Co-occurrence of Acute Retinal Artery Occlusion and Acute Ischemic Stroke: Diffusion-Weighted Magnetic Resonance Imaging Study


To evaluate the co-occurrence of acute ischemic stroke and acute retinal artery occlusion (RAO).


Retrospective observational case series.


We included 33 consecutive patients with acute RAO who underwent diffusion-weighted magnetic resonance imaging within 7 days of the onset of visual symptoms. The causes of RAO were classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, which are based on clinical features and the results of etiological evaluations for atherosclerosis, cardioembolism and other prothrombotic conditions. We evaluated the prevalence of accompanying acute ischemic stroke in subjects with acute RAO and examined the relationships with etiological parameters.


Acute ischemic stroke was detected in 8 (24.2%) subjects with RAO. Among these subjects, 3 (37.5%) patients did not exhibit any neurologic symptoms or signs. Most of the infarction patterns were small, multiple and scattered. All of the subjects with RAO who were positive for lesions on diffusion-weighted imaging had identifiable causes, whereas only 36% of the subjects who were negative for lesions had identifiable etiologies ( P = .003). Carotid stenosis or cardioembolic sources were found more commonly in cases of central retinal artery occlusion (CRAO; 7/18, 38.9%) than in cases of branch retinal artery occlusion (BRAO; 1/15 6.7%, P = .046).


Acute cerebral infarctions frequently accompany RAO. We recommend diffusion-weighted imaging for patients with RAO because the presence of lesions on diffusion-weighted imaging is accompanied by a significantly increased probability of identifying the cause.

Retinal artery occlusion (RAO) is a rare condition caused by an acute occlusion of the retinal vasculature that frequently leads to sudden visual impairment. Regarding its pathogenesis, RAO is analogous to cerebral infarction, which is caused by an acute interruption of blood flow to the brain that results in a focal neurologic deficit. Diverse underlying conditions have been reported to cause RAO. Emboli from the carotid artery or heart have been suggested to be the main causes of RAO. The incidence of coexisting ipsilateral carotid artery disease ranges from 3%-96%, and emboli with cardiac sources have been observed in 24%-72% of patients with RAO. In addition to embolic sources, systemic cardiovascular risk factors and certain hematologic, immune-mediated and infectious conditions have been suggested to be potential causes of RAO. Given that embolisms from the carotid arteries and heart are the main causes of RAO, we may expect that brain lesions would be observed commonly in patients with RAO. Because the ophthalmic artery arises from the distal internal carotid artery at an acute angle, and the diameter of the ophthalmic artery is approximately one-third that of the internal carotid artery, it is possible for emboli to enter the cerebral circulation, occlude the cerebral arteries and result in cerebral infarction.

Diffusion-weighted magnetic resonance imaging is a magnetic resonance imaging (MRI) sequence that is the most sensitive and specific tool for detecting early ischemic changes in the brain. The sensitivity and specificity of diffusion-weighted imaging for detecting acute cerebral infarctions have been reported to be 88%-100% and 95%-100%, respectively. Compared to conventional T2-weighted MRI, diffusion-weighted imaging is superior in detecting acute lesions and can discriminate new infarcts from old ischemic lesions. Furthermore, diffusion-weighted imaging can identify silent infarcts without accompanying neurologic symptoms. Thus, diffusion-weighted imaging plays a key role in the diagnosis of ischemic stroke.

The guidelines of the American Heart Association/American Stroke Association (AHA/ASA) recommend that all patients with suspected retinal ischemia should undergo immediate brain imaging. Helenius and associates supported this recommendation after reporting on the presence of concurrent acute brain infarcts in patients complaining of monocular visual loss that was presumed to be due to retinal ischemia. However, a recent survey revealed that only 1 in 3 ophthalmologists refer central retinal artery occlusion (CRAO) patients to the emergency room for the evaluation. The purposes of the present study were to determine the prevalence of concomitant acute cerebral infarction in subjects with acute RAO by assessing diffusion-weighted images and to assess the association of the concomitant occurrence of these conditions with the underlying causes of RAO.

Materials and Methods


This study was a retrospective observational case series that included consecutive nonarteritic cases of RAO between June 2005 and December 2012 that were evaluated at the Department of Ophthalmology and Neurology of Yonsei University Medical Center. Among the 53 subjects with diagnoses of RAO who underwent brain MRI, the 33 subjects who underwent diffusion-weighted imaging within 7 days of the onset of symptoms were enrolled. The University of Yonsei Institutional Review Board approved this retrospective research, and the research adhered to the tenets of the Declaration of Helsinki and good clinical practices (IRB No. 4-2013-0142).

The diagnoses of RAO were based on the classic clinical findings on fundus photography and retinal fluorescein angiography. The demographic data, initial neurologic symptoms and signs, visual acuities, medical histories (including hypertension, diabetes mellitus, smoking habits, and renal disease); histories of previous cerebrovascular accidents or transient ischemic attacks; and laboratory findings (including lipid profiles, erythrocyte sedimentation rates and C-reactive protein levels) of the subjects were reviewed. Detailed neurologic examinations were performed by experienced neurologists. The results of the following evaluations that were performed for etiologic work-up were also reviewed: magnetic resonance angiography, catheter angiography, 12-lead electrocardiography, transthoracic echocardiography, transesophageal echocardiography, and hematology for hypercoagulable states.

