Timely diagnosis crucial in cases of transient monocular vision loss

This symptom may indicate impending carotid disease or cerebral hemorrhage.

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A temporary decrease or absence of vision is certainly a diagnostic challenge. It was not until the late 1800s that monocular vision loss was found to be related to extracranial artery dysfunction, and not until the early 1900s that Ramsay Hunt confirmed that transient visual symptoms were a warning sign of impending carotid disease and cerebral hemorrhage.

Transient monocular vision loss (TMVL), also referred to as transient monocular blindness and amaurosis fugax, describes episodes of acute loss of vision secondary to dysfunction of the optic nerve, retina or choroid. Narrowing down the lengthy and in some cases life-threatening etiologies involves a thorough neuroophthalmic history and will provide a working differential diagnosis and algorithmic approach to facilitate timely referral, testing and treatment.

The diagnosis of TMVL is ascertained when visual disturbance (i.e., blurring, fogging, graying, dimming) or frank vision loss is sustained for seconds to minutes.

Incidence of TMVL

According to Anderson and colleagues, the annual incidence of TMVL between the ages of 25 and 84 is 13.7/100,000 for men and 9.4/100,000 for women, with the greatest incidence occurring in the seventh decade of life. Subsequently, the annual incidence of stroke following TMVL ranges from 2.0% to 2.8%. Earlier studies on the natural history of TMVL report that about 12% of untreated transient ischemic attack (TIA) patients will suffer a stroke within a year of the onset of symptoms and up to 35% within 5 years, Lord reported.

Ocular symptoms

Given the complexity of TMVL, a thorough history is highly valuable and cannot be understated. It is important to evaluate the onset, frequency, location, duration, associated symptoms and pattern of loss. Despite the descriptive variability when it comes to loss of vision, it is prudent to keep a low threshold for continuing the onslaught of neuroophthalmic questions. While no one particular set of answers is diagnostic in its own right, a complete assessment will provide clues to the potential etiology.

Venables and colleagues reviewed 152 patients and concluded that 53% presented with complete visual loss, 32% had partial loss, and 14% experienced partial and complete loss. Ehrenfeld and colleagues evaluated 44 patients with TMVL and carotid occlusive disease. After a review of their symptoms, it was found that the majority of patients had specific complaints of vision loss that appeared as a shade over their vision, producing partial vision loss. And in a large review of the North American Symptomatic Carotid Endarterectomy Trial (NASCET), generalized loss of vision was reported in 53.4% of patients, whereby altitudinal loss was noted in 28.8% in either an ascending or descending pattern (Miller and Newman).

In addition to negative phenomenon (i.e., graying, darkening or frank vision loss), some patients also describe a sensation of color or photopsias consisting of stationary flecks of light. These “positive” stimuli are a rare occurrence in carotid disease but cannot be differentiated in and of itself from the more benign acephalgic migraine secondary to vasospasm.

The majority of vision loss is said to occur from 2 to 30 minutes with resolution occurring over seconds to minutes. In a retrospective evaluation of 67 patients with TMVL, Marshall and Meadows concluded that 75% of patients experienced vision loss in 30 minutes or less, with 43% experiencing loss for 5 minutes or less. In addition, both Pessin and Goodwin and others described a majority of their patients experiencing TMVL for less than 15 minutes. And in the NASCET study, the duration of episodic vision loss ranged from 15 seconds to 23 hours, with a median of 4 minutes (Miller and Newman).

In some patients, exposure to bright lights has been found to elicit episodic vision loss. According to Furlan and others, in a retrospective review of five patients who described this phenomenon, all were found to have severe ipsilateral carotid occlusive disease.

Bright exposure to light induces metabolic activity within the photoreceptors, retinal pigment epithelium and Bruch’s membrane complex. The retinal pigment epithelium depends on nourishment from the vascular rich choriocapillaris. Occlusion of the carotid artery results in hypoperfusion to the ophthalmic artery and ischemia of the choriocapillaris, thereby reducing metabolic activity and photoreceptor recovery.

