Int. Ophthal. 1,1: 9-18, 1978
Ischemic optic neuropathy* SOHAN SINGH Iowa City, USA
HAYREH
Keywords: Optic nerve, Blood supply, Ischemic optic neuropathy (ION), Anterior ischemic optic neuropathy (AION), Posterior ischemic ootic neuropathy (PION)
Abstract Ischemic optic neuropathy (ION), based on vascular anatomy of the optic nerve, pathogenesis and clinical picture, consists of two distinct entities: anterior (AION) and posterior (PION) ischemic optic neuropathies. AION is due to interference with posterior ciliary artery supply to the optic nerve head and retrolaminar part of the optic nerve; it initially presents with visual loss and optic disc edema which progresses to optic atrophy in a month or two. PION is due to occlusion of nutrient arteries to the posterior part of the optic nerve; in this condition during the initial stages the optic disc is normal in spite of marked visual loss, but the atrophy develops later on. Their pathogeneses, causes, clinical pictures, diagnosis and management are discussed briefly.
Ischemic optic neuropathy (ION) is a severe blinding disease, with sudden onset of blindness at first in one eye and then after a variable interval usually in the second eye. The erroneous impression that it is a rare disease is essentially based on frequent misdiagnosis and lack of adequate knowledge on the subject. This paper is primarily designed to create an awareness of this visually crippling disease, and its early diagnosis and adequate management.
Blood supply of the optic nerve To understand the pathogenesis and clinical picture of ION, it is essential to know the exact arterial blood supply of the optic nerve. Following is a very brief account of this. F o r this purpose the optic nerve can be divided into two parts:
Anterior part o f the optic nerve This consists of the optic nerve head and the retrolaminar region (i.e., part behind the lamina cribrosa),
The posterior ciliary arteries (PCAs) (directly or via the peripapillary choroid) are the only source of supply to the lamina cribrosa and prelaminar regions and the main (if not the only) source to the retrolaminar region, and they may also supply the temporal part of the surface nerve fiber layer (10, 11, 12, 16) (Fig. 1). The PCAs are therefore extremely important in the blood supply to the anterior part of the optic nerve; this is the crucial factor to be recognized in the pathogenesis of acute ischemia of this part of the nerve. There are usually two or three PCAs (designated medial and lateral PCAs) arising from the ophthalmic artery (9). The blood supply to this region is segmental, producing segmental ischemia in the event of occlusion of the corresponding PCA or one of its subdivisions.
* Some of the figures have been reproduced by courtesy of the British Journal of Ophthalmology (Figs. 2, 5, 7), American Academy of Ophthalmology and Otolarngology (Fig. t) and Springer-Verslag (Fig. 8). This investigation was supported by Public Health Service Grant EY-01151.
10
Fig. 1. Diagrammatic representation of blood supply of the optic nerve.
Posterior part of the optic nerve This consists of the rest of the orbital part and intracanalicular and intracranial parts (Fig. 2). The blood supply to this region is by the multiple pial branches derived from various sources, e.g., in the orbit by the collateral branches of the ophthalmic artery or its various intraorbital branches (9) (Fig. 1, 2), in the optic canal by branches of the ophthalmic artery and sometimes from the orbital arteries, and intracranially by branches of the ophthalmic, anterior superior hypophysial and other surrounding intracranial arteries (Fig. 2). In addition, in 75% of the nerves the intraneural part of the central retinal artery gives out 1-8 centrifugal branches within the optic nerve (8, 21) (Fig. 1).
Pathogenesis From this very brief account of the arterial supply of the optic nerve, it is evident that acute ischemia of the anterior part of the optic nerve develops in occlusive disorders of the PCAs or their subdivisions which supply that part of the nerve. This has been well established by various clinical, histopathological and experimental studies (13, 16). The blood supply in the optic nerve head depends upon the perfusion pressure (mean blood pressure minus intraocular pressure) in the feeding vessels: thus a temporary, but sufficiently prolonged, rise of intraocular pres-
Fig. 2. Schematic representation of peripheral arterial supply of the optic nerve, as seen from above. Abbreviations used in Figs. 1 and 2: A= Araehnoid; Ant. Sup. Hyp. Art. = Anterior superior hypophyseal artery; C = Choroid; CAR = Central retinal artery; Col. Br. =Collateral branches of the ophthalmic artery and orbital arteries; CRV = Central retinal vein; CZ = Circle of Zinn and Hailer or its substitute; D = Dura; ICA = Internal carotid artery; LC = Lamina cribrosa; LPCA = Lateral posterior ciliary artery; Med. Mus. = Medial muscular artery; MPCA = Medial posterior ciliary artery; OA = Ophthalmic artery; OD = Optic disc; ON = Optic nerve; P = Pia; PCA = Posterior ciliary artery; PR = Preqaminar region; R = Retina; Rec. Br. C.Z. = Recurrent pial branches of the circle of Zinn and Hailer or its substitute or peripapillary choroid; S = Sclera.
sure or a fall of blood pressure can reduce the perfusion pressure below a critical level and induce ION without complete occlusion of the PCAs. Since the supply by the PCas and their subdivisions is strictly
Ischemic optic neuropathy
11
Terminology
Fig. 3. Fluorescein fundus angiogtam during retinal arteriovenous phase of a 63 year old woman with temporal arteritis, AION, ESR 21 mm/hour and no perception of light, one day after onset of loss of vision which was preceded by transient amaurosis for 8 days. It shows normal filling of the temporal choroid up to the fovea (supplied by the lateral PCA) but no filling of the optic disc and choroid nasal to the fovea (supplied by the medial PCA). Superficial disc capillaries fill from the retinal circulation. Retinal circulation normal except for a small area of non-filling temporal to the disc due to non-filling of a small cilio-retinal artery supplying that area (arrow).
