Amaurosis Fugax - Clinical Case Discussion

Table of Contents

Introduction

This word may seem like a bit of a tongue-twister, but let us tell you now that the poor fellows unfortunate enough to experience this condition will end up with more than their tongues in a twist! To begin our understanding of this topic, let’s take a look at Mr. Brown.

Mr. Brown, a 65-year-old retired school teacher, presented to the out patients’ department after experiencing a few episodes where a “gray curtain fell progressively” over his right eye. The episodes were painless, and all of them lasted for less than five minutes. His wife, who was accompanying him, mentioned that she had noticed him having difficulty finding words on a recent occasion, along with a transient weakness of his left side, which had resolved within ten minutes.

He is a known patient with type 2 diabetes mellitus for the past six years and is also on treatment for both hypertension and dyslipidemia for the past eight years. He consumes the occasional alcoholic beverage at parties and smokes 3-5 cigarettes a day.

As the on-call doctor, you find him looking well. His pulse rate is 70 beats per minute and regular, blood pressure has shot up to 170/94 mmHg, and his respiratory rate is at a steady 13 breaths per minute. He has no audible murmurs on auscultation and his nervous system examination is unremarkable.

As the attending doctor, you realize that Mr. Brown has a condition known as amaurosis fugax. How you proceed from this point onwards could be the difference between life and death for him. With that in mind, it’s time to ask ourselves,

What is Amaurosis Fugax?

It is a term used interchangeably to describe transient visual loss. However, we will refer to amaurosis fugax when the transient visual loss occurs due to a vascular or thromboembolic phenomenon occurring in the internal carotid arterial system. As described, it is a sudden, painless loss of vision, usually unilateral; lasting between seconds and minutes, followed by spontaneous recovery.

How does it Come About?

As you may have realized, amaurosis fugax is more of a symptom than a diagnosis. It is usually part of an ischemic process in the internal carotid system, such as thromboembolism from a carotid plaque, atherosclerotic cerebrovascular disease, vasospasm, hypoperfusion or elevated plasma viscosity (such as in patients with polycythemia, leukemia or multiple myeloma).

The commonest cause for amaurosis fugax is when a plaque from the carotid artery bifurcation migrates into the anterior cerebral circulation and occludes either the central retinal artery or a branch of it. These plaques are usually made up of platelets or cholesterol with hardly any fibrin. This is because platelets are the first to adhere to an unstable cholesterol plaque without a full-blown activation of the clotting cascade. In fact, you might even be able to see a cholesterol embolus (called a Hollenhorst plaque) if you look at Mr. Brown’s eyes under the slit-lamp microscope! It would appear as a bright, yellow, refractile particle lodged within a retinal vessel. Other than cholesterol plaques, there may be cardiac thrombi thrown off from valvular disorders or arrhythmias because of the stasis of blood in the heart, predisposing to the formation of thrombi.

Amaurosis fugax may also occur due to carotid artery stenosis, which may result in hypoperfusion of the retinal circulation and thereby cause a type of transient ischemic attack of the eyes. If there is chronic hypoperfusion, we call this “ocular ischemic syndrome,” which is a different topic altogether.

Except for these causes, it may also be the result of vasculitis (such as temporal arteritis, systemic lupus erythematosus or polyarteritis nodosa), where inflammation of the vessel wall predisposes to the adherence of platelets.

Why is it so Important to Diagnose and Treat Immediately?

Amaurosis fugax is something we like to refer to as a “sinister symptom” in medicine. This is because it is usually a warning sign of a more life-threatening condition, such as an ischemic stroke or an adverse cardiac event, which will obviously have more severe consequences. We will discuss more of this under the section on complications.

How would these Patients Present?

It is more commonly seen in male patients over the age of 45 years, like in the case of Mr. Brown. They present with a sudden, painless, unilateral loss of vision, which spontaneously resolves between 2-30 minutes. As Mr. Brown perfectly describes, it is like a curtain falling over the vision, beginning from the periphery and progressing towards the center of the visual field. It is important to distinguish between unilateral and bilateral visual loss, as unilateral occlusion points towards the occlusion of carotid vessels, whereas bilateral occlusion suggests a pathology in the posterior cerebral circulation or even the occipital region of the brain.

Patients can have either single or multiple episodes. If a patient over 60 years of age presents with more than one episode of amaurosis fugax (like our patient, Mr. Brown), he must be investigated for another condition that can predispose to transient visual loss called “giant cell arteritis,” which is a discussion for another day.

