Ординатура / Офтальмология / Английские материалы / Essentials in Ophthalmology Pediatric Ophthalmology Neuro-Ophthalmology Genetics_Lorenz, Borruat_2008

often elderly with multiple and complex medical problems, we routinely provide inpatient therapy, under the supervision of an internist. Oral prednisone at doses of at least 1 mg/kg per day is recommended after intravenous therapy (or initially if the intravenous route is not utilized), and is tapered slowly, monitoring for control of systemic symptoms and ESR level; therapy is usually maintained for at least 4–6 months, often up to a year. Systemic symptoms typically subside within a week, a response so characteristic that if it is absent, an alternative disease process should be strongly considered. Alternate-day corticosteroid therapy is inadequate for GCA.

Some degree of visual recovery in the affected eye may be obtained on therapy, but is not generally anticipated. Reports of visual improvement on corticosteroids vary widely with regard to delay to therapy, dosage, and parameters for visual recovery. Aiello et al. [1] reported improvement of vision in 5/34 patients (15%), while Liu et al. [41] noted it in 14/41 (34%). Foroozan et al. [17] reported improvement in visual acuity in 5/39 eyes (13%), although visual fields remained severely constricted. Hayreh et al. [29] studied 114 eyes in 84 patients for evidence of visual improvement, finding only 5 eyes (4%) with both improved visual acuity and central visual field after therapy.

The major goal of therapy other than prevention of systemic vascular complications is to prevent contralateral visual loss. Untreated, fellow eye involvement occurs in up to 95%, often within weeks. With therapy, Aiello et al. [1] found that 2/24 (6.3%) patients with AAION developed such involvement; Liu et al. [41] detected fellow eye AAION on therapy in 3 cases. While corticosteroid therapy reduces risk of further visual loss, it is not uniformly effective; breakthrough involvement of an affected eye while on therapy occurred in 9%–17% [1, 41]. Liu et al. [41] found 6 cases developing AAION while on systemic corticosteroid therapy for systemic symptoms alone, without previous visual loss. The risk of recurrent or contralateral optic nerve involvement with tapering of medications has been reported to be 7% [41].

Thrombocytosis in GCA and its possible predisposition to visual loss suggests the possibility that antiplatelet therapy may be of benefit in con-

junction with corticosteroids. Nesher et al. [46] reviewed 175 cases with GCA for evidence of cranial ischemic complications (predominantly AION and stroke), comparing those with and without low-dose aspirin therapy for other conditions. At presentation, 3 (8%) of aspirin-treated cases had cranial ischemic complications, compared with 40 (29%) of non-aspirin-treated cases (p=0.01). During follow-up of at least 3 months on steroid therapy, cranial ischemic complications developed in 3% of aspirin-treated cases versus 13% on steroids alone (p=0.02). Further study may confirm a benefit for low-dose aspirin or other antiplatelet therapy in GCA.

Summary for the Clinician

■Therapy of AAION should be instituted immediately upon suspicion of the disease, before biopsy, and consists of high-dose systemic corticosteroids; the primary goal is protection of the fellow eye.

2.2.2Nonarteritic Anterior Ischemic Optic Neuropathy (NAION)

2.2.2.1Clinical Presentation

The majority (94.7%) of cases of AION are nonarteritic [20]; NAION is the most common acute optic neuropathy in patients over 50 years of age, with an estimated annual incidence in the United States of 2.3–10.2 per 100,000 population [22, 33] accounting for at least 6000 new cases annually. The prevalence of NAION in the Medicare Database has been reported at 0.30% [19]. The disease occurs with significantly higher frequency in the white population than in black or Hispanic individuals [33]. There is no gender predisposition [10, 20, 31, 52]. The mean age at onset in most studies ranges from 57 to 65 years [10, 20, 52]; in the IONDT, mean age was 66 years [31].

Nonarteritic AION presents with loss of vision occurring over hours to days, often described as blurring, dimness, or cloudiness in the affected region of the visual field, most often infe-

26

2

Ischemic Optic Neuropathies

riorly. Although Hayreh et al. [27] reported that visual loss was most frequently reported upon awakening, this feature was not confirmed in the IONDT [31]. Nonarteritic AION typically presents without pain, although some form of periocular discomfort has been reported in 8%–12%. In contrast to patients with optic neuritis, those with NAION usually do not report pain with eye movement. Headache and other symptoms associated with GCA are absent. Episodes of transient visual loss as seen in GCA are rare, but vague intermittent symptoms of blurring, shadows, or spots were reported in 5% of patients in the IONDT [31]. The initial course may be static, with little or no fluctuation of visual level after initial loss, or progressive, with either episodic, stepwise decrements or a steady decline of vision over weeks to months prior to eventual stabilization; the progressive form has been reported in 22%–37% of nonarteritic cases [2, 10], and in 29% in a limited group of patients with visual acuity of >20/64 in the IONDT [31].

