known. Interestingly, several eyes with no detectable flow in the temporal short posterior ciliary artery but with preserved albeit low flow in the nasal short posterior ciliary artery maintained 20/40 vision or better. In conclusion, we believe that COl is useful for the evaluation and management of patients with ocular ischemic syndrome. It is uniquely suited to assess rapidly and quantitatively blood flow within both the retrobulbar and carotid systems. Although our study population is limited and our findings preliminary, COl data suggest that both reductions in peak systolic blood flow velocity as well as increased vascular resistance to diastolic blood flow in ocular end arteries characterize the retrobulbar circulation in ocular ischemic syndrome. Reversal of flow within ocular ischemic syndrome ophthalmic arteries represents collateral blood flow to lower resistance vasculature. Short posterior ciliary artery hypoperfusion and ischemia of the structures it serves may correlate with markedly reduced vision in ocular ischemic syndrome. Color Doppler imaging may provide a more complete understanding of the natural history and pathophysiology of ocular ischemic syndrome and perhaps form the basis for rational treatment of this condition.
References I. Sivalingham A, Brown GC, Magargal LE, Menduke H. The ocular ischemic syndrome. II. Mortality and systemic morbidity. Int Ophthalmol 1989;13:187-91. 2. Sturrock GD, Mueller HR. Chronic ocular ischaemia. Br J Ophthalmol 1984;68:716-23. 3. Lieb WE, Cohen SM, Merton DA, et al. Color Doppler imaging of the eye and orbit. Technique and normal vascular anatomy. Arch Ophthalmol 1991;109:527-31. 4. Gosling RG, King DH. Arterial assessment by Dopplershift ultrasound. Proc R Soc Med 1974;67:447-9.
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5. Gee W. Carotid physiology with ocular pneumoplethysmography. Stroke 1982; 13:666-73. 6. Kearns TP, Hollenhorst RW. Venous-stasis retinopathy of occlusive disease of the carotid artery. Mayo Clin Proc 1963;38:304-12. 7. Brown GC. The ocular ischemic syndrome. In: Ryan SJ, ed. Retina. vol. 2: Medical Retina. St. Louis: CV Mosby, J 990; chap. 88. 8. Erickson SJ, Hendrix LE, Massaro BM, et al. Color Doppler flow imaging of the normal and abnormal orbit. Radiology 1989;173:511-16. 9. Lieb WE, Aaharty PM, Sergott RC, et al. Color Doppler imaging provides accurate assessment of orbital blood flow in occlusive carotid artery disease. Ophthalmology 1991 ;98: 548-52. 10. Taylor KJW, Holland S. Doppler US. Part I. Basic principles, instrumentation, and pitfalls. Radiology 1990;174:297-307. 11. Pitts FW. Variations of collateral circulation in internal carotid artery occlusion. Comparison of clinical and x-ray findings. Neurology 1962;12:467-71.
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12. Hodek-Demarin V, Mueller HR. Reversed ophthalmic artery flow in internal carotid artery occlusion. Are-appraisal based on ultrasonic Doppler investigations. Stroke 1979; 10: 461-3. 13. Tatemichi TK, Chamorro A, Petty GW, et al. Hemodynamic role of ophthalmic artery collateral in internal carotid artery occlusion. Neurology 1990;40:461-4. 14. Evans DH, Barrie WW, Asher MJ, et al. The relationship between ultrasonic pulsatility index and proximal arterial stenosis in a canine model. Circ Res 1980;46:470-5. 15. Schneider PA, Rossman ME, Bernstein EF, et al. Effect of internal carotid artery occlusion on intracranial hemodynamics. Transcranial Doppler evaluation and clinical correlation. Stroke 1988;19:589-93. 16. Ross Russell RW, Ikeda H. Clinical and electrophysiological observations in patients with low pressure retinopathy. Br J Ophthalmol 1986;70:651-6. 17. McFadzean RM, Graham DI, Lee WR, Mendelow AD. Ocular blood flow in unilateral carotid stenosis and hypotension. Invest Ophthalmol Vis Science 1989;30:487-90.
Although ocular ischemic syndrome is relatively uncommon in the general population, its ocular sequelae in addition to associated cardiac and cerebrovascular morbidity Originally received: July 5, 1991. Revision accepted: February 17, 1992. I
Neuro-Ophthalmology Service, Wills Eye Hospital, Philadelphia.
Universitets Augenklinik, Johannes Gutenberg Universitat, Mainz, Germany. 3 Retina Vascular Unit, Wills Eye Hospital, Philadelphia. 2
Presented at the American Academy of Ophthalmology Annual Meeting, Anaheim, October 1991, and the Wills Eye Hospital/Pennsylvania Academy of Ophthalmology Annual Meeting, April 1991. The authors have no proprietary interest in the development or marketing of this device. Reprint requests to Robert C. Sergott, MD, Wills Eye Hospital, Ninth and Walnut Sts, Philadelphia, PA 19107.