A correct terminology to denote a disease is extremely important for understanding and communication. Unfortunately acute ischemia of the optic nerve has been called by all sorts of eponyms (16). The most popular term in the European literature has been 'vascular pseudo-papillitis' (6), and in English 'ischemic optic neuropathy'. Based on the pattern of arterial supply of the optic nerve, it is evident that acute ischemic disorder of the optic nerve consists of two distinct entities, i.e. anterior and posterior IONs, involving the anterior and posterior parts of the optic nerve respectively. The anterior ION (AION) is an occlusive disorder of the PCA, while the posterior ION (PION) is due to occlusion of one or more arteries supplying the posterior part of the nerve. The clinical pictures of the two types of ION
segmental in the optic nerve, the commonest type of ION involving the anterior part of the optic nerve is segmental. One of the PCAs (usually the medial PCA) may supply the entire anterior part of the optic nerve (Fig. 3), and occlusion of such an artery would produce complete loss of vision in that eye. The optic nerve head may be supplied by both medial and lateral PCAs so that occlusion of one of them produces a segmental involvement of the optic disc and corresponding visual field defect (Fig. 4, 5).
If the occlusive disorder in~/olves one or the other of the arteries supplying the posterior part of the optic nerve, it would produce acute ischemia of the area of the nerve supplied by the occluded artery (Fig. 1, 2). This also produces a segmental involvement of the optic nerve.
Fig. 4. Fluorescein fundus angiogram during retinal arteriovenous phase of an 82 year old man with temporal arteritis, AION, ESR 34 ram/hour, 6/7.5 visual acuity and a tiny central island visual field 6 days after onset. It shows normal filling of the lateral PCA distribution which included temporal half of the choroid up to the temporal edge of the optic disc, including a small zone of the papillo-macular bundle in the optic disc (responsible for 6/7.5 visual acuity and the central island of visual field). Medial PCA did not flU and involved major part of optic disc. Retinal circulation normal.
12
Sohan Singh Hayreh cause and may involve not only the elderly and the middle-aged but even the juvenile d i a b e t i c - a fact not adequately stressed in the past. Among the less frequent causes are systemic arterial hypertension or hypotension, collagen vascular diseases, and other systemic or local diseases associated with microvascular occlusive disorders. AION may also be due to ocular causes, e.g., raised intraocular pressure or other factors producing precipitous fall of perfusion pressure in the anterior part of the optic nerve, and lesions compressing the blood vessels to this part of the nerve. In a number of cases it may not be possible to be definite about the cause of ION because of the limitations in the diagnostic techniques.
Clinical picture
Fig. 5. Fluorescein fundus angiorgram during retinal arterial phase of left eye of a 78 year old man with visual acuity 6/12 in that eye, a negative temporal artery biopsy, ESR 69 mm/hour, bilateral AION and 5 weeks after onset in the left eye. It shows filling of. the nasal choroid and nasal part of the optic disc (supplied by the medial PCA) while the temporal part of the disc and choroid (supplied by the lateral PCA) did not fill (some fluorescence of the temporal part of the disc due to previous injection of fluorescein a few minutes earlier).
are also distinct (see below). Thus, it is important to recognize the two types of I O N - a fact not fully appreciated in the past.
ION is most commonly a disease of persons past middle-age but sometimes does occur in much younger individuals (occasionally in second or third decades). In the young persons it is usually due to diabetes mellitus, arterial hypertension, collagen vascular diseases or other vascular or hematological disorders. The disease usually starts as a unilateral condition but after days, months or years frequently becomes bilateral-the longer the follow-up, the higher the frequency of bilaterality, so that for practical purposes it may be considered ultimately a bilateral disease. The loss of vision in the eye is of a sudden onset and mostly sectoral although in temporal arteritis it is frequently total. If this loss of vision is preceded by attacks of transient blurring or loss of vision, it is highly suggestive of temporal arteritis as the cause. The visual acuity may vary from no perception of light to perfectly normal central vision, being much worse in temporal arteritis than other type. The most
Causes
important and essential method of evaluating the loss o f vision and diagnosis of ION is meticulous perimetry
The commonest cause of ION is atherosclerosis and arteriosclerosis, which explains its most frequent occurrence in elderly individuals. However, the most important cause, particularly for the PCA occlusion, is temporal (or giant cell) arteritis, which occasionally may involve one of the arteries supplying the posterior part of the nerve. In my experience, diabetes mellitus is the next common and important
because in the vast majority of these eyes optic nerve related visual field defects are seen irrespective of the fact whether the central vision is normal or abnormal. The commonest visual field defects are inferior altitudinal, inferior nasal and central scotoma; the other types include segmental defect, nerve fiber bundle defects, vertical defects and peripheral constriction.