Nonarteritic AION usually presents with a less severe visual loss than in AAION, with visual acuity >20/200 in 58%–61.2% [10, 52]. In the IONDT, 49% had initial visual acuity of at least 20/64; 66%, better than 20/200 [31]. Color vision loss in NAION tends to parallel visual acuity loss, as opposed to that in optic neuritis, in which color loss is often disproportionately greater than visual acuity loss. Visual field defects in NAION may follow any pattern related to optic nerve damage, but altitudinal loss, usually inferior, occurs in the majority, ranging from 55% to 80% of reported cases [10, 52].

The optic disc edema in NAION may be diffuse or segmental, hyperemic or pale, but pallor occurs less frequently than in the arteritic form. A focal region of more severe swelling is often seen and may display an altitudinal distribution, but it does not consistently correlate with the sector of visual field loss [3]. Diffuse or focal telangiectasia of the edematous disc may be present, occasionally prominent enough to resemble a vascular mass (pseudohemangioma). Peripapillary retinal hemorrhages are common, seen in 72% in the IONDT [31]. Retinal exudates are unusual, but both soft and hard exudates may occur (7% in the IONDT) [31]; a partial or complete macular star pattern of exudate, as seen in neu-

roretinitis, is occasionally seen. The retinal arterioles are focally narrowed in the peripapillary region in up to 68% of cases. The optic disc in the contralateral eye is typically small in diameter and demonstrates a small or absent physiologic cup [6]. The disc appearance in such fellow eyes has been described as the “disc at risk,” with postulated structural crowding of the axons at the level of the cribriform plate, associated mild disc elevation, and disc margin blurring without overt edema.

Summary for the Clinician

■NAION presents as less severe, painless, unilateral visual field loss, most often altitudinal.

■Optic disc edema is present, usually less pale than in AAION, with associated flame hemorrhages.

■Vasculopathicent. risk factors are often pres-

2.2.2.2 Pathophysiology

Nonarteritic AION is presumed to result from circulatory insufficiency within the optic nerve head, but the specific location of the vasculopathy and its pathogenic mechanism remain unproven.

There are few histopathologically studied cases of typical NAION, the majority of which were atypical. Tesser et al. [59] indicated that the optic disc infarct studied in their case did not follow a specific vascular territory and may have represented a compartment syndrome. Knox et al. [37] reported a series of 193 eyes with a histopathologic diagnosis of ischemic optic neuropathy, but those with typical NAION were not identifiable due to lack of clinical information. No confirmation of lipohyalinosis or other occlusive process or inflammation within the disc’s vascular supply has been documented in these or other cases. The available evidence does, however, highlight one important fact: the infarctions were predominantly located in the retrolaminar region of the optic nerve head, with extension to

the lamina and prelaminar layer in some. This pattern suggests that the vasculopathy responsible for NAION does not lie within the choroidal circulation, since the contribution of the choroid to the optic nerve head vascular supply is to the more anterior laminar and prelaminar layers.

In the acute phase of NAION, fluorescein angiography studies show delayed filling of the prelaminar layers of the edematous optic disc; this is the most compelling in vivo evidence to date of optic disc circulatory impairment in NAION [3, 16]. In studies by Arnold and Hepler [3], delayed prelaminar optic disc filling (≥5 s later than choroid and retinal vasculature) was demonstrable in 76% of subjects with acute NAION (Fig. 2.6). This feature was not seen in normal controls or in subjects with nonischemic optic disc edema [4], suggesting that the delayed filling represents a primary ischemic process rather than a mechanical process secondary to obstruction from the disc edema itself.