and mortality underscore its importance. l It is estimated that carotid occlusion occurs in 4% to 18% of patients with ocular ischemic syndrome. 2 Because ocular hypoperfusion is the hallmark of ocular ischemic syndrome, indirect measures of blood flow such as continuous-wave Doppler spectra and duplex ultrasonography of the carotid arteries searching for potentially treatable vascular lesions are important in the evaluation of these patients. These conventional methods, which image blood flow within the larger vessels of the head and neck, are unable to describe the circulation of the smaller caliber vessels within the retrobulbar space, including the op~thalmic, central retinal, and short posterior ciliary artenes. Color Doppler imaging (CDI) facilitates the study of this orbital vasculature by color encoding the Doppler frequency shifts of blood flow, superimposing this color on B-scan anatomic detail, and thereby allowing local-
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ization and orientation of vessel angles. We examined color Doppler blood flow characteristics of the orbital vasculature in 16 eyes with ocular ischemic syndrome to define the hemodynamics of the ophthalmic, central retinal, and short posterior ciliary arteries.
Materials and Methods The QAD 1 color Dopplerimaging unit (Quantum Medical Systems, Inc, Issaquah, WA) with 5.0 or 7.5 MHz linear phased transducers was used to examine all patients according to the method of Lieb and co-workers. 3 The estimated in situ peak temporal average intensity in the color imaging mode is 2 to 3 mW/cm 2 for the 7.5 MHz transducer. During spectral analysis, the in situ peak temporal average intensity is approximately 50 to 100 m W/ cm 2 , exceeding the currently approved Food and Drug
Administration upper guidelines of 17 m W/cm 2 • For specific use of this higher in situ peak temporal average intensity, we obtained approval from the Institutional Review Board of Wills Eye Hospital. Informed consent was received from all patients. Depending on the direction of flow with respect to the transducer, flow is displayed either in red or blue. The colors may be arbitrarily assigned but by convention, and, in this study, flow toward the transducer is depicted as red and away from the transducer as blue. Therefore, most arterial flow is red and venous flow is blue. When examining the eye and orbit through the eyelids, we attempted to align the ultrasound beam parallel to the vessel of regard and its stream of blood flow. In the imaging mode, arteries can usually be distinguished from veins by their pulsatility. Spectral analysis distinguishes between the usually pulsatile arterial and nonpulsatile venous flow and allows for quantification of Doppler shifts of moving acoustic reflectors such as red Table 1. Patient
Patient No./ Age (yrs)/Sex
Medical History
1/58/M
Myocardial infarction
2/76jM
Hypertension, stroke
3/76jM
Diabetes mellitus, hypertension, stroke Transient ischemic attacks
4/53/M
5/76/F
Diabetes mellitus, chronic obstructive pulmonary disease
6/75/M
Stroke
7/74jM
Diabetes mellitus
8/71jM
Hypertension, stroke, myocardial infarction, diabetes mellitus
9/81jM
Hypertension, hypercholesterolemia
1O/62/M
Cervical radiculopathy, paresthesias
11/57/M
Diabetes mellitus, myocardial infarction, hypercholesterolemia
Eye
Ocular History
Visual Acuity
lOP (mmHg)
OD OS OD OS OD OS OD
Graying of vision, colored lights None None None Intermittent dimming, ocular ache Loss of vision, ocular ache Loss of vision
20/40 20/30 20/30 20/30 20/50 HM NLP
8 13 7 12 12 10 4
OS OD
None Intraocular lens
20/30 20/40
19 14
OS
Central retinal vein occlusion
NLP
38
OD OS OD OS OD OS
None None Intraocular lens Intraocular lens Loss of vision Loss of vision
20/30 20/30 20/40 20/30 20/50 LP
17 17 11 13 11 10
OD OS OD OS
None None None Flickering lights
20/50 20/25 20/20 20/20
19 17 18 16
OD
Loss of vision
20/40
20
OS
Loss of vision
20/30
22
lOP = intraocular pressure; OA = ophthalmic artery peak systolic velocity cm/sec; CRA = central retinal artery peak systolic velocity cm/sec; PCAN = nasal short posterior ciliary artery peak systolic velocity cm/sec; PCAT = temporal short posterior ciliary artery peak systolic velOcity cm/sec; OD = right eye; OS = left eye; NFD = no flow detected; HM = hand motions; NLP = no light perception. • Denotes eyes with clinical ocular ischemic syndrome. t Percent stenosis of internal carotid artery via duplex scan ultrasound.
