Chapter 5 Ischemic Optic Neuropathies

5

Ischemic Optic Neuropathies VALE´RIE BIOUSSE

Nonarteritic Anterior Ischemic Optic Neuropathy Diagnosis Risk Factors and Recurrence Treatment Arteritic Anterior Ischemic Optic Neuropathy Diagnosis Diagnostic Tests Treatment and Outcome

Posterior Ischemic Optic Neuropathy Perioperative Ischemic Optic Neuropathy Radiation Optic Neuropathy Diabetic Papillopathy and PreAION Optic Disc Edema References

Key Points  Ischemic optic neuropathies include anterior ischemic optic neuropathy (always associated with disc edema), and posterior ischemic optic neuropathy (when the optic nerve appears normal acutely).  Anterior ischemic optic neuropathies are categorized as nonarteritic anterior ischemic optic neuropathies and arteritic anterior ischemic optic neuropathies (usually in the setting of giant cell arteritis).  Nonarteritic anterior ischemic optic neuropathies typically occur in the setting of a disc at risk (small crowded optic nerve with a small cup-to-disc ratio).  In a patient with suspected ischemic optic neuropathy, the first step should always be to rule in or out giant cell arteritis.

Ischemic optic neuropathies (IONs) are the most common acute optic neuropathies in patients older than 50 years. The term ischemic optic neuropathy is used as a general term to refer to all presumed ischemic causes of optic neuropathy. Depending on the segment of optic nerve affected, they are divided into anterior and posterior IONs (Fig. 5–1). Optic disc edema from ischemia to the anterior nerve is, by definition, present in anterior ischemic optic neuropathy (AION) (Fig. 5–2) and absent in posterior ischemic optic neuropathy (PION) (Fig. 5–3).1 AION is much more common than PION, accounting for 90% of cases of optic nerve ischemia. IONs can also be divided into nonarteritic and arteritic etiologies (nonarteritic AION [NAION] and arteritic AION). Arteritic ION, classically resulting from

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Figure 5–1

Vascularization of the optic nerve. The eye has a dual vascular supply, with arterial contributions from the choroidal and central retinal circulations, both of which originate from the ophthalmic artery, a branch of the internal carotid artery. The choroidal circulation is comprised of choroidal arteries, which primarily supply the outer retina, and posterior ciliary arteries, which supply the optic nerve. The intraocular optic nerve is supplied by an anastomotic arterial circle (the circle of Zinn-Haller) or directly from short posterior ciliary arteries. Contributions to the circle of Zinn-Haller include short posterior ciliary arteries, branches from the nearby pial arterial network, and choroidal feeder vessels, with the most significant contribution from the short posterior ciliary arteries. The posterior optic nerve is supplied by the surrounding pial plexus. The central retinal artery supplies the inner retina. (From Zide BM, Jelks GW: Surgical Anatomy of the Orbit. New York, Raven Press, 1985.)

giant cell arteritis, is an ophthalmologic emergency, requiring prompt recognition and treatment to prevent devastating blindness.1

Nonarteritic Anterior Ischemic Optic Neuropathy NAION is presumably secondary to small vessel disease of the short posterior ciliary arteries, with resultant hypoperfusion and infarction of the anterior optic nerve.1 Diagnosis is primarily clinical, and, despite its high incidence, NAION remains largely untreatable. The Ischemic Optic Neuropathy Decompression Trial (IONDT), a large, multicenter, prospective treatment trial, has provided valuable information on the natural history of NAION.2–5 DIAGNOSIS NAION typically occurs after the age of 50 years, but cases in younger patients and even in children are well documented. Incidence is estimated at 2.3 to 10.2 cases per year per 100,000 persons 50 years and older, and 95% of cases occur in Caucasians.1 The typical presentation is of sudden, painless monocular visual loss that progresses over hours to weeks. Premonitory transient visual loss and ocular discomfort are infrequent in NAION.1,6 Examination in typical NAION reveals an

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Figure 5–2 Anterior ischemic optic neuropathy. A, Optic nerve appearance at the acute phase (top) showing diffuse disc edema with peripapillary hemorrhages; 1 month later (middle), the disc edema has almost completely resolved; there is segmental superior pallor and persistent inferior disc edema with an adjacent hemorrhage; 2 months later (bottom), the disc edema has completely resolved and there is superior segmental optic nerve pallor corresponding to the inferior visual field defect shown in B. B, Humphrey visual field of the right eye showing an inferior arcuate defect in this patient with nonarteritic anterior ischemic optic neuropathy. Visual acuity is 20/25 and color vision is normal.

