REVIEW

Anterior Ischemic Optic Neuropathy (AION)

Harinder Singh Sethi, MD,DNB,FRCS Vimla Menon, MS, Rohit Saxena, MD Anterior ischemic optic neuropathy (AION) is the most common cause of acute optic neuropathy in older age groups. AION is a potentially blinding disorder. Field defects typical of ischemic optic neuropathy were first described by Knapp in 1875. Miller and Smith first used the term ischemic optic neuropathy in 1966, and Hayreh later added the term anterior. In 1924, Uhthoff first described severe visual loss, with field defects and swollen optic discs. Clinical Classification of AION Depending upon the underlying cause, AION is of two types 1. 2. Arteritic : This is the most serious type and is due to giant cell arteritis. Non-arteritic: This is the most common one, and consists of all cases other than those due to giant cell arteritis. 1. Due to Thrombosis or Embolism of the posterior ciliary arteries or their Subdivisions. (i) Thrombosis: Most common cause is giant cell arteritis (temporal arteritis), and less commonly other types of vasculitis. (ii) Embolism: These seem to occur much less frequently than those due to thrombosis. In this group, there is usually massive, severe, and permanent damage to the optic nerve head, the extent of which depends on the size of the artery involved and the area of the optic nerve head supplied by the blocked artery. 2. Due to transient poor circulation or no circulation in the Blood Vessels of the Optic Nerve Head

Etiopathogenesis AION is due to acute ischemia of the anterior part of the optic nerve (the optic nerve head) due to involvement of posterior ciliary artery circulation in the optic nerve head. There is marked inter-individual variation in the blood supply and blood flow patterns in the optic nerve head . This is responsible for a marked variation in the clinical features of AION in different individuals. According to Hayreh , from the mechanism of development point of view, AION cases can be broadly classified into two groups:

This is by far the most common cause of AION , indeed almost all AION cases which are not due to inflammation of the arteries (i.e. non-arteritic AION). Transient poor circulation or loss of circulation in the optic nerve head can occur due to a transient fall of blood pressure below a critical level in its vessels, which in turn, in susceptible persons, would produce AION. In this mode of development of AION there is no actual blockage of the posterior ciliary arteries. A fall of the blood pressure below the critical level in the capillaries of the optic nerve head may be caused either by a marked fall in blood pressure (e.g., in shock, fall of blood pressure during sleep at night, blockage or severe narrowing of the internal carotid artery and/or ophthalmic artery, and other causes) or by a rise in the eye pressure, or a combination of these factors The optic nerve head damage is usually less extensive and less severe than that due to thrombosis or embolism. Risk factors for Non-arteritic AION The non-arteritic AION is multifactorial disorder and the risk factors for it are as follows : Systemic risk factors Various systemic risk factors are arterial hypertension , diabetes mellitus, and ischemic heart disease, thyroid disease, chronic obstructive pulmonary disease and cerebrovascular disease, systemic collagen vascular diseases, systemic arterial hypotension, arteriosclerosis, internal carotid artery disease, cardiac valvular disease, migraine and other vasospastic disorders. Among these , nocturnal arterial hypotension (i.e. fall of blood pressure during sleep) seems to play a very important role in the development of non-arteritic AION and is often considered a precipitating factor.

Right AION (Pallid Disc Odema with Splinter Hemorrhages)

Dr. R.P. Centre for Ophthalmic Sciences AIIMS, New Delhi

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Ocular risk factors These conditions include absent or small cup in the optic disc, raised intraocular pressure (e.g., during the immediate post-operative period after cataract extraction, in acute angle closure glaucoma, or prolonged pressure on the eyeball from any cause), marked optic disc edema due to any cause and defective blood flow autoregulation etc Clinical Features Arteritic AION is a disease of patients aged 55 years and older while Non-arteritic AION can occur at any age . No age is immune from non-arteritic AION - although most often patients are middle aged and elderly, about 10% of the patients are young. Arteritic AION is almost three times more common in women than in men. while non-arteritic AION usually affects men and women almost equally. A typical patient of non-arteritic AION presents with sudden and painless deterioration of vision, usually discovered on waking in the morning. Patient often complains of involvement of the lower part of the visual field in one eye. In arteritic AION, patient may have complaints of transient blurring or loss of vision in the involved eye before the permanent loss of vision in that eye. In non-arteritic AION visual acuity may vary from 6/ 6 to marked loss of vision, depending upon the part of the ONH involved by the AION. By contrast, in arteritic AION the visual loss usually is much worse. Perimetry is the most important visual function test to evaluate the visual loss in AION. Perimetry usually shows partial or complete loss of vision in one or the other part of the field of vision. On ophthalmoscopic examination, during the initial stages, the optic disc shows pallid edema which may be more marked in one part of the disc than the other . Splinter hemorrhages may be present at the disc margin. The optic disc swelling has a characteristic chalky white appearance in arteritic AION. Within 2-3 months the optic disc swelling resolves spontaneously and the disc becomes pale either in only one region or all over .In non-arteritic AION the fellow, normal optic disc shows either no cup or a very small cup. Investigations The most important test in any patient with AION is the erythrocyte sedimentation rate (ESR). In patients with arteritic AION, the ESR usually is elevated, although 10% of patients may have a normal ESR. In NAION, the ESR is more likely to be normal, assuming no comorbid condition is present. The Westergren ESR is thought to be more reliable than the Wintrobe ESR. The C-reactive protein (CRP), have been found useful in diagnosing giant cell arteritis in cases with normal ESR levels. Fluorescein

