What to tell your next patient with non-arteritic anterior ischemic optic neuropathy (NAION) … other than “nothing can be done”

Andrew G. Lee

Department of Ophthalmology, Neurology, and Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA

Introduction

Non-arteritic anterior ischemic optic neuropathy (NAION) is a common cause for visual loss in adults but the precise etiology remains elusive and is likely multifactorial. This chapter will review several hypotheses regarding the pathogenesis of NAION; will discuss some preventive measures that might decrease the chance of fellow eye involvement; will summarize the current status of treatment; and will make some recommendations for counseling patients with NAION. The author emphasizes however, that the pathogenesis and etiology of NAION remain controversial and that the recommendations of this article reflect the author’s opinions, experience and current practice and should not be construed as a ‘standard of care’.

Case

A 60-year-old man presented with acute painless loss of vision OD. Past medical history was significant for poorly controlled hypertension (blood pressure of 200/ 80) and variably controlled diabetes mellitus (blood sugars in 300 mg/dL and hemoglobin A1C of 10), elevated cholesterol, and coronary artery disease. The patient had a 40-pack-year smoking history and drank three glasses of wine each evening before bed. Medications included oral atenolol at night, insulin, and atorvastatin. He occasionally used sildenifil and took a sleeping pill at night on a periodic basis. He had daytime sleepiness and the wife stated that he snored loudly. The visual acuity was 20/200 OD and 20/20 OS. There was a right relative afferent pupillary defect. Visual field testing was normal OS but showed an inferior altitu-

Address for correspondence: A.G. Lee, MD, Department of Ophthalmology, 200 Hawkins Drive, PFP, Univerisity of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. E-mail: andrewlee@uiowa.edu

Eye on the Bayou, New Concepts in Glaucoma, Cataract and Neuro-Ophthalmology, pp. 25–30 Transactions of the 54th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, February 18-20, 2005

edited by Jonathan D. Nussdorf

© 2006 Kugler Publications, The Hague, The Netherlands

Fig. 1. Optic disc photograph shows a swollen optic nerve of the right eye with peripapillary hemorrhage in a patient with non-arteritic anterior ischemic optic neuropathy.

dinal defect OD. Ophthalmoscopy showed a small cup to disc ratio and a few disc drusen OS. The right optic nerve showed optic disc edema with a few peripapillary hemorrhages (Fig. 1). Serum erythrocyte sedimentation rate and C-reactive protein were normal. There was no headache, scalp tenderness, or jaw claudication. The patient was diagnosed with NAION and was told: “You have had a stroke in your optic nerve, there is no treatment, and nothing can be done.” The patient left depressed and with a feeling of hopelessness.

What causes non-arteritic ischemic optic neuropathy?

The cause for NAION is unknown. Several vasculopathic risk factors have been implicated but no single factor is likely to be sufficient or necessary for the disor- der.1-12 Table 1 lists a number of proposed associated factors in NAION.

What is the evaluation for NAION?

The ophthalmologist should consider contacting the patient’s primary care physician to diagnose, evaluate, and possibly treat any underlying vasculopathic risk factors (e.g., hypertension, diabetes, atherosclerosis, high cholesterol). Smoking cessation should be strongly encouraged.11 Although the evidence for aspirin use to prevent fellow eye involvement in NAION is conflicting, patients with specific

Table 1. Some proposed risk factors for NAION (courtesy of Robert Sergott, MD)

•Hypertension or Hypotension (nocturnal, iatrogenic, or post-surgical)

•Hyperglycemia (Diabetes mellitus)

•Hyperlipidemia (hypercholesterolemia)

•Hyperhomocysteinemia

•Hypoxia (e.g., smoking)

•Hypoperfusion (e.g., fluid overload, atherosclerosis, rarely embolic)

•Hematocrit low (e.g., anemia, severe blood loss)

•Hypersomnia (obstructive sleep apnea)

•High intraocular pressure (? role in post cataract surgery NAION)

Table 2. Selected medications that might cause or worsen hypotension

•Anti-hypertensives (e.g., beta blockers, calcium channel blockers)

•Diuretics (e.g., furosemide, acetazolamide, hydrochlorthiazide)

•MAO inhibitors (e.g., isocarboxazid, phenelzine, tranylcypromine for depression)

