Posterior ischemic optic neuropathy

INTRODUCTION — Ischemic optic neuropathy is the most common optic nerve disorder in patients over age 50 years [1]. Ischemic optic neuropathy is generally categorized as anterior (affecting the optic disc) versus posterior (retrobulbar) and as arteritic versus nonarteritic. Posterior ischemic optic neuropathy (PION) is less common than anterior ischemic optic neuropathy (AION).

PION is believed to result from an infarction of the retrobulbar optic nerve and is distinguished clinically from AION by a normal-appearing optic nerve head. As such, the diagnosis of PION can be somewhat more challenging than AION; PION must be distinguished from other causes of retrobulbar optic neuropathy as well as other causes of abrupt vision loss.

This topic discusses PION. Other forms of ischemic optic neuropathy and other optic neuropathies are discussed separately. (See "Nonarteritic anterior ischemic optic neuropathy: Epidemiology, pathogenesis, and etiologies" and "Clinical manifestations of giant cell arteritis" and "Optic neuropathies".)

VASCULAR ANATOMY — The vascular supply of the retrobulbar optic nerve is distinct from that of the optic nerve head. (See "Nonarteritic anterior ischemic optic neuropathy: Epidemiology, pathogenesis, and etiologies", section on 'Vascular anatomy'.)

The posterior segment of the optic nerve is supplied by a pial capillary plexus that surrounds the nerve and is derived from collateral branches of the ophthalmic artery (figure 1) [2,3]. Most of the vascular supply is superficial; only a small number of capillaries penetrate the nerve and extend to its central portion, making this area somewhat poorly vascularized in comparison with its anterior portion. Because it is encased in the sphenoid optic canal, the early swelling that occurs after ischemic insult can lead to axonal compression further exacerbating optic nerve damage [4].

The histopathology of PION occurring in the perioperative setting has been reported in at least four cases that showed intraorbital optic nerve infarction extending from retrobulbar to intracanalicular portions bilaterally [5-9]. Consistent with its vascular supply, predominant involvement of the central axial portion of the retrobulbar nerve, with relatively sparing of the periphery, was observed in three of these cases [6,10]. Relative sparing of the central portion of the nerve in one case suggests that there may be some variability in the vascular supply; some individuals may have an axial supply stemming in retrograde fashion from the central retinal artery [2,5].

EPIDEMIOLOGY — PION is relatively uncommon compared with anterior ischemic optic neuropathy (AION).

Two large published case series describe the epidemiologic features of PION in 42 and 72 patients, respectively [2,11]:

●The mean patient age was 62 years in one series (range 18 to 90 years). The mean age varies by etiology category; patients with giant cell arteritis (GCA) are older (mean 78 years, range 50 to 82 years), while those with PION in the setting of spine surgery are younger on average.

●There is a higher than expected prevalence of atherosclerotic risk factors and comorbid vascular disease, especially in patients with nonarteritic (idiopathic) PION, with 87 percent of patients having at least one risk factor for, or one other manifestation of, atherosclerotic vascular disease.

●Gender does not appear to be a risk factor for PION.

●Over 90 percent of patients with PION are Caucasian.

ETIOLOGIES AND PATHOGENESIS — PION is typically categorized etiologically as surgical (perioperative), arteritic, and nonarteritic (idiopathic). Among the two case series previously mentioned, these made up 7 to 39, 8 to 29, and 53 to 67 percent of cases, respectively [2,11]. These wide ranges likely reflect differences in case sampling and referral bias.

Perioperative PION — Both anterior and posterior ischemic optic neuropathy are reported complications of a wide range of surgical procedures [2,4,9-13]. The most common surgical procedures that are associated with perioperative ischemic optic neuropathy are cardiac surgery and spine surgeries [4,10,14-16]. While anterior ischemic optic neuropathy (AION) appears to be more common than PION after cardiac surgery, PION is relatively more common in cases of spine surgery and radical neck dissection [15,17-25]. The incidence of PION after spine surgery is estimated between 0.03 to 0.11 percent [19,22,23,26], while the incidence of ischemic optic neuropathy after cardiac surgery was found to be 0.014 percent in a study using the National Inpatient Sample database between 1998 and 2013 [16]. (See "Nonarteritic anterior ischemic optic neuropathy: Epidemiology, pathogenesis, and etiologies", section on 'Perioperative ischemic optic neuropathy'.)

