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Review Article

Current Guidelines on Management of Amaurosis Fugax and Transient Ischemic Attacks

Mbonde, Amir A. MBChB; O’Carroll, Cumara B. MD, MPH; Dulamea, Octaviana A. MD, PhD; Anghel, Daniela MD, PhD; Chong, Brian W. MD; Dumitrascu, Oana M. MD, MSc∗,§

Author Information
Asia-Pacific Journal of Ophthalmology: March-April 2022 - Volume 11 - Issue 2 - p 168-176
doi: 10.1097/APO.0000000000000511
  • Open


A transient ischemic attack (TIA) is defined by the American Heart Association/American Stroke Association (AHA/ ASA) as a transient episode of neurological dysfunction resulting from focal brain, spinal cord, or retinal ischemia, without associated infarction.1 This definition, therefore, encompasses amaurosis fugax (AF) that refers to momentary visual loss occurring as a result of transient retinal ischemia.2

Consequently, the use of the word TIA in this review includes both cerebral TIA (occurring in the brain) and AF (occurring in the retina). This new TIA definition is tissue-based and requires brain imaging to confirm the absence of cerebral infarction, which if present would indicate a diagnosis of cerebral infarction or stroke.3 Traditionally, TIAs were defined as the sudden occurrence of focal neurologic deficits of presumed vascular origin, lasting less than 24 hours.4 This time-based definition was found to be less specific, as up to 40% of patients presenting with focal neurological symptoms lasting less than 24 hours have evidence of abnormal diffusion restriction on brain magnetic resonance imaging (MRI), consistent with an acute ischemic stroke (IS).5 To better illustrate this point, we present a case of a 64-year-old woman evaluated in our emergency department for a transient 10-minute episode of right-arm weakness. Physical examination was unremarkable, but brain MRI diffusion-weighted imaging (Fig. 1A) and apparent diffusion coefficient (Fig. 1B) showed a small acute infarct in the anterior left caudate nucleus. This illustrates that the evaluation of patients presenting with TIA symptoms is not complete until an urgent brain MRI is obtained and has definitively ruled out cerebral infarction. Similarly, to meet the diagnostic criteria of AF, the lack of retinal infarction needs to be demonstrated by using either ophthalmoscopic examination and/or ancillary retinal imaging studies, such as fluorescein angiography, optical coherence tomography (OCT), and/or OCT-angiography. Thus, there is the need for emergent ophthalmologic and cerebrovascular evaluation in all patients presenting with transient visual loss.

Case 1: A 64-year-old female seen in the Emergency Department after a resolved 10-minute episode of right-arm weakness. Examination was normal, with NIHSS of 0. Brain MRI imaging with DWI (A) and ADC (B) showed a small acute infarct in the anterior left caudate nucleus, and CT angiography of the head showed severe focal stenosis of the M1 segment of the left middle cerebral artery (C and D). Given symptomatic severe intracranial atherosclerosis, antiplatelet management consisted of a combination treatment of aspirin and clopidogrel for 90 days, followed thereafter by aspirin. Rosuvastatin and control of all traditional vascular risk factors were endorsed. ADC indicates apparent diffusion coefficient; CT, computed tomography; DWI, diffusion-weighted imaging; MRI, magnetic resonance imaging; NIHSS, National Institutes of Health Stroke Scale.

In this review, we discuss the latest guideline-directed components of a comprehensive evaluation and management of patients with TIA/AF. We aim to provide a resource for both ophthalmologists and neurologists who care for these patients. Patients with AF can initially present to the ophthalmologists’, optometrists’, or the neurologists’ office, hence there is the need for all providers to be aware of current guidelines regarding optimal evaluation and management of TIA/AF, especially considering the associated short-term risk of stroke, hospitalization for cardiovascular events, and death.6–8