•Tricyclics (e.g., amitriptyline)

•Phenothiazines (e.g., thioridazine)

•Vasodilators (e.g., nitrates, hydralazine)

•Alpha-blockers (e.g., doxazosin, terazosin, tamsulosin)

•Sedatives (e.g,. barbiturates, opiates)

•Other medications (e.g., quinidine, levodopa, vincristine, sildenifil)

vasculopathic risk factors might benefit from anti-platelet therapy to reduce the risk of myocardial infarction. Aspirin therapy however has no apparent effect on visual outcome in NAION.16

A small cup to disc ratio has been proposed as a structural risk factor for NAION. Patients with no other vasculopathic risk factors, especially young patients, might have underlying optic disc drusen (and a crowded and small optic disc).17 Ocular ultrasound for buried disc drusen might be useful in establishing a risk factor for NAION in such patients. Obstructive sleep apnea might be an additional treatable risk factor and the clinician might inquire about snoring and excessive daytime sleepiness, especially in obese middle aged males.18

Nocturnal alcohol use, bed-time dosing of anti-hypertensives, and other medications at night (including topical beta blockers, sedative, and sildenifil19,20) might also be related to NAION. Table 2 lists potential medications that might cause hypotension and overaggressive treatment of hypertension should be avoided. Appropriate consultation with the primary care physician is advised before altering the medication regimen of the patient, however.

Although the precise etiology of NAION is unknown, embolic and hypercoaguable state are rare causes. In typical NAION, no hypercoaguable state work up is indicated. Likewise, cardiac echo and carotid Doppler are not necessary. Patients with a visible embolus, involvement of multiple circulations (e.g., choroidal or retinal artery occlusion or cotton wool patches), or prior transient visual loss episodes preceding the AION might benefit from more aggressive thrombotic and embolic evaluation however. Anti-phospholipid antibody and plasma homocysteine have been implicated in NAION especially in young patients without vasculopathic risk factors or with recurrent disease but there is insufficient evidence to

make a firm evidence-based recommendation on the diagnostic yield for these tests especially for typical NAION.21-27

Neuroimaging studies are not necessary in typical unilateral NAION. Patients with atypical features including progressive visual loss, optic atrophy at presentation, or persistent optic disc edema (> 2 months) might benefit from magnetic resonance imaging of the head and orbit with gadolinium and fat suppression to exclude a compressive etiology (e.g., optic nerve sheath meningioma).

Role of the ophthalmologist

The most important priority for the ophthalmologist dealing with AION is to exclude giant cell arteritis (e.g., laboratory testing, temporal artery biopsy, corticosteroids as necessary).28 The roles of the ophthalmologist in NAION should be to reassure the patients; to educate them on the treatable vasculopathic, lifestyle, and pharmaceutical risk factors, and to give hope to the patient. Typical NAION usually remains static or slightly improves over time once the disc edema phase resolves. The incidence of fellow eye involvement in NAION was 14.7% in the ischemic optic neuropathy decompression trial (IONDT) cohort over 5 years.29 Patients should be told that once the disc edema resolves NAION is unlikely to recur in the same eye (6%) and that NAION is not typically a progressive or blinding disorder once the optic disc edema subsides.

Physicians should avoid telling the patient that “nothing can be done” as it is not helpful to the patient and probably not true. Patients with visual loss may suffer a grief reaction, depression and feelings of hopelessness that might respond to simple counseling regarding the natural history of NAION. Patients with bilateral AION may benefit from low vision services.

What are the treatments for NAION?

Although many interventions have been tried (e.g., anticoagulants and antiplatelet agents, diphenylhydantoin, levodopa, and hyperbaric oxygen), there remains no proven effective and widely accepted therapy in NAION. The major recommendation for NAION is to evaluate and treat any underlying risk factors and reduce the risk to the fellow eye. This should be done in coordination with the patient’s primary care physician.