To complete his history, it is important to ask about any risk factors and precipitating factors that may have led to this condition. For example, ask him about any recent episodes of palpitations (which may indicate an arrhythmia, such as atrial fibrillation), a past history of valvular heart disease, any recent myocardial infarctions, or if he has features of heart failure like peripheral edema or dyspnea. It may also be useful to question him about past episodes of postural hypotension, as it may give a clue towards a carotid artery stenosis leading to cerebral hypoperfusion.

Besides these, most patients have cardiovascular risk factors such as diabetes mellitus, hypertension, dyslipidemia (like Mr.Brown), and rarely they may have a history of unilateral pulsatile headaches with scalp tenderness and jaw claudication if they have giant cell arteritis. It is also important to ask about their alcohol and cigarette consumption as they remain strong modifiable vascular risk factors in all patients.

Your Differentials

At the end of your history, based on the duration of the episode, as well as its frequency, and based on other clinical features, you can also consider the following:

Visual TIA – both these conditions are similar in many respects except for the progressive loss of vision seen in amaurosis fugax, described above.
Migraine with aura – this usually evolves over a number of hours, and presents with other positive symptoms (like hyperalgesia and zigzag lines)
Ocular ischemic syndrome – has a more chronic course, and is usually precipitated by an episode of exposure to bright lights (which increases the metabolic demand of the retina).
Giant cell arteritis – was mentioned previously
Central retinal vein occlusion.

On Examination

Following general examination to ensure that Mr. Brown isn’t acutely ill, examination of the cardiovascular system can be performed. Pulse rate and rhythm are important parameters, as they may indicate the presence of an arrhythmia (like atrial fibrillation), or give evidence of cardiac failure. Look for a carotid artery bruit as it is a sign of carotid atherosclerosis. Standard measurement of blood pressure, as well as routine auscultation of the precordium looking for murmurs, is mandatory.

Other than the basic cardiac parameters, the examination must be done with the idea of confirming or excluding a TIA. Therefore, it is a must to carry out a complete neurological examination and refer Mr. Brown to a neurologist for further evaluation. While doing the examination, pay close attention to unresolved weakness of one side, accompanied by a hemisensory loss, and also look out for difficulties with pronunciation and finding words. All these indicate an anterior cerebral circulation TIA.

As opposed to this, the posterior cerebral circulation TIAs would present with completely different symptoms, of which amaurosis fugax wouldn’t be a manifestation.

Lastly, the eyes must be examined. Check the visual fields and visual acuity, with the objective of excluding ocular ischemic syndrome, in which there is a progressive loss of visual acuity. It is also necessary to observe the fundus for papilledema, and grayish-white discoloration of the retina if we suspect a central retinal artery occlusion. Conversely, we may observe dot and blot hemorrhages in the event of central retinal vein occlusion.

There may be evidence of emboli within the retinal arteries. These could be the famous yellow-colored “Hollenhorst plaques”, whitish-gray platelet emboli, or rarely white, calcific plaques.

Scalp tenderness and or jaw claudication can be elicited to diagnose giant cell arteritis.

How would you Investigate the Patient?

Amaurosis fugax is primarily a clinical diagnosis, but additional investigations are necessary to identify risk factors, differentiate between subtypes, and assess the risk of complications.

To evaluate cardiovascular risk factors:

Carotid doppler is the first line investigation as it is a readily available, non-invasive imaging technique to assess the extracranial vessels. MR and CT angiography can also be used to evaluate the patency of both intra and extracranial vessels.
A 12-lead ECG with a rhythm strip to exclude any arrhythmias
Echocardiography to rule out valvular heart disease, cardiac failure, and identify any other potential sources of emboli (such as a patent foramen ovale)
Blood work which includes:
- Full Blood count – to check for conditions like polycythemia
- Coagulation tests – to exclude rare causes like antiphospholipid syndrome
- Hb electrophoresis – if you suspect a sickle cell disease
A random blood glucose followed by an HbA1c test, to check his glycemic control, and to assess the need for revising his oral hypoglycemic medication
Lipid profile to assess his triglyceride status
Additionally, we may consider carrying out Holter monitoring to assess his blood pressure, which may be transiently elevated in response to stress in this situation.

To rule out temporal arteritis:

Inflammatory markers – most likely ESR would be elevated
Temporal artery biopsy

In addition, neuroimaging studies such as

The standard non-contrast CT brain to exclude a hemorrhagic stroke
T2 diffusion-weighted MRI which is the gold standard in showing early ischemic changes following a transient ischemic attack

may also be undertaken.

What would be your Plan for Managing Mr. Brown?

As we continually reiterate, it is important to keep in mind that we are attempting to prevent a more life-threatening event in the future. Once we confirm the diagnosis of amaurosis fugax, the patient can be referred to a physician for investigation and management of cardiovascular and cerebrovascular risk factors, or to a neurologist if the patient is suffering from recurrent TIAs.