Ischemic optic neuropathy
13 On ophthalmoscopy, the appearance of the optic disc differs in AION and PION. (i) In AION: the optic disc shows edema during the initial stages of the disease. In the vast majority the edema is associated with visual field defect; however, occasionally in very early and mild cases the visual acuity and fields may be apparently normal in spite of the presence of optic disc edema (Fig. 6a). In temporal arteritis, about half the eyes may show chalky-white swelling of the optic disc with a rare hemorrhage (Fig. 7a). In the other cases the disc usually shows pink or pale-pink edema with frequent flame-shaped hemorrhages at the disc margin and/or adjacent retina (Fig. 6b, 8a). In juvenile diabetics and some of the middleaged diabetics, the swollen disc may be covered with a network of prominent fine vessels, mimicking optic disc neovascularization (Fig. 9); the latter may mislead the physician. The optic disc edema usually starts to subside in about a week or two, completely disappearing in a month or two when a variable degree of pallor of the optic disc is seen, depending upon the severity of AION. The vast majority of optic discs with AION due to temporal arteritis develop cupping of the optic disc (Fig. 7b), and this is u n c o m m o n when AION is due to other causes. (ii) In PION: the optic disc shows no abnormality in spite of marked visual field of loss with or without deterioration of visual a c u i t y - a state of affairs similar to that of optic neuritis in the posterior part of
Fig. 7. Right eye of a 72 old woman with temporal artefitis, AION, ESR 52 mm/hour and no perception of light in that eye preceded by transient amaurosis for one week. (a) Three days after onset of blindness, showing chalky-white swelling of the disc, with no hemorrhages. (b) 131/4months later, showing cupping of the discs and atrophy. Fig. 6. Fundus photographs of (a) left and (b) right eyes of a 67 years old woman, with bilateral AION, negative temporal artery biopsy, ESR 30 turn/hour, sudden deterioration of vision in the right eye for 2 weeks, visual acuity only perception light and 6/6 in the right and left eye respectively, visual fields with Goldmann Perimeter were normal in the left eye except for an enlarged blind spot. Both optic discs showed edema and flame-shaped hemorrhages-right disc somewhat pale, and more swollen than the left disc. On treatment with systemic corticosteroids the left disc recovered to normal with normal visual acuity and fields, and the right became atrophic with a visual acuity 6/90 and normal peripheral fields with a dense central scotoma with V4.
14
Sohan Singh Hayreh
Fig. 8. Right eye of a 61 year old man with right inferior altitudinal hemianopia of sudden onset 10 days previously, preceded by attacks of transient amaurosis in that part for one week, AION involving upper half of the disc, visual acuity 6/12, no evidence of temporal arteritis and ESR 7 mm/hour. (a) Fundus photograph showing swelling of the optic disc with hyperemia of the superficial layer and some flame-shaped hemorrhages below. (b, c) are fluoreseein angiograms during the retinal arteriovenous and late phases respectively- (b) shows non-i'filing of superior temporal peripapillary ehoroid and patchy filling of the upper half of the choroid; (c) shows diffuse fluorescein staining of the optic disc with blurred margins.
the nerve. The fundus is normal on ophthalmoscopy. After a month or two the optic disc develops pallor which is the only ophthalmoscopic abnormality. Fluorescein fundus angiographic changes are seen only during the acute stages of AION and depend upon the time since onset (14, 16). In complete AION, the optic disc shows no filling of vessels of PCA origin during the first, and maybe even second, week after onset (Fig. 3, 4, 5); some filling is seen after this. The filling of vessels in the optic disc also depends upon whether the AION was the result of transient or permanent i s c h e m i a - t h e former type being the commonest. The edematous disc stains with fluorescein during the late stages. In segmental
Ischemic optic neuropathy
15 A I O N , t h e w h o l e disc s h o w s late staining (Fig. 8c), initially m a r k e d in t h e n o r m a l p a r t o f t h e o p t i c disc. T h e a t r o p h i c p a r t o f t h e disc s h o w s p o o r or n o fluorescence. In t e m p o r a l arteritis, d u r i n g t h e very early stages o f A I O N , t h e area o f t h e c h o r o i d a n d o p t i c disc supplied b y t h e o c c l u d e d
P C A does n o t fill
till late (Fig. 3 , 4 ) . In o t h e r cases o f A I O N , d u r i n g t h e early stages t h e peripapillary c h o r o i d ( w i t h or w i t h o u t c h o r o i d a l w a t e r s h e d zones) shows d e l a y e d a n d p o o r filling (Fig. 8b, 10). A f t e r a few days or weeks, t h e c h o r o i d a l c i r c u l a t i o n is r e s t o r e d to n o r m a l . T h e r e t i n a l c i r c u l a t i o n is n o r m a l unless it is o f a cilioretinal t y p e w h i c h m a y show e v i d e n c e o f o c c l u s i o n d u r i n g t h e early stages (Fig. 3). In P I O N t h e r e are n o anglographic a b n o r m a l i t i e s . T h e rest o f t h e o c u l a r e x a m i n a t i o n usually reveals n o a b n o r m a l i t y . I n t r a o c u l a r pressure m u s t b e recorded in all p a t i e n t s and m a y b e elevated in s o m e eyes.
Fig. 9. Fundus photographs of left eye of a 20 year old man with diabetes mellitus since the age of 3 years and on insulin, was seen after onset of blurred vision in both eyes, with visual acuity 6/18 and 6/7.5 in the right and left eye respectively and optic disc related visual fields in the left eye in lower half and a small central scotoma to I_ of Goldmann perimeter in the fight eye. (a) Left optic ~ s c one month after onset, showing swelling, abnormally prominent fine vessels on the disc (like neovascularization), some pefipapillary retinal hemorrhages and engorged veins but no other evidence of diabetic retinopathy in the rest of the fundus. He was treated with systemic cortico-steroids which produced resolution of both fundi to normal (b) and normal visual acuity and visual fields. Now followed for 4 years with normal optic discs, fundi and vision, and stable diabetes.
Fig. 10. Fluorescein fundus angiogram of left eye of a 64 year old man with bare counting finger vision in a small temporal island, which was plotted with V 4 only of the Goldmann perimeter, AION of 12 days duration, ESR 5 mm/hour, no evidence of temporal arteritis, swollen optic disc, and showing f'flling defect in the pefipapillary choroid and the optic disc. He was treated with systemic corticosteroids-the visual acuity recovered to 6/12 - 6/15 and normal peripheral visual fields with 12 of Goldmann perimeter and small central scotoma.