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Ho et al . Color Doppler Imaging blood cells. When the Doppler ultrasound beam is at an angle of 90° in relation to the flow stream, or the vessel of interest exhibits very low flow velocity, no frequency shift is recorded and therefore no color flow information is generated. In these instances, vessels are depicted in gray scale only. The study group comprised II patients, 9 men and 2 women, ranging in age from 53 to 81 years with a mean age of 67 years (Table I). Patients were examined in the supine position after applying a contact gel, sterile ophthalmic methylcellulose, to closed eyelids. Transverse (axial) scans through the eye and orbit were performed using the 7.5 MHz probe. Color-encoded blood flow of the central retinal artery is identified within the B-scan gray scale image of the optic nerve, while short posterior ciliary arterial flow is depicted just adjacent to the optic nerve within the retrobulbar space. Right ophthalmic artery blood flow is most easily imaged with patient left gaze and right gaze for the left ophthalmic artery. With
these maneuvers, the ophthalmic artery is typically identified as a larger caliber pulsatile vessel adjacent to the optic nerve. Doppler frequency shifts (Hz) within the ophthalmic, central retinal, and posterior ciliary arteries were measured to determine peak systolic, end diastolic, and mean blood flow velocities (cm/sec). For all orbital vessels with detectable blood flow, vascular resistance was calculated by the formula of Gosling and King (Gosling's pulsatility index = [peak systolic velocity minus end diastolic velocity divided by mean velocity in cm/sec]).4 Velocity measurements are dependent on and can vary with the angle of Doppler insonation, but pulsatility is angle independent. We determined these angles by aligning the angle cursor with color pixels that identified blood flow within the vessel of regard. When examining carotid and vertebral arteries, a 7.5 MHz probe using an 18° wedge or a 5.0 MHz probe using a 14 °wedge is used, depending on the depth of the vessels
Characteristics Clinical Findings
Internal Carotidst
OA
CRA
PCAN
PCAT
Dilated retinal veins, midperipheral intraretinal hemorrhage· Normal Midperipheral intraretinal hemorrhage, dilated retinal veins· Normal Dilated retinal veins, midperipheral intraretinal hemorrhage" Iris neovascularization, optic disc pallor, dilated retinal veins· Optic disc and iris neovascularization, dilated retinal veins, midperipheral intraretinal hemorrhages· Minimally dilated retinal veins Anterior chamber cell and flare, dilated retinal veins, midperipheral intraretinal hemorrhages· Relative afferent pupillary defect, attenuated arterioles, chorioretinal laser photocoagulation scars Normal Dilated retinal veins, midperipheral intraretinal hemorrhage· Dilated retinal veins, midperipheral intraretinal hemorrhage" Dilated retinal veins, midperipheral intraretinal hemorrhage" Dilated retinal veins, midperipheral intraretinal hemorrhage· Dilated retinal veins, optic disc pallor, midperipheral intraretinal hemorrhage" Dilated retinal veins, midperipheral intraretinal hemorrhages· Dilated retinal veins, midperipheral intraretinal hemorrhages· Normal Macular edema, dilated retinal veins, midperipheral intraretinal hemorrhages· Iris neovascularization, dilated retinal veins, midperipheral intraretinal hemorrhages· Iris neovascularization, dilated retinal veins, midperipheral intraretinal hemorrhages"
90% RICA 4O%LICA 100% RICA 90%LICA 100% RICA 100% LICA 100% RICA 20%LICA
19.6 28.2 (-60.2) 34.1 (-40.3) (-47.0) (-23.3) 15.8
5 .1 7.8 4.9 5.1 2.8 4.2 4.5
3 12.1 8.1 5.8 6.1 NFD NFD 9.1
3.6 11.9 5.9 NFD 8.3 NFD NFD 11
100% RICA
40.5
5.4
5.4
6.7
100% LICA
27.3
2.4
7.9
5.4
100% RICA 100% LICA 100% RICA 98%LICA 90% RICA
27.8 (-8.9) (-66.1) (-40.7) (-55.8)
6.3 2.6 1.5 2.1 2.9
9.9 5 8.2 4 3.2
7 4.1 8.4 4.8 4.3
100%LICA 70% RICA 100% LICA 30% RICA
(-32.3) (-15.4) (-20.3) 44.2
1.3 5.6 4.8 9.7
NFD NFD 6.5 4.7
NFD 6.8 NFD 7.7
100% LICA 90% RICA
(-40.0) 17.8
4 6
3.8 8.6
3.3 NFD
90%LICA
21
3.4
7.7
NFD
1.7
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Table 2. Study Group Controls (n = 21 Patients, 27 Eyes) Artery
Peak Systolic Velocity em/sec Mean ± 1 SD
Pulsatility Index Mean ± 1 SD
30.6 ± 8.9 10.5 ± 2.4 9.1 ± 2.6
1.5 ± 0.5 1.5 ± 0.5 1.2 ± 0.4
OA CRA PCA
Gosling's pulsatility index = peak systolic velocity minus end diastolic velocity divided by average velocity in cm/ sec. SD = standard deviation; OA = ophthalmic artery; CRA = central retinal artery; PCA = short posterior ciliary artery.
as determined by individual body habitus. A probe wedge facilitates study of vessels that course parallel to the skin surface. Doppler spectra were obtained in several locations within the vessels of interest. The study control group comprised 21 patients, 16 men and 5 women, ranging in age from 54 to 85 years with a mean age of 67 years and no known history of carotid occlusive disease. Peak systolic velocities and pulsatility indices were determined for ophthalmic, central retinal, and posterior ciliary arteries (Table 2).