Thromboembolism from ipsilateral carotid atherosclerotic disease is seen in nearly 20% of AF cases.9 In Figure 2, we present a patient with AF and severe cervical carotid artery stenosis (CAS) that caused the transitory visual symptoms. Giant cell arteritis (GCA) is another notable etiology of AF, particularly in patients older than 50 years who are presenting with concurrent headache or systemic symptoms.10 Cardioembolism does occur in AF, but at a much lower rate than in cerebral TIAs.10 For example, 1 study found that atrial fibrillation (AFib) occurred in 4% of patients with AF as opposed to 20% of those with cerebral ischemia.11 Other causes of transient retinal ischemia include retinal arterial/arteriolar vasospasm, retinal hypoperfusion from hemodynamic disorders, vasculitis, retinal vein occlusion, retinal migraine, optic neuropathy (including compressive), optic disc edema, and papilledema.12 Cerebral TIAs can have multiple causes ranging from cardioembolism to large vessel or small vessel steno- occlusive disease, hypercoagulable states, and arterial dissec- tion.13–15 Modifiable risk factors for TIAs, such as physical inactivity, poor dietary habits, obesity, social isolation, tobacco, and illicit drug use, should be identified. Up to one-third of TIAs will not have an identifiable etiologic mechanism and are classified as cryptogenic. A comprehensive and systematic clinical etiological evaluation is required before a diagnosis of cryptogenic TIA is made.16 Most cryptogenic TIAs/strokes seem to be of embolic origin, leading to the term embolic stroke of undetermined source (ESUS).16 Embolic TIAs mainly present with transitory aphasia, neglect, homonymous hemianopia, and asymmetric appendicular weakness, that localize to cerebral cortices.16,17

Case 2: A 65-year-old male seen in the Emergency Department after resolved episode of transient monocular visual disturbance described as abrupt onset of a curtain of darkness descending over his left eye, lasting approximately 1 minute, with gradual resolution over 5 minutes. He was asymptomatic at presentation, with a normal neurological and ocular examination and NIHSS of 0. Brain MRI was normal (not shown). CT angiogram of the neck showed severe (greater than 90%) stenosis of the proximal left internal carotid artery (not shown). Patient underwent a conventional digital subtraction angiography which confirmed the left cervical carotid severe stenosis (preintervention images), for which he underwent revascularization with carotid stent placement (postintervention images). CT indicates computed tomography; MRI, magnetic resonance imaging; NIHSS, National Institutes of Health Stroke Scale.

The above etiologic mechanisms can be further classified into 5 major categories according to the Trial of ORG 10172 in Acute Stroke Treatment criteria.18 These categories are cardioembolism, large-artery atherosclerosis, small-artery disease, stroke of other determined causes, and stroke of undetermined causes.18 For example, paroxysmal AFib and patent foramen ovale (PFO) are classified under cardioembolic, whereas large- artery thrombosis and artery-to-artery embolism are classified under the large-artery atherosclerotic category. The Trial of ORG 10172 in Acute Stroke Treatment classification is helpful in guiding tailored diagnostic workup for individuals, based on the suspected stroke mechanism.18


Patients presenting with TIA/AF are at high risk of developing IS both in the short and long term,19 estimated to be as high as 10% to 15% at 3 months.8 In a large multicenter TIA registry study, the 1-year stroke risk was 5.1% and 5-year stroke risk was 9.5%.6 The combined risk of IS, acute coronary syndrome, or death attributable to cardiovascular causes was 6.2% at 1 year and 12.9% at 5 years.6,19 More concerning is the fact that a significant proportion of TIA subjects will have an IS within the first 2 to 7 days of the index event.20 Prior literature has demonstrated that risk factors for recurrent cerebral ischemic events after TIA include age ≥ 60 years, diabetes mellitus (DM), symptom duration longer than 10 minutes, and limb weakness or speech impairment as a presenting feature.20 The ABCD2 score is a validated risk stratification tool used to identify TIA patients with heightened risk of subsequent IS. It consists of the following 5 factors: age ≥ 60 years, blood pressure (BP) ≥140/90 mm Hg, clinical features such as unilateral weakness and speech impairment without weakness, duration of symptoms, and presence of DM (Table 1).20 The total score is further categorized into high risk (score 6–7), moderate risk (score 4–5), and low risk (score 03).21 The 2-day risk of recurrent stroke in individuals with a low-, moderate-, or high-risk is estimated at 1.0%, 4.1%, and 8.1%, respectively.22 The ABCD3 score that adds a recent history of TIA to the original score, and the ABCD-I score that adds imaging findings to the original score, have been found to be superior to the ABCD2 score in risk-stratifying TIA patients.23,24 These scores are, therefore, useful in identifying patients in whom emergent inpatient evaluation is prudent, such as those with moderate- and high-risk scores. For those with an ABCD2 score of less than 3, the use of the score alone as a triage tool is discouraged by the European Stroke Organization, as the sensitivity of predicting recurrent ischemic events is particularly suboptimal in patients with low scores.25 Therefore, the urgency by which individuals with low scores should be evaluated, ought to be determined on a case-by-case basis. Further, the utility of these predictive tools in risk-stratifying patients with AF is not fully known.26 Yet, it is well recognized that patients with retinal artery occlusion or ocular ischemic syndrome have increased risk of IS, TIA, and AF, both before and after the diagnosis.27