A phenomenon related to the above-mentioned light-induced amaurosis is postprandial vision loss. This occurs after the ingestion of a large meal. Levin and Mootha postulated that the coexistence of carotid occlusive disease and increased blood flow to the gut after a large meal results in hypoperfusion and ischemia to the retinal and choroidal circulation. Interestingly, patients who present for ophthalmic consultation during an acute attack have been noted as having an afferent pupillary defect, pupillary mydriasis and retinal arterial occlusion, suggesting hypoperfusion of the retina, choroid, optic nerve, ciliary ganglion or short ciliary nerves.

Ophthalmologic examination

In addition to the standard comprehensive exam, additional testing should include color vision, red cap desaturation testing, automated perimetry and gonioscopy to rule out intermittent angle closure. Patients older than 50 years should be evaluated for temporal arteritis.

Clinical examination of a stiff, tender, temporal artery without pulsation indicates an emergent evaluation for giant cell arteritis (GCA). In addition, detailed observation of both the retinal and optic disc circulation with regard to emboli and perfusion is helpful in determining co-existent optic neuropathy and retinal vascular occlusive disease.

Differential diagnosis

A proper differential diagnosis is fairly lengthy. The most common causes of TMVL are ischemia and hypoperfusion. Three likely mechanisms must be investigated: carotid artery stenosis, carotid or cardiac embolic events, and temporal arteritis. This must be at the forefront of the diagnostic list and should serve to guide timely testing. All represent sight- and life-threatening sequelae and should be managed in an emergent manner.

TIAs are defined as episodes of focal neurologic dysfunction lasting less than 24 hours followed by a return to normal function. According to Gaul and colleagues, ipsilateral carotid stenosis was responsible for 79% of TMVL symptoms and 57% for less specific complaints such as blurring or binocular scintillations. Occlusion of the carotid artery involves atheromatous plaque formation, ulceration, increased stenosis and thrombus formation, which results in hypoperfusion and ischemia.

In contrast, both irreversible and prolonged reversible ischemic neurologic deficits represent cerebrovascular accidents (CVAs) that last longer than 24 hours and may take weeks to many months to resolve. Interestingly, carotid TIAs have been associated with computed tomography (CT) confirmed CVA in 15% to 30% of patients, and up to 4% of patients are at risk for permanent blindness with the combination of both TMVL and hemispheric TIA (Lord). Aside from symptoms of vision loss, questions pertaining to the effects of postural changes or head maneuvering, which exacerbate hypoperfusion, are indicated and can help to corroborate the chief symptoms.

Clinically, approximately 20% of patients will describe the typical loss of vision as superior to inferior loss followed by a return of vision in a reverse pattern. So, from a clinical standpoint, in the absence of retinal emboli, hypoperfusion from carotid insufficiency or inflammation remain at large.

Derived from the Greek word embolus, meaning a wedge or stopper, an embolus is a piece of material that lodges in a blood vessel and blocks the flow of blood. In contrast to a thrombus, which is a localized disturbance, emboli originate from an external source and arise proximal to the vessel where they reside. The presence of retinal emboli elicits a plausible cause and investigation of carotid and cardiac sources. Most commonly, emboli found in the retinal circulation are often liberated from atheromas originating from the carotid artery and consist of both white platelet aggregates and cholesterol crystals.

Fisher was the first to describe and observe platelet-fibrin emboli in a patient with recurrent TIA found to have carotid occlusive disease. These emboli appeared as dull, gray-white plugs. Platelet emboli are variable in size, averaging 100 microns to 600 microns. Their size allows for distribution into the retinal artery branches where the diameter is about 250 microns. Unfortunately, diagnostic yield is low because they are too large to traverse the retinal capillaries, thereby lysing after initial impact. These emboli typically arise from the atheromas on large arteries or from the heart, most commonly from the valves. These structures have also been observed in patients with hypercoagulable disorders.

