Preretinal Causes

Patients with preretinal causes of transient visual disturbances may be recognized by their longstanding, vague, and often innocuous visual complaints. The term transient visual blurring may be more accurate for these patients, because they have mild visual changes and complain of episodic blurry, hazy, distorted, or foggy vision. These characteristics distinguish the typically benign preretinal causes from serious causes more typically associated with frank visual loss. Typically these patients are concerned by a reduced quality to their vision with a superimposed, momentary worsening or change that causes their vision to vary during the course of the day. They often have difficulty determining which eye is having the problem. Patients may report problems under one specific set of circumstances, such as when reading small print or seeing words on the television or computer screen. Patients may describe transient monocular diplopia or image ghosting. They rarely describe a discrete visual field defect. Other neurologic complaints or new headaches are absent.

Retinal-Vascular Causes

Sudden, transient, monocular central or peripheral vision loss with full or partial recovery would be more consistent with a retinal-vascular cause. Patients tend to be more definitive in their description of the visual loss with regard to the onset of symptoms, the number of episodes, and their duration. Altitudinal (“shade coming down”) or lateralized transient monocular visual loss is highly suggestive of this category. Pain, headache, scalp tenderness, jaw claudication, accompanying neurologic signs or symptoms, or the presence of cerebrovascular risk factors are additional historic features that suggest an ischemic (embolic, thrombotic, or vasculitic) cause of retinal vascular insufficiency.

Etiologies Related to Optic Nerve Dysfunction

A patient with a history of optic neuritis might complain of transient visual loss with a rise in body temperature (Uhthoff’s phenomenon). Vision loss with eye movements is consistent with gaze-evoked amaurosis and suggests transient optic nerve compression by an underlying orbital mass. Patients with papilledema and pseudopapilledema may have transient visual obscurations that are typically elicited by changes in posture, such as standing up, or rapidly changing head position.

Migraine

Migrainous transient visual loss is suggested by accompanying symptoms of headache, nausea, or vomiting and may be monocular or binocular. Previous migraines, a history of affected family members, or accompanying positive phenomena such as scintillations, prisms, or colored lights also support the diagnosis of migrainous visual loss. When numerous, recurrent, unexplained episodes of visual loss occur, particularly in a young person, a migrainous cause should be considered.

Cerebral Causes

Transient visual field loss that is binocular, particularly if homonymous and hemianopic, might be caused by cerebral ischemia, although hemianopic visual loss is more commonly caused by migraine. A history of seizures, loss of consciousness, or abnormal motor activity would suggest ictal or postictal visual loss.

Ocular Surface Abnormalities

Tear film or corneal abnormalities are probably the most common preretinal causes of transient visual blurring. Patients with tear film abnormalities typically describe a pattern in which their visual complaints occur for hours many times per week, often at the end of the day, and sometimes during one particular activity. For instance, symptoms may occur in the afternoon at work, in the evening when sitting down to read, or after a walk on a windy day. These patients often note excessive tearing. Repeat blinking or lubrication of the eyes in this setting will often improve the vision. Slit-lamp examination may show abnormal tear film break up, blepharitis, or corneal and conjunctival fluorescein staining. Patients with blepharitis may be more symptomatic in the morning due to increased accumulation of abnormal meibomian gland secretions overnight. Good eyelid hygiene and eyelid scrubs usually lead to prompt improvement. If corneal epithelial breakdown due to excessive dryness or a tear film abnormality is present, there may be associated foreign body sensation, pain, or redness. Those with dry eyes will frequently have an abnormal Schirmer’s test (see Chapter 2 ).

In addition, patients with corneal endothelial dysfunction can develop blurred vision from corneal epithelial and stromal edema. These episodes often last for hours and occur most commonly in the morning. The diagnosis can be made by examining patients during symptomatic periods. The presence of corneal endothelial guttata usually suggests this diagnosis.

Other Ocular Causes

Subacute transient attacks of narrow-angle glaucoma may cause episodes of transient visual blurring accompanied by halos or eye pain. During asymptomatic periods the intraocular pressure may be normal. Gonioscopy may reveal shallow or occluded anterior chamber angles. Rarely, spontaneous recurrent anterior chamber hemorrhages (hyphema) may also cause episodic visual blurring. Such recurrent hemorrhages can occur in patients with juvenile xanthogranuloma, those with a uveitis–glaucoma–hyphema syndrome due to a malpositioned intraocular lens with iris contact, and patients with iris neovascularization.