Perioperative factors that have been implicated in the development of PION include intraoperative hypotension, long duration of surgery, intraoperative blood loss and anemia, the type and amount of intraoperative fluid administration, and prone position [4,11,17,19,20,24,27-29]. Vascular risk factors (male sex, diabetes, obesity), prevalent in these patients, may play a role [29]. In theory, an atherosclerotic vasculopathy may impair autoregulatory function, particularly in the setting of hypotension [4,10,24]. In a case series of ischemic optic neuropathy after spine surgery, 94 percent of ischemic optic neuropathy cases had an anesthetic duration over six hours and 82 percent had estimated blood loss of one or more liters [24]. Because this and other reports were uncontrolled observations, it is uncertain that these factors truly increase risk of ischemic optic neuropathy. However, in one multicenter case-control study that included 80 cases of ischemic optic neuropathy occurring after prone spinal surgery and 315 controls, factors independently associated with ischemic optic neuropathy were male sex, obesity, use of Wilson frame, longer anesthetic duration, greater estimated blood loss, and a lower percentage of colloid used [29].

In patients undergoing spine surgery, prolonged use of the prone position is implicated as a risk factor for PION [4,10,11,19,20,27,28,30]. The presumed mechanism is an increase in central venous pressure caused by increased intra-abdominal and intrathoracic pressure. The increase in ocular venous pressure in turn may compromise optic nerve perfusion, particularly in the setting of the other factors mentioned previously. The posterior optic nerve may be particularly susceptible to increased venous pressure because the arterial vessels that supply the posterior optic nerve are small end vessels from the surrounding pia. A multicenter case-control study found that the use of the Wilson frame during spinal fusion surgery was associated with an increased odds ratio for ischemic optic neuropathy of 4.3 [29]. This device places the patient in a prone position with the head lower than the heart, potentially exacerbating venous pressure in the orbit. In one case report, markedly dilated superior ophthalmic veins were demonstrated on a brain magnetic resonance imaging (MRI) in a patient who sustained bilateral PION after prolonged prone position during lumbar laminectomy [31]. This finding disappeared on follow-up brain MRI five months later. This finding is, however, not universally demonstrated in all patients who sustain a PION.

Patients undergoing radical neck dissection may develop ocular venous hypertension as a result of jugular vein ligation [5,17,18,21,32]. Prolonged use of a steep supine (Trendelenburg) position during surgery may also increase venous pressure and has been suggested to play a role in cases of PION after prostate surgery [33].

Arteritic PION — PION is a rare complication of giant cell arteritis (GCA). In a study of 85 patients with visual loss due to biopsy-proven GCA, PION was the mechanism in just six patients (7 percent) [34]. In these cases, PION results from inflammatory occlusion of the ophthalmic and/or short posterior ciliary arteries. (See "Pathogenesis of giant cell arteritis".)

Vision loss in arteritic PION is often severe (finger-counting or worse) and is more likely to be bilateral, either at onset or in rapid sequence [11,35]. Prodromal episodes of transient vision loss are more common in GCA than in nonarteritic PION.

The clinical syndrome of GCA-associated PION is similar to GCA-associated AION, with older age at presentation and symptoms of polymyalgia rheumatica, which includes jaw claudication, proximal myalgias and arthralgias, scalp tenderness, headache, and fatigue. Laboratory investigation will typically reveal elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). (See "Clinical manifestations of giant cell arteritis".)

Nonarteritic (idiopathic) PION — Among patients with nonarteritic (idiopathic) PION, vascular risk factors and comorbid vascular disease are prevalent [11,36]. Among 38 patients with idiopathic PION in one series, 33 had at least one vascular risk factor or comorbid disease, 15 had hypertension, 9 had diabetes, and 15 had a smoking history. Thirty-two patients had comorbid cardiac, cerebral, or peripheral vascular disease [11]. Similar findings were found in another case series [2]. This suggests that in these patients, PION may represent a manifestation of systemic vascular disease, perhaps a microangiopathy, although this has not been identified pathologically.

Others — PION has also been described in the setting of acute volume loss (trauma, gastrointestinal bleeding) [4,8,37,38], dialysis with hypotension and/or anemia [39], and acute hypotension resulting from other causes [40].

Vasospasm has been implicated as the mechanism of PION occurring in the setting of migraine and with vasoactive stimulant drugs (eg, methamphetamine) [41-43].

While embolism from carotid disease is not understood to be a common mechanism of PION, acute carotid occlusion in cases of carotid dissection has been implicated as the underlying cause in a few reported cases [44-46]. This presumably leads to an abrupt decrease in arterial perfusion downstream, causing a watershed-type infarction in a vulnerable arterial territory.

There have also been isolated case reports of PION occurring in the setting of other rare conditions such as Takayasu arteritis [47], granulomatosis with polyangiitis [48], systemic lupus erythematosus [49,50], cavernous sinus fistula [51], and sickle cell hemoglobinopathy [52].

CLINICAL PRESENTATION — The typical presentation of idiopathic PION is sudden, painless, monocular vision loss [1]. In the postoperative setting and with sudden hypotension from other causes, a bilateral presentation is somewhat more common, occurring in 50 to 67 percent of patients [4,10,11,19,24]. Arteritic PION can also present with bilateral vision loss, but more commonly there is a sequential loss of vision with a mean interval between each eye involvement of 22 days [11].