Topical brimonidine and memantine have been purported to have neuroprotective properties in animals but any effect in NAION would be strictly theoretical and is completely unproven in humans. Corticosteroids have been the mainstay of treatment for arteritic ION but are unproven in NAION. Levodopa is a controversial therapy in NAION. The published studies showed some positive effect for levodopa on visual acuity in NAION but the studies were compromised by small sample sizes and significant statistical and methodologic concerns. Optic nerve decompression was shown in a randomized trial to be ineffective, may in fact be harmful, and has largely been abandoned. Other surgical procedures have been proposed (e.g., transvitreal optic neurotomy) but remain unproven and have weak biological rationale for efficacy.

Summary

In summary, the diagnosis of NAION is a clinical one. The major responsibility of the ophthalmologist is to exclude giant cell arteritis (i.e., arteritic AION). The evaluation and management should be directed to the underlying vasculopathic risk factors. Smoking cessation should be encouraged. Patients might consider discontinuing exacerbating factors for nocturnal hypotension (e.g., nocturnal alcohol use, nocturnal sedative or antihypertensive use). Aspirin therapy might be useful for reduction of myocardial infarction risk in at-risk patients. To date, there is no proven effective and widely accepted therapy for NAION. Patients should be counseled regarding the natural history of the disorder, the risk to the fellow eye, and provided with low vision services as needed.

References

1.Arnold AC: Ischemic optic neuropathies. Ophthalmol Clin North Am 14:83-98, 2001

2.Hayreh SS: Treatment of IOH and risk of visual complications. Arch Intern Med 162:15261528, 2002

3.Hayreh SS: Risk factors in AION. Ophthalmology 108:1717-1718, 2001

4.Hayreh SS: Blood flow in the optic nerve head and factors that may influence it. Prog Retin Eye Res 20:595-624, 2001

5.Hayreh SS, The blood supply of the optic nerve head and the evaluation of it - myth and reality. Prog Retin Eye Res 20:563-593, 2001

6.Hayreh SS: Role of nocturnal arterial hypotension in the development of ocular manifestations of systemic arterial hypertension. Curr Opin Ophthalmol 10:474-482, 1999

7.Hayreh SS, Podhajsky P, Zimmerman MB: Beta-blocker eyedrops and nocturnal arterial hypotension. Am J Ophthalmol 128:301-309, 1999

8.Hayreh SS, Podhajsky P, Zimmerman MB: Role of nocturnal arterial hypotension in optic nerve head ischemic disorders. Ophthalmologica 213:76-96, 1999

9.Hayreh SS, Podhajsky PA, Zimmerman B: Nonarteritic anterior ischemic optic neuropathy: time of onset of visual loss. Am J Ophthalmol 124:641-647, 1997

10.Hayreh SS, Joos KM, Podhajsky PA, Long CR: Systemic diseases associated with nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 118:766-780, 1994

11.Chung SM, Gay CA, McCrary JA 3rd: Nonarteritic ischemic optic neuropathy. The impact of tobacco use. Ophthalmology 101:779-782, 1994

12.Deramo VA, Sergott RC, Augsburger JJ, et al: Ischemic optic neuropathy as the first manifestation of elevated cholesterol levels in young patients. Ophthalmology 110:1041-1046, 2003

13.Beck RW, Hayreh SS: Role of aspirin in reducing the frequency of second eye involvement in patients with non-arteritic anterior ischaemic optic neuropathy. Eye 14:118, 2000

14.Salomon O, Huna-Baron R, Steinberg DM, Kurtz S, Seligsohn U: Role of aspirin in reducing the frequency of second eye involvement in patients with non-arteritic anterior ischaemic optic neuropathy. Eye 13:357-359, 1999

15.Kupersmith MJ, Frohman L, Sanderson M, Jacobs J, Hirschfeld J, Ku C, Warren FA: Aspirin reduces the incidence of second eye NAION: a retrospective study. J Neuroophthalmol 17:250-253, 1997

16.Botelho PJ, Johnson LN, Arnold AC: The effect of aspirin on the visual outcome of nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 121:450-451, 1996

17.Purvin V, King R, Kawasaki A, Yee R: Anterior ischemic optic neuropathy in eyes with optic disc drusen. Arch Ophthalmol 122:48-53, 2004

18.Mojon DS, Hedges TR 3rd, Ehrenberg B, et al: Association between sleep apnea syndrome and nonarteritic anterior ischemic optic neuropathy. Arch Ophthalmol 120:601-605, 2002