16 Apart from the ocular findings there may be systemic abnormalities indicative of the causative systemic disease. Thus it is essential to do systemic evaluation o f the patient to find out the cause o r l O N .
Diagnosis In a patient with ION, the first important step is to rule out the presence o f temporal arteritis because of the potential danger of bilateral total b l i n d n e s s observance o f this fact can prevent many tragic blindnesses. This can be done by doing an emergency estimation of the erythrocyte sedimantation rate (ESR) in these patients. The question of normal ESR in elderly persons is highly controversial. In m y series of patients with AION and confirmed temporal arteritis (on biopsy of the superficial temporal artery) the ESR has varied from 21 to 135 (mean 85) m m / hour by the Westergren method although in extremely rare instances some authors have reported an ESR as low as 13, 12 and even 6 m m / h o u r (2, 3, 4, 17, 20). In m y patients with AION and a negative temporal artery biopsy for temporal arteritis, the ESR varied from 1 to 115 (mean 22) mm/hour. This indicates that while elevated ESR is highly suggestive of temporal arteritis, a normal ESR in the elderly does not rule out temporal arteritis. Small and Gavrillescu (23) showed the presence of serum C-reactive the ESR has varied from 21 to 135 (mean 85) m m / hour by the Westergren m e t h o d although in extremely rare instances some authors have reported an ESR as low as 13, 12 and even 6 ram/hour (2, 3, 4, 17, 20). and in assessing the activity of the disease. This requires further exploration. Biopsy o f the superficial temporal artery should be performed in all cases suspected of temporal arteritis to establish the diagnosis; since temporal arteritis is in fact a systemic disease, general symptoms (e.g., malaise, weakness, muscular and joint pains, anorexia, fever, etc.) and headache, particularly in the temporal region, may be helpful in suggesting the disease. The presence of euphoria in these patients or of the occult variety of the disease may mislead the physician. Recently some investigators have indicated the presence of normal areas in a superficial temporal artery otherwise involved by giant cell arteritis, so that a section through the nor-
Sohan Singh Hayreh mal segment would give a false negative result (1, 18); in m y series of about a hundred patients with AION so far I have had no reasons to believe that there has been a false negative temporal artery biopsy. As a result of this, I am of the opinion that in patients with temporal arteritis and AION, the chances of having a false negative temporal artery biopsy are extremely small. It has been suggested by some observers that carotid angiography should be performed in these patients (21). I feel there is no need to subject the vast majority of patients with AION to such a procedure, because the chances of finding any helpful information from it are so small that it does not justify the hazards involved; it should only be done if there is an evident carotid artery abnormality clinically. O p h t h a l m o d y n a m o m e t r y routinely has also been suggested in these patients (21). It is not only an unreliable and unreproducible test but also does not give any useful information in the vast majority about the state of circulation in the PCAs, because AION is not due to occlusion of the central retinal artery but to involvement of the P C A s - a normal ophthalmic artery pressure does not rule out PCA and small optic nerve vessel disease and vice versa. As mentioned earlier, a systemic evaluation of a patient with ION is extremely important, for both diagnosis and management of these patients.
Differential diagnosis It depends upon whether the patient is seen soon after onset of AION (i.e., with optic disc edema) or late (i.e., with optic atrophy). If an elderly individual is seen with a history of sudden loss of vision and optic disc related visual field defects with (i) unilateral optic disc edema, or (ii) optic disc edema in one eye and optic atrophy in the fellow eye, or (ii) bilateral optic atrophy, the diagnosis is AION unless proved otherwise. A lack of appreciation of these facts has resulted in not only wrong diagnosis but also unnecessary, hazardous, time consuming and expensive neuro-surgical investigations. In diabetics of any age, if the disc is swollen and there are disc related visual field defects, AION must be considered as a most probable cause; diabetics get a particularly rough deal from ophthalmologists because
Ischemic optic neuropathy
any visual loss in them tends to be attributed to diabetic retinopathy and the patient tragically may be treated with panretinal photocoagulation under the erroneous impression that the prominent vessels on the optic disc represent neovascularization. In collagen vascular diseases, a sudden loss of vision with a normal fundus during the early stages must be considered due to PION unless proved otherwise. It is beyond the scope of this paper to go into any more details on the differential diagnosis of ION.
Treatment The management of ION can be divided into the following categories: 1. 1ON due to temporal arteritis: This is an ocular emergency. If in doubt, AION in persons over the age of 60 years should be regarded as due to temporal arteritis, particularly if a patient suddenly develops attacks of transient altitudinal hemianopic amaurosis or sudden complete blindness in an eye preceded b y attacks of transient amaurosis. The treatment is to institue therapy immediately with systemic corticosteroids in adequately high doses, e.g., prednisone 80-100 mg or even more daily. The object of the treatment is to prevent the loss of vision in the second eye. Occasionally the treatment may produce some visual recovery which tends to be insignificant. Dosage and duration of therapy is guided by the ESR level. These patients require prolonged steroid therapy, usually for years, and suddenly reducing or stopping the drug prematurely may produce visual symptoms in the normal eye and a rise of ESR. 2. I O N due to collagen vascular disease: These patients should be treated by high doses of systemic corticosteroids during the initial stages of the disease. In m y experience there is a significant recovery of visual function in some of these patients after an early and adequate corticosteroid therapy. 3. A I O N with diabetes mellitus: There is no weUestablished treatment available for this category. In m y experience so far there has been a significant recovery of visual function on treatment with high doses of systemic corticosteroids during the initial stages of the disease when the disc is edematous. The steroids aggravate the diabetes and these patients require very stringent inpatient control o f their dia-
17 betes by a diabetes specialist-without such strict control this therapy should not be given. 4. A I O N due to causes other than vasculitis: Most of the patients with AION fall in this category, where, apart from arteriosclerosis and atherosclerosis, there is no evident abnormality. Their management is highly controversial. Most physicians do not treat them, and dismiss them with a philosophical advice to accept blindness as an 'act of God'. However, there are some reports suggesting that systemic corticosteroids in high doses during the initial stages of the disease (i.e., with optic disc edema) have a beneficial effect in a significant number of these patients (5, 7, 15, 16).