Case Reports Case 1. A 58-year-old man experienced intermittent graying
of vision in his right eye, lasting between 5 and 10 minutes and associated with colored lights. He denied headache or ocular pain. Medical history was significant for a myocardial infarction, but there was no history of diabetes mellitus or systemic hypertension. Best-corrected visual acuities were 20/40 in the right eye and 20/30 in the left, and applanation tonometry intraocular tensions
were 8 mmHg in the right eye and 13 in the left. No iris neovascularization was observed. The right fundus demonstrated dilated nontortuous retinal veins and dot and blot intraretinal hemorrhages in the midperipheral retina and a normal optic nerve. There were no spontaneous retinal arterial pulsations. The left fundus was normal. Duplex scan (Biosound 2000SA, Indianapolis, IN) ultrasonography showed 90% stenosis of the right internal carotid artery, 40% stenosis ofthe left internal carotid artery, and 20% stenosis in the left and right external carotid vessels. Ocular pneumoplethysmography (Electro-Diagnostics Instruments, Burbank, CA) using the Gee technique 5 was markedly abnormal on the right with an ophthalmic artery systolic pressure of 60 mmHg versus 107 mmHg on the left. Westergren erythrocyte sedimentation rate was 19 mm/hr. With a supine pulse rate of 55/min and a brachial blood pressure of 110/50 mmHg, CDI showed marked reductions of peak systolic blood flow velocity within the retrobulbar arterial circulation of the right eye. Peak systolic flow velocity of the right ophthalmic artery was 19.6 cm/sec compared with the left ophthalmic artery velocity of28.2 cm/sec. The right ophthalmic artery peak systolic velocity was much less than control group ophthalmic artery peak systolic velocity of 30.6 ± 8.9 cm/sec, mean ± I standard deviation. The right central retinal artery showed a peak systolic flow velocity of 5.1 cm/sec compared with 7.8 cm/sec for the left central retinal artery (Fig I), and both were below control group central retinal artery peak systolic flow velocity of 10.5 ± 2.4 cm/sec, mean ± I standard deviation. Peak systolic blood flow velocity of a representative short right nasal and short right temporal posterior ciliary artery was 3.0 and 3.6 cm/sec, respectively. These slow velocities were markedly less than corresponding nasal 12.1 cm/sec and temporal 11.9 cm/sec short left posterior ciliary arteries. Control group peak systolic velocity for the short posterior ciliary arteries is 9.1 ± 2.6 cm/sec, mean ± I standard deviation. Intravenous fluorescein angiography of the affected eye showed delayed choroidal filling, delayed retinal arterial filling (30 seconds), slow arteriovenous transit time (45 seconds), and late staining of retinal vessels, all consistent with ocular ischemic syndrome (Fig 2).
Figure 1. COl of the right central retinal artery (CRA) in patient 1 with ocular ischemic syndrome (left). Notice the reduced systolic peaks of the time-velocity waveform (graph below color image) in contrast to the normal pattern of the uninvolved side (right). Adjacent central retinal venous flow is below the baseline.
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Ho et al . Color Doppler Imaging
Figure 2. Red-free Ulumination shows dilated retinal veins and intraretinal hemorrhages of the right eye, patient 1 (A). Intravenous fluorescein angiography of the right eye, patient 1, demonstrates patchy peripapillary choroidal filling worse temporal to the optic disc than nasal as well as delayed retinal arterial filling (30 seconds) (B). Late phase of the angiogram reveals staining of the retinal arterioles (C).
The same CDI unit used for orbital imaging was used to characterize the structure and flow characteristics within the carotid arterial system. Color Doppler imaging showed greater than 90% stenosis of the right internal carotid artery (Fig 3). The left
internal carotid artery revealed only mild stenosis and normal arterial wave forms. Before this patient could be completely evaluated for possible carotid endarterectomy, he experienced a stroke with residual left sided hemiparesis. His ophthalmic status remains unchanged. Case 2. A 76-year-old hypertensive man with a medical history of a "mild stroke" in 1987 was seen for a routine eye examination and had no ocular complaints. Best-corrected visual acuity was 20/30 in both eyes. Applanation tonometry intraocular tensions were 7 mmHg in the right eye and 12 mmHg in the left. No iris neovascularization was present. Funduscopic examination of the right eye showed dilated nontortuous retinal veins as well as midperipheral intraretinal dot hemorrhages. The left fundus was unremarkable. Duplex scan evaluation of the carotid vessels showed an occlusion of the right internal carotid artery, 90% stenosis of the left internal carotid artery, and mild stenoses of the external carotid arteries right greater than left. With a supine pulse rate of 70/min and a brachial blood pressure of 137/96, CDI documented reversal of ophthalmic artery blood flow in the right eye (-60.2 cm/sec) and antegrade ophthalmic artery peak systolic blood flow in the left (34.1 cm/ sec) (Fig 4). Peak systolic blood flow velocity of the right central retinal artery (4.9 cm/sec) and the left central retinal artery (5.1 cm/sec) were less than the control group (10.5 ± 2.4 cm/sec). Peak systolic blood flow velocity of a right nasal short posterior ciliary artery (8.1 cm/sec), a right temporal short posterior ciliary artery (5.9 cm/sec), and a left nasal short posterior ciliary artery (5.8 cm/sec) all were low compared with the control group (9.1 ± 2.6 cm/sec). There was no detectable blood flow in the left temporal short posterior ciliary arteries. This patient's clinical