Mr. Brown most likely had a cholesterol or platelet embolus obstructing his retinal artery, and would benefit from antiplatelet therapy once hemorrhagic stroke has been excluded. A loading dose of 300 mg of aspirin, and 300 mg of clopidogrel (a P2Y12 inhibitor) followed by maintenance doses of dual antiplatelet therapy is recommended for 3 weeks if we suspect a TIA. After 3 weeks, the patient is switched to monotherapy (preferably aspirin) for a period of 21 days, as dual antiplatelet therapy only increases the side effect profile beyond this period.

Other than this, Mr. Brown’s current risk factors must be treated. As a rule, we begin treating the risk factors by making lifestyle modifications. He must be educated about the hazardous effects of smoking, and if possible, should be encouraged to completely give up smoking. He can be referred to a rehabilitation center to help with this process. Alcohol consumption must also be limited, and he must take care to remain within an optimum BMI with proper diet and exercise. The importance of both glycemic and blood pressure control must be emphasized and Mr. Brown should be advised against a high-salt diet. At least 30 minutes of moderate physical activity on 5 days of the week is recommended to ensure a healthy cardiovascular status.

Coming to his drug treatment, since he has diabetes mellitus, it would be worthwhile revising his oral hypoglycemic agents, where it may be necessary to switch to an agent offering tighter control of blood glucose. A glycemic target where Fasting Plasma Glucose remains below 126 mmol/dl or HbA1c between 7-8% is acceptable. The HbA1c is maintained at a higher target as elderly patients are more prone to episodes of hypoglycemia which could ultimately be more dangerous than hyperglycemia.

It is also important to control his hypertension with ACE inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, thiazide diuretics or beta-blockers as necessary, in adequate doses. A blood pressure target of 140/90 mmHg is generally acceptable, whereas a target of 130/80 mmHg is preferable as he is a patient with co-existing diabetes mellitus.

Furthermore, to maintain his plasma LDL levels below 70 mg/dl it would be necessary to revise his statin drugs and dosage.

In patients with coagulation disorders and cardiac causes for amaurosis fugax, antithrombotic agents may be prescribed. There are also various immunosuppressants and anti-inflammatory medications prescribed in the event of diagnosing giant cell arteritis or other types of vasculitis.

Once the medical management is taken care of, Mr. Brown may need surgical management with carotid endarterectomy. Being a complicated patient, he will have to be evaluated for his fitness to undergo local or general anesthesia. There is variability in the time to undergo carotid endarterectomy, but we currently think that the best period is within 4-8 weeks of presentation. Before surgery, it may be necessary to stop antiplatelet therapy.

What Complications can you Expect?

The main problem we are gearing up to expect is a future full-blown stroke. Especially considering the fact that Mr. Brown also describes a history of a TIA, he is definitely at a greater risk of facing an ischemic stroke in the coming 12 months.

Other than that, he is at risk of adverse cardiac events such as a future myocardial infarction or sudden cardiac death. If he had an arrhythmia, or a cardiac pathology, he is also at risk of developing heart failure. Similarly, he could develop complications based on anything which may have predisposed the amaurosis fugax.

Follow-up

A multi-disciplinary approach is important in following up patients with amaurosis fugax, as they are considered potential stroke patients. In fact, handling the risk factors and preparing for a future stroke plays a huge role in reducing strokes and their long-term impacts on the patient’s quality of life.

In our case, it is important that Mr. Brown is regularly followed up in the 21 days where he is taking dual antiplatelet therapy, and later at less frequent intervals for a period of 12 months. It is mandatory to ensure that his blood sugar control is good, and that he is reaching his blood pressure and triglyceride targets. His lifestyle modifications should be inquired into, and it may be helpful to refer him to a dietician. An occupational therapist and regular support groups may be instrumental in making a smooth transition from smoking and alcohol consumption to staying clean.

As we have come to see, Amaurosis fugax may seem simple at first glance, but it is a warning sign of a preventable devastating incident in the future, and as responsible doctors, it is up to us to be aware of the condition and take appropriate measures.

References

Kumar & Clark’s Clinical Medicine – Edition 10 [Cited May 06, 2021]

Davidson’s Principles and Practice of Medicine – Edition 23 [Cited May 06,2021]

Oxford Handbook of Acute Medicine [Cited May 07, 2021]

Tadi P, Najem K, Margolin E. Amaurosis Fugax. [Updated 2021 Jan 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470528/

https://emedicine.medscape.com/article/1435495-overview

https://www.amboss.com/us/knowledge/Retinal_vessel_occlusion