The severity of vision loss in PION is related to the underlying etiology. In the setting of giant cell arteritis (GCA) or after surgery, 70 to 90 percent of cases have severe acuity loss, finger-counting, or worse [2,10,11,19]. By contrast, those with idiopathic nonarteritic PION often have milder degrees of vision loss.

In the acute setting of PION, the optic disc appears normal, in contrast with nonarteritic anterior ischemic optic neuropathy (NAION) [2]. Another feature that is dissimilar to NAION, is that the contralateral eye does not typically demonstrate a small optic disc cup, the so-called disc at risk. Among 72 patients with PION, only 4 percent of patients were found to have a crowded optic nerve head [11]. Patients with PION develop optic nerve atrophy with disc pallor over four to six weeks. Optic disc cupping may develop later in arteritic but not in other forms of PION [2,10].

As with other optic neuropathies, patients with PION have an afferent pupillary defect unless there is bilateral involvement [11]. Impaired color vision is observed in most patients (80 percent). Perimetry, if performed, typically demonstrates an altitudinal defect or central scotoma [2,11].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of PION includes other retrobulbar optic neuropathies (table 1) [1]. Most compressive and infiltrative optic neuropathies produce vision loss that is more insidious and gradual in onset than with PION. Visual loss in optic neuritis can be abrupt, but is typically accompanied by pain and usually occurs in younger patients than does PION. (See "Optic neuritis: Pathophysiology, clinical features, and diagnosis".)

In the postoperative setting, PION must be distinguished from other causes of perioperative vision loss, including central retinal artery occlusion, cerebral infarction, globe injury, and pituitary apoplexy [9,19,22,24,26,28,30].

There are numerous other causes of optic nerve disease (table 1). Some of the clinical features of the more common disorders are contrasted in the table (table 2); these are discussed in more detail separately. (See "Optic neuropathies".)

DIAGNOSIS — Diagnostic criteria for PION have been proposed as follows [10,39]:

●Acute deficit in visual acuity and/or visual field

●Ipsilateral relative afferent pupillary defect unless bilateral

●Normal optic disc appearance at onset of visual loss

●Exclusion of other causes (retinal vascular occlusion, glaucoma, chorioretinal scars)

●Exclusion of other causes of optic neuropathy such as compression, demyelination, or inflammation with neuroimaging, preferably brain magnetic resonance imaging (MRI) with gadolinium

●Abnormal visual evoked response, either absent or decreased amplitude

●Normal electroretinogram

●Development of optic disc pallor within four to eight weeks of onset

There is no confirmatory diagnostic test for PION, which is a diagnosis of exclusion. In that regard, some diagnostic evaluation, including testing for giant cell arteritis (GCA), ophthalmologic examination, and brain MRI, is essential to exclude other causes of acute visual loss:

●It is imperative to exclude the diagnosis of GCA in patients with PION. This evaluation is urgent in order to institute treatment and prevent vision loss in the second eye. Older patients with PION should be questioned regarding headache, scalp tenderness, and jaw claudication, symptoms that suggest GCA. Regardless of the presence or absence of these other symptoms, if the patient is older than 50 years, an erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels should be obtained. Temporal artery biopsy should be considered if ESR or CRP are abnormal or if there is an otherwise high clinical suspicion for GCA because of suggestive symptoms such as headache or jaw claudication. Empiric corticosteroid therapy should be initiated for high-risk patients pending biopsy results. (See "Diagnosis of giant cell arteritis".)

Both CRP and ESR can be elevated after major surgical procedures and are unreliable tests in the postoperative setting to rule out GCA [10]. However, in the absence of other premorbid symptoms, such as prodromal episodes of transient visual loss or those that suggest polymyalgia rheumatica, GCA would be considered unlikely in a patient with perioperative PION.

●An ophthalmologic examination is essential in all patients to exclude other causes of acute monocular visual loss including central retinal artery occlusion or retinal vein occlusion [19]. (See "Approach to the adult with acute persistent visual loss".)

Visual evoked response and electroretinogram are not essential in the diagnosis of PION and are not routinely performed. Fluorescein angiography is usually normal in PION, but this test is also not required for the diagnosis [2].

●A brain MRI performed with contrast enhancement should be performed to exclude other inflammatory, infiltrative, and compressive causes of a retrobulbar optic neuropathy [11].

In patients with PION due to GCA, enhancement of the optic nerve has been noted on MRI. This must be differentiated from other causes of optic neuropathies, such as inflammation or tumor infiltration, by the clinical setting and temporal artery biopsy results [53,54]. MRI is usually normal in nonarteritic and perioperative PION, but cases demonstrating restricted diffusion in the optic nerve on diffusion-weighted MRI studies have been reported [10,35,55,56].

