Transient Vision Loss (TVL) and Amaurosis Fugax

In adults, transient vision loss (TVL) is a frequently encountered complaint that, in most cases, has an identifiable cause. ^[1] Transient vision loss may be unilateral or bilateral and may last from seconds to hours. Episodes often are ischemic in origin, but other more benign conditions should be considered in the differential diagnoses (eg, dry eye, migraine). Causes of ischemic transient vision loss include giant cell arteritis, cerebrovascular ischemia, and retinal arteriolar emboli. Some authors refer to ischemic transient vision loss as amaurosis fugax syndrome, so transient vision loss can be a symptom of a serious vision or life-threatening condition, requiring urgent investigation and treatment, or it may have a more benign origin (eg, migraine, dry eye). ^[1]

Transient vision loss in children is less common than in adults and is more likely to have a benign origin. ^[1]

Transient vision loss is a symptom rather than a diagnosis. It may be a manifestation of a number of different ophthalmic and systemic conditions, ^[2] including the following ^[1] :

• Thromboembolism
• Hypoperfusion (eg, hypotension, cardiac arrhythmias, anemia, heart failure)
• Increased plasma viscosity (eg, leukemia, lymphoma)
• Angiospasm
• Atherosclerotic and arteritic cerebrovascular disease
• Compressive neuropathies (eg, tumors, Graves orbitopathy)
• Orbital apex mass or retrobulbar tumors (gaze-evoked transient vision loss)
• Epileptic seizures (occipital lobe seizures)
• Sexual intercourse

Transient hypoxia of any part of the visual system can result in a temporary disturbance of vision. Compromised perfusion of the occipital lobe, the visual pathways, or the eye may be secondary to thromboembolism, hypoperfusion, or angiospasm.

Embolic occlusions of the arteries supplying the eye are a common cause of transient vision loss in adults. Emboli causing circulatory disturbances may originate in the heart or the carotid arteries. Embolic events usually are isolated, so, if visual disturbance occurs frequently, it is less likely that emboli are responsible.

Hypoperfusion may be due to hypotension, cardiac arrhythmias, anemia, heart failure, or atherosclerotic and arteritic cerebrovascular disease. Arteritic anterior ischemic optic neuropathy (AAION) also may present with transient vision loss, but in general, transient vision loss does not occur prior to nonarteritic AAION. Fluorescein angiography in patients with Giant Cell Arteritis (GCA) may detect total retinal occlusion of retinal circulation. Slight rises in intraocular pressure (even from rubbing eyes) in GCA may compromise optic nerve blood flow by thrombosing the posterior ciliary artery. ^{[1, 3]}

Vasospasm may cause a temporary reduction in blood flow to the visual system and transient vision loss. Some patients have had ocular examinations during the transient vision loss event that demonstrate the visible vasospasm on clinical exam, fundus photography, or fluorescein angiography.

Children with transient vision loss are less likely to have an ischemic cause for their symptoms and are more likely to have a benign disorder. Causes of bilateral vision loss in children include migraine and, less commonly, epileptic seizure. ^{[4, 5]} In some children, a cause for the visual disturbance cannot be identified, and the symptoms remain medically unexplained. ^[4]

The etiology of transient vision loss includes the following ^[1] :

• Local ocular conditions (including intraocular masses)
• Ingestion of a large meal
• Exercise
• Entopic phenomena
• Elevated intracranial pressure (ICP)
• Minor head injury (occipital trauma)
• Familial factors
• Migraine
• Ocular treatments (intravitreal injections, trabeculectomy)
• Closed-angle glaucoma

Gaze-evoked amaurosis (compression) is transient vision loss occurring when looking in a particular direction. Transient vision loss may be related to local ocular conditions, such as ocular surface disorders (eg, dry eyes), intraocular foreign bodies or masses, central or branch retinal vein occlusion, central or branch retinal artery occlusion, arteritic anterior ischemic optic neuropathy, intermittent angle closure glaucoma, hyphema, and optic neuritis. Transient vision loss also is recognized in association with optic disc drusen and colobomas. ^{[6, 7]} The mechanism for transient vision loss in these conditions is not fully understood but may be related to local hypoperfusion of the optic nerve or retina.