Table 1 - ABCD2 Score
Parameter Score
Age, years
 ≥60 1
 <60 0
Blood pressure
 SBP ≥140 or DBP ≥90 mm Hg 1
 SBP <140 or DBP < 90 mm Hg 0
Clinical presentation
 Unilateral leg weakness 2
 Speech impairment 1
Duration of symptoms
 ≥ 60 min 2
 10–59 min 1
 <10 min 0
Diabetes mellitus
 Yes 1
 No 0
Total score
The total score is derived from the sum of the individual parameter scores and this is further categorized into high-risk (score 6–7), moderate-risk (score 4–5), and low-risk (score 0–3).DBP indicates diastolic blood pressure; SBP, systolic blood pressure.


Clinical History

TIA evaluation should begin with a detailed history and examination. The diagnosis of a TIA is heavily reliant on clinical history given that symptoms are transient and absent at the time of the assessment. To differentiate AF from other causes of transient monocular visual loss (TMVL), it is important to assess the patient's own description of visual symptoms, duration of visual loss, abrupt versus gradual onset, monocular versus binocular visual loss, associated symptomatology, and recurrence patterns, if applicable. The abruptness of symptom onset helps differentiate symptoms due to vascular (TIA) from nonvascular etiologies (TIA mimics), as all TIAs have abrupt onset. Physicians should encourage patients to provide a specific description of their symptoms in their own words. Common AF descriptions may include visual blurring, fogging, dimming, shadowing, or complete darkness (visual loss) in 1 eye. The classic AF description, although reported by only a small proportion of patients, is that of TMVL descending upon the field of vision of 1 eye,2 referred to as the “curtain” or “shade-down” phenomenon. It is important to inquire if the patient attempted to close either eye during the episode, to ascertain whether the visual disturbance is monocular or binocular. Although most patients do not perform this simple maneuver, they should be instructed to do so in case of future events of visual loss. Other clues such as inability to read can point towards binocular visual pathology. It is similarly important to ascertain whether binocular diplopia or hemianopsia are present, as these would localize outside of the retina and thus be an AF mimic. Homonymous hemianopia is a typical postchiasmal pattern of visual loss due to damage to the optic tracts, optic radiations, or occipital cortex, however, it can be misperceived by patients as monocular visual loss. Symptoms associated with cerebral TIAs can be due to ischemia involving the anterior circulation such as hemiparesis, aphasia, neglect, or to posterior circulation such as dizziness, incoordination, dysarthria, binocular visual loss, hemianopsia, and diplopia.

Clinical history should clarify whether the symptoms are completely resolved at the time of assessment. Ongoing visual loss may signify the patient is having persistent retinal artery occlusion, warranting emergent stroke evaluation and treatment.2,28 Symptom duration lasting seconds may point towards optic disc drusen or optic disc edema, including papilledema.29,30 Duration between 5 and 60 minutes, followed by a headache may suggest retinal migraine.31,32 In younger patients with history of Raynaud, the occurrence of patchy faded vision lasting approximately 1 minute, followed by poor visual acuity, without any positive visual phenomena, can be due to retinal arterial vasospasm.33