Arnold and Hepler [3] and Siatkowski et al. [57] both found that segmental parapapillary choroidal filling delay (≥5 s) was not a consistent feature in NAION (Fig. 2.6) (46% versus 58% in normal controls). These data speak against a

Fig. 2.6.  Fluorescein angiography in nonarteritic AION. There is significant filling delay of the optic disc after choroidal and retinal arteries have filled. The peripapillary choroid fills normally adjacent to the optic disc which fills poorly

proximal vascular occlusion in the short posterior ciliary arteries, which would produce a delay in both optic disc and choroidal filling, and against a choroidal origin, which would produce consistently delayed choroidal filling. They are consistent with flow impairment at the level of the paraoptic branches of the short posterior ciliary arteries described by Olver et al. [47].

2.2.2.3 Risk Factors

Although carotid occlusive disease may occasionally result in optic nerve ischemia, most often in the setting of more general ocular ischemia and occasionally with associated cerebral ischemia, the vast majority of cases are unrelated to carotid disease. Neither Fry et al. [18] nor Muller et al. [45] found hemodynamically significant stenosis in their series of subjects with NAION.

It is clear that acute severe systemic hypotension, particularly associated with anemia, can produce optic nerve ischemia (see below). Hayreh et al. [27] have proposed that less severe nocturnal systemic hypotension may play a role in the development of NAION, suggesting that the relative hypotension which normally occurs with sleep may chronically compromise optic disc circulation, particularly in those patients with an exaggerated nocturnal “dip,” or in patients, such as those with systemic hypertension, whose optic disc circulation autoregulatory mechanisms are impaired. This effect might be worsened with aggressive antihypertensive therapy, particularly if administered at night, by further exacerbating the nocturnal pressure drop. Hayreh et al [27] performed 24-h ambulatory blood pressure monitoring in a total of 114 NAION, 131 normal tension glaucoma (NTG), and 30 primary open angle glaucoma (POAG) subjects, implying that nocturnal systemic hypotension played a significant role in the development of NAION in certain susceptible subjects. No control subjects were studied. In contrast, Landau et al. [39] performed 24-h ambulatory blood pressure monitoring in 24 subjects with NAION and 24 age-, disease-, and medication-matched controls. Mean decreases of 11% systolic and 18% diastolic were measured in NAION, compared with 13% and 18% respectively in controls, showing

28

2

Ischemic Optic Neuropathies

no significant difference. The conflicting data from these two groups leave the role of nocturnal hypotension in NAION unresolved. We do, however, discuss with our patients and their physicians the possible accentuation of nocturnal hypotension by nighttime use of antihypertension medications; consideration of dosing other than at bedtime is recommended.

The sleep apnea syndrome (SAS) has been associated in some cases with optic disc edema, presumed to be the result of occult elevations in intracranial pressure. Occasional optic nerve damage was documented, but whether it resulted from chronic papilledema, the hypoxemia of SAS, or both has been unclear. In 2002, Mojon et al. [44] compared 17 consecutively seen NAION patients to 17 ageand sex-matched controls for evidence of SAS. Diagnostic criteria for SAS were met in 71% of the NAION patients versus 18% of controls. These studies are preliminary and involve small patient numbers, insufficient data from which to draw conclusions.

Nonarteritic AION has been reported in association with many conditions which may predispose to decreased optic nerve head perfusion via microvascular occlusion. Several cross-sec- tional case series have estimated the prevalence of systemic diseases which might predispose to vasculopathy in patients with NAION [10, 20, 31, 52]. Systemic hypertension was documented in 34%–49.4% of patients (47% in the IONDT) [31]; however, in several of the studies which compared these figures to matched population data from the National Health Survey, statistical significance was reached only in the younger age group, 45–64 years [20, 52]. Diabetes was reported in 5%–25.3% (24% in the IONDT) [31], with statistically significant increased prevalence in all ages in all but one study. Diabetes was associated with the development of NAION at a younger age in most series as well. In these series, the association of NAION with other cardiovascular events such as stroke and myocardial infarction was inconsistent.

Recent studies have addressed additional vasculopathic risk factors. Jacobson et al. [32] performed a case–control study in NAION, addressing hypertension and diabetes, along with smoking and hypercholesterolemia in 51

patients compared with two separate control groups. While hypertension was found in 57% of patients, it was not found to be significantly more prevalent than in controls in any age group; however, diabetes, found in 34%, was a significant risk factor in all age groups. Neither hypercholesterolemia nor smoking demonstrated significant risk. The 61-patient case–control study of Salomon et al. [55] also confirmed diabetes but not hypertension as a risk factor; hypercholesterolemia was found to be significant, while smoking was not. A large-scale (137 cases) but uncontrolled study by Chung et al. [12] concluded that smoking was a significant risk factor on the basis that smokers developed NAION at a significantly younger age than nonsmokers. Deramo and associates [15] reported 37 patients with NAION presenting before the age of 50, in which mean serum cholesterol was significantly elevated when compared with age-and gender-matched controls.

