After ocular and orbital causes of TMVL have been ruled out, vascular causes must be considered. The term “amaurosis fugax” refers specifically to a retinal transient ischemic attack (RTIA). Retinal arterial ischemia, whether transient or permanent, is a form of anterior circulation ischemic stroke caused by decreased blood flow in the ophthalmic branches of the internal carotid artery.
Vascular TMVL is a well-known prodromal syndrome of cerebral infarction. Vascular causes of TMVL are most often related to retinal emboli. However, TMVL may also result from optic nerve ischemia in patients with GCA or diffuse ocular hypoperfusion in patients with severe carotid artery disease, or it may precede central retinal vein occlusion. Retinal emboli typically result in acute, painless visual loss in 1 eye, which is often described as a descending (or ascending) curtain over part or all of the visual field. The visual loss usually resolves over a few minutes. The examiner should conduct a careful interview and neurologic examination in order to look for contralateral neurologic symptoms and signs such as weakness and aphasia. Results of the ocular examination are often normal, although abnormalities of the retinal vasculature can occasionally be seen.
Figure 5-1 shows the 3 most common types of emboli: cholesterol (Hollenhorst plaque), platelet-fibrin, and calcium. The characteristics of these emboli are reviewed in Table 5-2. Other less common varieties of emboli include those resulting from cardiac tumors (myxoma), fat (long-bone fractures, pancreatitis), sepsis, talc, air, silicone, and depot drugs (corticosteroids).
Atheroma formation occurs most commonly at the bifurcation of the common carotid artery into the internal and external carotid arteries and in the carotid siphon (Fig 5-2). Atheroma can remain stationary, become fibrotic, ulcerate, narrow and occlude the lumen, or release emboli. The internal carotid lumen must be reduced by 50%–90% before distal flow is affected, but emboli may occur on ulcerated atheromatous plaques with any degree of stenosis. Emboli from aortic arch atheroma are also common. Treatable risk factors include hypertension, diabetes mellitus, hypercholesterolemia, and smoking. In younger patients with TMVL and periorbital pain or headache, a carotid dissection should be considered.
Figure 5-1 Common retinal emboli. A, Cholesterol embolus (Hollenhorst plaque) at the bifurcation of a retinal arteriole. B, Platelet-fibrin embolus. C, Calcific embolus with branch retinal artery occlusion.
(Courtesy of Karl C. Golnik, MD.)
Table 5-2 Clinical Aspects of Common Retinal Emboli
Cardiac emboli can arise from many causes, including cardiac arrhythmia, particularly atrial fibrillation, ventricular aneurysms, hypokinetic wall segments, endocarditis (infectious [associated with bacterial endocarditis] and noninfectious [marantic]), and valvular heart disease (including atrial myxoma).
Clinical and laboratory evaluation
If an embolic cause of TMVL is suspected in a patient, a complete vascular and cardiac evaluation is urgently required; such patients have increased rates of morbidity and mortality from stroke, myocardial infarction, aortic aneurysm, and other related vascular events (see the following sections). Clinical examination should include assessment of the patient’s pulse (in particular examining for atrial fibrillation), blood pressure, cardiac auscultation, and carotid artery auscultation (best done at the angle of the jaw, where the bifurcation is located). A carotid bruit indicates turbulent flow within the vessel, and it may be heard with narrowing of the external or internal carotid artery. However, a bruit will be absent if flow is undisturbed or if carotid occlusion is complete.
Figure 5-2 Magnetic resonance angiogram shows high-grade stenosis (arrow) of the cervical internal carotid artery at the bifurcation.
(Courtesy of Aki Kawasaki, MD.)
Once GCA is ruled out (in patients older than 50 years), an immediate workup for a source of emboli must be initiated. Because RTIA may herald a devastating cerebral stroke, all patients with acute vascular TMVL should undergo a thorough vascular workup at once. It is best to immediately refer these patients to the nearest emergency department (preferably one affiliated with a stroke center). Sending a patient away for outpatient workup or to a primary care physician delays appropriate management.
It is important to obtain noninvasive vascular imaging of patients with TMVL urgently. The carotid arteries (in patients with TMVL), the vertebral arteries (in patients with binocular visual loss), and the aortic arch can reliably be evaluated by carotid ultrasonography (duplex scanning), magnetic resonance angiography (MRA), or computed tomographic arteriography (CTA). Ultrasonography, while it is a sensitive method of detecting cervical ulcerated plaques, has varying reliability. MRA and CTA results enable the visualization and characterization of the plaque in question, as well as of the surrounding arterial wall; they are also extremely useful for detecting internal carotid artery dissection.
Brain imaging performed to search for associated cerebral ischemia (ideally brain magnetic resonance imaging [MRI] with diffusion-weighted imaging [DWI]), should be obtained at the same time as the other tests for all patients with acute retinal ischemia, even those with TMVL. Results of studies have shown that up to 1 of every 4 patients with acute retinal ischemia has acute brain infarctions on DWI (often silent infarctions in patients who are neurologic asymptomatic). The probability of an abnormal MRI is higher in patients with embolic retinal ischemia (compared with patients with nonembolic retinal ischemia) and in patients with permanent visual loss (compared with patients with TVL). According to the 2013 guidelines from the American Heart Association (AHA), if the brain MRI shows acute cerebral ischemia, even if the patient is neurologically asymptomatic, the patient should be admitted to the hospital for a stroke and managed accordingly.