optic neuropathy, with decreased visual acuity and color vision, a relative afferent pupillary defect, visual field loss, and optic disc edema, often with peripapillary hemorrhages. Disc edema may be diffuse or segmental, involving only the superior or inferior portion of the optic disc (Figs. 5–2 and 5–4). This may correspond with the division of the circle of Zinn-Haller into distinct upper and lower halves.1 Similarly, the corresponding visual field defect is often an inferior (most common) or superior altitudinal or arcuate defect (Figs. 5–2 and 5–4). Initial visual acuity varies widely from 20/20 to no light perception. It is better than or equal to 20/60 in 31% to 52% of patients and worse than or equal to 20/200 in 34% to 54% of patients.1,6 Four to 6 weeks after visual loss, disc edema resolves and optic disc pallor develops, often in a sectoral pattern (Fig. 5–2).1 Although the onset of visual loss is classically sudden (as in all vascular events), progressive worsening of vision over a few days or weeks is common in NAION. The IONDT showed that up to 43% of patients spontaneously regained three lines of visual acuity at 6-month follow-up, with 31% sustaining that benefit at 24 months.2–5 An important examination finding, usually considered essential to diagnosis of NAION, is the presence of a small optic nerve with a small or absent physiologic cup (termed the disc at risk) in the unaffected eye (Figs. 5–5 and 5–6).1,7,8

5  Ischemic Optic Neuropathies

Figure 5–3 Bilateral posterior ischemic optic neuropathies. A, Normal-appearing optic nerves in a 35-year-old man who complained of profound visual loss in the right eye after spine surgery. His visual acuity was “hand motion” in the right eye and 20/25 in his left eye. He had a right relative afferent pupillary defect and his fundus examination was normal. B, Goldmann visual fields showed a central scotoma and inferior defect in his right eye as well as an inferonasal defect in his left eye (the right eye visual field is on the right and the left eye visual field is on the left). C, Two months later, his right optic nerve appears pale; his left optic nerve is only very mildly pale temporally (the right eye is on the left and the left eye is on the right).

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Figure 5–4

Luxury perfusion in nonarteritic anterior ischemic optic neuropathy. A, Disc edema secondary to anterior ischemic optic neuropathy with telangiectatic, dilated small vessels superiorly corresponding to luxury perfusion. B, Humphrey visual field in the left eye of the same patient showing an inferior altitudinal defect.

A

Figure 5–5 Illustration of the cup-to-disc ratio. The physiologic cup of the optic nerve corresponds to the size of the scleral canal (the opening in the sclera through which the optic nerve exits the eye). The ratio of cup size to the diameter of the optic disc determines if the patient has a disc at risk for NAION. A, Middle, Normal cup with cup-to-disc ratio (0.5). Left, Large cup-to-disc ratio (0.8) such as in patients with glaucoma. Right, Small optic disc with cup-to-disc ratio (<0.1). This is the classic “disc at risk” in nonarteritic ischemic optic neuropathy (NAION). B, Corresponding fundus photos.

5  Ischemic Optic Neuropathies

Figure 5–6 Four weeks after nonarteritic anterior ischemic optic neuropathy in the right eye. Both optic nerves are small and crowded, the so-called disc at risk. There is mild residual disc edema and superior pallor in the right eye (left image) and the left eye (right image) is normally pink, without disc edema. Both optic nerves are lacking a physiologic cup.

It is widely thought that an anatomically small, crowded optic nerve predisposes patients to NAION by virtue of mechanical factors such as crowding with impaired axonal flow resulting in compromise of the laminar microcirculation.1,7,8 Caucasians tend to have small cup to disc ratios, which may explain why NAION predominates in this group.1,9 NAION must be differentiated from other causes of acute optic neuropathies, such as idiopathic optic neuritis, infectious optic neuritis, or compressive optic neuropathies.1,10,11 The absence of pain, rapid loss of vision, relatively good color vision and the finding of a disc at risk in the fellow eye support the diagnosis of NAION (Table 5–1). Occasionally, magnetic resonance imaging (MRI) of the optic nerve (with contrast) may be helpful, wherein the finding of enhancement of the optic nerve or optic nerve sheath should suggest an alternative diagnosis.1 RISK FACTORS AND RECURRENCE Although the pathophysiology of AION remains unknown, studies have reported the association of AION with optic nerve anomalies and systemic disorders (Table 5–2).1,7 As emphasized above, the main risk factor for NAION is the presence of an anomalous optic nerve. A disc at risk (small optic nerve with a small or absent physiologic cup) is usually present even in patients who may have another reason to develop NAION (such as perioperative AION or AION occurring in association with drugs). Other optic nerve anomalies such as papilledema or optic nerve head drusen can also be complicated by AION (Fig. 5–7), most likely because of impaired axonal flow and resultant compromise of the laminar microcirculation.1,7,12 Systemic diseases associated with increased risk of NAION include systemic hypertension (in about 50%) and diabetes (in about 25%).1,4,7,13,14 Ischemic heart disease, hypercholesterolemia, stroke, tobacco use, sleep apnea, and systemic atherosclerosis have also been associated,1,15,16 but few rigorous population-controlled studies have been performed. In patients younger than 50,