Osmotic changes in the lens can occur with widely fluctuating blood glucose levels, such as in patients with diabetes or those taking corticosteroids. This blurring is associated with a change in refractive error, for instance an increase in myopia with hyperglycemia, without visible lens alterations. Pinholes usually improve the visual acuity in these cases. Vitreous abnormalities, particularly acute posterior vitreous detachments and opacities associated with uveitis, can also cause transient visual blurring. Posterior opacities can move or float over the macula and alter visual acuity, but some patients report a more fixed opacity that blurs vision.

Patients with age related macular degeneration, retinal degenerations and diabetic retinopathy may note transient loss of vision with exposure to bright light due to prolonged photostress recovery time (see Chapter 2 ).

Carotid Disease

Extracranial internal carotid artery stenosis or occlusion is a common cause of retinal-vascular transient visual loss. In this setting, transient visual loss is more often labeled as transient monocular blindness, amaurosis fugax, or a retinal transient ischemic attack (TIA). The origin of the internal carotid artery at the bifurcation may be narrowed by atherosclerotic plaque formation ( Fig. 10.2 ) and related mural thrombi, plaque ulceration, and intraplaque hemorrhage. More recent evidence points to carotid plaque morphology rather than extent of stenoses alone as being responsible for transient or permanent retinal vascular events. In one study over 40% of patients with central retinal artery occlusion (CRAO), a plaque was found in the distal internal carotid artery closer to the origin of the ophthalmic artery as opposed to the carotid bulb.

Right common carotid artery angiogram in a patient with amaurosis fugax and carotid artery stenosis. A . Magnified view of the right common carotid artery injection demonstrating filling defects within the common carotid ( lower arrow ), internal carotid ( upper arrow ), and external carotid arteries ( thin arrow ). These filling defects represent extensive clots within the carotid circulation. B . Oblique view showing the high-grade stenosis of the internal carotid artery ( arrow ) with the filling defect from the clot above. The small caliber of the cervical portion of the right internal carotid artery extending superiorly should be noted.

(From Balcer LJ, Galetta SL, Yousem DM, et al. Pupil-involving third nerve palsy and carotid stenosis: rapid recovery following endarterectomy. Ann Neurol 1997;41:273–276, with permission.)

Nonatherosclerotic causes of carotid disease include carotid dissection (see Chapter 13 ), fibromuscular dysplasia, Takayasu arteritis, carotid trauma, and radiation arteritis. Carotid-related amaurosis fugax can be due to emboli from an atherosclerotic proximal internal carotid artery segment to the retinal artery circulation. Alternatively the etiology could be nonembolic from retinal hypoperfusion due to occlusive carotid disease, particularly when the collateral circulation to the eye is also compromised.

The risk of stroke from carotid-related amaurosis fugax (2% annually) is less than half of that associated with hemispheric TIAs (5–8% annually). It is unclear why transient monocular visual loss has a decreased stroke risk compared with hemispheric TIAs. Possible explanations include vasospasm or disturbance of orbital venous circulation, smaller-sized emboli passing into the ophthalmic circulation preferentially, or increased retinal vulnerability to reduced flow (highly energy dependent), making patients more likely to be symptomatic and to present before a hemispheric event occurs. However, two other studies have reported that retinal ischemia, whether transient or permanent, carries the same overall poor prognosis as cerebral ischemia, with over a quarter of patients in both studies having imaging evidence of acute brain infarctions. Further details are discussed in Chapter 4 .

Symptoms. The characteristics of monocular embolic retinal-vascular visual loss are summarized in Box 10.3 . Typically acute in onset, it is often described as a shade or curtain that obscures vision in one eye. Visual loss may be altitudinal, peripheral, central, or even vertical. A nasal visual field defect may suggest an embolic mechanism because of the tendency of these particles to lodge in the temporal retinal circulation. Most episodes last 5 minutes or less. Rarely, associated scintillating scotomas or tiny bright lights may be experienced. Pain is uncommon, and its presence should raise the possibility of temporal arteritis (see later discussion).

Rarely, patients may complain of transient monocular blindness after exposure to sunlight or even after viewing a white wall. Bright-light–induced amaurosis fugax in patients with carotid occlusive disease is well recognized. Presumably, impaired blood flow to the outer retinal segments compromises the regeneration of retinal pigments required for visual perception.

In patients with carotid stenosis, ipsilateral eye symptoms may be accompanied by those of ipsilateral cerebral ischemia. These include contralateral hemiparesis, sensory loss, or even hemianopia. Ischemia of the dominant hemisphere may cause language deficits.