angiography has been suggested as a possible method of distinguishing arteritic AION from NAION. With arteritic AION, a markedly prolonged choroidal filling time usually is present. Temporal artery biopsy is used to diagnose giant cell arteritis. It is especially useful in patients with any of the symptoms of giant cell arteritis or in a patient with visual loss and a high ESR. Whenever possible, a biopsy specimen of at least 2-3 centimeters should be obtained to minimize the possibility of skip lesions. Bilateral temporal artery biopsy should be considered if giant cell arteritis is still suspected despite initial negative temporal artery biopsy. Biopsy generally should be performed within 4 weeks of initiation of steroid treatment. Giant cell arteritis has a characteristic inflammatory infiltrate that has a granulomatous appearance, sometimes with giant cells. The use of frozen section for temporal artery biopsy is very useful in determining arteritis, and it may establish the diagnosis with a single temporal artery biopsy. Rarely, if the initial temporal artery biopsy is negative, contralateral biopsy may be positive due to minimal involvement or skip areas. Fluorescein Fundus Angiography In non-arteritic AION, during the very early stages of the disease, angiography may show filling defects in the optic disc, peripapillary choroid and/or choroidal watershed zones . In arteritic AION this test is extremely helpful in making the diagnosis because it shows that the choroid and the optic disc in the area supplied by the involved posterior ciliary artery do not fill. During the late phase of angiography, the disc stains with fluorescein; this is a nonspecific finding in both types of AION. Management of AION Once the diagnosis of AION is made, the first, most important step in all patients aged 55 and over is to rule out giant cell arteritis immediately - because that is a prime ophthalmic emergency, since patients with giant cell arteritis are in danger of bilateral total blindness. Blindness is almost always preventable with aggressive treatment. It is of utmost importance to differentiate arteritic AION due to giant cell arteritis from non-arteritic AION to prevent this tragedy ( Table 1 ) . A) Arteritic AION and giant cell arteritis The treatment of choice for giant cell arteritis is systemic corticosteroids. If there is a reasonable index of suspicion of giant cell arteritis in patients presenting with AION, it is essential to start high doses of systemic corticosteroid, immediately, as an emergency measure. One should not wait for the result of temporal artery biopsy to start the steroids because by the time the biopsy is done and its results available, the patient could have lost further vision DOS Times - Vol.10, No. 4

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in one or both eyes. The visual loss due to arteritic AION is almost always permanent. Temporal artery biopsy should be done as soon as possible. Starting the treatment does not interfere with the results of biopsy. If the biopsy result is negative , the drug can be stopped. Treatment should be started with high-dose corticosteroid therapy (80 - 120 mg of prednisone orally daily). It is important to stress to the patient that the treatment is essentially suppressive and not curative, and most probably life-long. All patients are maintained at the high dose of Prednisone till both the ESR and CRP have stabilized at low levels (This usually requires 2-3 weeks CRP comes down much faster than ESR ) after that very gradual tapering of Prednisone is started, guided by the ESR and CRP levels only. Some Neuro-ophthalmologists prefer initial 3 days of intravenous steroid therapy with dexamethasone ( 100 mg ) or methylprednisolone ( 1g) followed by oral steroids. Results of Hayrehs series of cases showed no evidence that intravenous megadose steroid therapy was more effective than oral therapy in cases of Giant cell arteritis. The most reliable and sensitive parameters to regulate and taper down steroid therapy are the levels of ESR and CRP. Tapering down of steroids is not indicated till both ESR and CRP have stabilized.The lowest level of ESR and CRP achieved provides a guideline for future management also. The lowest maintenance dose of prednisone at which the ESR and CRP stayed low and stable should be reached. The tapering down of steroid therapy and determining the maintenance dose is a slow and laborious job which requires individualization. B) Non - arteritic AION There is no established treatment for non-arteritic AION. Over the years a number of medical and surgical treatments have been tried without much success. There is no role of oral steroids in NAION Currently, many Ophthalmologists advise use of an aspirin daily to prevent involvement of the second eye. Its long term efficacy is not known. A study by Johnson et al has shown that levodopa improves visual function in nonarteritic AION. But the results still need to be reconfirmed with randomised controlled trial and longer follow-up. Surgical Treatments Optic nerve fenestration was advocated for AION until the completion of the Ischemic Optic Neuropathy Decompression Trial (IONDT). This study conclusively showed no effect of the surgery. Advocates for decompression in the patient with progressive AION still exist, but, to date, no evidence is available to establish the effectiveness of this treatment. Soheilian et al had tried transvitreal optic neurotomy for NAION with improvement in visual acuity in their patients. Despite October, 2004