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Disc edema, segmental Small cup-to-disc ratio Segmental pallor Variable 15% second eye at 5 years HTN (51%), DM (24%) GCA to be ruled out

Normal (2/3) or disc edema (1/3)

Temporal pallor Good 25% recurrence risk Risk of multiple sclerosis

Older (>50 years) Unilateral Acute Acuity variable Pain infrequent Commonly spared if vision good Altitudinal defect

AION Nonarteritic

Younger Unilateral Rapidly progressive Acuity rarely spared Orbital pain frequent with eye movements Commonly abnormal Central defects

Optic Neuritis

Disc edema, pallid Retinal/choroidal infarction Diffuse pallor, cupping Poor 75% second eye within 2 weeks GCA 25% have no GCA symptoms

Older (>65 years) Unilateral or bilateral Acute Severe visual loss Headache common Correlates with visual acuity Any defect (severe)

AION Arteritic

Clinical Characteristics of Inflammatory Optic Neuritis, Nonarteritic Anterior Ischemic Optic Neuropathy (AION), and Arteritic Anterior Ischemic Optic Neuropathy

DM, diabetes mellitus; GCA, giant cell arteritis; HTN, hypertension.

Systemic diseases

Late Visual prognosis

Pain Color vision Visual field Optic disc Acute

Age of patients Laterality Visual loss

TABLE 5–1

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TABLE 5–2

Disorders and Drugs Suggested Associated with the Occurrence of Anterior Ischemic Optic Neuropathies

Arteritic anterior ischemic optic neuropathy Giant cell arteritis þþþ Periarteritis nodosa Churg-Strauss syndrome Wegener’s granulomatosis Connective tissue diseases such as systemic lupus erythematosus Rheumatoid arthritis Relapsing polychondritis Nonarteritic anterior ischemic optic neuropathy Anomalous optic nerve: Disc-at-risk: small crowded optic nerve Papilledema Optic nerve head drusen Elevated intraocular pressure (acute glaucoma, ocular surgery) Radiation-induced optic neuropathy Diabetes mellitus Other vascular risk factors (atherosclerosis) Hypercoagulable states* Acute systemic hypotension/anemia Bleeding Cardiac arrest Perioperative (especially cardiac and spine surgeries) Dialysis Sleep apnea Drugs Amiodarone Interferon-alpha Vasoconstrictor agents (such as nasal decongestant) Erectile dysfunction drugs *Hypercoagulable states are rarely responsible for anterior ischemic optic neuropathy (AION) and should only be tested in younger patients without other risk factors for AION.

Figure 5–7

Left nonarteritic anterior ischemic optic neuropathy in a patient with optic nerve head drusen. Both optic nerves are crowded because of drusen, which are easily seen in the right eye (left). There is visual loss and disc edema in the left eye (right), with peripapillary hemorrhages suggesting superimposed acute nonarteritic anterior ischemic optic neuropathy.