Any triggers of transient visual disturbance should be noted. TMVL triggered by bright lights suggests retinal claudication from ipsilateral atherosclerotic CAS.34 Other triggers such as change in head or eye position were reported in certain forms of AF, although these ought to be differentiated from transient visual obscurations associated with raised intracranial pressure.29

Patients should be asked about associated features such as headache, as this can be associated with GCA or migraine. Positive visual phenomena involving scintillations, sparkling or flickering lights marching across the visual field over several minutes are consistent with a diagnosis of scintillating scotoma, as seen in visual aura.32 Associated eye pain can be seen in acute angle-closure glaucoma or optic neuritis.35,36 Transient contralateral hemiparesis or sensory disturbance, contralateral homonymous hemianopia, aphasia, or dysarthria can be seen in AF with concurrent hemispheric TIA.

Recurrence of visual symptoms is also important. Patients with TMVL from migraine or ischemia may have multiple episodes separated by various epochs, ranging from minutes to years. However, multiple stereotypic episodes of TMVL recurring over years in the absence of stroke or permanent visual loss suggest migraine pathophysiology. Binocular TVL may also seem during an occipital seizure, either during ictal or postictal state. Visual epileptic aura may include elementary hallucinations (eg, flickering lights, stars, flashes of light) and visual loss, which has been described as blurred vision, “white out,” or scotoma. Postictal blindness typically lasts minutes to hours but may last days to weeks.

History of vascular risk factors should include AFib or atrial flutter, heart failure, valvular pathology, coronary artery disease, cardiomyopathy, DM, sleep-disordered breathing, dyslipidemia, and arterial hypertension (HTN). Hypercoagulable or hematologic disorders, hyperviscosity states, recurrent pregnancy loss particularly after the first trimester, and trauma to the neck are important, especially below the age of 50 years.37,38 Family history of stroke/TIA is important to elicit, as this has been shown to be an independent stroke risk factor, more so in patients younger than 65 years who have a history of stroke in a sibling.39 A thorough social history is equally important after a TIA, as it provides avenues for initiating behavioral modifications aimed at modifiable risk factors such as excessive alcohol intake, physical inactivity, poor diet, low sleep duration, significant psychosocial stress, illicit drug, and tobacco use.39–41

Physical Examination

A thorough neurological examination is needed to confirm the absence of any residual deficits that would suggest IS rather than TIA. The National Institutes of Health Stroke Scale is a widely used clinical assessment tool that helps determine if there are any residual deficits attributable to stroke.42 TIA patients should have a National Institutes of Health Stroke Scale score of 0 and no other subtle acute focal neurologic signs, consistent with the transient nature of the syndrome. For instance, both cases presented in Figures 1 and 2 had normal neurologic exams.

In addition to a complete neurologic exam, patients with AF should undergo a comprehensive ocular examination, including visual acuity, Amsler grid, color vision, visual field testing, pupillary examination, and dilated fundoscopic examination. Ophthalmoscopy is helpful in ruling out other causes of visual loss such as retinal detachment, retinal vein infarction, or central retinal artery occlusion.43 The appearance of the retinal emboli may provide clues for the underlying etiology and may guide targeted workup: cholesterol emboli (small, yellow, refractile, multiple plaques at points of arteriolar bifurcation) are indicative of ipsilateral CAS or aortic atheroma; platelet fibrin emboli (white-grey, pale, distal, within the small retinal arterioles) suggest the presence of a proximal thrombus (aortic, cardiac, carotid) or cardiac prosthesis; calcium emboli (white, large, in the proximal large vessels) suggest calcified cardiac valves or atheromatous plaque; talc emboli (multiple, yellow, refractile) in intravenous drug users; neoplastic emboli (multiple, white) in cardiac myxoma; fat emboli (multiple whitish spots associated with hemorrhages) in long bones fractures; and white Roth spots in bacterial endocarditis or candidemia.44 However, ophthalmoscopic examination in AF is most often normal. AF patients should undergo a comprehensive ocular examination in the ophthalmologist's office, as the emergency room evaluation may be suboptimal in cases with subtle ocular pathology.


