Amaurosis fugax, or a temporary loss of vision, is thought to occur from a transient occlusion of the ophthalmic circulation and is a known risk factor for acute stroke. Patients often report a dimming of the vision that lasts 10 to 20 minutes before resolution. Funduscopic findings are most commonly normal but can reveal evidence of prior retinal arterial emboli or arterial attenuation, which is an associated finding of hypertension. Elderly patients with amaurosis fugax should have carotid ultrasonography and cardiac echography in an attempt to find a source for the embolic phenomena (6).

Amaurosis fugax was one of the three symptoms evaluated in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Patients with carotid stenosis of 70% to 99% by ultrasonography who had endarterectomy had a reduced risk of subsequent stroke (9%) compared with those treated medically (26%) 2 years after treatment (58). A retrospective analysis of the NASCET trial found that patients with amaurosis fugax who had at least three of the following characteristics had a significant benefit from carotid endarterectomy: age _75 years old, history of hemispheric transient ischemic attack (TIA) or stroke, history of intermittent calf claudication, male sex, ipsilateral internal carotid artery stenosis of 80% to 94%, and no collaterals see on cerebral angiography (5). In the absence of visible emboli, patients with amaurosis fugax should be evaluated for GCA with an erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) because elderly patients with this disorder can present with transient episodes of visual loss.

Acute painless loss of vision occurs with central retinal vein occlusion (CRVO). Risk factors for CRVO include hypertension, diabetes mellitus, and glaucoma (14). Funduscopy reveals hemorrhagic optic disc swelling, with diffuse surrounding retinal hemorrhages and dilated and tortuous retinal veins (Fig. 12-5). Exudate and subretinal fluid within the macula—the most important prognostic factors in patients presenting with vein occlusions—are chiefly responsible for the decrease in vision at presentation. Bilateral vein occlusions are atypical and should prompt a hematologic assessment for severe anemia, hypertension, thrombocytopenia, and other blood dyscrasias.

Patients with CRVO typically have visual acuities of 20/40 or worse. Ophthalmologic follow-up is essential because as many as 30% of patients with CRVO can develop neovascularization of the iris,
leading to an aggressive form of glaucoma, which requires retinal laser photocoagulation (15).

Similar fundus findings as seen in patients with CRVO can occur in patients with carotid occlusive disease. A 90% or greater occlusion of the carotid artery can lead to chronic ipsilateral diffuse retinal hemorrhages, mostly in the midperipheral retina, and dilated retinal veins in the ocular ischemic syndrome (OIS) (10). Patients often complain of photophobia, ocular pain, and decreased visual acuity with bright light because the hypoxia caused by carotid insufficiency is believed to cause impairment in photoreceptor metabolism, which is accentuated in bright light. Patients can have mild corneal edema and inflammation within the anterior chamber that can cause the eye to appear red from conjunctival injection. OIS is distinguished from CRVO by its chronic course, absence of optic nerve swelling, and absence of tortuous retinal veins. Patients with OIS should have close ophthalmologic follow-up because chronic hypoxia of the retina predisposes to neovascularization of the iris and can cause neovascular glaucoma (51).

Retinal dysfunction can occur in cases of cancer-associated retinopathy (CAR, or MAR for melanoma-associated retinopathy). This is a paraneoplastic syndrome caused by antibodies to retinal elements, which causes photopsia (sensation of seeing lights), nyctalopia (difficulty seeing at night), and constricted visual fields associated with retinal degeneration (42). Patients may present with sudden or subacute painless vision loss. Serum autoantibodies against retinal proteins (such as recoverin and alpha-enolase) may be seen in patients with CAR, and autoantibodies against rod bipolar cells may be seen in MAR. Patients with MAR typically already have a history of melanoma, whereas CAR usually precedes the diagnosis of the causative malignancy (usually small-cell lung cancer). No abnormality may be seen during funduscopy, especially early on in the disorder, and electrophysiologic studies with ERG may be required to document the reduced photoreceptor amplitudes. Several months later, patients may develop attenuated retinal arterioles, retinal pigment epithelial changes, and mild optic disc pallor. Intravenous methylprednisolone and plasmapheresis have been shown in some case reports to be associated with variable improvements in visual acuity, color vision, and visual fields (16).

The causes of optic neuropathy are extensive; however, optic nerve dysfunction, including RAPD, visual field defect, acquired color vision deficit (dyschromatopsia), and impaired contrast sensitivity, is invariably present. The onset, duration, and progression of visual symptoms will help differentiate acute from chronic causes of optic nerve dysfunction. Funduscopy in optic neuropathy often shows optic disc swelling acutely; over time, however, all causes of optic neuropathy will cause the optic nerve to appear pale. In many cases (e.g., traumatic optic neuropathy and neuropathy from compressive lesions), disc swelling may not be noted because the site of pathology lies posterior to the optic nerve head.

The presence of bilateral disc edema requires immediate attention. Associated retinal hemorrhages and cotton wool spots, including cotton wool spots of the optic nerve, are suggestive of hypertensive retinopathy. Central nervous system tumors can cause bilateral disc swelling secondary to increased intracranial pressure. Thus, patients with bilateral disc edema should have their blood pressure taken, and neuroimaging should be performed emergently to exclude a compressive lesion (see Fig. 12-6 for assessment of the elderly patient with optic disc swelling).