Echocardiography is useful for detecting valvular and cardiac wall defects, intracardiac tumors, and large thrombi. Transesophageal echocardiography, which is more sensitive than conventional transthoracic echocardiography, also allows evaluation of the aortic arch. A normal-appearing echocardiogram does not exclude the possibility of emboli because very small particles are not revealed. Prolonged inpatient cardiac monitoring or ambulatory Holter monitoring may document previously undetected cardiac arrhythmias. Suspected endocarditis should prompt blood culture testing.
If a cardiac or carotid source of embolism formation is not found, other systemic processes that could contribute to the stroke need to be considered. Major risk factors include advanced age, hypertension, ischemic heart disease, diabetes mellitus, hypercholesterolemia, smoking, and sleep apnea. Most of these conditions are treatable. Laboratory studies should be obtained to evaluate for these conditions and any others under clinical suspicion such as hypercoagulable states, collagen vascular diseases, vasculitis, or syphilis, depending on the presenting signs and symptoms of the patient.
Biousse V. Acute retinal arterial ischemia: an emergency often ignored. Am J Ophthalmol. 2014;157(6):1119–1121.
Biousse V, Trobe JD. Transient monocular visual loss. Am J Ophthalmol. 2005;140(4):717–721.
Jauch EC, Saver JL, Adams HP Jr, et al; American Heart Association; American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Interdisciplinary Council on Peripheral Vascular Disease. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870–947.
Prognosis and treatment
Among patients with TMVL, significant carotid artery stenosis or occlusion is present in 53%–83% of cases. RTIA is a well-known prodromal syndrome of ischemic cerebral stroke; indeed, a transient ischemic attack (TIA) is a medical emergency associated with a high risk of early ischemic stroke and other cardiovascular events. Among patients with TIA (RTIA or hemispheric TIA [HTIA]), 10%–15% have a stroke within 90 days, with approximately half occurring within 48 hours. Individuals with TIA who survive the initial high-risk period have a 10-year stroke risk of approximately 19% and a combined 10-year risk of stroke, myocardial infarction, and vascular death of 43% (or approximately 4% per year). These statistics demonstrate the need for the urgent referral of patients with all types of TIA to an emergency department for expert evaluation and immediate treatment. As mentioned earlier, the most recent international guidelines from the AHA recommend that all patients with presumed retinal ischemia (whether transient or permanent) undergo urgent brain imaging and etiologic testing similar to patients with acute cerebral ischemia. According to these guidelines, an acute stroke is diagnosed in patients with abnormal DWI (these patients are then admitted to the hospital and managed accordingly), regardless of the patients’ initial clinical presentation, whereas patients with normal MRI results usually are evaluated within 24 hours in a stroke clinic or an emergency department observation unit affiliated with a stroke center. Although the risk of stroke after an RTIA related to carotid atherosclerosis is lower than that after an HTIA, RTIAs must be managed similarly to HTIAs.
Several factors have been used to stratify the stroke risk in patients with RTIA, including male sex, age 75 years or older, previous history of HTIA or cerebral stroke, intermittent leg claudication, stenosis of 80%–94%, and absence of collateral vessels on cerebral angiography. Patients with none or only 1 of these risk factors have a 3-year ipsilateral stroke risk of 1.8%. However, for patients with 2 risk factors, the stroke risk is 12.3%, and for patients with 3 or more risk factors, the stroke risk increases to 24.2%. Thus, surgical management of carotid atheromatous stenosis (eg, carotid endarterectomy) may be more beneficial for those patients who have RTIA and 3 or more of these risk factors.
Medical treatment of RTIA due to carotid artery stenosis begins with antiplatelet agents (aspirin, aspirin-dipyridamole, or clopidogrel). Treating the vascular risk factors and employing other secondary prevention measures (eg, carotid endarterectomy, treating arrhythmia, treating cardiac sources of emboli) is essential; treatment should be initiated as soon as possible by a stroke neurologist.
Benavente O, Eliasziw M, Streifler JY, Fox AJ, Barnett HJ, Meldrum H; North American Symptomatic Carotid Endarterectomy Trial Collaborators. Prognosis after transient monocular blindness associated with carotid-artery stenosis. N Engl J Med. 2001;345(15): 1084–1090.
Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/ American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke. 2009;40(6):2276–2293.
Helenius J, Arsava EM, Goldstein JN, et al. Concurrent acute brain infarcts in patients with monocular visual loss. Ann Neurol. 2012;72(2):286–293.
Lauda F, Neugebauer H, Reiber L, Jüttler E. Acute silent brain infarction in monocular visual loss of ischemic origin. Cerebrovasc Dis. 2015;40(3–4):151–156.
Lee J, Kim SW, Lee SC, Kwon OW, Kim YD, Byeon SH. Co-occurrence of acute retinal artery occlusion and acute ischemic stroke: diffusion-weighted magnetic resonance imaging study. Am J Ophthalmol. 2014;157(6):1231–1238.