Transient vision loss has been reported to occur after ingestion of a large meal. ^[8] In this case, visual loss results from hypoperfusion of the eye, as blood is shunted to the mesenteric system. Postprandial visual loss is most common in individuals whose ocular perfusion is already compromised (eg, carotid disease, giant cell arteritis). ^[8]

Transient vision loss during exercise may result from increased heat exposure, causing decreased nerve conduction through demyelinated nerves (as in multiple sclerosis), also known as the Uhthoff phenomenon. Exercise also can cause pigment release (eg, pigment dispersion syndrome) or lenticular (dislocation/subluxation) abnormalities, causing transient vision loss.

Entopic phenomena are images produced by the eye’s own structures. These images may occur in the normal eye or may reflect abnormalities of ocular structures. Examples of entopic phenomena include the following:

• Floaters: These may be due to posterior vitreous detachment, vitreous hemorrhage, or the normal vitreous.
• Phosphenes: These are luminous sensations that may be induced by mechanical distortion of the retina resulting from eye rubbing or saccadic eye movements. ^[9]
• After-images: These are persistent images that remain after an object in the visual field is removed; this is a normal sensation that depends on the intensity and duration of the stimulus.

Increased ICP is a well-known cause of transient vision loss (ie, transient visual obscurations lasting seconds at a time). Increased pressure in the CSF can transfer through the optic sheath and cause compression on the optic nerve. The increased intracranial pressure can cause retinal dysfunction through choroidal compression folds, choroidal neovascularization, and, in severe cases, serous retinal elevation around the nerve head. ^[10]

Posttraumatic transient cortical blindness is thought to result from vasospasm and transient ischemia leading to cerebral dysfunction. ^{[11, 12, 13]} In these cases, vision returns to normal within minutes to hours, with no permanent neurologic sequelae.

Occasionally, transient vision loss is familial. Multiple episodes of transient vision loss have been described in children with elicited repetitive stereotyped daily blindness of unknown etiology. This rare condition is associated with childhood epilepsy, hemiplegic migraine, and other epileptic disorders through genetic links such as missense mutations in SCN1A. ^{[14, 15]}  Factor V Leiden mutations, an inherited thrombophilia, also have been found to have an elevated odds ratio for TVL incident. ^[16]

Migraine with aura is a common cause of transient visual disturbance at any age. Migraine probably is the most common organic cause of organic transient visual loss in children. ^[5] In a study of 83 patients younger than 45 years with episodic visual loss, migraine was the most likely cause in the majority of cases. ^[17] In children, 3.5-5% suffer from recurrent migraine headaches; however, only 18% of those have migraine with aura, and only 5% have aura without headache.

Migrainous visual disturbances also are common in the elderly. Visual aura occurs in 1-2% of elderly patients, and in 58%, aura is not associated with a headache. ^[18]

Migraine auras typically are bright and shimmering with a dynamic quality, whereas ischemia tends to produce dark and static defects. These differences notwithstanding, it may be difficult to distinguish between migraine with aura and amaurosis fugax. The International Headache Society (IHS) defines a migraine aura as a recurrent disorder that develops over 5-29 minutes and lasts for less than 1 hour. ^[19]

Migraine with visual aura is thought to be due to dysfunction of the striate cortex arising from a reduction in cerebral blood flow from the terminal branches of the basilar artery. Visual symptoms include photopsia, teichopsia (fortification spectra), scotoma, hemianopia, and diplopia and are usually homonymous. ^[20] There also may be other associated neurologic symptoms, such as paresthesia, weakness of limbs, speech disturbance, and vertigo.

Unilateral symptoms are rare but may occur in retinal or ocular migraine. Retinal migraine is presumed to result from retinal vasospasm causing isolated hypoperfusion of the retina or the optic nerve. ^{[20, 21]} This condition is defined as a fully reversible monocular visual disturbance associated with migraine headache and a normal neuro-ophthalmic examination between attacks. Retinal migraine is not as common as was once thought; one literature review found only 5 cases meeting the IHS criteria for diagnosis. ^[22]

Intravitreal injection of ocriplasmin, used to treat symptomatic vitreomacular adhesion, has been reported to cause transient vision loss due to presumed direct retinal side effects but with unknown molecular mechanism. ^[23] Vision loss also has been reported after surgical procedures involving the eye, such as a trabeculectomy. One study showed that more than 50% of patients experienced transient vision loss after trabeculectomy. ^[24]

There is no test to disprove a patient report of transient vision loss. In addition, eye examination findings may be normal in patients with transient vision loss of both organic and nonorganic etiologies. Patients with medically unexplained symptoms are frequent attenders. In primary care, 1 of every 5 new consultations involves a patient with symptoms for which no organic cause is found. ^[25] Despite the frequency of unexplained symptoms, there has been little research in this area.