Elevated plasma homocysteine levels have been associated with an increased risk of premature ischemic events (peripheral vascular disease, stroke, myocardial infarction) in patients under 50, but the relation to NAION remains unclear. Kawasaki et al. [36] reported hyperhomocysteinemia in 2/17 cases of NAION under the age of 50, while Biousse et al. [9] reported normal values in 14/14 patients with a mean age of 43 years. Pianka et al. [48] reported elevated levels in 45% of 40 NAION patients (mean age 66 years) versus 9.8% of controls, and Weger et al. [60] also reported mean elevation (11.8 versus 9.8 µmol/l) in 59 NAION patients versus controls. The clinical significance of these statistically significant findings is uncertain, limited by small patient numbers and widely varying results.

Isolated reports have documented prothrombotic risk factors in patients with NAION, but a larger-scale recent study by Salomon et al. [55] has not confirmed an association with lupus anticoagulants, anticardiolipin antibodies, prothrombotic polymorphisms (factor V Leiden), or deficiencies of protein C, S and antithrombin III in a series of 61 patients with NAION versus 90 controls. However, they recently compared 92 consecutive patients with NAION to 145

controls for evidence of platelet glycoprotein polymorphisms [56]. They found a statistically significant association with the VNTR B allele in NAION versus controls; second eye involvement was more frequent and earlier in onset in those with the polymorphism. Further investigation is required to definitively establish these and other associations.

2.2.2.4 Medications

Two medications have been associated with the development of NAION (interferon-alpha and sildenafil), although the number of cases is insufficient to confirm a definite causative effect. A third, amiodarone, has been linked to NAION but probably produces a toxic optic neuropathy which mimics it.

lopathic risk factors. The optic discs in each case with available data showed the typical “crowded” configuration commonly seen in NAION; one patient had prior NAION in the fellow eye. The onset of visual loss was within 3 h of medication use in five cases. The postulated mechanism in these cases has been systemic hypotension in patients with structurally predisposed optic discs, possibly complicated by an exaggerated nocturnal dip in blood pressure. While the number of cases is extremely small, particularly considering the widespread use of the drug, the authors suggest that the drug may be contraindicated in patients with prior NAION, and that this group of patients should be counseled regarding the risk of developing NAION with further use. Additional data are required for definitive recommendations in this regard.

2.2.2.4.1 Interferon-alpha

This glycoprotein with antiviral, antitumor, and antiangiogenic effects is in use as adjuvant therapy for malignancies, including melanoma, leukemia, and lymphoma, and for chronic hepatitis C. Several reports [51] confirm the development of NAION, usually bilateral, sequential, and temporally associated with the institution of interferon therapy; recurrences with re-starting the medication have also been described. The clinical course is variable, with some cases showing improvement with discontinuance of therapy. Possible pathogenic mechanisms include in- terferon-induced systemic hypotension or immune complex deposition within the optic disc circulation.

2.2.2.4.2 Sildenafil

This commonly used therapy for erectile dysfunction may produce systemic hypotension; the therapeutic dose may reduce systemic BP by at least 10 mmHg. Pomeranz and Bhavsar [50] reviewed 14 cases of NAION reported in association with the use of sildenafil through 2005. The patients ranged in age from 42 to 69 years; 12 had known vascu-

2.2.2.4.3 Amiodarone

Amiodarone is in widespread use as a cardiac anti-arrhythmic agent and has been associated with the development of optic neuropathy. Macaluso et al. [42] summarized the data from 73 patients, including 16 published case reports and 57 patients with information recorded in the National Registry of Drug-Induced Ocular Side Effects, with optic neuropathy associated with amiodarone use. They emphasized that these patients with significant cardiovascular disease have risk factors for NAION and that many cases of optic neuropathy with amiodarone use may be typical NAION unrelated to the drug. A syndrome more consistent with medication toxicity, including insidious bilateral onset, generalized rather than altitudinal visual field loss, and chronic optic disc edema persisting months after onset of visual loss, was suggested as the more likely optic neuropathy related to amiodarone use. Limited visual recovery occurred in most cases after discontinuance of medication. The small number of cases precludes definitive conclusions; it remains to be seen whether, as in the case of certain antineoplastic agents such as cisplatin and BCNU [1,3-bis(2-chloroethyl)- 1-nitroso-urea], there may be a medication-in- duced microvasculopathy.