status has remained stable for 8 months after his orbital CD!. Case 3. A 58-year-old diabetic, hypertensive woman whose medical history was significant for a stroke and mild residual right-sided hemiparesis, presented with progressive loss of vision in her left eye during the last year as well as intermittent dimming of vision in her right eye and dull ocular aching in both eyes. Best-corrected visual acuity was 20/50 in the right eye and hand motions in the left. Applanation tonometry intraocular tensions were 12 mmHg in the right eye and 10 mmHg in the left. Bilateral iris neovascularization was present. The right anterior chamber angle was normal. The angle on the left was closed for 360 0 with haphazard new vessel growth crossing Schwalbe's line. Results of funduscopic examination of the right eye showed retinal venous dilation with midperipheral intraretinal hemorrhages. There was no evidence of posterior segment neovascularization in the right eye. The left fundus showed moderate pallor of the optic disc with retinal venous dilation and attenuated retinal arterioles. Duplex scan evaluation of the carotid vessels showed occlusions of both internal carotid arteries and normal left and right common and external carotid vessels. With a supine pulse rate of 80/min and a brachial blood pressure of 140/94 mmHg, CDI documented reversal of blood flow with turbulence in both right (-40.3 cm/sec) and left ophthalmic arteries (-47.0 cm/sec). Peak systolic blood flow velocity in the left central retinal artery (1.7 cm/sec) was less than the right central retinal artery (2.8 cm/sec) and these values were less than control (10.5 ± 2.4 cm/sec). Peak systolic blood flow velocity ofthe right nasal and temporal short posterior ciliary arteries of 6.1 cm/sec and 8.3 cm/sec, respectively, were less than control (9.1 ± 2.6 cm/sec). No short posterior ciliary artery flow was detected in the left orbit (Fig 5).
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Top, Figure 3. COl of the right internal carotid artery of patient 1 demonstrates a greater than 90% stenosis (left). The time-frequency display (graph, below color image) shows high Doppler frequency shifts and therefore high flow velocity (>250 em/sec) at the filiform stenosis. High velocity blood flow is also indicated by the white color in the lumen of the poststenotic vessel. The left internal carotid artery demonstrates a more normal color image and time-velocity waveform (right). Center, Figure 4. Reversal of ophthalmic artery (OA) blood flow in the right eye in patient 2 (left) as shown by the blue color and pulsatile waveform demonstrating arterial not venous hemodynamics. In contrast, the flow of blood in the unaffected left eye is red and toward the globe with an arterial pulsatile waveform (right). Bottom, Figure 5. Red anterograde short posterior ciliary artery (PCA) flow in the right eye, patient 3 (left). In contrast, note the relative absence of Doppler signal in the region of the temporal and nasal short posterior ciliary arteries of the left eye with hand motion visual acuity (right). The cursor is placed on the Doppler signals of the central retinal artery (CRA) and central retinal vein (CRV) in the left eye within the B-scan shadow of the optic nerve. COl demonstrates severe impairment of short posterior ciliary arterial blood flow in this eye.
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Ho et al . Color Doppler Imaging Intravenous fluorescein angiography in the left eye showed profoundly delayed, patchy choroidal filling, a retinal arteriovenous transit time of greater than 45 seconds, and multiple sites ofleading edges of fluorescein dye within retinal arterioles, all indicative of severely compromised ocular perfusion. Her clinical status has remained unchanged for 6 months.
OA PEAK SYSTOLIC . VELOCITY 60 40
20
Results
OA PSV 0
.J4-JH...I~:r=ir=iir==.=t-'=r"ir'iT'rnii=in=in=i:r=iL...f:lJ;j
CM/SEC
A total of22 eyes were studied with CDI, and 16 of these eyes had clinical signs of ocular ischemic syndrome; five patients (patients 3, 7, 8, 9, and 11) had bilateral disease. Vasculopathic diseases such as diabetes mellitus, hypertension, or prior myocardial infarction were present in nearly all patients. Visual acuity of ocular ischemic syndrome eyes ranged from 20/20 to no light perception. Five of 11 ocular ischemic patients (patients 2, 5, 6, 7, and 9) did not present with any new ocular or visual complaint (patient 5 had longstanding poor vision in the left eye from a prior central retinal vein obstruction). However, five patients (patients 1, 3, 4, 8, and 11) experienced diminished visual acuity. One patient (patient 3) with bilateral ocular ischemia experienced ocular aching in both eyes and two patients (patients 1 and 10) noted flickering lights. All 16 affected eyes presented with dilated nontortuous retinal veins and 15 affected eyes had midperipheral intraretinal hemorrhages. Four affected eyes (patients 3, 4, 11) had iris neovascularization and 1 affected eye (patient 4) had optic disc neovascularization. Duplex ultrasonographic evaluation of the carotid arteries revealed that all 16 eyes with the ocular ischemic syndrome were associated with high grade ipsilateral internal carotid artery lesions ranging from 70% stenosis to CRA PEAK SYSTOLIC VELOCITY 12~------------------------------'
10 8
CRA PSV CM/SEC
6 4
N 12345678910111213141516
OIS EYES
Figure 6. Central retinal artery peak systolic velocity in normal eyes (mean ± SD = 10.5 ± 2.4 em/sec) and in eyes with ocular ischemic syndrome (3.5 ± 1.5 em/sec). Note the significantly reduced values of ocular ischemic syndrome eyes. CRA = central retinal artery; PSV = mean peak systolic velocity; OIS = ocular ischemic syndrome; N = normal eyes.