Other history . Screening for atherosclerotic risk factors such as hypertension, smoking, diabetes, peripheral vascular disease, and cardiac arrhythmias should be performed. In addition, symptoms suggestive of temporal (giant cell) arteritis (see later discussion) should be excluded.

Neuro-ophthalmic signs . Retinal emboli are the most common associated finding in embolic retinal-vascular disease, and there are two main types seen in carotid disease: (1) cholesterol (Hollenhorst plaques), which have a refractile, metallic gold appearance and are typically a sign of carotid disease; and (2) platelet–fibrin emboli, which are creamy white–gray longitudinal intravascular opacifications that fill the entire lumen. Platelet–fibrin emboli are likely a result of either carotid thrombosis or thrombosis associated with recent myocardial infarction. Retinal emboli and their clinical characteristics and implications are discussed in more detail in Chapter 4 .

Severe carotid disease may produce hypoperfusion of the globe and chronic ocular ischemia, which is associated with anterior- and posterior-segment ocular abnormalities. Anterior-segment ischemia may lead to episcleral and conjunctival injection. Corneal edema may obscure vision, while cells and flare in the anterior chamber may be mistaken for an inflammatory process. If new iris vessels form, neovascular glaucoma may ensue. In the retina, a venous stasis retinopathy characterized by microaneurysms and midperipheral dot and blot hemorrhages may be evident ( Fig. 10.3 ). The retinal abnormalities are similar to those seen in diabetic retinopathy and retinal vein occlusion, except they are located in the midperiphery instead of the posterior pole and they tend to be unilateral, corresponding to the side of the more obstructed carotid artery. Optic nerve head swelling is typically not seen until the very late stages of posterior segment ischemia. When vision is severely affected, the visual prognosis is poor.

Midperipheral venous stasis retinopathy in a patient with ocular ischemic syndrome due to ipsilateral 95% carotid artery stenosis.

(Courtesy of Dr. Albert Maguire.)

Rarely, signs of orbital ischemia may be caused by severe carotid disease, with proptosis, chemosis, conjunctival injection, ophthalmoparesis, and retinal ischemia heralding its onset. Orbital ischemia and infarction are uncommon because of the rich anastomoses between the ophthalmic and external carotid arteries.

Other neuro-ophthalmic findings associated with carotid disease include central and branch retinal artery occlusions (see Chapter 4 ) and Horner syndrome (see Chapter 13 ). Fluorescein angiography can be used to document delayed ocular perfusion with prolonged arm–to–retinal circulation times. Ophthalmoplegia due to ischemia of the extraocular muscles or ocular motor nerves has been reported following carotid occlusion and dissection. These motility disturbances do not occur in isolation, as patients typically have severe unilateral visual loss and hemispheric signs of varying degrees. Although anterior ischemic optic neuropathy (AION) has also been described in association with carotid disease, a causative relationship is unlikely, because AION is more likely the result of decreased blood flow in the small vessel posterior ciliary arteries rather than either artery-to-artery emboli or a low-flow state resulting from large vessel occlusive disease.

General examination . Often patients are seen after the episode of transient visual loss, and the examination during the asymptomatic phase may be normal. The presence or absence of a carotid bruit cannot be used to diagnose significant carotid stenosis or predict a carotid source of emboli.

Diagnostic tests . The laboratory evaluation of a patient with suspected ischemic monocular visual loss begins with noninvasive assessment of the carotid artery using either ultrasound, magnetic resonance angiography (MRA), or computed tomography angiography (CTA). Carotid ultrasound and Doppler ( Fig. 10.4 ) are effective screening tools for identifying and estimating the degree of internal carotid artery stenosis. When atherosclerotic plaques are present, B-mode ultrasound can often provide morphologic details. Hypoechoic plaques, plaque neovascularization, and intraplaque hemorrhage are markers of high-risk carotid lesions. Doppler waveforms allow analysis of blood flow velocity. Because of technical limitations, one major drawback is the technique’s relative inability to differentiate between 99% stenosis and total occlusion. Sometimes the occlusion is complete, and the source is presumed to be a stump embolus.

Carotid ultrasound and Doppler in the evaluation of carotid disease. A . Normal carotid ultrasound ( upper left ) and corresponding color Doppler ( upper right ) and Doppler velocity waveforms ( bottom ). B . Ultrasound and color Doppler demonstrating internal carotid narrowing due to plaque ( asterisk ) and turbulent flow ( large arrow ) distal to the stenosis. CCA, Common carotid artery; ECA, external carotid artery; ICA, internal carotid artery.

(Courtesy of Maria Stierheim, RVT.)