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diabetes, hypertension, and hypercholesterolemia are more strongly associated with NAION than in older patients.4,15,16 In the IONDT, 60% of patients had one or more risk factors associated with cerebrovascular disease, including hypertension, diabetes, and cigarette use.4 NAION is a disease of the small vessels supplying the optic nerve head and is not associated with ipsilateral internal carotid artery stenosis; embolic AION is extremely rare.1,17 As with small vessel disease affecting the central nervous system, some association between carotid occlusive disease and acute AION has been suggested. However, in most cases of AION, the optic neuropathy is a sign of widespread atherosclerosis affecting both large and small vessels, reflecting shared risk factors such as hypertension, diabetes mellitus, or tobacco use, or is isolated and a reflection of the disc at risk. Rarely, optic nerve infarction results from reduced perfusion pressure secondary to severe carotid occlusive disease (especially dissections) and poor collateral blood supply.18 Thus, although most cases of AION are probably due to local vascular factors involving a small, cupless optic disc, rare cases are caused by ipsilateral carotid artery disease. It is not necessary to obtain a carotid ultrasound examination in all patients who develop AION. However, if the patient complains of visual symptoms suggestive of hypoperfusion of the eye (i.e., blurred vision with changes of posture, with bright light or during exercise), or if the AION was preceded by or associated with contralateral neurologic symptoms and signs, transient monocular visual loss, Horner’s syndrome, or orbital pain, noninvasive carotid imaging may be appropriate to identify patients at risk of further embolic or hemodynamic events.1,18 Rarely, hypercoagulable states have been associated with NAION; however, case-controlled studies have given various results. It is suggested that thrombotic factors, in particular homocysteine, be measured in patients younger than 45 years with NAION without vascular risk factors, in bilateral simultaneous NAION, in NAION recurrent in the same eye, in NAION in the absence of a small cup-to-disc ratio, and in familial NAION.1,19–23 Acute bleeding with anemia and systemic hypotension can result in unilateral or bilateral AION. Similarly, fluctuations in blood pressure, especially in anemic patients such as those with chronic renal insufficiency receiving dialysis, have been implicated as a precipitant of AION.1,7 Multiple medications have been implicated in the occurrence of NAION, such as amiodarone, interferon-alpha, nasal decongestants, various vasopressors or vasoconstricting drugs, and erectile dysfunction drugs.1,24–27 However, establishing a direct relationship between use of a specific medication and NAION is problematic because most patients have concurrent vascular risk factors and an underlying disc at risk. When possible, it is generally recommended to discontinue such medications in patients with AION. Acute elevation of intraocular pressure such as during ocular surgeries or during an attack of angle closure glaucoma may precipitate NAION.1,28–30 NAION recurs in the affected eye in less than 5% of patients.5 It is possible that atrophy of the nerve after NAION relieves crowding and reduces recurrence risk. Because patients often have a disc at risk in both eyes, it is not uncommon to observe bilateral NAION, usually sequentially rather than simultaneously. The risk of second eye involvement is 12% to 15% at 5 years and appears to be related to poor baseline visual acuity in the first eye and to diabetes but not to age, sex,

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smoking history, or aspirin use.1,5,7 There is a modest correlation of final visual acuities between eyes in bilateral, sequential NAION, with approximately 50% of patients having Snellen visual acuities within three lines of one another.5 TREATMENT There is no established treatment for NAION, although a number of medical and surgical treatments have been evaluated. The clinician’s primary role in managing patients with this disorder is exclusion of giant cell arteritis and detection and control of vascular risk factors.1 Phenylhydantoin, subtenon injection of vasodilators, intravenous intraocular pressure-lowering agents, vasopressors, stellate ganglion block, levodopa, anticoagulation, aspirin, oral corticosteroids, hyperbaric oxygen, transvitreal optic neurotomy (opening of the scleral canal), and optic nerve sheath decompression have not proven useful for the treatment of acute NAION (Table 5–3 summarizes the most recent studies).1,2,5,31–38 However, most studies were retrospective, nonrandomized, and small. Although it has been suggested that neuroprotective agents (especially those that can be administered topically or directly in the eye) may be efficacious in the acute treatment of NAION, this remains to be demonstrated in a controlled study. Although a few retrospective studies have suggested that aspirin may help prevent fellow eye involvement, this remains debated. However, because aspirin is beneficial in primary and secondary prevention of most atherosclerosis-related vascular diseases, it is reasonable to prescribe aspirin in NAION patients.1

Arteritic Anterior Ischemic Optic Neuropathy AION is the most common ophthalmic manifestation of giant cell arteritis (Table 5–4).1 Arteritic AION is exceedingly important to recognize and differentiate from NAION to prevent further devastating visual loss. Although giant cell arteritis is the most common cause of arteritic AION, other vasculitides such as periarteritis nodosa should also be considered (Table 5–2).1 DIAGNOSIS Giant cell arteritis occurs predominantly in women and in Caucasians older than the age of 65. The annual incidence is approximately 20 per 100,000 persons aged 50 years or older.39,40 Up to 50% of patients with giant cell arteritis present with ocular symptoms; of those, 70% to 80% have arteritic AION (Table 5–4).1,39 The clinical presentation of arteritic AION is similar to that of NAION, but numerous red flags should raise clinical suspicion for arteritic AION rather than NAION (Table 5–1)1,6,41–43: (1) systemic symptoms such as jaw claudication, neck pain, headache, scalp tenderness, malaise, weight loss, and fever may precede visual loss by months; however, about 25% of patients with positive temporal artery biopsies do not exhibit these systemic symptoms42; (2) permanent visual loss from arteritic AION is sometimes preceded by episodes of transient visual loss (30%) or transient diplopia (5% to 10%) secondary to ischemia to the optic nerve head, extraocular muscles, or cranial nerves42,43; (3) the finding