19.Boshier A, Pambakian N, Shakir SA: A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil. Int J Clin Pharmacol Ther 40:422-423, 2002

20.Pomeranz HD, Smith KH, Hart WM Jr, Egan RA: Sildenafil-associated nonarteritic anterior ischemic optic neuropathy. Ophthalmology 109:584-587, 2002

21.Pianka P, Almog Y, Man O, et al: Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic neuropathy, central retinal artery occlusion, and central retinal vein occlusion. Ophthalmology 107:1588-1592, 2000

22.Biousse V, Kerrison JB, Newman NJ: Is non-arteritic anterior ischaemic optic neuropathy related to homocysteine? Br J Ophthalmol 84:555, 2000

23.Kawasaki A, Purvin VA, Burgett RA: Hyperhomocysteinaemia in young patients with nonarteritic anterior ischaemic optic neuropathy. Br J Ophthalmol 83:1287-1290, 1999

24.Kalogeropoulos CD, Spyrou P, Stefaniotou MI, et al : Anticardiolipin antibodies and occlusive vascular disease of the eye: prospective study. Doc Ophthalmol 95:109-120, 1998

25.Togashi M, Numata K, Yamamoto S, Hayasaka S: Anterior ischemic optic neuropathy in a patient with positive antinuclear antibody and lupus anticoagulant findings. Ophthalmologica 210:132-135, 1996

26.Acheson JF, Sanders MD: Coagulation abnormalities in ischaemic optic neuropathy. Eye 8:89-92, 1994

27.Galetta SL, Plock GL, Kushner MJ, Wyszynski RE, Brucker AJ: Ocular thrombosis associated with antiphospholipid antibodies. Ann Ophthalmol 23:207-212, 1991

28.Kay MC: Ischemic optic neuropathy. Neurol Clin 9:115-129, 1991

29.Newman NJ, Scherer R, Langenberg P, Kelman S, et al: Ischemic Optic Neuropathy Decompression Trial Research Group. The fellow eye in NAION: report from the ischemic optic neuropathy decompression trial follow-up study. Am J Ophthalmol 134:317-328, 2002

30.Arnold AC, Levin LA: Treatment of ischemic optic neuropathy. Semin Ophthalmol 17:3946, 2002

31.Soheilian M, Koochek A, Yazdani S, Peyman GA: Transvitreal optic neurotomy for nonarteritic anterior ischemic optic neuropathy. Retina 23:692-697, 2003

32.Fazzone HE, Kupersmith MJ, Leibmann J: Does topical brimonidine tartrate help NAION? Br J Ophthalmol 87:1193-1194, 2003

33.Bojic L, Ivanisevic M, Gosovic G: Hyperbaric oxygen therapy in two patients with nonarteritic anterior optic neuropathy who did not respond to prednisone. Undersea Hyperb Med 29:86-92, 2002

34.Kim TW, Kim DM, Park KH, Kim H: Neuroprotective effect of memantine in a rabbit model of optic nerve ischemia. Korean J Ophthalmol 16:1-7, 2002

35.Wheeler LA, Woldemussie E: Alpha-2 adrenergic receptor agonists are neuroprotective in experimental models of glaucoma. Eur J Ophthalmol 11 Suppl 2:S30-5, 2001

36.Guy J: New therapies for optic neuropathies: development in experimental models. Curr Opin Ophthalmol 11:421-429, 2000

37.Johnson LN, Guy ME, Krohel GB, Madsen RW: Levodopa may improve vision loss in re- cent-onset, nonarteritic anterior ischemic optic neuropathy. Ophthalmology 107:521-526, 2000

38.Hayreh SS: Does Levodopa improve visual function in NAION? Ophthalmology 107:14341438, 2000

39.Cox TA: Does levodopa improve visual function in NAION? Ophthalmology. 107:1431, 2000

40.Beck RW: Does Levodopa improve visual function in NAION? Ophthalmology 107:14311434, 2000

41.Ischemic Optic Neuropathy Decompression Trial: Twenty-four-month update. Arch Ophthalmol 118:793-798, 2000

42.Dickersin K, Manheimer E: Surgery for nonarteritic anterior ischemic optic neuropathy. Cochrane Database Syst Rev CD001538, 2000