On the contrary, cholesterol plaques are much smaller and more durable, allowing them entry into retinal capillaries. According to Hollenhorst, these particular particles are described as bright, glistening structures with yellow or orange coloration. Fortunately, their elongated shapes do not always fully occlude the vessel, unlike platelet-fibrin emboli.

In the majority of cases, cholesterol emboli are asymptomatic and typically found incidentally during routine examination. While these plaques usually cause local retinal ischemia, there is little long-term evidence of ischemic damage. Hollenhorst concluded that these plaques were cholesterol in nature originating from ulcerating atheromas in the aorta or carotid arteries. According to Arruga, Sanders, Young and Miller, these refractile structures are globular or rectangular, with their appearance changing depending on the direction of light during ophthalmoscopy. Occasionally they appear as though they are located adjacent to the vessel wall. Patients in whom these emboli are seen have been noted to have increased risk of morbidity and mortality as compared to age- and sex-matched control population secondary to atherosclerosis, hypertension and stroke.

Lastly, calcific emboli, albeit much more uncommon, are capable of both retinal and cerebral ischemia and have been observed in patients with rheumatic heart disease, calcific aortic stenosis, calcification of the mitral valve annulus and other disorders of the heart and vessels that predispose them to calcium formation. Less common emboli include tumor emboli from cardiac myxoma and metastatic neoplasms, fat emboli from the fracture of long bones, septic emboli, talc emboli and miscellaneous emboli of depot drugs, silicone or air that occurs after injections in the region of the face or scalp.

Other arterial lesions that affect the carotid system include: external carotid stenosis, the persisting stump of an occluded internal carotid artery embolus, ulceration of the innominate artery or proximal aortic arch, congenital anomalies of the carotid system, moyamoya disease, drug-induced angiopathy, granulomatous angitis, cranial arteritis and other vasculitides.

GCA is a systemic necrotizing vasculitis characterized by inflammatory lesions of medium- and large-sized arteries with an average onset at 70 years of age, with a range of 50 to 90 years. GCA typically begins with slowly progressive systemic symptoms consisting of fatigue, anorexia, weight loss, jaw and neck claudication, temporal artery tenderness, headache, scalp sensitivity, nonspecific arthralgias and myalgias as well as cardiovascular, respiratory and neurologic manifestations.

The most common ocular symptom is vision loss. It may be transient or permanent, unilateral or bilateral and occur with a frequency of 10% to 60% (Miller and Newman). The majority of vision loss typically occurs over the course of a few days or hours before permanent vision loss sets in.

It is indistinguishable from that produced by carotid artery disease, as it is caused by transient ischemia of the retina, optic nerve, choroid or a combination of these structures. Thus, central or branch arterial occlusions, choroidal infarction or ischemic optic neuropathy may occur. However, given that the symptoms are typically identical to that of atheromatous-causing vision loss, differentiation is critical.

Patients with intermittent angle closure typically complain of eye pain and vision loss. Narrowing of the anterior chamber angle is evident on gonioscopy, and transient vision loss is variable. The condition may occur in one or both eyes and be associated with pupillary dilation, but rarely does it occur simultaneously. Gonioscopy will reveal narrow angles and, in some instances, provocative testing can clinch the diagnosis. A low threshold should be kept in these patients with unilateral eye pain and history of headache. Detailed inspection of the angle may save the patient much unnecessary neurologic testing and worry. It may be prudent to have patients return for examination during a “headache” attack.

Transient vision loss secondary to increased intracranial pressure typically occurs in young, obese females. The condition is usually bilateral, lasts for a few seconds to minutes, occurs in clusters throughout the day and can be exacerbated by changes in posture. It is postulated that increased intracranial pressure can cause episodic vision loss via compression of the optic nerve as it enters its sheath or via frank disc swelling causing compression of arteries secondary to optic disc crowding. This subset of patients may also complain of chronic headache, tinnitus and neck pain.