Etiological Classification

Causes were classified based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtype classification system, which is the most widely used etiologic classification system for patients after acute stroke. The TOAST system categorizes causes into the following 5 subgroups: 1) large-artery atherosclerosis; 2) cardioembolism; 3) small-artery occlusion; 4) stroke of other determined cause; and 5) stroke of undetermined cause. The classifications are based on clinical symptoms and the results of etiologic evaluations that include brain imaging, cardiac evaluation, angiography, and other laboratory tests that evaluate prothrombotic conditions. Large-artery atherosclerosis is diagnosed when brain imaging reveals significant (>50%) stenosis or occlusion of a relevant artery (the carotid artery in cases of RAO) that is most likely due to atherosclerosis. Potential sources of cardioembolism should be excluded. Cardioembolism is diagnosed in patients with cardiac sources of emboli without large-artery atherosclerotic sources. Small-artery occlusion is diagnosed when patients present with traditional lacunar syndromes or have brain stem or subcortical lesions of <15 mm without evidence of large-artery atherosclerosis or cardioembolism. The diagnosis of stroke of other determined causes includes patients with rare stroke causes that include hypercoagulable states, hematologic diseases, or nonatherosclerotic vasculopathies with no evidence of large-artery atherosclerosis or cardioembolism. Acute strokes due to iatrogenic causes are classified as stroke of other determined cause. Stroke of undetermined cause is further divided into the following 3 subgroups: 1) 2 or more causes identified; 2) negative evaluation; and 3) incomplete evaluation. The negative evaluation subgroup includes patients who have no recognized potential causes despite extensive evaluations. The incomplete evaluation subgroup includes patients with no identified cause and insufficient evaluation.

In this study, the subjects were divided into the following 4 diagnostic subgroups: large-artery atherosclerosis, cardioembolism, stroke of other determined cause, and stroke of undetermined cause. No subject met the criteria for 2 or more identified causes or incomplete evaluation; therefore, all subjects included in the category of stroke of undetermined cause were categorized into the negative evaluation subgroup. Large-artery atherosclerosis and cardioembolism, the 2 most common causes of stroke, were considered to be the major causes, and the other causes were considered to be minor causes.

Diffusion-weighted MRI

Subjects who underwent diffusion-weighted imaging within 7 days of the onset of symptoms were included in this study. Brain MRIs were performed with a 1.5-Tesla system (Intera or Achieva; Philips Medical Systems, Best, The Netherlands; or Signa Horizon, GE Medical Systems, Milwaukee, WI, USA) or a 3.0-Tesla system (Intera or Achieva, Philips Medical Systems). Lesions that were hyperintense on diffusion-weighted images were regarded as acute ischemic lesions. Acute ischemic lesions remain hyperintense for only 7-14 days. The sizes of the lesions were defined by the maximum diameter of the hyperintense areas as measured across the axial slices. Diffusion-weighted imaging lesions were classified as lesions in 1 vascular territory (single or multiple lesions in the unilateral anterior circulation or in the posterior circulation) or as lesions in multiple vascular territories (multiple lesions in the bilateral anterior circulations or in both the anterior and posterior circulations).

Statistical Analyses

Chi-square tests or the Fisher exact test (for categorical variables) and t tests (for continuous variables) were used to compare the baseline demographic characteristics, risk factors and etiologies between the central retinal artery occlusion (CRAO) and branch retinal artery occlusion (BRAO) groups. Chi-squared tests or the Fisher exact test were used to compare the underlying etiologies between the diffusion-weighted imaging lesion-positive and lesion-negative groups. A P value <0.05 was considered statistically significant. Statistical analyses were performed with SPSS software (v 18.0, SPSS, Chicago, IL, USA).


Of the 33 subjects with RAO who underwent diffusion-weighted imaging within 7 days of symptom onset, 18 subjects were diagnosed with CRAO and 15 subjects with BRAO. The mean age of the subjects was 58.3 ± 13.9 years. The demographic and clinical characteristics of the subjects are shown in Table 1 . There were no significant differences between the groups with the exception of better initial visual acuity in the BRAO group. The proportion of subjects with initial Snellen visual acuities equal to or better than 20/200 was higher in the BRAO group (73.3%) than in the CRAO group (22.2%, P = .003).