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Year

1996

2000

2002

2003

2003

Botelho et al.32

Johnson et al.33

IONDT2

Soheilian et al.34

Fazzone et al.35

Topical brimonidine

Transvitreal optic neurotomy

ONSD

Levodopa

Aspirin

Hyperbaric oxygen

Treatment

R

R

P

R

R

P

Study Type

total treated untreated total treated untreated

31 total 14 treated 17 untreated

7 treated

258 total 127 treated 131 untreated

78 23 55 37 18 19

22 treated/27 untreated

Number of Patients

The group treated with brimonidine had worse visual function at 8–12 weeks

Improved VA at 6 months: 76.9% of treated 30% of untreated No change in VF No difference in visual outcome; 24% of surgical patients worsened 6/7 patients had some improvement in VA

No significant difference in final VA

No significant difference in final VA

Outcome

Transvitreal optic neurotomy may be helpful in AION with severe visual loss

There is no role for ONSF in acute NAION treatment

Hyperbaric oxygen does not improve visual outcome of affected eye Aspirin does not improve visual outcome of affected eye Levodopa may improve visual outcome of affected eye

Conclusions of the Study

Studies Evaluating the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) Published Since 1996

Acute treatment of AION Arnold et al.31 1996

Author

TABLE 5–3

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1999

2002

Salomon et al.38

IONDT5

Aspirin

Aspirin

Aspirin

P*

R

R

52 total 36 treated 16 untreated 326 total At baseline{: 87 treated 237 untreated After baseline{: 86 treated 240 untreated

431 total 153 treated 278 untreated

NAION in fellow eye: At 2 years: 17.5% of treated 53.5% of untreated NAION in fellow eye: At 2 years: 7% of treated 15% of untreated At 5 years: 17% of treated 20% of untreated NAION in fellow eye: 22.2% of treated 50% of untreated NAION in fellow eye: Aspirin at baseline: 20% of treated 13% of untreated Aspirin after baseline: 15% of treated 15% of untreated Aspirin may decrease risk of AION in the fellow eye Aspirin does not decrease risk of AION in the fellow eye

Aspirin does not decrease risk of AION in the fellow eye

Aspirin may decrease risk of AION in the fellow eye

*Although the IONDT was a prospective trial to evaluate optic nerve sheath decompression, it was not a prospective trial to evaluate aspirin therapy. Aspirin data are observational only. {Reported starting regular aspirin use 1 month before onset of symptoms at baseline visit. {Responded positively to “started regular use” of aspirin on at least one study visit after baseline. IONDT, Ischemic Optic Neuropathy Decompression Trial; ONSF, optic nerve sheath fenestration; P, prospective; R, retrospective; VA, visual acuity; VF, visual field.

1997

Beck et al.37

Secondary prevention of AION (prevention of fellow eye involvement) Kupersmith et al.36 1997 Aspirin R 100 total 57 treated 43 untreated

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TABLE 5–4

Ophthalmologic Manifestations of Giant Cell Arteritis

Ischemic optic neuropathy Anterior ischemic optic neuropathy Posterior ischemic optic neuropathy Choroidal infarction Central retinal artery occlusion Branch retinal artery occlusion Cilioretinal artery occlusion Central retinal vein occlusion Ophthalmic artery occlusion Ischemic ocular syndrome Corneal edema Anterior uveitis Cataract Ocular hypertony (neovascular glaucoma) Ocular hypotony Retinal hemorrhages (venous stasis retinopathy) Retinal neovascularization Orbital ischemia Orbital pain Diplopia (ischemia of the extraocular muscles) Proptosis Cranial nerve ischemia Diplopia (third, fourth, and sixth nerve ischemia) Cerebral ischemia Brainstem ischemia (diplopia) Occipital lobe infarction (cerebral blindness) Visual hallucinations Tonic pupil Horner’s syndrome

of peripapillary, retinal, or choroidal ischemia in addition to the AION is highly suspicious for giant cell arteritis (Figs. 5–8 and 5–9); (4) the degree of visual loss tends to be more severe in arteritic AION, with initial visual loss between count fingers and no light perception in 54% of patients, compared with 26% of NAION patients1,42; if untreated, arteritic AION becomes bilateral within days to weeks in at least 50% of cases1,42; (5) the affected swollen optic nerve is often pale acutely in giant cell arteritis (Fig. 5–10), whereas pallor is delayed in NAION; and (6) a disc at risk is not necessary for arteritic AION.1,6 Therefore, a thorough history and ocular examination evaluating the cup-to-disc ratio and looking for other signs of ocular ischemia are of paramount importance in the diagnosis of arteritic AION. In difficult cases, retinal fluorescein angiography can be very helpful at detecting choroidal hypoperfusion (Fig. 5–11).1 DIAGNOSTIC TESTS The erythrocyte sedimentation rate (ESR) is greater than 40 mm/hour in at least 77% of patients with active, untreated giant cell arteritis. An ESR greater than 50 mm/hour is one of the five diagnostic criteria used by the American College

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Figure 5–8 Acute arteritic anterior ischemic optic neuropathy in a patient with giant cell arteritis. In addition to the optic nerve head swelling which is already pallid, there are peripapillary changes suggesting extensive ischemia of the posterior pole of the eye (involving the retina and the choroid). Involvement of more than one vascular territory is highly suggestive of arteritic anterior ischemic optic neuropathy.