30

2

Ischemic Optic Neuropathies

Summary for the Clinician

■Risk factors for NAION may include hypertension, diabetes, hyperlipidemia, smoking, sleep apnea syndrome, and medications such as interferon-alpha, sildenafil, and amiodarone.

2.2.2.5 Clinical Course

Untreated, NAION generally remains stable, the majority of cases showing no significant improvement or deterioration over time [2, 10, 52]. Recent studies, however, indicate that spontaneous improvement of visual acuity occurs in a minority of patients. Recovery of at least three Snellen acuity lines has been reported in up to 42.7% (in the IONDT) [30] of patients.

After stabilization of vision, usually within 2 months, recurrent or progressive visual loss in an affected eye is extremely unusual and should prompt evaluation for another cause of optic neuropathy. Repka et al. [52] reported recurrent episodes in only 3 of 83 (3.6%) patients. Hayreh et al. [28] reported recurrence more than 2 months after the initial episode in 53 of 829 eyes (6.4%).

The optic disc becomes visibly atrophic, in a sectoral or diffuse pattern, usually within 4– 6 weeks; persistence of edema past this point should prompt consideration of an alternative diagnosis. Eventual involvement of the contralateral eye has been reported in 24%–39% with varying follow-up. Beck et al. [7], however, reviewed 431 patients with NAION, finding a substantially lower 5-year risk of 12%–19%; in the IONDT, fellow eye involvement at 5 years was estimated at 14.7%. Occurrence in the second eye produces the clinical appearance of the “pseudoFoster Kennedy syndrome,” in which the previously affected disc is atrophic and the currently involved nerve head is edematous. Significantly impaired visual field in the eye with disc edema distinguishes this condition from the true Foster Kennedy syndrome, in which disc edema is due to elevated intracranial pressure caused by a mass and does not produce visual loss acutely.

2.2.2.6 Differential Diagnosis

Nonarteritic AION must be differentiated from idiopathic optic neuritis, syphilitic or sarcoidrelated optic nerve inflammation, particularly in patients under 50 years of age; infiltrative optic neuropathies, anterior orbital lesions producing optic nerve compression, and idiopathic forms of optic disc edema, including diabetic papillopathy, are also considerations. Optic neuritis may resemble ischemia with regard to rate of onset, pattern of visual field loss, and optic disc appearance; however, in most cases, the patient’s younger age, pain with eye movement, and character of the disc edema (diffuse and hyperemic rather than pale or segmental) make distinction clear. Occasionally, ancillary testing such as fluorescein angiography, ultrasonography, or magnetic resonance (MR) imaging of the optic nerve may be helpful in differentiation. Fluorescein angiography often shows delayed optic disc filling in optic disc ischemia, whereas filling is normal in papillitis [4]. Ultrasonography and MR imaging are typically normal in NAION, while increased optic nerve diameter and a positive 30 degree test for perineural fluid may be seen on ultrasound in optic nerve inflammation. Intraorbital optic nerve swelling and enhancement are frequently seen on MR with inflammation and infiltration. Optic nerve inflammation associated with syphilis or sarcoidosis often is associated with other intraocular inflammatory signs, which should prompt further testing. Orbital lesions producing disc edema usually are associated with gradually progressive visual loss, but occasionally onset is more rapid. The detection of subtle signs of orbital disease, including mild proptosis, lid or eye movement abnormalities, or the persistence of optic disc edema past the usual 4–6 weeks in NAION, may indicate the need to perform neuroimaging to detect orbital inflammation or a tumor such as optic nerve sheath meningioma. In the great majority of cases, however, such testing is not required. Diabetic papillopathy typically does not produce significant afferent pupillary defect or visual field loss (see below).

In cases with typical presentation, without symptoms or signs to suggest GCA and with normal ESR and CRP, we do not routinely per-

form additional testing. Evaluation by a primary care physician for evidence and control of risk factors such as hypertension, diabetes, and hyperlipidemia is essential. Neuroimaging is not performed unless the patient follows an atypical course, such as prolonged optic disc edema, or continued progressive or recurrent visual loss more than 2 months after initial presentation.