All TIA/AFs should be evaluated as medical emergencies as they may herald a devastating hemispheric or basilar stroke or permanent visual loss. Despite transitory symptoms, TIA patients should be expeditiously evaluated in the same manner as those with an acute stroke (Fig. 3).

Recommended evaluation for patients presenting with transient ischemic attack and amaurosis fugax.

Imaging of the Brain and Extracranial/Intracranial Blood Vessels

Structural brain imaging is helpful in establishing the diagnosis of a TIA by confirming the absence of an infarct and excluding other nonneurovascular diagnoses. In 1 study, 30% to 50% of subjects presenting with TIA had an acute stroke on brain MRI as opposed to only 4%23 of those who underwent head computed tomography (CT). Thus, AHA/ASA recommends MRI with diffusion-weighted imaging/apparent diffusion coefficient sequences as the preferred diagnostic study in patients with suspected TIA/AF.23 AHA/ASA further recommends [Class 1, level of evidence (LOE) B] that subjects with suspected TIA should preferably undergo brain MRI within 24 hours of initial presentation.23 Head CT can be considered if MRI is unavailable or contraindicated. Patients with anterior circulation TIA/AF should also undergo expeditious imaging of intracranial and extracranial vasculature, ideally, within 24 hours of initial presentation (Class 1, LOE B),23 using either carotid ultrasound and transcranial doppler (TCD), magnetic resonance angiography, or CT angiography of the head and neck. The choice of test largely depends on availability. Magnetic resonance angiography is more sensitive than carotid ultrasound/transcranial doppler45 and can be obtained at the same time as the brain MRI, although individuals with non-MR compatible pacemakers may not be candidates for this study, in which case a CT angiography can be completed.23 These studies are crucial in the early identification of patients with moderate-severe cervical carotid stenosis (greater than 50% of stenosis) who are candidates for early carotid artery endarterectomy (CEA) or stenting.23

Cardiac Investigations

All patients with TIA/AF should undergo a baseline electrocardiogram to evaluate for AFib or myocardial infarction at the time of the initial presentation, as up to 8% of patients with stroke/ TIA will have AFib on initial electrocardiogram.46 A transthoracic echocardiogram (TTE) to evaluate for cardiac sources of emboli is recommended in all. A transesophageal echocardiogram (TEE) should be completed in those with cryptogenic TIA or ESUS.47 TTE with contrast is preferred for left ventricle thrombus detection, whereas TEE is more sensitive in identifying other proximal sources of embolism such as PFO, valvular disease, endocarditis, left atrial appendage thrombus, atrial myxoma, atrial cardiopathy, and aortic arch atherosclerosis.48–50 In 1 study involving 61 ESUS patients who underwent TEE, this test revealed additional findings in 52% and informed management decisions in 16% of the study population.51 The ASA/AHA recommends cardiac monitoring in all individuals with cryptogenic TIA/stroke.23 The optimal duration of cardiac monitoring in TIA is unknown and should be tailored according to the suspected risk of AFib in a particular patient.16 AHA recommends at least 30 days of extended cardiac monitoring within 6 months of the index TIA event.1 Longer periods of monitoring should further be considered in select individuals in whom the suspicion for AFib is extremely high. Several trials have shown that a longer-term of cardiac monitoring of 3 to 6 months yields greater chances of capturing paroxysmal AFib in cryptogenic stroke patients. For instance, significant greater Afib detection at 6 months was noted in patients that were randomized to insertable cardiac monitoring versus conventional follow-up [8.9% vs 1.4%, 95% confidence interval (CI): 1.9–21.7; P < 0.001].46 PFO evaluation should start with noninvasive TTE with bubble study. TEE has better sensitivity for PFO detection and allows for a better assessment of the PFO and atrial septum features.47 Cryptogenic TIA/AF patients may undergo noninvasive TCD with bubble testing, as TCD had a sensitivity of 96.1% (95% CI: 93.0–97.8) and specificity of 92.4% (95% CI: 85.5–96.1) compared with TEE for PFO detection.47