Figure 5–9 Acute bilateral visual loss in giant cell arteritis. The right optic nerve (left image) is swollen inferiorly, suggesting an anterior ischemic optic neuropathy; the left optic nerve (right image) is normal, suggesting a posterior ischemic optic neuropathy. In addition, the peripapillary areas in both eyes are abnormal secondary to choroidal ischemia, and there are cotton wool spots in the left eye related to inner retinal ischemia.

Figure

5–10 Acute arteritic anterior ischemic optic neuropathy in a patient with giant cell arteritis. The nerve is swollen and the arteries very attenuated. Although the visual loss is acute, the nerve is already pale with a chalky appearance.

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Figure 5–11 Acute right arteritic anterior ischemic optic neuropathy, left retinal ischemia, and bilateral choroidal ischemia in a patient with giant cell arteritis. A, The right optic nerve is swollen (left image), suggesting an anterior ischemic optic neuropathy. Although the patient has no visual symptoms in her left eye (right image), there is a cotton wool spot below the optic nerve, suggesting an area of retinal ischemia. B, Retinal fluorescein angiography of the same patient showing delayed and patchy choroidal filling in both eyes; normal choroid should appear “white” (filled with fluorescein) approximately 30 seconds after injection. In this patient, filling is still patchy more than 1 minute after injection.

of Rheumatology. When the ESR is raised, the disease process correlates well with the ESR level and, hence, facilitates monitoring of the disease. However, the ESR is a nonspecific marker of a variety of inflammatory, infectious, and neoplastic disorders and may be normal in 7% to 20% of patients with giant cell arteritis before treatment. Therefore, a normal ESR does not rule out giant cell arteritis.39,40 In patients with clinical symptoms suggestive of giant cell arteritis and a normal ESR, the ESR should be repeated weekly because its elevation can be delayed. In addition, levels of other acute phase response markers, such as C-reactive protein or fibrinogen, should be obtained. Other laboratory tests such as complete blood count, platelet count, and hepatic alkaline phosphatase may also be useful in this setting, because most patients have a mild-tomoderate anemia of chronic disease, and approximately one third of patients have mildly abnormal liver function tests. Thrombocytosis (elevated platelet count) is also common.39,40 They may also be used to monitor patients with giant cell arteritis. As emphasized previously, fluorescein angiography is often very useful in the diagnosis of giant cell arteritis (Fig. 5–11). It is a widely available, safe, and relatively inexpensive diagnostic tool for many retinal, choroidal, and optic nerve disorders. As opposed to NAION (which tends only to affect the posterior ciliary circulation), the multifocal nature of arteritic AION often leads to involvement of both the posterior ciliary and choroidal circulations; therefore, when extensive