2.2.2.7 Therapy

There is no proven effective therapy for NAION. Early medical therapies attempted included anticoagulants, diphenylhydantoin for its effect in improving conduction in hypoxic neurons, subtenons injections of vasodilators, intravenous intraocular-pressure-lowering agents and vasopressor agents (norepinephrine) to improve the gradient of nerve head perfusion pressure to intraocular pressure, thrombolytic agents and stellate ganglion block, oral corticosteroids in an attempt to decrease neuronal edema and any secondary damage related to it, aspirin, and hepa- rin-induced low-density lipoprotein/fibrinogen precipitation or hemodilution. None has been proven effective.

More recently applied nonsurgical modalities include hyperbaric oxygen and levodopa/carbidopa. Arnold et al. [5] treated 22 eyes in 20 patients with acute NAION, using hyperbaric oxygen at 2.0 atm (202,650 Pa) twice a day for 10 days, comparing visual outcome to 27 untreated acute NAION controls; no beneficial effect was found. Johnson et al. [34] reported 18 patients with NAION treated with a 3-week course of levodopa/carbidopa within 45 days of visual loss, compared with 19 historical untreated controls. At 6 months, 10/13 (76.9%) treated versus 3/10 (30%) controls improved at least three lines in Snellen visual acuity testing. The study was limited by small numbers and possible confounding factors, and results have not been corroborated by other investigators. This therapeutic modality remains unproven.

The Ischemic Optic Neuropathy Decompression Trial (IONDT) of optic nerve sheath decompression surgery for NAION was based on the beneficial effect of the surgery in the optic

neuropathy of elevated intracranial pressure and the postulate that reduction of perineural subarachnoid cerebrospinal fluid pressure could improve local vascular flow or axoplasmic transport within the optic nerve head, thus reducing tissue injury in reversibly damaged axons. Recruitment for the study was ceased after 2 years, with 119 treated versus 125 controls, when data analysis revealed no significant benefit for treatment (improvement in visual acuity by at least three lines in 32.6% treated versus 42.7% control) [30]. Moreover, the treatment group showed a statistically significantly greater risk for worsening by three lines or more (23.9% treated versus 12.4% control). The 24-month follow-up data from the study confirmed the initial 6 months report. This technique is not currently recommended for the treatment of NAION.

Transvitreal radial optic neurotomy has been proposed as a therapy for both central retinal vein occlusion (CRVO) and NAION [58]. The procedure involves a pars plana vitrectomy and induced posterior vitreous detachment, associated with a stab incision at the nasal margin of the optic disc, with the purpose of opening the scleral canal and relieving compression of an edematous optic nerve. If a compartment syndrome is at least a component of the pathophysiology of NAION, then such a procedure in theory could break the cycle of edema and vascular compression. Soheilian et al. [58] reported the results of transvitreal neurotomy performed in seven cases of NAION with severe visual loss (visual acuity range CF-20/800) and onset prior to surgery ranging 15–90 days. Improvement of visual acuity was noted in six patients with a final range of CF-20/60. This study was limited by several factors, including small patient numbers, sample bias (i.e., severe visual loss with difficulty accurately measuring preand postoperative visual levels), and delayed onset of therapy. The authors emphasized the experimental nature of this procedure and recommended a randomized clinical trial prior to considering this approach.

2.2.2.8 Prevention

There is no proven prophylactic measure for NAION. Although aspirin has a proven effect in

32

2

Ischemic Optic Neuropathies

reducing stroke and myocardial infarction (MI) in patients at risk, published data regarding its role in decreasing the incidence of fellow-eye involvement after the initial episode have been controversial. Both Kupersmith et al. [38] and Salomon et al. [54] found a significant beneficial effect, while a larger retrospective review by Beck et al. [7] studied 431 patients with NAION for second-eye involvement with and without aspirin use. The 5-year risk for fellow-eye involvement was calculated at 12%–19%, and no long-term benefit for aspirin use was found [7]. Although beneficial long-term effects remain unproven for NAION, many experts recommend the use of aspirin after an initial episode, if only for its role in decreasing risk for stroke and MI in this vasculopathic population group.

Summary for the Clinician

■There is no proven effective therapy for NAION.

■Low-dose aspirin may reduce the risk of fellow-eye involvement.