·20 ·40
·60
N 12345678910111213141516
OIS EYES
Figure 7. Ophthalmic artery peak systolic velocity in normal eyes (mean ± SD = 30.6 ± 8.9 em/sec) and in eyes with ocular ischemic syndrome (mean ± SD, -21.9 ± 32.2 em/sec). Reversal of flow within the ophthalmic artery is depicted below the horizontal. Twelve of 16 eyes with OIS demonstrated ophthalmic artery reversal of flow. OA = ophthalmic artery; PSV = mean peak systolic velocity; N = normal eyes; OIS = ocular ischemic syndrome.
total occlusion. Ten of 16 ocular ischemic syndrome eyes were associated with ipsilateral occlusion of the internal carotid artery. Two of 10 eyes with internal carotid artery occlusion had no signs of the syndrome. Only 1 of 3 patients with bilateral internal carotid artery occlusion had bilateral signs of ocular ischemic syndrome. Color Doppler imaging demonstrated markedly reduced central retinal artery peak systolic blood flow velocity in all eyes with ocular ischemic syndrome versus control subjects (Fig 6). The ocular ischemic syndrome central retinal artery peak systolic blood flow velocity ranged from 1.3 to 6.0 cm/sec with a mean of 3.5 cm/ sec, while control group central retinal artery peak systolic blood flow velocity is 10.3 ± 2.1 cm/sec. Color Doppler imaging documented reversal of ophthalmic artery blood flow in 12 of 16 eyes with ocular ischemic syndrome. Ophthalmic artery peak systolic blood flow velocity ranged from -66.1 to 40.5 cm/sec with a mean of - 21.9 cm/sec (Fig 7). The ocular ischemic syndrome mean peak systolic blood flow velocity was significantly less than control group ophthalmic artery peak systolic flow velocity of 30.6 cm/sec ± 8.9 cm/sec. Ocular ischemic syndrome short posterior ciliary artery peak systolic blood flow velocity ranged from no detectable flow to 8.6 cm/sec with a mean of 3.9 em/sec (Fig 8). This mean peak systolic flow velocity was significantly less than control group short posterior ciliary artery peak systolic flow velocity of 9.1 ± 2.6 em/sec. Table 3 compares mean pulsatility indices of this vasculopathic study group with study group control values for the ophthalmic, central retinal, and short posterior ciliary arteries. Mean ophthalmic artery pulsatility index
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Ophthalmology
of 2.0 ± 0.5 was greater than control ophthalmic .artery pulsatility index of 1.5 ± 0.5; the mean ophthalmic artery pulsatility index of those vessels with reversal of flow of 1.2 ± 0.4, however, was less than control. The central retinal artery mean pulsatility index of 2.2 ± 0.7 was greater than the control group central retinal artery pulsatility index of 1.5 ± 0.5. The mean pulsatility index of the short posterior ciliary arteries of 2.0 ± 0.5 also was greater than the control group posterior ciliary artery pulsatility index of 1.2 ± 0.4.
The ocular ischemic syndrome is a relatively uncommon condition with a rather broad presentation. Patients may complain of visual loss, photopsia, eye pain, or may be asymptomatic. Visual acuity can range from 20/20 to no light perception. The diagnosis is made from a constellation of signs including but not limited to anterior chamber cell and flare, iris neovascularization, retinal venous dilation retinal arteriolar attenuation or pulsation, midperiphe;al retinal hemorrhages, macular edema, and optic disc neovascularization. Most eyes are associated with ipsilateral carotid arterial occlusive disease and most patients have multiple vasculopathic risk factors such as hypertension and diabetes mellitus. Vascular hypoperfusion has been recognized for many years as the major cause of the ocular ischemic syndrome. 6 ,7 It is unclear, however, why certain eyes with carotid arterial occlusive disease manifest ocular ischemic syndrome and maintain good visual acuity, others dete-
PCA PEAK SYSTOLIC VELOCITY 10
-
8
CM/SEC
6
4
2
-
Il-
e---
~
I----
o N 12345678910111213141516
015 EYES
Figure 8. Short posterior ciliary artery peak systolic velocity in normal eyes (mean ± SD = 9.1 ± 2.6 em/sec) and in eyes with ocular ischemic syndrome (3.9 ± 3.2 em/ sec). Note the reduced values of ocular ischemic syndrome eyes and that three OIS eyes with marked visual loss had no detectable nasal or temporal short posterior ciliary artery blood flow. PCA = short posterior ciliary artery; PSV = mean peak systolic velocity; N = normal eyes; OIS = ocular ischemic syndrome. Solid white bar represents nasal PCA; other bar represents temporal PCA.
