Download 58 Cases of Ocular Ischemic Diseases Caused by Carotid Artery

58 Cases of Ocular Ischemic Diseases Caused by Carotid
Artery Stenosis
Abstract
PURPOSE: To evaluate the clinical characteristics and risk factors of ocular ischemic
diseases caused by carotid artery stenosis. METHODS: This study was a retrospective
review of 145 patients with carotid artery stenosis. Fifty-eight patients who had symptoms
of ocular ischemic disease caused by carotid artery stenosis formed group A and the other
87 patients who only had carotid artery stenosis formed group B. We analyzed the causes
and course of disease, and relative risk factors, by comparing the two groups. RESULTS:
The degree of carotid artery stenosis in group A was higher than in group B. and group A
had a greater decrease of ophthalmic artery flow. Male gender, hypertension,
hyperlipidemia, and smoking were significantly related to carotid artery stenosis.
Amaurosis fugax was the most common ocular symptom in group A. The ocular ischemic
diseases mainly included ischemic optic neuropathy，central（branch）retinal artery
occlusion，ophthalmoplegia externa, and ocular ischemic syndrome. CONCLUSIONS: There
is a close relation between carotid artery stenosis and ocular ischemic diseases. Ophthalmologists
must observe for ocular symptoms, which were the onset symptoms in some patients.
Introduction
The carotid artery is the main route by which the blood is supplied to the cerebrum
and other areas of the head from the heart. Carotid artery stenosis refers to the stenosis
of the lumen owing to carotid atherosclerotic plaque, arteritis, or fibromuscular dysplasia.
Its incidence is high, accounting for 10% of the population older than 60 years. Carotid
artery stenosis is one of the leading causes of ischemic stroke and patients usually arrive at
neurological clinics with stroke symptoms of hemiplegia and homonymous hemianopia.[1]
In recent years, an increasing number of patients with carotid artery stenosis have arrived
at ophthalmological clinics because of eye discomfort. Therefore, these patients who have
carotid artery stenosis accompanied by ocular ischemic presentations have received
increasing attention.[2] We retrospectively reviewed the clinical data of patients with
carotid artery stenosis who had been treated in departments of ophthalmology, intervention,
and vascular surgery.
Materials and Methods
Subjects
A total of 145 patients, who were residents in multiple cities of south China, with
carotid artery stenosis from January 2002 to June 2007 were treated at our hospital. There
were 81 male and 64 female patients; their mean age was 63.31±9.41 years (range, 25-87
years). Diagnoses were confirmed by carotid artery color Doppler ultrasound or digital
subtraction angiography (DSA), and other primary ophthalmological conditions such as
primary glaucoma, iridocyclitis, retinal vein occlusion, high myopia, retinitis pigmentosa,
choroiditis, diabetic retinopathy, and other congenital fundus abnormalities were ruled out.
Diagnostic criteria
Patients were defined as having symptoms of ocular ischemia if they presented
symptoms of transient syncope, flash, pain on the eye and perio rbital region, diplopia,
and reduced eyesight. Patients were defined as having ocular ischemic disease when
they presented signs of retinal artery occlusion, increased ocular pressure, rubeosis
iridis, altered visual field, optic nerve atrophy, and patchy hemorrhage on the retina as
confirmed by the determination of the degree of carotid artery stenosis, visual field , and
visual acuity, as well as by fundus fluorescein angiography and visual electrophysiology.
In the entity of ocular ischemic disease, ocular ischemic syndrome refers to a series of
symptoms involving the eye and brain owing to the shortage of blood supply that is
caused by chronic carotid artery occlusion or stenosis.
Methods
Clinical data for all the patients were reviewed retrospectively. Among the 145
patients, 58 had signs or symptoms of ocular ischemia (group A) and 87 had no signs nor
symptoms of ocular ischemia (group B). An additional 57 patients without carotid artery
stenosis who were matched by age were selected as controls.
The site and degree of the stenosis were determined by angiography. Color Doppler
ultrasound (Philips HD7) was used to examine the hemodynamics of the ophthalmic artery
with a frequency of 10 MHz. Hemodynamic parameters of the ophthalmic artery of each
patient were recorded, including systolic peak blood flow velocity (Psv), end-diastolic
blood flow velocity (Edv), mean blood flow velocity (Vm), resistance index (RI), and
pulse index (PI). Each parameter was measured three times and the mean value was used.