PROGNOSIS, TREATMENT, AND PREVENTION — There is no treatment for perioperative PION; vision loss does not typically improve significantly.

The appropriate treatment of arteritic PION is with corticosteroids. Prognosis and treatment of this condition are discussed separately. (See "Treatment of giant cell arteritis".)

Patients with nonarteritic PION are also occasionally treated with corticosteroids, particularly if giant cell arteritis (GCA) has not been excluded. While some authors believe that steroid therapy may improve prognosis in these patients, the evidence is limited to uncontrolled observations, and corticosteroids are not recommended for nonarteritic PION [2,57].

Case reports of intravenous infusion of prostaglandin E1 (PGE1) describe possible benefit in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and PION [57-59]. PGE1 is a potent vasodilator and, when given as an intravenous infusion at a dose of 1 microgram/kg within 12 hours of symptom onset, appeared to improve vision and visual fields in affected patients. The efficacy of this treatment is considered unproven pending confirmation by other investigators.

Recurrences of PION in the same or fellow eye have been described, but the incidence rate is not well established [11,57]. In one series of patients with nonarteritic, nonperioperative PION, PION subsequently developed in the fellow eye in 21 percent of patients with a mean interval of 256 days between occurrences [11].

As with NAION, treatment with daily aspirin and atherosclerosis risk factor management is appropriate for most patients as primary prevention of cardiovascular disease (see "Overview of primary prevention of cardiovascular disease"). However, these measures are not known to improve visual prognosis or to prevent recurrence in patients with PION.

Based upon the risk factors identified as noted above, the American Society of Anesthesiologists recommends that patients undergoing spine surgery undergo continuous hemodynamic monitoring and that colloids along with crystalloids be administered in patients who have substantial blood loss [60,61]. Additional recommendations include that patients should be positioned to keep the head at or above heart level, with the neck in a neutral forward position when possible, and that staged rather than single, long-duration procedures should also be considered when appropriate. Vision should be assessed when the patient becomes alert.

SUMMARY AND RECOMMENDATIONS — Posterior ischemic optic neuropathy (PION) is believed to result from an infarction of the retrobulbar optic nerve. While there is much overlap, the vascular anatomy, etiologies, and clinical presentation of PION are distinct from those of anterior ischemic optic neuropathy (AION), which is more common and affects the optic nerve head.

●There are three distinct etiologic categories that account for the majority of patients with PION: perioperative, arteritic, and nonarteritic (idiopathic) PION. (See 'Etiologies and pathogenesis' above.)

●Perioperative PION is most often described in the setting of spinal surgeries and radical neck dissection, although a wide range of operative procedures have been implicated. Hypotension and blood loss are the most universal risk factors for this complication. Localized venous hypertension resulting from prolonged use of the prone position in spine surgery and from internal jugular venous ligation in neck dissections are believed to contribute to PION in these cases. (See 'Perioperative PION' above.)

●PION is an infrequent complication of giant cell arteritis (GCA), a condition occurring exclusively in older adults (>50 years) and associated with a prodrome of polymyalgia rheumatica. (See 'Arteritic PION' above.)

●More than half of PION cases are classified as nonarteritic, idiopathic. Associated comorbidities in these patients suggest that nonarteritic PION is a manifestation of systemic vascular disease. (See 'Nonarteritic (idiopathic) PION' above.)

●Most patients with PION present with abrupt, painless, monocular vision loss. Approximately half of patients with perioperative PION will have bilateral vision loss, while patients with arteritic PION are at risk for rapidly sequential vision loss affecting first one eye then the next. Vision loss is usually severe in patients with perioperative and arteritic PION, but is more variable in patients with nonarteritic PION. (See 'Clinical presentation' above.)

●PION is a diagnosis of exclusion. The most urgent diagnostic imperative is to diagnose or exclude GCA with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and/or a temporal artery biopsy. Patients also require ophthalmologic examination and a contrast-enhanced magnetic resonance imaging (MRI) study that focuses on the optic nerves. (See 'Diagnosis' above.)

●Patients with PION and GCA are treated with corticosteroids. While significant visual recovery is unlikely, treatment is aimed at preventing vision loss in the other eye. (See 'Prognosis, treatment, and prevention' above.)

●Patients with perioperative PION do not usually experience significant visual recovery, while up to one-third of patients with nonarteritic (idiopathic) PION may improve. There is no treatment for perioperative or nonarteritic PION. Patients with nonarteritic PION may experience a subsequent episode in the other eye over the next months and years, but interventions (such as atherosclerosis risk factor management and aspirin) are not known to prevent this. (See 'Prognosis, treatment, and prevention' above.)