High-resolution MRA, either with time-of-flight or contrast-enhanced methods, is another effective noninvasive method for assessing the carotid artery plaque morphology. The results are generally reported within a range—mild (0–30% occluded), moderate (30–70% occluded), and severe (70–99% occluded)—along with a description of the carotid plaque. MRA in particular is best at identifying ulcerative areas with stenotic plaques. Unlike carotid ultrasound, MRA also provides a view of the intracranial circulation. MRA has a role in identifying the degree of carotid stenosis, although it tends to overestimate it. However, a normal MRA ( Fig. 10.5 ) is very helpful, because it makes any clinically important carotid disease very unlikely. CTA ( Fig. 10.6 ) is a suitable alternative screening test, particularly for individuals who are unable to undergo magnetic resonance imaging (MRI), and it may be used to confirm the MRA or carotid ultrasound findings.

Normal contrast-enhanced magnetic resonance angiogram of the neck, demonstrating the right carotid artery, in a patient with monocular transient visual loss.

Computed tomography angiogram of the neck, contrast enhanced, demonstrating an approximately 60% narrowing of the right internal carotid artery ( large arrow ). Hyperdense calcium is seen ( small arrow ).

Conventional angiography still remains the most accurate method for evaluating and quantifying carotid stenoses (see Fig. 10.2 ). The specificity and sensitivity of angiography exceed those of any noninvasive test. Disadvantages of angiography include potential allergy to intravenous contrast and risk of stroke (1.2%) and renal failure. Many surgeons prefer formal angiography before endarterectomy, although some may operate on stenotic arteries when the ultrasound, CTA, or MRA examinations are in agreement.

Other studies for the evaluation of retinal ischemia include a complete blood count and cholesterol, triglyceride, and serum glucose levels. An erythrocyte sedimentation rate and C-reactive protein should be obtained when giant cell arteritis (see later discussion) is a suspected cause of the amaurosis. A cardiac source embolus should be excluded (see later discussion). In select patients, neuroimaging of the head to look for evidence of emboli to the brain may be obtained.

In many elderly patients with suspected retinal ischemia the workup outlined previously is unrevealing. In this setting cardiac sources of embolism, including valvular lesions as well as atheroma arising from the more proximal vessels such as the aorta, should be ruled out. A prospective study found cardiac embolism to occur in 8.7% of patients presenting with amaurosis. After a negative workup, other etiologies such as acephalgic migraine can be considered. In younger patients vasospasm and hypercoagulable states, due to abnormal antiphospholipid antibodies or protein C, protein S, or antithrombin III levels, need to be excluded.

Treatment (medical) . If not contraindicated, antiplatelet therapy with aspirin (81 or 325 mg) should be started for all patients with amaurosis fugax to reduce the risk of stroke. If episodes are recurrent, then larger doses of aspirin (doses may vary between 40 and 1300 mg), clopidogrel (75 mg p.o. q.d.), aspirin in combination with dipyridamole, and warfarin can be considered as alternatives in patients without surgical carotid disease (see the next section). If crescendo TIAs are present or suspected, then heparinization and an inpatient workup and treatment should be considered. Medical treatment or stenting (see the next section) are alternatives in patients with moderate to high-grade stenosis in which medical problems prohibit endarterectomy.

Other treatments include statins, which have been shown to be beneficial in the prevention of cardiovascular events including stroke, irrespective of the presence or absence of hypercholesterolemia. Control of hypertension, tight glycemic control in those with diabetes, smoking cessation, and weight loss are other medical strategies that can reduce future stroke risk.

Treatment (surgical) . Traditionally symptomatic carotid artery stenoses of more than 70% has been treated by performing carotid endarterectomy (CE) to prevent future strokes. In 2008 updated guidelines on the management of carotid disease were proposed ( Box 10.4 ). Both the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) demonstrated the benefit of CE vs medical management in persons with >70% stenosis (2-year stroke risk, 9% vs 26% NASCET and 6.8% vs 20.6% ECST) and mild to moderate benefit in patients with 50–69% stenosis (5-year stroke risk, 15.7% vs 22.2% NASCET).

Surgery is usually recommended within 14 days of symptom onset to reduce the risk of stroke due to the possible unstable nature of the atheromatous plaque. The plaque subsequently acquires a thrombotic cap, which stabilizes and is subsequently less prone to embolization.

The perioperative complication rate for major stroke and death was 2.1% in the NASCET study, emphasizing the importance of the skills of the angiographer, anesthetist, and vascular surgeon or neurosurgeon for patients requiring CE.