Not unlike those patients with increased intracranial pressure, patients with optic nerve sheath meningioma may experience brief episodes of vision loss. It is postulated that compression of the central retinal artery by the effect of the meningioma produces episodic vision loss. In some instances, vision loss is made worse when the eye is turned in a certain position of gaze. Patients with gaze-evoked vision loss usually have an orbital mass that interferes with the blood supply when the eye is turned in a particular direction. These cases typically occur during eccentric fixation. Each episode is characterized by the disappearance of vision followed by clear vision when the eye is returned to primary gaze.

Diagnostic work-up

While the diagnostic work-up in patients who present with TMVL can be complex, a thorough neuroophthalmic history and a comprehensive ophthalmologic examination drive subsequent testing. For diagnostic purposes, it is helpful to broadly categorize patients based on associated symptoms of TIA, GCA, demyelination, headache and age.

TMVL and associated TIA is an emergency. In addition to TMVL, these patients often present with symptoms of central nervous system dysregulation.

It is important to directly ask these questions and not rely on patient history because patients may not understand the importance of divulging such information. If there is any suspicion of the signs or symptoms listed in the accompanying table, the patient should be directed to the emergency room with written orders of the presumed diagnosis and for an immediate CT of the brain, orbit and neck.

Emergency room departments typically assess patients with CT imaging to rule out intracranial hemorrhage, orbital imaging to discount the rare retro-orbital process and neck imaging to evaluate for carotid artery dissection. In the absence of intracranial pathology, the patient will be referred to a neurologist for a comprehensive TIA work-up and a cardiologist for evaluation of cardiac and carotid systems. In these patients, a carotid lesion is found on the suspected side approximately 50% of the time, with the risk of CVA and myocardial infarction (MI) found to be 14% and 33%, respectively (Miller and Newman). In the presence of neuroimaging-confirmed acute hemorrhagic stroke, the patient will be evaluated by neurosurgery.

Patients who present with a history of TMVL and symptoms of GCA also require emergent evaluation.

These cases should be referred immediately to the emergency room with written orders for complete blood count (CBC) with differential and platelets, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). It is helpful to leave a reliable phone number, as the results of the testing may not be completed until after hours. In highly suspicious cases of GCA without frank optic neuropathy, a written prescription for systemic prednisone, 1 mg/kg, can be given to the patient.

The first results are likely to be the CBC and ESR, as the CRP is typically delayed. The combination of ESR/platelet levels and patient symptoms will drive the diagnosis and urgency of initiating treatment with prednisone; an average dose is 60 mg to 100 mg per day (Pacella et al.). It is important to have a complete list of the patient’s current medications and systemic history. Those with active peptic ulcer disease, diabetes, hypertension and bleeding disorders are at increased risk for complications with high doses of prednisone. In these cases, consultation with the primary physician is important. In addition, these patients usually benefit from a proton-pump inhibitor such as omeprazole 20 mg to 40 mg once daily or ranitidine 150 mg twice daily to reduce the risk of gastrointestinal disturbances.

Patients who begin systemic prednisone for GCA have 7 to 14 days to have a temporal artery biopsy. Those determined to have definitive GCA should be comanaged with a rheumatologist because systemic steroid treatment is typically continued for years. In patients who do not have definitive GCA but are considered high risk given their clinical symptoms, it may be prudent to begin treatment due to the risk of permanent vision loss and systemic morbidity. In addition, a rheumatology consult is advisable because up to 20% of cases of GCA are temporal artery biopsy negative (Chang et al.). In the presence of a negative biopsy or alternative diagnosis, the prednisone must be tapered over 1 to 2 weeks to prevent dysregulation the of steroid hormone synthesis pathway.

Patients with TMVL should also be questioned as to whether they have associated symptoms of demyelination.