Data were expressed as x±s or percentage. The t test and chi-square test were
performed using SPSS version 14.0 software to compare the differences between groups.
For factors that might influence the disease, univariate and unconditional logistic stepwise
regression methods were used to adjust for confounding factors and analyze the
interactions between factors. Factors that might influence the disease were screened out.
Results
1. Age and gender predisposition for the disease: Among the 145 patients, there were
15 patients younger than 50 years, 31 between 51 and 60 years, 52 between 61 and 70
years, 35 between 71 and 80 years and 8 patients older than 80 years. The mean age of
group A was older than group B but the difference was not significant (64.37±9.70 vs
62.45±11.27 years; P>0.05).
2. The site and degree of carotid artery stenosis: The most frequent sites of stenosis
were bifurcation of the common carotid artery and the inlet of the internal carotid artery.
There were 13 patients with right internal carotid artery stenosis, 11 with left internal
carotid artery stenosis, and 121 with bilateral internal carotid artery stenosis. A
significantly higher proportion of patients had bilateral involvement than unilateral
involvement. Thirty-eight patients in group A (65.51%) had stenosis of more than 50%
(43-100%; mean: 69.13±7.46%). The mean stenosis in group B was 48.34±9.23%
(34-100%). There was a significant difference of stenosis degree between the two groups
(P<0.05).
3. Risk factors for the development of carotid artery stenosis: In group A, there were
33 male and 25 female patients, 36 patients with concomitant hypertension, 31 patients
with hyperlipidemia, and 28 patients with a history of smoking (smoking is defined as smoking
one cigarette per day for 1 year or 18 packs per year). In group B, there were 49 male and 38
female patients, 46 patients with concomitant hypertension, 39 patients with
hyperlipidemia, and 40 patients with a history of smoking. Univariate and unconditional
logistic stepwise regression analyses showed that carotid artery stenosis was associated
with gender (predilection in males), hyperlipidemia, hypertension, and smoking (odds
ratios of 2.78，3.13 ，2.53 ，and 2.34, respectively; P < 0.05).
4. Constituent ratio of patients with ocular ischemia: Clinical presentations of ocular
ischemia in group A included transient pre-syncope, pain in the eye and orbit, diplopia,
hypopsia (defect in visual field), retinal hemorrhage or edema, and increased intraocular
pressure. Transient pre-syncope was the most common symptom, and carotid artery
stenosis was also associated with pain in the eye and orbit and hypopsia (defect in the
visual field; P < 0.05; Table 1).
Table 1 Constituent ratio of presentations of ocular ischemia （n＝58）
Signs and symptoms
No. of patients
constituent ratio (%)
transient pre-syncope
27
46.55
pain in the eye and orbit
21
36.21
hypopsia (defect in visual field)
17
29.31
retinal hemorrhage or edema
15
25.87
diplopia
10
17.24
increased intraocular pressure
3
5.17
Note: Among the 58 patients shown in Table 1, some had two or more presentations
5. Constitution of ocular ischemic diseases: Categorization was based on the final
diagnosis; there were 26 patients in group A who had been diagnosed as having ocular
ischemic diseases (Figs 1 and 2).
Table 2 Constitution of ocular ischemic diseases （n＝26）
diseases
No. of patient
constituent ratio（%）
Ischemic optic nerve disorders
9
34.61
Ocular ischemic syndrome
6
23.08
Retinal central (branch) vein occlusion
5
19.23
External ophthalmoplegia
4
15.39
Neovascular glaucoma
2
7.69
6. Comparisons of hemodynamic parameters among three groups: Compared with the
control group, ophthalmic artery perfusion of patients in group A and B was reduced
remarkably (Tables 3 and 4). Some parameters (Psv, Edv and RI) of group A were also
reduced compared with group B (Table 5).