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choroidal hypoperfusion is identified by fluorescein angiography (Fig. 5–11) in the setting of ION, an arteritic etiology is highly likely.1 Magnetic resonance imaging (MRI) is not a classic diagnostic test for AION. However, MRI is often obtained as a component of the diagnostic evaluation for a unilateral optic neuropathy. Although the MRI is normal in NAION, orbital fat enhancement and optic nerve and nerve sheath enhancement have been reported in arteritic AION.1 Temporal artery biopsy is the gold standard for definitive diagnosis. Although diagnosis of arteritic AION may be suspected on clinical grounds, biopsy confirmation of giant cell arteritis is essential, especially given the complication rate associated with the subsequent necessary long-term steroid therapy.1,39,40 TREATMENT AND OUTCOME Corticosteroid responsiveness and improved outcome with early treatment make immediate and aggressive initiation of therapy the goal to prevent permanent visual loss. The following treatment suggestions are those generally recommended by neuro-ophthalmologists confronted with patients with a significant danger of high visual morbidity. The aggressive treatment suggestions differ from those often recommended by rheumatologists, who may more regularly treat the systemic symptoms of giant cell arteritis in patients unaffected by visual loss. In a patient with arteritic ION, systemic corticosteroids should be promptly instituted on suspected diagnosis and should not be delayed for temporal artery biopsy. In the setting of visual loss, high-dose (1 to 2 g/day for 2 to 3 days) intravenous steroids followed by high-dose oral steroids are recommended, although no prospective studies evaluating this therapy have been performed.1,39–41,43–46 If oral prednisone alone is used, doses in the range of 1 to 2 mg/kg/day are suggested. Maintenance therapy in this dose range should be continued for at least 4 to 6 weeks, until normalization of laboratory inflammatory markers occurs, to be followed by a slow taper over the next 12 to 18 months, with careful follow-up of ESR and C-reactive protein. The rate of steroid taper is approximately 10 mg per month initially, then decreased to 5 mg per month, and even as low as 1 mg per month, once a dose of 10 or 15 mg per day is reached. A maintenance dose of 5 to 7.5 mg/day is generally adequate after the first 6 to 12 months of therapy. Alternate-day steroid regimens are not recommended, because rebound arteritis has been associated with this regimen. Response of systemic symptoms is usually rapid and dramatic, with relief of headache and malaise within 24 hours. Unfortunately, only 4% to 15% of patients with arteritic AION experience improvement in visual loss with therapy.1,41,44,45 Recent reports emphasize that, if improvement does occur, it usually consists of improvement in visual acuity in the presence of persistent, often severe, visual field defects.44,45 Steroid treatment also aims to prevent involvement of the unaffected eye; however, progression of visual loss or second eye involvement occasionally occurs despite high-dose systemic therapy. If this occurs, it tends to be within a few days of initiation of therapy.46 Recurrence of symptoms or relapse elevation of ESR and C-reactive protein occurs in more than half of patients as steroids are tapered.41,42,44 Immediate

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elevation of the steroid dose to the last dose before relapse is suggested. Because of the high rate of steroid complications, especially in the elderly population, there is substantial interest in steroid-sparing agents; however, none has proven useful in randomized studies to date.40 The anti-inflammatory effects of aspirin have been suggested as potentially beneficial for visual outcome, but there are no prospective studies.1,40 Anticoagulation has also been tried, with no proven benefit.1

Posterior Ischemic Optic Neuropathy PION is relatively uncommon compared with AION. The diagnosis of PION is usually made only after other causes of a retrobulbar optic neuropathy (e.g., inflammatory, toxic, compressive) have been excluded.1,47,48 Although both AION and PION are manifestations of vascular insufficiency to the optic nerve, they represent two very different pathophysiologic entities. This distinction is related primarily to the marked difference in vascular supply between the anterior and posterior segments of the optic nerve (see previous discussion) (Fig. 5–1). The posterior segment of the optic nerve is supplied only by the pial capillary plexus that surrounds it; only a small number of capillaries actually penetrate the nerve and extend to its central portion among the pial septae. As a result, the center of the posterior portion of the optic nerve is relatively poorly vascularized compared with its anterior portion.1,48 There is no known structural abnormality of the optic nerve that has been identified in patients with PION similar to the disc at risk seen with AION. However, the portion of the optic nerve affected in PION, by definition, is not visible during ocular funduscopic examination. Acutely, patients with PION have sudden vision loss in one eye, typically painless. Examination reveals decreased visual acuity, visual field loss, and a relative afferent pupillary defect but a normal-appearing optic disc (Fig. 5–3).1,47,48 The two main causes of PION are perioperative PION and giant cell arteritis, and the latter should be excluded in all patients older than 50 years.

Perioperative Ischemic Optic Neuropathy Perioperative visual loss is a devastating injury that has been reported after various types of surgeries. AION may occur rarely after intraocular surgery such as cataract extraction or after intraocular injections. The presumed mechanism is optic nerve head ischemia secondary to fluctuations in intraocular pressure.28–30 IONs may also occur after nonocular surgeries and during procedures such as dialysis or even cardiac catheterization.1,49 Although this complication has been reported after many types of surgery, the two most classic are coronary artery bypass procedures (Fig. 5–12) and spine surgery (Fig. 5–3).1,50–52 During coronary artery bypass, AION is probably more common than PION, presumably related to fluctuations in blood pressure and blood loss.1,50 During the past decade, there has been a growing concern about ION in the setting of spine surgery performed in the prone position.52 Most of the reported cases are PION, are frequently bilateral, and typically have a poor visual prognosis. The etiology

5  Ischemic Optic Neuropathies

Figure 5–12 Bilateral anterior ischemic optic neuropathies after coronary artery bypass graft surgery. This 68-year-old man underwent an uncomplicated coronary artery bypass graft procedure. He awoke from anesthesia with visual loss in both eyes that worsened over a few days. Visual acuity was 20/400 in the right eye and 20/80 in the left eye. His vision did not improve. A, Bilateral optic nerve head edema suggesting bilateral anterior ischemic optic neuropathies. B, Goldmann visual fields show bilateral inferior altitudinal defects involving the central field in the right eye. C, Six weeks later, both optic nerves are pale. The disc edema has resolved and there are peripapillary changes consistent with previous disc edema.