Table 1

Baseline demographic and clinical characteristics of enrolled retinal artery occlusion subjects

CRAO (n = 18) BRAO (n = 15) P value
Age (years) 58.1 ± 16.5 58.7 ± 10.6 .902
Gender (men) 9 (50) 8 (53.3) .849
Affected side (right side) 11 (61.1) 8 (53.3) .653
Risk factors
Hypertension 8 (44.4) 10 (66.7) .202
Diabetes mellitus 4 (22.2) 2 (13.3) .672
Smoking 3 (16.7) 1 (6.7) .617
Renal disease 3 (16.7) 2 (13.3) 1.000
Previous history of CVA or TIA 2 (11.1) 2 (13.3) 1.000
Laboratory finding
Total cholesterol (mg/dl) 162.4 ± 27.9 176.6 ± 21.2 .175
Triglyceride (mg/dl) 115.9 ± 51.4 159.5 ± 106.1 .202
HDL-cholesterol (mg/dl) 51.6 ± 18.9 48.1 ± 9.8 .600
LDL-cholesterol (mg/dl) 94.2 ± 27.5 104.3 ± 23.2 .364
ESR 35.4 ± 24.4 12.6 ± 5.2 .075
CRP 9.6 ± 20.9 1.3 ± 1.1 .312
Visible retinal emboli 2 (11.1) 3 (20) .639
Initial visual acuity .003
≥20/200 (Snellen VA) 4 (22.2) 11 (73.3)
<20/200 (Snellen VA) 14 (77.8) 4 (26.7)

CRAO, central retinal artery occlusion; BRAO, branch retinal artery occlusion; CVA, cerebrovascular accident; TIA, transient ischemic attack; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; VA, visual acuity.

Values are expressed as number of subjects (%) or mean ± SD.

Acute cerebral infarctions were observed on diffusion-weighted images in 8 (24.2%) subjects. Of the 18 CRAO subjects, 5 (27.8%) and of the 15 BRAO subjects 3 (20%) had concurrent cerebral infarctions. The involved eyes were ipsilateral to the lesion in all of the subjects with lesions in 1 vascular territory. The numbers of lesions identified on diffusion-weighted images ranged from 2-84. The maximum observed lesion diameter was 18 mm, and 93.5% of the lesions had diameters <10 mm. The average diameter of the lesions was 3.2 mm.

The causes, diagnoses and initial neurologic symptoms and signs of the diffusion-weighted imaging lesion-positive (n = 8) and lesion-negative (n = 25) groups are shown in Table 2 . The subjects with negative evaluations (ie, no probable cause despite extensive evaluation) were significantly more likely to be in the diffusion-weighted imaging lesion-negative group (64%) than in the lesion-positive group (0%, P = .003). No significant association was detected between diagnosis (CRAO vs BRAO) and the presence of lesions on diffusion-weighted images. Neurologic symptoms and signs were more common in the lesion-positive group (62.5%) than in the lesion-negative group (0%, P < .001). No neurologic symptoms or signs were observed in 3 subjects (37.5%) who were positive for lesions on diffusion-weighted images. The detailed clinical and MRI features of the patents with diffusion-weighted imaging-identified lesions are described in Table 3 . Additionally, fundus photography, carotid angiography and MRI images are shown in Figure 1 and Figure 2 .

Table 2

Etiology, diagnosis, and initial neurologic symptoms and signs in the retinal artery occlusion subjects with and without acute cerebral infarctions in diffusion-weighted imaging

Lesion +
n = 8
Lesion −
n = 25
P value
Large artery atherosclerosis 2 (25) 1 (4) .139
Cardioembolism 2 (25) 3 (12) .574
Other determined etiology 4 (50) 5 (20) .171
Negative etiologic evaluation (no potential etiology despite an extensive evaluation) 0 (0) 16 (64) .003
Diagnosis .699
CRAO 5 (62.5) 13 (52)
BRAO 3 (37.5) 12 (48)
Neurologic symptom and sign <.001
Yes 5 (62.5) 0 (0)
No 3 (37.5) 25 (100)

CRAO, central retinal artery occlusion; BRAO, branch retinal artery occlusion.

Values are expressed as number of subjects (%).

Table 3

Clinical and imaging features of retinal artery occlusion subjects with concurrent acute cerebral infarction

Patient No./Sex/Age Involved eye Diagnosis Etiology DWI Neurologic symptoms and signs
Vascular terriroty Anatomical location Lesion number Lesion size
1/M/74 Right CRAO Right ICA 73% stenosis One Right fronto-parietal area 18 3 (1-18) Left arm and leg weakness, sensory change
2/M/73 Right BRAO Right ICA 83% stenosis One Right fronto-parietal area 3 3 (3-4) Left arm weakness
3/F/77 Right CRAO MV annular calcification One Right internal capsule and caudate 2 5.5 (2-9) None
4/M/75 Left CRAO PFO Multiple Right cerebellum, bilateral occipital and frontoparieral area 84 4 (1-12) Left arm and leg weakness, ataxia
5/F/51 Right CRAO APAS Multiple Bilateral basal ganglia 2 15 (12-18) Right facial palsy
6/F/66 Left BRAO Left ICA endovascular coiling One Left fronto-parietal area 15 3 (1-8) None
7/M/22 Right CRAO Cardiac surgery for VSD One Right basal ganglia and white matter 4 3.5 (2-4) Left leg weakness
8/M/48 Right BRAO Surgery for aortic dissection Multiple Bilateral fronto-patieral area 20 5 (2-16) None

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Jan 8, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Co-occurrence of Acute Retinal Artery Occlusion and Acute Ischemic Stroke: Diffusion-Weighted Magnetic Resonance Imaging Study

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