Studies in adults suggest that childhood experiences, including illness in family members and previous medical consultations, are contributing factors to unexplained symptoms in later life. A series by Taich et al found that 26.7% of patients with medically unexplained visual loss had a previous diagnosis of depression, anxiety, or attention deficit hyperactivity disorder, and 31% had significant stress at school or at home. ^[26] Many patients have been seen by other specialties with unexplained symptoms.

If no medical explanation is found for visual loss in a child, parents may be anxious and keen for further investigations. A supportive approach is required, and the need for investigations must be balanced against the risks of exacerbating fears of disease. ^[27] It is important to establish a good rapport with the parents and the child with transient vision loss.

Worldwide, transient vision loss is uncommon. Transient visual disturbance is more common in adults than in children. In addition, its etiologic profile in adults differs from that in children.

Migraine, a common cause of transient vision loss at all ages, is more common in females than in males. In the United States, the 1-year prevalence of migraine is 14-18% in females and 6% in males, although the female predominance is not seen until after menarche. ^[28] In children younger than 7 years, boys are affected by migraine approximately as often or slightly more often than girls are. ^[29]

Medically unexplained visual symptoms are more common in women than in men. According to Griffiths et al, of those affected with medically unexplained (nonorganic) visual loss, 79% are female and 21% are male. ^[30] Of these patients, 36% had been seen by other medical specialists with unexplained symptoms. Improvement in visual function varies with age, symptom duration, early treatment, employment status, and psychiatric history but generally completely resolves in 42-44% of cases. ^{[31, 32]}

Patient history

Because of the many causes of transient visual disturbance, a structured approach to both the assessment and the management of these patients is essential. The likely causes of transient vision loss (TVL) vary according to the age of the patient. Ischemic causes are more common in patients older than 45 years; however, cases of impending central retinal artery occlusion and central retinal vein occlusion have been reported in children. ^[33]

Perhaps the most important element to ascertain from the history is whether the visual disturbance is monocular or binocular. ^{[1, 34, 35]}  A monocular visual disturbance is more likely to be secondary to a circulatory disturbance of the anterior circulation (eg, carotid artery) than a binocular visual disturbance, which often is due to a disturbance of the posterior circulation (eg, vertebral or basilar artery). Unfortunately, patients, particularly children, often have difficulty distinguishing between monocular and binocular symptoms.

Transient monocular visual loss often is referred to as amaurosis fugax, irrespective of the cause. However, it is more accurate to reserve the term amaurosis fugax for episodes of transient monocular blindness resulting from ischemia of the ocular vessels. ^[4] A vertebrobasilar disturbance may cause a visual transient ischemic attack (TIA).

Amaurosis fugax and a visual TIA are similar in several respects: Both are of sudden onset, last 2-30 minutes, and resolve quickly without pain. Amaurosis fugax typically consists of a gray curtain that progresses from the periphery and moves toward the center of vision. It is vital to identify patients whose visual disturbance is ischemic because these patients are at greater risk for cerebrovascular accident, cerebral TIA, and myocardial infarction (MI).

The risk for further thromboembolic events is lower after amaurosis fugax than after a visual TIA. ^[36] Repeated episodes of visual loss may be of thrombotic rather than embolic origin.

Whereas amaurosis fugax lasts only a few minutes (rarely longer), with vision returning to normal within 10-30 minutes, a migraine headache tends to last 2-3 hours (rarely more than 12 hours). The visual disturbance in migraine expands slowly over 10-20 minutes and rarely lasts more than 30 minutes.

Any precipitating factors for the visual loss should be elicited. For example, visual loss related to orthostatic changes may occur in patients with papilledema. The patient should be asked about the specific nature of the disturbance. Ischemic visual disturbances, such as amaurosis fugax, are classically associated with negative phenomena (eg, a blackout of vision or a curtain across the vision). Migraine tends to produce positive phenomena (eg, sparkling lights or zigzag lines).