I would like to emphasize very strongly that if systemic corticosteroid therapy is to show beneficial effect in categories 2, 3 and 4 above, the treatment must be instituted as early as possible, while the optic disc still shows a fair amount o f edema, starting with at least 80 mg prednisone daily and maintained on adequate doses (not less than 40 mg. daily) so long as the disc shows edema (which lasts at the maximum for 4-8 weeks from its onset). Once the disc has become atrophic, no treatment is worthwhile. Since the treatment is given for not more than 4-6 weeks at the maximum, none of the serious sideeffects associated with long-term steroid therapy are seen in the vast majority except those with diabetes meUitus (see above). Since the whole of this treatment is somewhat controversial, we are at present conducting a double masked randomized therapeutic trial with systemic corticosteroids versus placebo to evaluate further the role of this therapy in AION. In addition to this, I feel every attempt should be made to reduce the intraoccular pressure to as low a level as possible in patients with AION, with a view improve perfusion pressure in the optic disc vessels (Perfusion pressure = Mean Blood pressure minus intraocular pressure).
Prophylactic measures against ION Since ION, particularly in temporal arteritis, is a blinding disease with poor prognosis for recovery o f vision, and with a high risk of the second eye being involved after the first, it is worthwhile to consider the possible preventive measures that could
18 be taken to lower the incidence of blindness due to ION. These are discussed at length elsewhere (16). Briefly these consist of early diagnosis of temporal arteritis, i.e., before ocular symptoms develop, and, if a patient has ION in one eye, therapy should be started immediately even if the diagnosis of temporal arteritis is not conclusive.
References
1. Albert, D.M., M.C. Ruchman & J.L. Keltner. Skip areas in temporal arteritis. Arch. Ophthal. (Chicago) 94: 2072-2077 (1976). 2. Bethlenfalvay, N.C. & M.L. Nusynowitz. Temporal arteritis, a rarity in the young adult. Arch. Inter. Med. 114:487-489 (1964). 3. Cullen, J.F. Occult temporal merits. Trans. Ophthal. Soc. U.K. 83:725-736 (1963). 4. Eagling, E.M., M.D. Sanders & S.J.H. Miller. Ischaemic papillopathy. Br. J. Ophthal. 5 8 : 9 9 0 - 1 0 0 8 (1974). 5. Foulds, W.S. Visual disturbances in systemic disorders - optic neuropathy and systemic disease. Trans. Ophthal. Soe. U.K. 89:125-146 (1969). 6. Francois, J. Les pseudo-papillites vasculalres. Rapport Soc. fran~. Ophtal. (1956). 7. Georgiades, G., N. Stangos &E. lliadelis. The anterior ischemic opticopathy or vascular pseudothilitis. Ophthal. Chron. (Athens) 13:32-56 (1976). 8. Hayreh, S.S. A study of the central artery of the retina in human beings. Thesis for Master of Surgery. Panjab University, India (1958). 9. Hayreh, S.S. The ophthalmic artery - III. Branches. Br. J. Ophthal. 46:212-247 (1962). 10. Hayreh, S.S. Blood supply in the optic nerve head and its role in optic atrophy, glaucoma and oedema of the optic disc. Br. J. Ophthal. 53:721-748 (1969). 11. Hayreh, S.S. Pathogenesis of visual field defects - role of the ciliary circulation. Br. J. Ophthal. 54: 289311 (1970). 12. Hayreh, S.S. Anatomy and physiology of the optic nerve head. Trans. Am. Acad. Ophthal. Otolaryng. 7 8 : 0 P - 2 4 0 - 2 5 4 (1974a). 13. Hayreh, S.S. Anterior ischaemic optic neuropathy -I. Temainology and pathogenesis. Br. J. Ophthal. 58: 955-963 (1974h). 14. Hayreh, S.S. Anterior isehaemic optic neuropathy-lI. Fundus on ophthalmoscopy and fluorescein angiography. Br. J. Ophthal. 58:964-980 (1974c). 15. Hayreh, S.S. Anterior ischaemic optic neuropathy-III. Treatment, prophylaxis, and differential diagnosis. Br. J. Ophthal. 58: 981-989, (1974 d). 16. Hayreh, S.S. Anterior ischemie optic neurophaty. Springer-Verlag, New York (1975). 17. Kansu, T., J. Corbett, P. Savino & N. Schatz. Giant cell arteritis with normal sedimentation rate. Arch. Neurol. (Chicago) 34: 624-625 ( 1977 ). 18. Klein, R.G., R.J. CampveU, G.G. Hunder & J.A. Carney. Skip lesions in temporal arteritis. Mayo Clin. Proc. 51:504-510 (1976).