Patients with co-existent symptoms will have a comprehensive dilated fundus exam along with visual field testing, color vision and red cap desaturation. These tests may provide evidence as to whether there have been previous episodes of optic neuropathy. Regardless, urgent referral for MRI of the brain and orbits with and without contrast and fat suppression is warranted.

After a thorough history, if it is concluded that the TMVL is associated with headache, it is important to determine frequency and duration of the headaches and whether there has been a previous diagnosis or positive family history. The most common cause of concomitant visual disturbance and headache is migraine.

These patients may report positive phenomenon, such as sparkling lights or fortification spectra, which start in the central field and slowly expand to the periphery over 20 to 30 minutes. Most cases are followed by headache and may be accompanied by photophobia, phonophobia, nausea or emesis. The challenge is when patients report TMVL with negative phenomenon (i.e., blur, gray-out and black-out) and headache. In these instances, the differential diagnosis is broad and may be more ominous.

After a thorough history, if it is concluded that TMVL is isolated, the next step is to consider the age of the patient. A young patient who presents with isolated TMVL must undergo thorough neuroophthalmic questioning related to systemic symptoms. If the vision loss is truly isolated, the likely mechanism is presumed vasospasm.

Tippin and colleagues found isolated TMVL in patients younger than 50 to be benign. According to Slavin, most neuro-ophthalmologists would also determine this to be benign and not require ancillary testing. Patients with more than one episode, or those who return for evaluation due to repeated episodes, should be re-evaluated. In these cases, it may be prudent to evaluate for structural anomalies of the carotid and cardiac systems and to search for hyperviscosity and coagulopathy syndromes.

Hypercoagulable syndromes, including the antiphospholipid antibody syndrome, have been associated in patients with systemic lupus erythematosus and retinal infarction in young patients. Urgent referral to their primary physician with written orders for CBC with differential and platelets, ESR, prothrombin time (PT), partial thromboplastin time (PTT), urinalysis to evaluate for proteinuria as well as coagulopathy, hyperviscosity and vasculitis panels is recommended. Depending on the outcome of these tests, a cardiology exam should be performed. While the yield is typically low, carotid occlusive disease or cardiac defects present a risk for stroke and death and, if found, may be easily treated.

An elderly patient with isolated TMVL requires an evaluation similar to that for TIA or CVA. After a fundus examination, the patient should be referred urgently for a cardiac examination to search for a source of emboli or underlying cardiac disease. Additionally, blood tests should be ordered urgently and include: CBC with differential and platelets, ESR, serum cholesterol and urinalysis to evaluate for proteinuria.

The next step is to evaluate the carotid and cardiac system with ultrasound, electrocardiography (EKG) and echocardiography (echo). According to Gaul and colleagues, patients with symptoms of TMVL and bilateral loss had about a 79% incidence of ipsilateral carotid plaques, as compared with those with unilateral blurred vision and bilateral scintillations.

Electrocardiography measures the heart’s electrical impulses and translates them to line tracings. It is a good first test and can show if there is an irregularity that is associated with heart disease. However, it is not accurate in evaluating the pumping ability of the heart.

On the contrary, echo often uses ultrasound waves or Doppler techniques to produce two-dimensional or three-dimensional images. Unlike EKG, echo shows the internal structure and perfusion of blood. It measures the size and shape of the heart, how well the valves are functioning, how the left and right side communicate, and the velocity of the blood leaving the heart. It is used to diagnose coronary artery disease and heart valve disorders, as well as enlargement or thickening of the heart muscle.

Next, an urgent referral to a neurologist for MRI/CT with or without associated angiogram should be obtained. Interestingly, carotid angiography, the gold standard of neurovascular imaging, is normal in approximately one-third of patients with amaurosis fugax. Albeit, those patients with high-grade stenosis, ranging from 70% to 90%, are typically referred for carotid endarterectomy (Miller and Newman). However, there are times when no causative agent is elicited. In these cases, presumed retinal vasospasm has been postulated and demonstrated angiographically.

Disclosure: DelGiodice has no relevant financial disclosures.