Details of visual symptom progression can yield etiological information. Altitudinal visual field loss, symptoms of retinal claudication, and visual loss duration of 1-10 minutes are more indicative of carotid artery stenosis as an etiology. ^[37]

Associated symptoms may provide important clues to the etiology. Adults should be specifically asked about the symptoms of giant cell arteritis. Children should be asked about headaches and specifically about features of headaches that may suggest raised intracranial pressure (ICP) or migraine.

As part of the medical history, the patient’s ischemic risk factors should be assessed, including any history of hypertension, diabetes, or high cholesterol levels. Inquire about a personal history of migraine, as well as about a family history. Consider whether the patient has any systemic conditions (eg, collagen vascular disease, sickle cell disease, or vasculitis).

Physical examination

The examination should look for ocular and systemic causes of the visual disturbance, as follows:

Check visual acuity; in children who are old enough to report a visual disturbance, it is possible to measure a Log Mar or Snellen visual acuity.

• Check the pupils for a relative afferent pupillary defect.
• Examine the visual fields, perform a cover test, and examine extraocular motility.
• Perform a slit-lamp examination of the anterior segment, including fluorescein examination of the tear film, conjunctiva, and cornea, and measure the intraocular pressure (IOP); anterior-segment causes of transient vision loss are many, ranging from tear film abnormalities to intermittent angle closure, corneal disease, or uveitis. ^[5]
• Perform dilated funduscopy; this may reveal optic disc edema, retinal emboli, or ocular ischemia.
• If the vision is still reduced at presentation, perform a refraction; in addition, consider tests (eg, fogging test, prism shift test, stereoscopic tests, visual evoked potentials, and pattern electroretinography [ERG]) that may help exclude nonorganic visual loss. ^{[38, 39]}
• If pain is present, look for its specific causes (eg, angle-closure glaucoma, optic neuritis, or optic disc edema, suggesting increased IOP).

The differential diagnoses of transient vision loss include the following ^[1] :

• Central Retinal Artery Occlusion
• Central Retinal Vein Occlusion
• Corneal Abrasion
• Dry Eye Syndrome
• Giant Cell Arteritis
• Multiple Sclerosis
• Optic Neuritis, Childhood
• Optic Neuropathy, Anterior Ischemic
• Optic Neuropathy, Compressive
• Papilledema
• Partial Epilepsies
• Sickle Cell Disease
• Migraine Headache with aura
• Orbital masses

Other problems to be considered include the following:

• Demyelinating disease
• Ocular surface problem
• Orbital apex lesion

Patients with transient vision loss (TVL) should undergo a basic laboratory workup. Blood pressure should be checked; hypotension is a not infrequent cause of visual disturbance. The following blood investigations should be considered in the appropriate clinical setting ^[1] :

• Complete blood count (CBC) to check for conditions such as anemia and polycythemia
• Connective tissue diseases (eg, Wegener granulomatosis)
• Coagulopathy studies (eg, for antiphospholipid syndrome)
• Sickle cell test
• Acute phase reactants in elderly patients suspected of having giant cell arteritis (eg, ESR and CRP)

A hypercoagulable thrombotic state may exist as a consequence of increased activity of procoagulant compounds (eg, prothrombin, factor Va, thrombin, factor VIII, lipoprotein [a], and fibrinogen), decreased levels of anticoagulants (eg, protein C, protein S, and antithrombin III), or decreased levels of fibrinolytic compounds (eg, plasminogen and plasmin).

Hypercoagulability may also be caused by antibodies against membrane phospholipids and plasma proteins (eg, lupus anticoagulant and anticardiolipin antibodies). Young people with transient focal neurologic events, particularly those with monocular visual symptoms and no family history of migraine, may have antiphospholipid antibodies. ^[40]

Urinalysis should be performed to test for glucose to evaluate for acute hypoglycemia or diabetes.

Although transient vision loss in children most often is benign, a serious underlying cause should be excluded. If symptoms are medically unexplained, clinical judgment should be used in deciding on appropriate circumstances for neuroimaging studies and further investigations.

Neuroimaging studies should be considered in the following:

• History of recent head trauma
• Focal neurological deficits
• Papilledema
• Proptosis
• Limited eye movement
• Patients at risk for TIA or stroke (eg, diffusion-weighted imaging [MRI])

There should be a low threshold for neuroimaging studies in young children or where there are any suspicious features.