improvement of visual acuity in their patients, transvitreal optic neurotomy should be considered experimental, requiring a randomized clinical trial. Prophylactic Measures Patients should be advised to reduce as many risk factors as possible to reduce the risk of developing any further episode of AION. The patients with evidence of nocturnal arterial hypotension should be managed appropriately for the prevention of non-arteritic AION in the second eye. Prognosis of AION Arteritic AION: Only 4% of eyes with visual loss due to arteritic AION improved, as judged by improvement in both visual acuity and central visual field. 4 % of eyes with Arteritic AION experience further visual deterioration while on high doses of steroid therapy.. It is clear from reports in the literature, that if a patient is given inadequate steroid therapy or the therapy is tapered off prematurely, visual deterioration can develop anytime. This shows that early, adequate steroid therapy is effective in preventing further visual loss in 96% of the giant cell arteritis patients. There is no evidence that intravenous megadose steroid therapy is more effective than oral therapy in preventing visual deterioration. Non-arteritic AION Once the optic disc edema has resolved, which usually takes 2-3 months, the vision usually remains stable in that eye. Recurrence of non-arteritic AION in the same eye is uncommon (only 6 % ) . The risk of second eye involvement by non-arteritic AION is about 25% on a follow-up of about 3 years. In non-arteritic AION, the risk of developing AION in the second eye is significantly greater in young persons especially if they are diabetic and in men as compared to females. Patient Counselling AION is a very frustrating disease for both patients and physicians, because little can be performed to treat it.. Once visual loss has occurred, little can be performed to restore it. Awareness of the entity of giant cell arteritis is important both to physicians and patients, as the intervention of steroids may prevent loss of vision in the other eye, as well as prevention of considerable comorbidity in other organ systems. General health measures (eg, control of blood pressure, obesity, diabetes, smoking) are important, but bear little result in recovery of vision that is already lost.

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Table 1 Arteritic Age Sex Preceding systemic Manifestations Preceding ocular symptoms (amaurosis fugax) Early massive visual loss Pain Second Eye involvement Disc appearance Associated with cilioretinal artery occlusion FFA ESR C reactive protein TEMPORAL ARTERY BIOPSY: Response to steroids Mostly over 70 yrs More in females Jaw claudication, headache, scalp tenderness , neck pain, fever etc Highly Suggestive Highly suggestive Common 75 % within days or weeks Chalky white swollen Disc Almost diagnostic Choroidal filling defects Raised Raised Single Most reliable test : Positive Systemically - definite Vision - Sometimes 7. 8. Extremely rare Seen in 20 % cases Rare 30 - 40 % in mths or yrs Sectoral and pallid disc oedema May be normal ; can have delayed ONH filling Normal Normal Negative Nil Nonarteritic Usually 60 - 70 yrs NO

References 1. Beck RW, Ferris FL. Does Levodopa improve visual function in NAION? Ophthalmology 2000;107:14314,1804. Beck RW, Hayreh SS, Podhajsky PA, Tan E-S, Moke PS. Aspirin therapy in nonarteritic anterior ischemic optic neuropathy. Amer J Ophthalmol 1997;123:212-7. Hayreh SS. Anterior ischaemic optic neuropathy III. Treatment, prophylaxis, and differential diagnosis. Br J Ophthalmol 1974;58:98l-9. Hayreh SS. Ischemic optic neuropathy. Int Ophthalmol 1978;1:9-l8. Hayreh SS. Anterior ischaemic optic neuropathy: Differentiation of arteritic from non-arteritic type and its management. Eye 1990;4:25-41. Hayreh SS. The role of optic nerve sheath fenestration in management of anterior ischemic optic neuropathy. Arch Ophthalmol 1990;108:1063-4.

Hayreh SS. Ischaemic Optic neuropathy. Indian J Ophthalmol 2000;48:171-94,317. Hayreh SS, Podhajsky PA, Zimmerman B. Role of nocturnal arterial hypotension in optic nerve head ischemic disorders. Ophthalmologica 1999;213:76-96. Ischemic Optic Neuropathy Decompression Trial Research Group: Optic nerve decompression surgery for nonarteritic anterior ischemic optic neuropathy (NAION) is not effective and may be harmful. JAMA 1995;272:625-32.

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10. Johnson LN, Guy ME, Krohel GB, Madson RW: Levodopa may improve vision loss in recent-onset, nonarteritic anterior ischemic optic neuropathy. Ophthalmology 2000;107:521-526. 11. Soheilian M, Koochek A, Yazdani S, Peyman GA. Transvitreal optic neurotomy for nonarteritic anterior ischemic optic neuropathy. Retina 2003;23:692-7. DOS Times - Vol.10, No. 4

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