Serologic Tests

Routine blood tests such as a complete blood count, chemistry panel, basic coagulation studies (prothrombin time, partial thromboplastin time), hemoglobin A1C and lipid profile, and urine drug (eg, amphetamine, cocaine) screen, are suggested in all TIA/stroke patients, to inform the vascular risk-factor profile.23 Additional or specialized serologic testing such as coagulation studies (anticardiolipin and anti-beta-2 glycoprotein IgM and IgG antibodies, lupus anticoagulant, factor V Leiden mutation, factor VIII, prothrombin 20210A mutation, protein C, protein S, antithrombin III activity, serum homocysteine) may be completed in subjects with TIA at a young age (≤ 50 years), who do not have other vascular risk factors. Erythrocyte sedimentation rate and Creactive protein are recommended in subjects with AF in whom GCA is suspected.23 A more comprehensive evaluation for young-onset TIA/stroke can be considered when relevant.52 Cerebral or systemic vasculitis (eg, systemic lupus erythematosus, polyarteritis nodosa, sarcoidosis, Churg-Strauss, granulomatosis with polyangiitis), infectious diseases (eg, Borrelia burgdorferi, toxoplasma, toxocara, human immunodeficiency virus, syphilis, varicella-zoster virus, mucormycosis), and hyperviscosity states including hematologic disorders (eg, sickle cell disease, leukemia, lymphoma) should be considered in specific cases, when a high index of suspicion exists.

In patients with AF, in addition to a comprehensive ophthalmologic evaluation that may include computerized perimetry, fluorescein/indocyanine green angiography, OCT and/or OCTangiography, ambulatory electroencephalogram may be considered to differentiate recurrent AF from occipital seizures.


Management of TIA patients, including those with cerebral TIA or AF, is the same and is primarily aimed at stroke prevention, given that patients are asymptomatic at presentation. The urgent diagnostic workup is aimed at identifying any potential etiological mechanisms that can be targeted using stroke prevention measures. For the purpose of this review, we have categorized the stroke prevention measures into general (applicable to all TIA/AF patients) and specific (measures that target an identified TIA/ stroke etiological mechanism).

Given the elevated risk of stroke after a TIA, we recommend that all patients presenting with TIA (cerebral or AF) in an outpatient setting, be referred emergently for comprehensive evaluation and treatment. A specialized outpatient TIA clinic with around-the-clock access has been associated with improved TIA outcomes.53,54 If emergent evaluation in an outpatient TIA clinic is not possible, same-day referral to an emergency room with on-call neurology availability is preferred.

General Stroke Prevention Measures

Lifestyle Measures

Mediterranean diet with regular consumption of fish, fruits, and vegetables is highly recommended after TIA/AF.23 Dietary Approaches to Stop Hypertension diet is recommended in case of concurrent HTN. Other recommended lifestyle measures include encouraging tobacco/illicit drug use cessation, alcohol use moderation, weight management, routine at least moderate-intensity aerobic activity, and medication compliance.55–57

Antiplatelet Therapy

All TIA/AF patients who do not have an indication for anticoagulation should be treated with aspirin 50 mg to 325 mg daily, clopidogrel 75 mg daily, or a combination of aspirin 25 mg and dipyridamole 200 mg twice daily, to reduce the risk of recurrent IS.23,58 All patients presenting to the office (ophthalmologist, optometrist, neurologist, family physician) with TIA/AF, should ideally be prescribed one of these antiplatelet agents before referral for a more comprehensive evaluation. Routine long-term dual antiplatelet therapy (DAPT) is not recommended.23 A short course of DAPT can be prescribed for high-risk TIA patients (ABCD2 score ≥ 4), in which case aspirin and clopidogrel are initiated within 24 hours of TIA symptoms and continued for 21 days.23 This recommendation is derived from the Clopidogrel in High-Risk Patients With Acute Non-Disabling Cerebrovascular Events (CHANCE)59 and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trials,60 which demonstrated a reduced risk of recurrent stroke when patients with high-risk TIA or minor IS were treated with short-course DAPT, started within 12 to 24 hours of presentation.60 Following this 21-day period, single antiplatelet (SAPT) agent only is recommended.23