2.3Posterior Ischemic Optic Neuropathy

Although the anterior form of ION is far more common than the posterior variety, ischemia of the retrobulbar portions of the optic nerve occurs in many settings, both arteritic and nonarteritic. Posterior ischemic optic neuropathy (PION) is a syndrome of acute visual loss with characteristics of optic neuropathy without disc edema and is marked by the subsequent development of optic atrophy. The diagnosis of PION is most often made in one of two settings [23]:

1.Giant cell arteritis (GCA) or, rarely, other vasculitides such as herpes zoster, polyarteritis nodosa, or lupus erythematosus. Evaluation for GCA is essential in cases without other apparent cause, and should be the primary consideration with this presentation in the elderly, with urgent ancillary testing as described earlier for AION.

2.The combination of systemic hypotension and anemia, usually related to blood loss either from surgery (coronary artery bypass and lumbar spine procedures most frequently reported), gastrointestinal bleed, or trauma.

The differential diagnosis includes compressive and infiltrative optic neuropathies, although the onset in PION is typically more abrupt. In most cases, neuroimaging is indicated to rule out these possibilities. While NAION typically shows no enhancement of the optic nerves on MR, presumably due to limitation to the optic nerve head, in PION enhancement has been demonstrated and must be differentiated from other causes, such as inflammation and infiltration.

Recently, Sadda et al. [53] reported a multicenter, retrospective review covering 22 years, revealing 72 patients with PION, classifying them in three groups:

1.Perioperative

2.Arteritic

3.Nonarteritic

The nonarteritic group accounted for 38 of the 72 patients, exhibited similar risk factors, and followed a clinical course precisely like that of NAION. In contrast to perioperative and arteritic PION, which were characterized by severe visual loss with little or no recovery, nonarteritic PION was less severe and showed improvement in 34% of patients. It is important to recognize this nonarteritic form in patients with acute optic neuropathy but no optic disc edema, a scenario that may be mistaken for optic neuritis. Such patients, as in some patients with AION and disc edema, particularly those with ischemic white-matter lesions on MRI, might be incorrectly begun on immunomodulatory therapy to reduce the risk of multiple sclerosis. PION differs from optic neuritis by its occurrence in older age groups, with lack of pain on eye movements. Table 2.1 summarizes the clinical and paraclinical characteristics of AION and PION.

Summary for the Clinician

■PION occurs most frequently in GCA and acute hypotension with blood loss, but occasionally is present in an idiopathic form.

■There is no proven effective therapy.

References

1.Aiello PD, Trautmann JC, McPhee TJ et al (1993) Visual prognosis in giant cell arteritis. Ophthalmology 100:550–555

2.Arnold AC, Hepler RS (1994) Natural history of nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol 14:66–69

3.Arnold AC, Hepler RS (1994) Fluorescein angiography in acute anterior ischemic optic neuropathy. Am J Ophthalmol 117:222–230

4.Arnold AC, Badr M, Hepler RS (1996) Fluorescein angiography in nonischemic optic disc edema. Arch Ophthalmol 114:293–298

5.Arnold AC, Hepler RS, Lieber M, Alexander JM (1996) Hyperbaric oxygen therapy for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 122:535–541

6.Beck RW, Servais GE, Hayreh SS (1997) Anterior ischemic optic neuropathy. IX. Cup-to-disc ratio and its role in pathogenesis. Ophthalmology 94:1503–1508

7.Beck RW, Hayreh SS, Podhajsky PA et al (1997) Aspirin therapy in nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 123:212–217

8.Beri M, Klugman MR, Kohler JA et al (1987) Anterior ischemic optic neuropathy. VII. Incidence of bilaterality and various influencing factors. Ophthalmology 94:1020–1028

9.Biousse V, Kerrison JB, Newman NJ (2000) Is non-arteritic anterior ischaemic optic neuropathy related to homocysteine? Br J Ophthalmol 84:554

10.Boghen DR, Glaser JS (1975) Ischaemic optic neuropathy. The clinical profile and natural history. Brain 98:689–708

11.Boyev LR, Miller NR, Gree WR (1999) Efficacy of unilateral versus bilateral temporal artery biopsies for the diagnosis of giant cell arteritis. Am J Ophthalmol 128:211–215

12.Chung SM, Gay CA, McCrary JA (1994) Nonarteritic anterior ischemic optic neuropathy. The impact of tobacco use. Ophthalmology 101:779–782

13.Danesh-Meyer HV, Savino PJ, Eagle RC Jr. et al (2000) Low diagnostic yield with second biopsies in suspected giant cell arteritis. J Neuroophthalmol 20:213–215

34

2