Sohan Singh Hayreh 19. Lancet. Editorial on 'C-reactive protein or E.S.R.?' Lancet 2:1166 (1977). 20. Permin, H., F. Juhl, A. Wiik & J. Balslov. Immunoglobniin deposits in the dermo-epidermal junction zones in patients with systemic lupus erythematosus. Rheumatoid arthritis and temporal arteritis compared by serological testing including a2 -macroglobniin. Scand. J. Rheum 6:105-110 (1977). 21. Sanders, M.D.s Neurol. Sci. 31:308 (1977). 22. Singh, S. & R. Dass. The central artery of the retina. II. A study of its distribution and anastomoses. Br. d. OphthaL 44: 280-229, (1960). 23. Small, J.M. & K. Gavrilescu. The serum protein changes in giant cell arteritis. J. Neurol. Neurosurg. Psychiat. 26:257-261 (1963). Author's address: University of Iowa Hospitals and Clinics Iowa City, Iowa 52242 USA
Ischemic optic neuropathy* SOHAN SINGH Iowa City, USA
HAYREH
Keywords: Optic nerve, Blood supply, Ischemic optic neuropathy (ION), Anterior ischemic optic neuropathy (AION), Posterior ischemic ootic neuropathy (PION)
Abstract Ischemic optic neuropathy (ION), based on vascular anatomy of the optic nerve, pathogenesis and clinical picture, consists of two distinct entities: anterior (AION) and posterior (PION) ischemic optic neuropathies. AION is due to interference with posterior ciliary artery supply to the optic nerve head and retrolaminar part of the optic nerve; it initially presents with visual loss and optic disc edema which progresses to optic atrophy in a month or two. PION is due to occlusion of nutrient arteries to the posterior part of the optic nerve; in this condition during the initial stages the optic disc is normal in spite of marked visual loss, but the atrophy develops later on. Their pathogeneses, causes, clinical pictures, diagnosis and management are discussed briefly.
Ischemic optic neuropathy (ION) is a severe blinding disease, with sudden onset of blindness at first in one eye and then after a variable interval usually in the second eye. The erroneous impression that it is a rare disease is essentially based on frequent misdiagnosis and lack of adequate knowledge on the subject. This paper is primarily designed to create an awareness of this visually crippling disease, and its early diagnosis and adequate management.
Blood supply of the optic nerve To understand the pathogenesis and clinical picture of ION, it is essential to know the exact arterial blood supply of the optic nerve. Following is a very brief account of this. F o r this purpose the optic nerve can be divided into two parts:
Anterior part o f the optic nerve This consists of the optic nerve head and the retrolaminar region (i.e., part behind the lamina cribrosa),
The posterior ciliary arteries (PCAs) (directly or via the peripapillary choroid) are the only source of supply to the lamina cribrosa and prelaminar regions and the main (if not the only) source to the retrolaminar region, and they may also supply the temporal part of the surface nerve fiber layer (10, 11, 12, 16) (Fig. 1). The PCAs are therefore extremely important in the blood supply to the anterior part of the optic nerve; this is the crucial factor to be recognized in the pathogenesis of acute ischemia of this part of the nerve. There are usually two or three PCAs (designated medial and lateral PCAs) arising from the ophthalmic artery (9). The blood supply to this region is segmental, producing segmental ischemia in the event of occlusion of the corresponding PCA or one of its subdivisions.
* Some of the figures have been reproduced by courtesy of the British Journal of Ophthalmology (Figs. 2, 5, 7), American Academy of Ophthalmology and Otolarngology (Fig. t) and Springer-Verslag (Fig. 8). This investigation was supported by Public Health Service Grant EY-01151.
10
Fig. 1. Diagrammatic representation of blood supply of the optic nerve.
Posterior part of the optic nerve This consists of the rest of the orbital part and intracanalicular and intracranial parts (Fig. 2). The blood supply to this region is by the multiple pial branches derived from various sources, e.g., in the orbit by the collateral branches of the ophthalmic artery or its various intraorbital branches (9) (Fig. 1, 2), in the optic canal by branches of the ophthalmic artery and sometimes from the orbital arteries, and intracranially by branches of the ophthalmic, anterior superior hypophysial and other surrounding intracranial arteries (Fig. 2). In addition, in 75% of the nerves the intraneural part of the central retinal artery gives out 1-8 centrifugal branches within the optic nerve (8, 21) (Fig. 1).
Pathogenesis From this very brief account of the arterial supply of the optic nerve, it is evident that acute ischemia of the anterior part of the optic nerve develops in occlusive disorders of the PCAs or their subdivisions which supply that part of the nerve. This has been well established by various clinical, histopathological and experimental studies (13, 16). The blood supply in the optic nerve head depends upon the perfusion pressure (mean blood pressure minus intraocular pressure) in the feeding vessels: thus a temporary, but sufficiently prolonged, rise of intraocular pres-
Fig. 2. Schematic representation of peripheral arterial supply of the optic nerve, as seen from above. Abbreviations used in Figs. 1 and 2: A= Araehnoid; Ant. Sup. Hyp. Art. = Anterior superior hypophyseal artery; C = Choroid; CAR = Central retinal artery; Col. Br. =Collateral branches of the ophthalmic artery and orbital arteries; CRV = Central retinal vein; CZ = Circle of Zinn and Hailer or its substitute; D = Dura; ICA = Internal carotid artery; LC = Lamina cribrosa; LPCA = Lateral posterior ciliary artery; Med. Mus. = Medial muscular artery; MPCA = Medial posterior ciliary artery; OA = Ophthalmic artery; OD = Optic disc; ON = Optic nerve; P = Pia; PCA = Posterior ciliary artery; PR = Preqaminar region; R = Retina; Rec. Br. C.Z. = Recurrent pial branches of the circle of Zinn and Hailer or its substitute or peripapillary choroid; S = Sclera.