Additional systemic causes
Other possible systemic causes of vascular TMVL are ophthalmic artery disease, vasculitis (including GCA), hyperviscosity syndrome, antiphospholipid antibody syndrome, and central retinal artery vasospasm.
TMVL in older patients (usually older than 50 years) can be caused by GCA and may signal impending acute and permanent visual loss in 1 or both eyes. Therefore, a directed history of older patients with monocular or binocular TVL should include inquiries about the following symptoms:
proximal joint pain
However, systemic symptoms of GCA are absent in up to 20% of patients with visual symptoms (so-called “occult GCA”). Erythrocyte sedimentation rate, C-reactive protein concentration, and platelet count should be assessed in all patients aged 50 years or more who present with TVL (see Chapter 14). If GCA is the suspected cause of TVL, immediate treatment with high-dose corticosteroids is the only way to prevent progression to permanent visual loss.
Hayreh SS, Podhajsky PA, Zimmerman B. Occult giant cell arteritis: ocular manifestations. Am J Ophthalmol. 1998;125(4):521–526.
Ocular hypoperfusion may lead to TMVL in 3 classic scenarios:
Central retinal vein occlusion (CRVO). Patients with CRVO may report TVL that lasts seconds to minutes, with full recovery to normal vision afterward. Such symptoms may predate more lasting visual loss by days or weeks, or the symptoms may cease when collateral vessels develop.
Change in posture from a sitting to a standing position. In these patients, the TMVL is usually related to severe stenosis of the great vessels, or GCA. The patient may note progressive restriction of vision from the periphery (“diaphragm pattern”) that lasts from seconds to 1–2 minutes.
Ocular ischemic syndrome (OIS). This syndrome is characterized in part by a hypotensive, ischemic retinopathy with low retinal artery pressure, poor perfusion, midperipheral dot-and-blot retinal hemorrhages, and dilated (nontortuous) veins (venous stasis retinopathy). Recurrent orbital pain that improves when the patient lies down is highly suggestive of carotid occlusive disease. In the early stages, patients may experience transient or persistent blurred vision or TMVL on exposure to bright light. Severe ocular ischemia causes anterior segment changes that may be confused with chronic intraocular inflammation. The patient may have decreased vision; a red, painful eye with episcleral vascular injection; and aqueous flare (ischemic uveitis). Even though neovascularization of the chamber angle and iris is common, IOP may be low, normal, or high. In this instance, low or normal IOP is the result of impaired ciliary body perfusion. Fundus changes may include dilated retinal veins, narrowed retinal arteries with microaneurysms, midperipheral dot-and-blot hemorrhages, and macular edema (Fig 5-3). Treatment of OIS is challenging and includes ocular reperfusion (via carotid endarterectomy, or carotid stenting when possible), IOP-lowering drugs, and treatment for neovascularization, including panretinal photocoagulation. If the preoperative IOP is low, restoration of blood flow may precipitate dangerously high IOP. Once the patient incurs signs of chronic hypoperfusion, however, improvement is unlikely. In other patients, carotid occlusion may be too advanced for surgical correction. Early detection is crucial because neovascularization and progressive ocular ischemia result from prolonged hypoperfusion (see also BCSC Section 12, Retina and Vitreous).
Mendrinos E, Machinis TG, Pournaras CJ. Ocular ischemic syndrome. Surv Ophthalmol. 2010;55(1):2–34.
Figure 5-3 Ocular ischemic syndrome. A, Fundus demonstrates retinal venous dilation and scattered hemorrhages. B, Midperipheral dot-and-blot hemorrhages.
(Reprinted with permission from John E. Carter, MD. From Carter JE. Panretinal photocoagulation for progressive ocular neovascularization secondary to occlusion of the common carotid artery. Ann Ophthalmol. 1984;16(6):572–576.)
Vasospasm, hyperviscosity, and hypercoagulability
TMVL can result from vasospasm of the retinal artery. Patients are generally young and experience stereotypic episodes of painless severe TMVL. The vision returns to normal in between episodes, and the prognosis is usually good. The ocular examination findings are usually normal, but occasionally, when the patient is seen during the episode of visual loss, funduscopic examination reveals constriction of the retinal arteries. The diagnosis of vasospastic TMVL is one of exclusion. Before a diagnosis of vasospastic TMVL is made, the workup should rule out all causes of embolic retinal TIA. If the patient is older than 50 years, tests for erythrocyte sedimentation rate and C-reactive protein concentration should be obtained to rule out GCA. Particularly in younger patients, hyperviscosity syndrome and hypercoagulable states (eg, antiphospholipid syndrome, thrombocytosis, or other thrombophilia disorders) should be considered.
Hyperviscosity is a rare cause of TVL. Approximately 10% of patients with polycythemia vera report episodes of TMVL.
Winterkorn JMS, Burde RM. Vasospasm—not migraine—in the anterior visual pathway. Ophthalmol Clin North Am. 1996;9:393–405.
Excerpted from BCSC 2020-2021 series: Section 5 - Neuro-Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.