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Subject Eyes
Artery
OA ROA CRA
PCA
Mean ± 1 SD
2.0 ± 0.5 (n 1.2 ± 0.4 (n 2.2 ± 0.7 (n 2.0 ± 0.5 (n
= 4) 12) = 16) = 22) =
Control Eyes
Mean ± 1 SD
1.5 ± 0.5 (n 1.5 ± 0.5 (n 1.5 ± 0.5 (n
=
1.2 ± 0.4 (n
=
=
=
27) 27) 27) 27)
Gosling's pulsatility index = peak systolic velocity minus end diastolic velocity divided by average velocity in em/ sec.
Discussion
PCA PSV
Table 3. Pulsatility Index in Subject Eyes Versus Control Eyes
SD = standard deviation; OA = ophthalmic artery; ROA = ophthalmic artery with reversal of flow; CRA = central retinal artery; PCA = short posterior ciliary artery; n = number of eyes.
riorate rapidly, and others do not manifest signs of ocular ischemia at all. Previous methods including carotid and cerebral angiography, transcranial Doppler analysis, and intravenous fluorescein angiography have been unable to assess directly the microcirculation of the retrobulbar space,3,8 Color Doppler imaging adds a new rapidly performed, noninvasive dimension to the understanding of ocular ischemic syndrome by providing a quantitative analysis of blood flow within the ophthalmic, central retinal, and posterior ciliary arteries. Although current CDI technology cannot determine volumetric flow within the relatively small caliber retroorbital vessels because of limitations in color Doppler spatial resolution, it does provide a method of measuring blood flow velocity as well as vascular resistance. In most physiologic circumstances, peak systolic blood flow velocity may be a gauge of systolic blood flow and vascular resistance as calculated by the pulsatility index may be an index of diastolic blood flow.4, lo Moreover, CDI data correlate well with intravenous fluorescein angiography and digital subtraction carotid arteriography as illustrated by a case of ophthalmic artery obstruction associated with occlusive carotid artery disease. 9 In summary, CDI provides quantitative data about retrobulbar blood flow characteristics in a rapid, noninvasive, and reproducible fashion . Color Doppler imaging documented reversal of ophthalmic artery flow in 12 of 16 eyes with ocular ischemic syndrome and decreased central retinal artery peak systolic flow velocity in all eyes with the syndrome. Previous reports note the association of ophthalmic artery flow reversal with internal carotid occlusion I 1-13; 9 of 12 eyes with ophthalmic artery blood flow reversal were associated with internal carotid artery occlusion while 3 eyes were associated with ipsilateral internal carotid artery stenosis. Flow reversal within the ophthalmic artery represents collateralization through the external carotid artery system in response to obstructions within the internal carotid and/or intracranial arterial systems. In our experience with over 400 CDI studies of the retrobulbar micro-
Ho et al . Color Doppler Imaging circulation, reversal of flow within the ophthalmic artery has been observed only in ocular ischemic syndrome with associated internal carotid artery stenosis, 1 case of giant cell arteritis and as a late development in ophthalmic artery occlusion. 9 Mean pulsatility indices of the ophthalmic, central retinal, and posterior ciliary arteries of all ocular ischemic syndrome eyes were greater than those of normal control eyes (Table 2). In an animal model, Evans et al 14 showed that for a proximal stenosis, pulsatility index was directly dependent on the vascular resistance of the distal vascular bed. IS Multiple vasculopathic risk factors, such as hypertension, diabetes mellitus, and atherosclerosis appear to account for the higher pulsatility indices of ocular ischemic syndrome eyes as compared to normal eyes. Differences in the pulsatility index of ocular end arteries such as the central retinal artery or the short posterior ciliary arteries may reflect asymmetric distal stenosis within these vessels and/or dynamic variations of distal retinal or choroidal arterial resistance. The mean pulsatility index of ocular ischemic syndrome eyes with ophthalmic artery reversal of flow (1.2 ± 0.4), however, was less than normal control eyes (1.5 ± 0.5). Reversed ophthalmic artery flow in the setting of high-grade internal carotid artery stenosis or occlusion results in a reduced pulsatility index as the ophthalmic artery now supplies the low resistance intracranial circulation rather than the somewhat higher resistance orbital circulation. Because ophthalmic artery flow reversal was observed in the majority of ocular ischemic syndrome eyes (12 of 16), we believe that this lower distal vascular resistance accounts for the lower mean pulsatility index of this group. Although ipsilateral high-grade carotid stenosis, reversal of ophthalmic artery flow, decreased central retinal artery flow, and higher pulsatility indices in ocular end arteries are very often associated with ocular ischemic syndrome, this combination was not sufficient to produce decreased vision. In 3 eyes (left eye of patient 3, right eye of patient 4, left eye of patient 8) in which ocular ischemic syndrome and its sequelae were responsible for markedly decreased visual acuity (hand motions or worse), severe impairment of flow in both the nasal and temporal posterior ciliary arteries was demonstrated with COL Although we recognize that only a small number of patients were studied, the COl data suggest that posterior ciliary artery hypoperfusion and therefore secondary ischemia of the optic nerve, choroid, retinal pigment epithelium, and outer segments of the photoreceptors may be responsible for visual loss in ocular ischemic syndrome. Furthermore, the lower rise of the electro-oculogram as described by Ross Russell and Ikeda I 6 and the experimental blood flow studies of McFadzean and co-workers l ? corroborate our COl findings in strongly suggesting posterior ciliary arterial hypoperfusion as a cause of visual loss in the ocular ischemic syndrome. The specific finding of posterior ciliary artery hypoperfusion may explain why patients with the ocular ischemic syndrome and similar degrees of carotid