The optimal management of asymptomatic carotid stenoses remains controversial. Given the 5% incidence of periprocedural stroke associated with CE and stenting, the current guidelines favor best medical therapy alone, which includes lifestyle modification (smoking cessation, exercise, weight loss, blood pressure control, and high-dose statin therapy). Endarterectomy can be offered to male patients younger than 75 years of age with >70% stenoses and restricted to asymptomatic women with >70% stenosis who are otherwise healthy.

Percutaneous transluminal angioplasty and stenting of the internal carotid artery have been proposed as possible alternatives to CE to prevent stroke in patients with cardiac and medical conditions for whom surgery would be risky. Multiple studies, however, have failed to show that these noninvasive procedures are superior to CE.

Additionally, in eyes with ocular ischemia, the intraocular pressure should be lowered if high. CE can be performed in surgical candidates with high-grade stenosis. Extracranial–intracranial arterial bypass and external CE have been occasionally performed with anecdotal success. Panretinal photocoagulation to prevent iris neovascularization is controversial, but most authors favor it. Occasionally the signs of ocular ischemia will spontaneously regress without specific therapy.

Cardiac Emboli

Less commonly, cardiac emboli, due to atrial fibrillation, valvular disease, atrial myxomas, and mitral valve prolapse, for instance, can reach the retinal circulation. The appearance of retinal emboli is discussed Chapter 4 . A careful cardiac examination should be directed at detection of an irregular pulse suggestive of atrial fibrillation or a murmur consistent with significant cardiac valvular disease. Cardiac evaluation, including electrocardiography, 24-hour cardiac monitoring, and transthoracic echocardiography (TTE), is also suggested. If the TTE is unrevealing but a cardiac source embolus is still highly suspected, transesophageal echocardiography (TEE) may be useful in certain patients with unexplained ocular ischemia. TEE is more helpful than TTE in viewing the left atrial appendage, the aorta, and the interatrial septum and in detecting a patent foramen ovale.

Nonmigrainous Retinal Vasospasm

Vasospastic vision loss may also occur outside of the context of migraine. These patients will have no associated pain or headache, and they may complain of several episodes of monocular visual loss per day. Rarely, during an event, temporary narrowing of the retinal vessels may be witnessed. The diagnosis is one of exclusion with negative cardiac and carotid evaluations. However, retinal vasospasm may occur with increased frequency in patients with connective tissue disorders such as systemic lupus erythematosus. If a vasospastic cause of the vision loss is suspected, symptoms may be improved with calcium channel blockers. We prefer using verapamil 120–360 mg/day, but amlodipine or propranolol are alternative medications that may be effective in this situation. If necessary, aspirin may also be added to the regimen.

Retinal vasospasm and transient monocular visual loss have also been reported in association with exercise and cocaine abuse.

Amaurosis Fugax in Adolescents and Young Adults

In patients younger than 45 years, the ischemic ocular causes of transient blurring are relatively uncommon. Most of these patients have migraine, and very few of them will develop significant visual or neurologic deficits. That being said, important diagnoses to exclude in young patients with transient monocular blindness include atrial septal defect, cardiac valvular disease, carotid dissection, hypercoagulable states, and connective tissue disorders such as fibromuscular dysplasia.

Giant Cell Arteritis

In patients older than 55 years with transient monocular or binocular vision loss, the diagnosis of giant cell (temporal) arteritis must be considered. Many patients with temporal arteritis who develop infarction of the optic nerve and blindness report multiple episodes of blurring or darkening of their vision before the permanent event. Transient visual loss may be positional in the setting of tenuous blood flow or as a result of viewing bright light (“bright-light amaurosis”). In fact, repeated episodes of amaurosis make embolic causes less likely and temporal arteritis more likely. In one series, amaurosis was reported to occur in a third of patients with temporal arteritis before vision loss. A careful historical review with attention to the presence of constitutional symptoms such as headaches, scalp tenderness, jaw claudication, fever, weight loss, and polymyalgia symptoms must be performed. In patients with giant cell arteritis and amaurosis fugax, the fundus is usually normal, but on occasion a cotton-wool spot (nerve fiber infarct) may be seen. Fluorescein angiography may demonstrate abnormally delayed choroidal perfusion in some cases.

Further details regarding the pathology, diagnosis, and management of giant cell arteritis are discussed in Chapter 5 .

Other Ocular Vascular Occlusive Disorders

Hayreh and Zimmerman reported a large series in which amaurosis fugax was the presenting symptom in 15% of patients with ocular ischemic syndrome. Amaurosis fugax occurred in 0.4% of patients with branch retinal vein occlusion and 37.8% of patients with central retinal vein occlusion in the same series.