Another indication for short-term DAPT is the presence of symptomatic intracranial atherosclerosis. For patients with high- risk TIA within 24 hours or symptomatic intracranial or extracranial ≥ 30% of stenosis of an artery that could account for the event, DAPT with ticagrelor plus aspirin for 30 days may be considered to reduce the risk of 30-day recurrent stroke, whereas acknowledging that it may also increase the risk of serious bleeding events, including intracranial hemorrhage.61


Screening and treatment of HTN after TIA is important and recent guidelines recommend a target office systolic BP of ≤ 130 mm Hg.23,62 A higher target may be reasonable in those with intracranial atherosclerosis who may be dependent on higher BP for cerebral perfusion.23 Screening for sleep-disordered breathing and its appropriate management may also help with BP reduction.63


Statin therapy with atorvastatin 80 mg daily to a goal of low- density lipoprotein cholesterol (LDL-C) of less than 100 mg/dL should be pursued in those without a known history of coronary artery disease.23,64 In the presence of atherosclerosis (intracranial carotid, aortic, coronary), a lower LDL-C target of less than 70 mg/dL is favored.23,64 High-intensity statin or maximally tolerated statin is preferred if no contraindications exist, and ezetimibe or proprotein convertase subtilisin/kexin type 9 serine protease (PCKS9) inhibitor can be added when the target LDL-C has not been achieved during follow-up.64 Icosapent ethyl 2 g twice a day and omega-3 fatty acids are indicated in patients with hypertriglyceridemia.23

Diabetes Mellitus

DM (type 1 and 2) and prediabetes [hemoglobin (Hb) A1C 5.5%–6.4%] are highly prevalent stroke risk factors.65 Current recommendations for patients with DM and a recent TIA are to treat to an individualized HbA1C target that does not place them at an increased risk of adverse effects of hypoglycemia, although for most adults a goal HbA1C target of less than 7% is reason- able.23,66 A less stringent HbA1C target of 7% to 8% is preferred in those with a limited life expectancy, history of hypoglycemia, long-standing disease, or advanced microvascular or macrovas- cular disease.66 Optimization of lifestyle measures, such as diabetic diet, weight control, regular exercise, and smoking cessation should also be emphasized.23,66


Individuals with TIA who are obese or overweight should be provided with resources to assist with weight loss.23


Symptomatic Extracranial Cervical Carotid Artery Atherosclerotic Stenosis (Fig. 2)

AHA/ASA strongly recommends (Class 1, LOE A) that patients with TIA/AF within the past 6 months, with ipsilateral severe (70%–99%) CAS, should undergo CEA to reduce the risk of subsequent stroke or death.23,67 It is reasonable to perform the procedure within 2 weeks of the index event rather than delay the intervention.23 For patients with moderate (50% to 69%) CAS, CEA is still recommended (Class 1, LOE B-R) if the perioperative morbidity and mortality risk is estimated to be less than 6%.68 CEA is preferred over carotid stenting in those who are ≥ 70 years of age and in those whose revascularization is being planned within 1 week of the TIA,23,69 to reduce the risk of the periprocedural stroke which is higher in those who undergo stenting. These recommendations are derived from the CREST trial, a large, randomized trial that compared CEA to stenting in patients with symptomatic and asymptomatic CAS, and found similar rates of recurrent stroke, myocardial infarction, and death.70 A subgroup analysis found that stenting may be preferred in those younger than 70 years of age and CEA may be preferred for those above age 70.23,70 Revascularization is not recommended in TIA/AF with CAS less than 50% or extracranial vertebral artery stenosis.23 These patients should instead be treated with optimal medical management that entails SAPT, statin, lifestyle modification, and control of relevant vascular risk factors. Patients with TIA due to complete carotid occlusion should also undergo medical management in lieu of extracranial-intracranial bypass surgery.71

Symptomatic Intracranial Large Artery Atherosclerosis (Fig. 1)