Unilateral disc swelling in elderly patients most commonly results from anterior ischemic optic neuropathy (AION). Nonarteritic ischemic optic neuropathy (NAION) occurs most commonly in vasculopathic patients in the fifth and sixth decades. Patients with NAION have an abrupt onset of painless visual loss (with visual acuities typically in the 20/60 to 20/200 range), often in the early morning hours, and an altitudinal visual field defect (36). Disc swelling, thought to be secondary to vascular insufficiency of the short posterior ciliary circulation that supplies the optic nerve head, is most often hyperemic and may be sectoral with splinter nerve fiber layer (NFL) hemorrhages. Examination of the uninvolved eye often reveals a small optic cup, suggesting a “disc at risk” for ischemia and crowding of the retinal blood vessels (19). Because NAION has only rarely been associated with embolic phenomena, carotid and cardiac ultrasonography are not indicated in the evaluation of patients with typical NAION. Some risk factors for NAION have been identified, including diabetes mellitus, hypertension, smoking, and nocturnal hypotension. In patients with NAION, the risk of infarction of the fellow optic nerve over 5 years is approximately 15% (57). The risk for ipsilateral
recurrence is quite small, at approximately 6% (30). Although some patients with NAION may have an improvement in visual acuity over the ensuing months, most will be left with a significant visual deficit. Inferior altitudinal and inferior nasal defects are the most common field cuts associated with NAION (33). No medical or surgical therapy has shown consistent benefit for patients with NAION. Some authors have suggested that aspirin may prevent infarction of the fellow eye (4), but long-term benefit has not been proven.

A number of patients using the antiarrhythmic amiodarone have been noted to have disc swelling that is virtually indistinguishable from that caused by NAION (49,56,61). However, patients in some of these cases have shown a more progressive visual deficit and bilateral involvement, which are uncommon in NAION. Amiodarone also causes crystalline deposits within the superficial cornea, in a whorl-like fashion, that are not visually disabling. Because the progression of visual loss has been halted in some patients after discontinuing this agent, patients on amiodarone with what appears to be NAION should be carefully observed for progression and fellow eye involvement (8). Patients should not discontinue amiodarone without first consulting their cardiologist (55).

Recently, there have been reports in the medical literature of an association between NAION and the use of erectile dysfunction medications, such as sildenafil, tadalafil, and vardenafil (81). It is unclear whether there is a causal relationship because some of the patients using erectile dysfunction medications have some vascular risk factors that are also associated with NAION, such as diabetes, hypertension, and hypercholesterolemia.

Patients with diabetes mellitus, often with poorly controlled blood sugar levels, may present with hyperemic disc swelling and mild visual dysfunction
(sometimes without visual complaints), which are consistent with diabetic papillopathy (65). The disc swelling and visual deficit will typically resolve weeks to months after the onset of symptoms.

AION from GCA occurs most commonly in patients in their sixth through eighth decades (mean age, 75 years), and women are affected more commonly than men. GCA is more common in whites and people from Northern Europe and is quite rare in African-Americans and Asians (63). Acute visual loss may occur after a history of brief episodes of transient visual loss. Visual acuities and visual field defects in AION caused by GCA are more commonly worse than those in patients with NAION. The disc edema of GCA is often noted to be “chalky white” in appearance because of the diffuse pallid swelling (Fig. 12-7). A history of headache, scalp tenderness, jaw claudication, fever, malaise, decreased appetite, weight loss, and symptoms of polymyalgia rheumatica should be sought (23). Other causes of vision loss from GCA include branch and CRAO and posterior ischemic optic neuropathy (PION). In addition to optic neuropathy from AION, other cranial nerves can be affected in GCA, and diplopia, facial nerve palsy, and facial pain have been noted.

Patients suspected of having GCA should have ESR and CRP drawn and be placed on corticosteroids without delay to prevent visual loss in the fellow eye; visual loss in the affected eye is typically irreversible. Although most patients with GCA will have an elevated ESR (estimates of up to 24% of biopsy-proved cases may not), those patients suspected of having GCA should have biopsy of the superficial temporal artery to confirm the diagnosis. An elevated CRP level may be helpful in suspicious cases with a normal ESR, and bilateral biopsy should be considered in cases with a high clinical suspicion because skip lesions can lead to a false-negative biopsy result. The variables with the highest positive predictive value for a positive temporal artery biopsy are jaw claudication, scalp tenderness, new headache, and vision loss (85). Most patients require high doses of corticosteroids (prednisone, 60 to 100 mg) for at least 6 months to 1 year. Attempts to taper steroid therapy should be very gradual, with close monitoring of visual function, ESR, and CRP.

Despite the differences outlined above, the disc swelling from NAION can be difficult to distinguish from that caused by GCA, and ESR and CRP studies are warranted in all patients _55 years with optic disc edema thought to be caused by ischemic optic neuropathy.

Optic nerve tumors (e.g., malignant optic gliomas and meningiomas) can cause optic disc swelling; however, more commonly, optic atrophy is present with these lesions. Patients may present with findings suggestive of an acute optic neuropathy without evidence of optic disc swelling, the so-called “posterior ischemic optic neuropathy” (PION) thought to be caused by ischemia of the retrobulbar circulation of the optic nerve (35). The average age of patients with PION is 52 years old (12). Optic neuropathy from PION has been noted after acute ischemic states, such as after cardiac bypass or spine surgery, and in patients with GCA. PION is a rare complication of spinal surgery and has been associated with spinal surgeries with blood loss of more than 1 L and anesthesia duration over 6 hours. Usually the vision loss is bilateral and severe (47). Patients suspected of having PION, without a history of an acute ischemic event, should have an ESR and CRP drawn to rule out GCA (31). Electrophysiologic testing showing a normal ERG and absent VEP is suggestive of PION and can help confirm the diagnosis.

A rare cause of vision loss in patients with cancer is paraneoplastic optic neuropathy. The vision loss is typically acute to subacute and painless. Patients may have associated neurologic signs such as chorea, ataxia, peripheral neuropathy, and dementia. Funduscopy shows bilateral optic disk swelling. Autoantibodies against collapsing response-mediating protein-5 (CRMP-5) are commonly found and are predominantly associated with small cell lung cancer (16).