stenosis and retinal findings can have very different levels of visual function. Therefore, in managing the ocular ischemic syndrome patient, one should consider monitoring for (1) decreased posterior ciliary artery flow by COl; (2) visual field defects consistent with optic neuropathy; and (3) peripapillary hypoperfusion as assessed by fluorescein angiography. The development of these findings may herald significant loss of vision and prompt consideration of medical therapies to attempt to improve blood flow or more aggressive management of the underlying high grade carotid occlusive disease. In contrast, patients retain excellent vision with ocular ischemic syndrome when the short posterior ciliary arterial circulation is maintained. Therefore, in patients with preserved short posterior ciliary artery perfusion, decisions concerning carotid surgery should be based only on the risk of cerebral infarction and not upon the theory that carotid surgery is necessary to prevent visual loss. Whether successful carotid endarterectomy will improve diminished posterior ciliary artery perfusion is not yet known. Interestingly, several eyes with no detectable flow in the temporal short posterior ciliary artery but with preserved albeit low flow in the nasal short posterior ciliary artery maintained 20/40 vision or better. In conclusion, we believe that COl is useful for the evaluation and management of patients with ocular ischemic syndrome. It is uniquely suited to assess rapidly and quantitatively blood flow within both the retrobulbar and carotid systems. Although our study population is limited and our findings preliminary, COl data suggest that both reductions in peak systolic blood flow velocity as well as increased vascular resistance to diastolic blood flow in ocular end arteries characterize the retrobulbar circulation in ocular ischemic syndrome. Reversal of flow within ocular ischemic syndrome ophthalmic arteries represents collateral blood flow to lower resistance vasculature. Short posterior ciliary artery hypoperfusion and ischemia of the structures it serves may correlate with markedly reduced vision in ocular ischemic syndrome. Color Doppler imaging may provide a more complete understanding of the natural history and pathophysiology of ocular ischemic syndrome and perhaps form the basis for rational treatment of this condition.
References I. Sivalingham A, Brown GC, Magargal LE, Menduke H. The ocular ischemic syndrome. II. Mortality and systemic morbidity. Int Ophthalmol 1989;13:187-91. 2. Sturrock GD, Mueller HR. Chronic ocular ischaemia. Br J Ophthalmol 1984;68:716-23. 3. Lieb WE, Cohen SM, Merton DA, et al. Color Doppler imaging of the eye and orbit. Technique and normal vascular anatomy. Arch Ophthalmol 1991;109:527-31. 4. Gosling RG, King DH. Arterial assessment by Dopplershift ultrasound. Proc R Soc Med 1974;67:447-9.
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5. Gee W. Carotid physiology with ocular pneumoplethysmography. Stroke 1982; 13:666-73. 6. Kearns TP, Hollenhorst RW. Venous-stasis retinopathy of occlusive disease of the carotid artery. Mayo Clin Proc 1963;38:304-12. 7. Brown GC. The ocular ischemic syndrome. In: Ryan SJ, ed. Retina. vol. 2: Medical Retina. St. Louis: CV Mosby, J 990; chap. 88. 8. Erickson SJ, Hendrix LE, Massaro BM, et al. Color Doppler flow imaging of the normal and abnormal orbit. Radiology 1989;173:511-16. 9. Lieb WE, Aaharty PM, Sergott RC, et al. Color Doppler imaging provides accurate assessment of orbital blood flow in occlusive carotid artery disease. Ophthalmology 1991 ;98: 548-52. 10. Taylor KJW, Holland S. Doppler US. Part I. Basic principles, instrumentation, and pitfalls. Radiology 1990;174:297-307. 11. Pitts FW. Variations of collateral circulation in internal carotid artery occlusion. Comparison of clinical and x-ray findings. Neurology 1962;12:467-71.
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12. Hodek-Demarin V, Mueller HR. Reversed ophthalmic artery flow in internal carotid artery occlusion. Are-appraisal based on ultrasonic Doppler investigations. Stroke 1979; 10: 461-3. 13. Tatemichi TK, Chamorro A, Petty GW, et al. Hemodynamic role of ophthalmic artery collateral in internal carotid artery occlusion. Neurology 1990;40:461-4. 14. Evans DH, Barrie WW, Asher MJ, et al. The relationship between ultrasonic pulsatility index and proximal arterial stenosis in a canine model. Circ Res 1980;46:470-5. 15. Schneider PA, Rossman ME, Bernstein EF, et al. Effect of internal carotid artery occlusion on intracranial hemodynamics. Transcranial Doppler evaluation and clinical correlation. Stroke 1988;19:589-93. 16. Ross Russell RW, Ikeda H. Clinical and electrophysiological observations in patients with low pressure retinopathy. Br J Ophthalmol 1986;70:651-6. 17. McFadzean RM, Graham DI, Lee WR, Mendelow AD. Ocular blood flow in unilateral carotid stenosis and hypotension. Invest Ophthalmol Vis Science 1989;30:487-90.