sure or a fall of blood pressure can reduce the perfusion pressure below a critical level and induce ION without complete occlusion of the PCAs. Since the supply by the PCas and their subdivisions is strictly
Ischemic optic neuropathy
11
Terminology
Fig. 3. Fluorescein fundus angiogtam during retinal arteriovenous phase of a 63 year old woman with temporal arteritis, AION, ESR 21 mm/hour and no perception of light, one day after onset of loss of vision which was preceded by transient amaurosis for 8 days. It shows normal filling of the temporal choroid up to the fovea (supplied by the lateral PCA) but no filling of the optic disc and choroid nasal to the fovea (supplied by the medial PCA). Superficial disc capillaries fill from the retinal circulation. Retinal circulation normal except for a small area of non-filling temporal to the disc due to non-filling of a small cilio-retinal artery supplying that area (arrow).
A correct terminology to denote a disease is extremely important for understanding and communication. Unfortunately acute ischemia of the optic nerve has been called by all sorts of eponyms (16). The most popular term in the European literature has been 'vascular pseudo-papillitis' (6), and in English 'ischemic optic neuropathy'. Based on the pattern of arterial supply of the optic nerve, it is evident that acute ischemic disorder of the optic nerve consists of two distinct entities, i.e. anterior and posterior IONs, involving the anterior and posterior parts of the optic nerve respectively. The anterior ION (AION) is an occlusive disorder of the PCA, while the posterior ION (PION) is due to occlusion of one or more arteries supplying the posterior part of the nerve. The clinical pictures of the two types of ION
segmental in the optic nerve, the commonest type of ION involving the anterior part of the optic nerve is segmental. One of the PCAs (usually the medial PCA) may supply the entire anterior part of the optic nerve (Fig. 3), and occlusion of such an artery would produce complete loss of vision in that eye. The optic nerve head may be supplied by both medial and lateral PCAs so that occlusion of one of them produces a segmental involvement of the optic disc and corresponding visual field defect (Fig. 4, 5).
If the occlusive disorder in~/olves one or the other of the arteries supplying the posterior part of the optic nerve, it would produce acute ischemia of the area of the nerve supplied by the occluded artery (Fig. 1, 2). This also produces a segmental involvement of the optic nerve.
Fig. 4. Fluorescein fundus angiogram during retinal arteriovenous phase of an 82 year old man with temporal arteritis, AION, ESR 34 ram/hour, 6/7.5 visual acuity and a tiny central island visual field 6 days after onset. It shows normal filling of the lateral PCA distribution which included temporal half of the choroid up to the temporal edge of the optic disc, including a small zone of the papillo-macular bundle in the optic disc (responsible for 6/7.5 visual acuity and the central island of visual field). Medial PCA did not flU and involved major part of optic disc. Retinal circulation normal.
12
Sohan Singh Hayreh cause and may involve not only the elderly and the middle-aged but even the juvenile d i a b e t i c - a fact not adequately stressed in the past. Among the less frequent causes are systemic arterial hypertension or hypotension, collagen vascular diseases, and other systemic or local diseases associated with microvascular occlusive disorders. AION may also be due to ocular causes, e.g., raised intraocular pressure or other factors producing precipitous fall of perfusion pressure in the anterior part of the optic nerve, and lesions compressing the blood vessels to this part of the nerve. In a number of cases it may not be possible to be definite about the cause of ION because of the limitations in the diagnostic techniques.
Clinical picture
Fig. 5. Fluorescein fundus angiorgram during retinal arterial phase of left eye of a 78 year old man with visual acuity 6/12 in that eye, a negative temporal artery biopsy, ESR 69 mm/hour, bilateral AION and 5 weeks after onset in the left eye. It shows filling of. the nasal choroid and nasal part of the optic disc (supplied by the medial PCA) while the temporal part of the disc and choroid (supplied by the lateral PCA) did not fill (some fluorescence of the temporal part of the disc due to previous injection of fluorescein a few minutes earlier).
are also distinct (see below). Thus, it is important to recognize the two types of I O N - a fact not fully appreciated in the past.
ION is most commonly a disease of persons past middle-age but sometimes does occur in much younger individuals (occasionally in second or third decades). In the young persons it is usually due to diabetes mellitus, arterial hypertension, collagen vascular diseases or other vascular or hematological disorders. The disease usually starts as a unilateral condition but after days, months or years frequently becomes bilateral-the longer the follow-up, the higher the frequency of bilaterality, so that for practical purposes it may be considered ultimately a bilateral disease. The loss of vision in the eye is of a sudden onset and mostly sectoral although in temporal arteritis it is frequently total. If this loss of vision is preceded by attacks of transient blurring or loss of vision, it is highly suggestive of temporal arteritis as the cause. The visual acuity may vary from no perception of light to perfectly normal central vision, being much worse in temporal arteritis than other type. The most
Causes
important and essential method of evaluating the loss o f vision and diagnosis of ION is meticulous perimetry
The commonest cause of ION is atherosclerosis and arteriosclerosis, which explains its most frequent occurrence in elderly individuals. However, the most important cause, particularly for the PCA occlusion, is temporal (or giant cell) arteritis, which occasionally may involve one of the arteries supplying the posterior part of the nerve. In my experience, diabetes mellitus is the next common and important
because in the vast majority of these eyes optic nerve related visual field defects are seen irrespective of the fact whether the central vision is normal or abnormal. The commonest visual field defects are inferior altitudinal, inferior nasal and central scotoma; the other types include segmental defect, nerve fiber bundle defects, vertical defects and peripheral constriction.