Treatment is aimed at averting the risk of recurrent stroke, which has been estimated to be as high as 20% at 30 days in severe intracranial large artery atherosclerosis with greater than 70% of stenosis.72 A combination of clopidogrel 75 mg and aspirin 325 mg daily for 90 days after TIA/IS, followed by SAPT is the preferred regimen. This is based on the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, which showed a significantly reduced risk of recurrent IS in patients with severe stenosis (70%–99%) of a major intracranial artery who were treated with maximal medical therapy versus those who received stenting (14.7% vs 5.8%, P = 0.002).73 In addition to DAPT, optimal medical management should include BP control to a goal of systolic 140 mm Hg, LDL-C cholesterol-lowering to less than 70 mg/dL using high-intensity statin, smoking cessation, and routine physical activity.73 In patients with recent (within 24 hours) high-risk TIA and concomitant ipsilateral greater than 30% of stenosis of a major intracranial artery, the addition of ticagrelor 90 mg twice a day to aspirin for up to 30 days might be considered to reduce recurrent stroke risk.74

Aortic Arch Atherosclerosis

Aortic arch atherosclerosis with high-risk features, defined as ulcerated plaque, plaque thickness of ≥ 4 mm, or mobile thrombus associated with the plaque, gives particularly heightened risk of IS/TIA recurrence 75 and should be promptly treated with antiplatelet therapy and intensive lipid-lowering to a goal of LDL target less than 70 mg/dL.23 AHA/ASA recommends long-term aspirin as the antiplatelet of choice.23 Long-term DAPT is not recommended due to increased bleeding risk.23,76 Equally, the role of anticoagulation in high-risk aortic arch atherosclerosis is not fully elucidated.23,77,78 The ARCH trial did not show a benefit for anticoagulation over DAPT in high-risk aortic arch atherosclerosis, although the study was grossly underpowered.78

Nonvalvular Atrial Fibrillation

There is compelling evidence to support the role of therapeutic anticoagulation using a direct oral anticoagulant, such as apixaban, edoxaban, dabigatran, or rivaroxaban, in stroke prevention after TIA/AF, regardless of whether the AF is paroxysmal, persistent, or permanent.23 direct oral anticoagulant is preferred over warfarin, except in those with mechanical heart valves or moderate-to-severe mitral stenosis.79 For patients who cannot tolerate life-long anticoagulation, percutaneous closure with Watchman device can be considered.80 After TIA/AF, the risk of anticoagulation-induced intracranial hemorrhage is minimal, and therefore, prompt initiation of anticoagulation is preferred.81 Intermittent and asymptomatic nonvalvular AFib is an important cause of cryptogenic TIA/stroke and most experts agree that anticoagulation should be initiated for secondary stroke prevention.

Other Specific Causes of Transient Ischemic Attack and Amaurosis Fugax

The evaluation and management of other specific, albeit rarer TIA causes, such as vessel dissection, intracardiac thrombus, infective endocarditis, marantic endocarditis, severe heart failure with reduced ejection fraction (less than 35%), mechanical aortic/mitral valve prosthesis, left ventricle mechanical assist devices, PFO, malignancy, hypercoagulable disorders, hyperviscosity states, and vasculitis, are beyond the scope of this review.


The diagnosis of a TIA (cerebral or AF) is reliant on a detailed clinical evaluation and brain/retinal imaging to confirm the absence of brain/retinal infarction. Cerebral TIA and AF should be managed in the same manner and as medical emergencies, as they may herald devastating hemispheric or vertebrobasilar stroke or permanent disabling visual loss. Given the elevated risk of stroke, we recommend that all TIA/AF patients presenting to an outpatient provider, be referred emergently for comprehensive evaluation and treatment. We recommend same-day referral to an emergency room with on-call neurology availability or to a specialized outpatient TIA clinic with around-the-clock access. Urgent clinical evaluation and a systematic staged diagnostic workup are crucial to investigate the underlying etiology and guide stroke prevention. The utility of testing cryptogenic TIA/AF for rarer etiologies, such as genetic, infectious, inflammatory, or metabolic disorders, remains uncertain and may warrant further investigation. New therapeutic approaches in specific TIA/AF etiologies using high-risk prognostic features should be studied in future clinical trials, to promote further personalized TIA therapy and stroke prevention.


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amaurosis fugax; eye ischemia; prevention; transient ischemic attack; transient visual loss

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