Consideration should be given to echocardiography, depending on the history and systemic examination findings.

When visual loss is medically unexplained, it is important to address the possibility that a subtle pathologic condition may be present that was missed on an initial examination. Accordingly, electrophysiology should be considered to exclude abnormalities such as Batten disease or Stargardt disease.

Transient monocular visual loss in adults usually is caused by an atheromatous plaque in the carotid bifurcation that creates a temporary reduction in retinal blood flow. ^[41] Therefore, in adults with transient monocular visual loss, it is essential to evaluate the carotid circulation, as early carotid surgery intervention can be effective in the prevention of stroke. ^[42] In contrast, no cases of transient vision loss due to atheromatous carotid disease have been reported in children.

The treatment of transient vision loss (TVL) depends on the cause. Some treatments for migraines, such as triptans, ergots, and beta-blockers, are avoided in migraine-induced transient vision loss owing to concern of worsening vasoconstriction. ^[37]  Aspirin or calcium channel blockers may also be indicated for retinal vasospasms that can contribute to retinal artery stenosis. ^[43]

If an ischemic event is suspected, the patient should be referred to a physician for investigation of any cardiovascular and cerebrovascular risk factors. A retrospective study from Japan showed 2.9% of patients admitted for TIA presented with transient vision loss. ^[44] Some of these patients benefit from antithrombotic therapy or carotid surgery. If the transient vision loss is monocular, the carotid system should be investigated, usually via carotid Doppler ultrasonography. Another study found that 49 of 213 consecutive patients (23%) with central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), or amaurosis fugax had acute brain infarctions detected by MRI. Of the 49 patients, 44 (~90%) were asymptomatic, which indicates that TVA patients should undergo neuroimaging, carotid, and cardiovascular checkup promptly after symptom onset. ^{[37, 45]}

Other investigations may include echocardiography, a complete blood count (to rule out anemia), and inflammatory markers (eg, CRP and ESR) when giant cell arteritis is suspected. If GCA is suspected, empiric steroid therapy and a temporal artery biopsy should be initiated. Neuroimaging is important for ruling out intracranial pathology affecting the visual pathway, particularly in patients with binocular disturbance. Empiric antiplatelet therapy (eg, daily aspirin) may be indicated while the evaluation is in progress for transient vision loss in patients with vasculopathy.

In cases where the diagnosis is uncertain, adequate follow-up care is important. Children with unexplained transient visual disturbances should be closely monitored. It is vital that patients with TVL are referred to the neurologist and ophthalmologist as soon as possible. An interprofessional team approach and prompt referral after evaluation will provide the best prognosis. ^{[37, 46]}

The prognosis of transient visual disturbance is better in children than in adults (usually because nonorganic and migraine are more common in children). ^[1] In a study of the long-term prognosis for adolescents and young adults with transient bilateral visual loss, Bower et al followed 13 patients aged 8-38 years who had 1 or more sudden transient attacks of bilateral blindness; none of the 13 suffered a major vascular event over a mean follow-up of 10 years. ^[36] The authors concluded that investigations are unlikely to reveal a cause for visual loss and that the prognosis for these patients appears benign.

When a patient presents with transient visual disturbance, the underlying cause must be ascertained and any serious treatable disorder excluded. In adults, identifying risk factors (eg, hypertension, hypercholesterolemia, and carotid artery disease) and treating systemic disease are important.

For example, if retinal emboli are found, the patient must be promptly referred for evaluation and management of cardiovascular risk factors. ^[1] The Beaver Dam Eye Study found that participants with retinal emboli who present at baseline had a 3-fold higher risk for 8-year mortality from stroke than persons without emboli. ^[47] A prospective study showed a 43% incidence of carotid artery stenosis affecting 70% or more of the lumen among patients with transient monocular vision loss. ^[42]

Details of visual loss progression are important, since close to 40% of patients with altitudinal visual field loss can progress to diffuse or total vision loss. Transient vision loss also serve as a warning sign for subsequent central and branch retinal artery occlusion. ^[37] Although children are more likely to have a benign cause of their symptoms, some may have a serious underlying problem. For example, cases of central retinal artery occlusion and central retinal vein occlusion in children have been reported to be associated with trauma, vasculitis, antiphospholipid antibody syndrome, sickle cell disease, and leukemia. ^{[48, 49]}