Table 3 Comparisons of hemodynamic parameters between group A and the control
group (x±s)
Groups
Psv（cm/s）
Edv（cm/s） Vm（cm/s）
Group A 9.12 ±2.28 7.03 ±1.35
RI
8.09 ±1.85 1.17±0.06
PI
1.69±0.29
Control group 29.23±3.63 21.84±2.89 26.83±3.36 0.31±0.09 0.57±0.13
t value
24.486
21.125
P value
<0.01
<0.01
26.241
<0.01
28.687
<0.01
18.065
<0.01
Table 4 Comparisons of hemodynamic parameters between group B and the control group
(x±s)
Groups
Psv（cm/s）
Edv（cm/s） Vm（cm/s）
RI
Group B 14.37±2.74 12.57 ±2.04 14.15 ±2.78 0.73±0.09
PI
1.16±0.23
Control group 29.23±3.63 21.84±2.89 26.83±3.36 0.31±0.09 0.57±0.13
t value
P value
4.675
0.029
3.512
3.357
5.574
0.041
0.043
0.023
4.493
0.031
Table 5 Comparisons of hemodynamic parameters between group A and B (x±s)
Groups
Psv（cm/s）
Edv（cm/s）
Vm（cm/s）
RI
PI
1.17±0.06
1.69±0.29
Group B 14.37±2.74 12.57 ±2.04 14.15 ±2.78 0.73±0.09
1.16±0.23
Group A 9.12 ±2.28 7.03 ±1.35 8.09 ±1.85
3.161
2.825
2.454
3.687
1.876
P value 0.046
0.049
0.057
0.038
0.067
t value
Discussion
The blood supply to the eye comes from the retinal central vascular system of the
ophthalmic artery and the ciliary vascular system. The ophthalmic artery stems from the
ipsilateral internal carotid artery. If occlusion or stenosis occurs in the carotid artery, the
blood perfusion to the ophthalmic artery becomes insufficient, leading to signs and
symptoms of anterior and posterior ocular ischemia. These series of presentations are
collectively termed ischemic ophthalmopathy, which includes retinal central (branch) vein
occlusion; external ophthalmoplegia; ischemic optic nerve disorders; ocular ischemic
syndrome; and neovascular glaucoma. The clinical manifestations in the acute phase are
transient pre-syncope and retinal central (branch) vein occlusion. If the condition remains
untreated, the chronic presentations of this disorder include chronic ocular ischemic
syndrome and hypoperfusion retinopathy, which ultimately will lead to neovascular
glaucoma and permanent blindness. [3, 4]
It has been reported that ischemic ophthalmopathy secondary to carotid artery stenosis
most commonly affects the elderly. The aged usually have concomitant systemic diseases,
such as hypertension, diabetes mellitus, coronary artery diseases, and hyperlipidemia,
which directly or indirectly aggravate atherosclerosis of the carotid artery, and ensuing
ocular ischemia. [3, 5] In the present study, the patients in groups A and B were older, with
a mean age of 63.31±9.41 years. Univariate and unconditional logistic stepwise regression
analyses showed that the development of carotid artery stenosis was associated with gender
(male), hypertension, hyperlipidemia, and smoking. It is well known that hyperlipidemia is
important risk factors for vascular sclerosis. Females are less likely to be affected by the
disorder, which is attributable to the protective effect of estrogen on the cardiovascular
system. Cigarette smoking may aggravate ischemia and spasm of the ophthalmic artery,
and thus is an important risk factor.
Our study showed that presentations of ophthalmic ischemia secondary to carotid
artery stenosis are protean, primarily including transient pre-syncope, pain in the eye and
orbit, diplopia, hypopsia (defect of visual field), retinal hemorrhage or edema, and
increased intraocular pressure. Of these presentations, transient pre-syncope was the most
common. Some patients may present with two or more of these symptoms. However,
ophthalmic ischemic symptoms such as transient pre-syncope may be caused by the
alteration of ophthalmic hemodynamics (hypoperfusion) and cerebral vascular spasm, or
even thrombosis of the retinal arterioles by detached emboli from atherosclerotic plaque of
the ipsilateral carotid artery. Gong yan et al [6] also found that carotid artery stenosis is the
most common underlying disorder in patients with transient pre-syncope, followed by
cardiogenic disorders such as atrial fibrillation. Some patients in our study came to the
ophthalmological clinic because of “transient pre-syncope” or “pain in the orbit.” This
informs us that caution should be raised in patients with such symptoms, and carotid artery
color Doppler ultrasound should be performed for the early diagnosis and intervention of
this disorder.