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remains debated and poorly understood. A recent review52 noted that these complications cannot be explained only by relative hypotension and anemia because these are common occurrences during spine surgery. The prone position, length of surgery, and amount of blood loss may be related, but no case-control study has yet determined any specific factor definitively associated with visual loss. Although direct pressure on the globes from the headrest has been postulated as a factor in a few cases, this would be an unlikely cause of PION (in which elevation of intraocular pressure by external compression should not affect retrobulbar blood flow) and even AION, but it accounts for the rare unilateral case of central retinal artery occlusion in this setting. Finally, there may be an anatomical “watershed” region involving the vascular supply of the posterior optic nerves in some individuals, rendering these patients susceptible to fluctuations in blood pressure and oxygen delivery that would not affect others.1,47,52 Further data are necessary to determine what factors are relevant, and the anesthesia community is currently acquiring such information. Until such data are available, both surgeons and anesthesiologists should be encouraged to discuss the small but significant potential risk for visual loss in patients undergoing prolonged spine surgery in the prone position, especially if the patient has underlying vascular risk factors and the surgery is expected to entail significant blood loss or hypotension, or both.

Radiation Optic Neuropathy Radiation optic neuropathy is thought to be an ischemic disorder of the optic nerve that usually results in irreversible severe visual loss months to years after radiation therapy to the brain, skull base, paranasal sinuses, and orbits.1,53 It is most often a retrobulbar process. Patients typically present with rapidly progressive painless loss of vision in one eye, which often becomes bilateral within weeks or months. Characteristically there is marked enhancement of the affected optic nerve on MRI.1,53 There is currently no known effective treatment, although corticosteroids and hyperbaric oxygen are often prescribed.1,53,54

Diabetic Papillopathy and Pre-AION Optic Disc Edema Patients may develop disc swelling from AION before they have any visual symptoms. 1,55 The asymptomatic disc swelling is often noted in the fellow eye of a patient with a previous history of AION. The mechanism of disc swelling in these cases is presumed to be ischemia.1,55 Similarly, young patients with diabetes mellitus may develop disc swelling in one eye with no or very mild visual loss; so-called diabetic papillopathy. The swelling may be unilateral or bilateral and the visual prognosis is usually excellent. In more than 80% of reported cases, diabetic retinopathy is present at the time of onset of diabetic papillopathy. The mechanism remains unknown, although ischemia of the optic nerve head is most likely. Another potential cause of optic nerve swelling is vitreal traction1,55 (Fig. 5–13).

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Figure 5–13 Diabetic papillopathy. Optic nerve head edema with some vitreous traction in a patient with proliferative diabetic retinopathy. The visual function is normal and there is no relative afferent pupillary defect.

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46. Hayreh SS, Zimmerman B: Visual deterioration in giant cell arteritis patients while on high doses of corticosteroid therapy. Ophthalmology 2003;110:1204–1215. 47. Sadda SR, Nee M, Miller NR, et al: Clinical spectrum of posterior ischemic optic neuropathy. Am J Ophthalmol 2001;132:743–750. 48. Hayreh SS: Posterior ischaemic optic neuropathy: Clinical features, pathogenesis, and management. Eye 2004;18:1188–1206. 49. Buono LM, Foroozan R, Savino PJ, et al: Posterior ischemic optic neuropathy after hemodialysis. Ophthalmology 2003;110:1216–1218. 50. Shapira OM, Kimmel WA, Lindsey PS, Shahian DM: Anterior ischemic optic neuropathy after open heart operations. Ann Thorac Surg 1996;61:660–666. 51. Cheng MA, Sigurdson W, Templehoff R, Lauryssen C: Visual loss after spine surgery: A survey. Neurosurgery 2000;46:625–631. 52. Ho VT, Newman NJ, Song S, Ksiazek S, Roth S: Ischemic optic neuropathy following spine surgery. J Neurosurg Anesthesiol 2005;17:38–44. 53. Lessell S: Friendly fire: Neurogenic visual loss from radiation therapy. J Neuro-ophthalmol 2004;24:243–250. 54. Miller NR: Radiation-induced optic neuropathy: Still no treatment. Clin Exp Ophthalmol 2004;32:233–235. 55. Almog Y, Goldstein M: Visual outcome in eyes with asymptomatic optic disc edema. J Neuroophthalmol 2003;23:204–207.

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