Zhao Jun et al [7] analyzed the association between varieties of ophthalmic ischemic
diseases with the carotid artery and found that the incidence of carotid artery stenosis was
remarkably increased in patients with symptoms of retinal central (branch) vein occlusion,
external ophthalmoplegia, ocular ischemic syndrome, and neovascular glaucoma. However,
the constituents of ophthalmic ischemic disorders were not investigated. Our study showed
that ischemic optic nerve disorder had the highest constituent ratio in ophthalmic ischemic
disorders, followed by ocular ischemic syndrome, retinal central (branch) vein occlusion.
And external ophthalmoplegia, and those with neovascular glaucoma had the least
common presentation. In our cohort study, three cases of ischemic optic nerve disorder and
two cases of retinal branch vein occlusion were found to be caused by carotid artery
stenosis on routine ophthalmological examination (Figs. 1 and 2). Thus, in evaluating
patients with ophthalmic ischemic disorders of unknown origin, ophthalmologists should
adopt the notion of system instead of “to treat only where the pain is.”
Carotid artery stenosis is usually severe when symptoms of ophthalmic ischemia are
present. [8,9] Our study showed that ophthalmic artery perfusion was reduced in patients
with carotid artery stenosis. More than 65% of the patients with ischemic presentations had
stenosis of more than 50%, and their ophthalmic artery perfusion reduction was more than
in those patients with silent carotid artery stenosis (group B). We propose that ophthalmic
ischemic presentations may occur when the perfusion is reduced to a threshold due to
progression of carotid artery stenosis. Therefore, the presentation of ophthalmic ischemic
symptoms can be used to predict the severity of carotid artery stenosis. [10,11]
In the present study we reviewed retrospectively clinical data and explored the
clinical features and risk factors of ophthalmic ischemia disorders secondary to carotid
artery stenosis from a variety of perspectives. The results showed that ophthalmic ischemic
symptoms secondary to carotid artery stenosis are indicative of severe stenosis, and that
ophthalmic symptoms may be the initial presentations of carotid artery stenosis.
Ophthalmologists must be cautious with these symptoms and obtain data from relevant
examinations to identify the underlying causes. Early intervention may be effective in the
treatment of carotid artery stenosis and reducing incidence of ophthalmic and cerebral
complications.
Acknowledgments
The authors thank all patients, We are grateful to the State Key Laboratory of
Ophthalmology at Zhongshan Ophthalmic Center, Sun Yat-sen University.
References
[1] Faries PL,Chaer RA,Patel S ,Lin SC, DeRubertis B, Kent KC. Current management of extracranial
carotid artery disease. Vasc Endovascular Surg，2006，40：165-175.
[2] Kastumi Hoya, Eiharu Morikawa, Akira Tamura .Common Carotid Artery Stenosis and Amaurosis
Fugax .Journal of Stroke and Cerebrovascular Diseases, 2008, 17( 1) 1-4
[3] Zhao HQ; Pan XD; Wang JH; Zhang Y. The common etiologies of carotid stenosis. Cerebrovascular
Diseases Foreign Medical Sciences. 2004,12(7):497-499
[4] Tang WQ; Wei SH; Li S，Clinical analysis of ocular manifestations related to carotid artery stenosis.
Chinese Journal of Ocular Fundus Diseases,.2006，6（22）
：376－378
[5] Albers GW, Hart RG, Lutsep HL, Newell DW, Sacco RL. Addendum to the supplement to the
guidelines for the management of transient ischemic attacks. Stroke, 2003, 31:1001
[6] Arnold M, Nedeltchev K, Sturzenegger M, Schroth G, Loher TJ, Stepper F, Remonda L, Bassetti C,
Mattle HP. Thrombolysis in patients with acute stroke caused by cervical artery dissection: analysis of 9
patients and review of the literature .Arch Neurol, 2002, 59 :549-553 .
[7] Zhao J; Hu LN; Wei SH. Clinical significance of ocular ischemia disease on predicted the happening
of carotid stenosis. International Journal of Ophthalmology.2009，9（2）：361－362
[8] Yang WL; Liu SM; Liu L，Color Doppler analysis of ocular vessel blood velocity in normal eyes.
Chinese Journal of Ocular Fundus Diseases，1997，13：99－101
[9]Hoya K, Morikawa E, Tamura A, Saito I. Common carotid artery stenosis and amaurosis fugax. J
Stroke Cerebrovasc Dis. 2008 Jan-Feb;17(1):1-4
[10]Costa VP, Kuzniec S, Molnar LJ, et al. The effects of carotid endarterectomy on the retrobulbar
circulation of patients with severe occlusive carotid artery disease. Ophthalmology, 1999,106:306-310.
[11]Sivalingam A, Brown GC, Magargal LE. The ocular ischemic syndrome Part III: visual prognosis
and the effect of treatment. Int Ophthalmol,1991,15:15-20.
prolonged fluorescein filling time in upper
retinal branch artery
Fig 1 Series presentations of retinal
branch artery occlusion caused by carotid
artery stenosis (Zhao, male, 67 years old)
Fig. 1c: Color Doppler ultrasound shows
blood flow disturbance in carotid artery
secondary to carotid artery stenosis.
Fig. 1a: Photo of the fundus shows
occlusion in the retinal branch artery.
Fig 1d: Carotid artery color Doppler
ultrasound shows patent carotid artery
lumen after carotid endarterectomy.
Fig.
1b:
FFA
shows
significantly
Fig.
1e:
Pathology
endarterectomy
shows
of
carotid
atherosclerosis
and attendant calcification in the intima
Fig. 2b: FFA shows leakage of fluorescein in optic
disc and suspected formation of
retinal arteriovenous anastomosis.
of the internal carotid artery
Fig.2 Series presentations of retinal
branch artery occlusion caused by carotid
artery stenosis (Wu, female, 72 years
old).
Fig. 2c: Carotid artery color Doppler
ultrasound shows severe stenosis of the
carotid artery.
Fig.2a: Photo of the fundus shows
occlusion in the retinal branch artery
Fig. 2d: Ophthalmic artery color Doppler
ultrasound
shows
remarkably
reduced
ophthalmic artery perfusion.
Fig. 2f: Pathology of carotid endarterectomy
Fig. 2e: TCD shows increased resistance
shows fibrotic thickening and hyaline
in the carotid siphon (indicating carotid
changes in arterial wall, and slit-like
artery stenosis)
cholesterol crystal.
审稿意见:
本文主要研究颈动脉狭窄所致眼缺血综合征的危险因素以及一些血流参数的变化，对临床有一定
参考价值，内容新颖。但是存在一些问题，请修改：
一、摘要结论部分不简练。 已做简化修改。
二、虽然本文研究对象是医院诊治的来自中国南部的病人，但是并不能代表中国南部的整体情况，
也没有交代中国南部的概念。如果是以人群为基础的研究，本文未进行整群抽样，如果是以医院
为基础，那么应对医院按流行病学方法进行选择，因为所在医院有来自南部的病人就认为代表中
国南部很不科学。题目中的“中国南部”的表达的确存在不合理之处，已做相应修改，删除“中
国南部”。
三、应交代颈动脉狭窄以及眼缺血综合征的诊断标准。如何界定吸烟史？应交代入选标准以及排
除标准。已在文中列出颈动脉狭窄以及眼缺血综合征的诊断标准。界定吸烟史:确定吸烟的标准
为,每天吸一只,连续吸一年以上,或每年累计达 18 包以上,符合条件者界定为吸烟。
四、方法第三行中“58 had symptoms of ocular ischemia (group A)”，完全按症状分组是否
合理？正常对照是否也要行颈动脉血管造影？如行，是否知情同意并通过伦理讨论，这一点未提
及。结果部分第一段年龄比较可用表格显示。已做修改：（1）有眼部缺血症状或体征者归 A 组，
无眼部缺血症状或体征归 B 组。（2）我们在对正常对照组行颈动脉血管造影检查前，均已口头
告知患者并征得了患者的同意。但并未签署同意书。（3）结果部分中第一段年龄的比较，由于
用文字可以完整表述，故未用表格显示。
五、提供表 2 中眼科疾病的诊断标准。是否可提供清晰度更高的图？已在文中列出眼科疾病的诊
断标准。抱歉，暂未能提供清晰度更高的图。
六、结果部分第三段危险因素的比较应用表显示，仅有 p 值是不够的，还应给出 OR 值。已做相
应修改。
七、结果部分第四段应进行率的比较，应有 P 值。已做相应修改。
八、删去讨论部分的"diabetes mellitus is important risk factors for vascular slerosis."
及"In earkly phase of reduced ophthtalmic perusion secondary to carotid artery stenosis,
visual function is not significantly impaired." 已删除相应内容。
九、补充支持研究结果的参考文献。已补充相应文献
衷心感谢编辑部老师的接纳！