Ischemic optic neuropathy
13 On ophthalmoscopy, the appearance of the optic disc differs in AION and PION. (i) In AION: the optic disc shows edema during the initial stages of the disease. In the vast majority the edema is associated with visual field defect; however, occasionally in very early and mild cases the visual acuity and fields may be apparently normal in spite of the presence of optic disc edema (Fig. 6a). In temporal arteritis, about half the eyes may show chalky-white swelling of the optic disc with a rare hemorrhage (Fig. 7a). In the other cases the disc usually shows pink or pale-pink edema with frequent flame-shaped hemorrhages at the disc margin and/or adjacent retina (Fig. 6b, 8a). In juvenile diabetics and some of the middleaged diabetics, the swollen disc may be covered with a network of prominent fine vessels, mimicking optic disc neovascularization (Fig. 9); the latter may mislead the physician. The optic disc edema usually starts to subside in about a week or two, completely disappearing in a month or two when a variable degree of pallor of the optic disc is seen, depending upon the severity of AION. The vast majority of optic discs with AION due to temporal arteritis develop cupping of the optic disc (Fig. 7b), and this is u n c o m m o n when AION is due to other causes. (ii) In PION: the optic disc shows no abnormality in spite of marked visual field of loss with or without deterioration of visual a c u i t y - a state of affairs similar to that of optic neuritis in the posterior part of
Fig. 7. Right eye of a 72 old woman with temporal artefitis, AION, ESR 52 mm/hour and no perception of light in that eye preceded by transient amaurosis for one week. (a) Three days after onset of blindness, showing chalky-white swelling of the disc, with no hemorrhages. (b) 131/4months later, showing cupping of the discs and atrophy. Fig. 6. Fundus photographs of (a) left and (b) right eyes of a 67 years old woman, with bilateral AION, negative temporal artery biopsy, ESR 30 turn/hour, sudden deterioration of vision in the right eye for 2 weeks, visual acuity only perception light and 6/6 in the right and left eye respectively, visual fields with Goldmann Perimeter were normal in the left eye except for an enlarged blind spot. Both optic discs showed edema and flame-shaped hemorrhages-right disc somewhat pale, and more swollen than the left disc. On treatment with systemic corticosteroids the left disc recovered to normal with normal visual acuity and fields, and the right became atrophic with a visual acuity 6/90 and normal peripheral fields with a dense central scotoma with V4.
14
Sohan Singh Hayreh
Fig. 8. Right eye of a 61 year old man with right inferior altitudinal hemianopia of sudden onset 10 days previously, preceded by attacks of transient amaurosis in that part for one week, AION involving upper half of the disc, visual acuity 6/12, no evidence of temporal arteritis and ESR 7 mm/hour. (a) Fundus photograph showing swelling of the optic disc with hyperemia of the superficial layer and some flame-shaped hemorrhages below. (b, c) are fluoreseein angiograms during the retinal arteriovenous and late phases respectively- (b) shows non-i'filing of superior temporal peripapillary ehoroid and patchy filling of the upper half of the choroid; (c) shows diffuse fluorescein staining of the optic disc with blurred margins.
the nerve. The fundus is normal on ophthalmoscopy. After a month or two the optic disc develops pallor which is the only ophthalmoscopic abnormality. Fluorescein fundus angiographic changes are seen only during the acute stages of AION and depend upon the time since onset (14, 16). In complete AION, the optic disc shows no filling of vessels of PCA origin during the first, and maybe even second, week after onset (Fig. 3, 4, 5); some filling is seen after this. The filling of vessels in the optic disc also depends upon whether the AION was the result of transient or permanent i s c h e m i a - t h e former type being the commonest. The edematous disc stains with fluorescein during the late stages. In segmental
Ischemic optic neuropathy
15 A I O N , t h e w h o l e disc s h o w s late staining (Fig. 8c), initially m a r k e d in t h e n o r m a l p a r t o f t h e o p t i c disc. T h e a t r o p h i c p a r t o f t h e disc s h o w s p o o r or n o fluorescence. In t e m p o r a l arteritis, d u r i n g t h e very early stages o f A I O N , t h e area o f t h e c h o r o i d a n d o p t i c disc supplied b y t h e o c c l u d e d
P C A does n o t fill
till late (Fig. 3 , 4 ) . In o t h e r cases o f A I O N , d u r i n g t h e early stages t h e peripapillary c h o r o i d ( w i t h or w i t h o u t c h o r o i d a l w a t e r s h e d zones) shows d e l a y e d a n d p o o r filling (Fig. 8b, 10). A f t e r a few days or weeks, t h e c h o r o i d a l c i r c u l a t i o n is r e s t o r e d to n o r m a l . T h e r e t i n a l c i r c u l a t i o n is n o r m a l unless it is o f a cilioretinal t y p e w h i c h m a y show e v i d e n c e o f o c c l u s i o n d u r i n g t h e early stages (Fig. 3). In P I O N t h e r e are n o anglographic a b n o r m a l i t i e s . T h e rest o f t h e o c u l a r e x a m i n a t i o n usually reveals n o a b n o r m a l i t y . I n t r a o c u l a r pressure m u s t b e recorded in all p a t i e n t s and m a y b e elevated in s o m e eyes.
Fig. 9. Fundus photographs of left eye of a 20 year old man with diabetes mellitus since the age of 3 years and on insulin, was seen after onset of blurred vision in both eyes, with visual acuity 6/18 and 6/7.5 in the right and left eye respectively and optic disc related visual fields in the left eye in lower half and a small central scotoma to I_ of Goldmann perimeter in the fight eye. (a) Left optic ~ s c one month after onset, showing swelling, abnormally prominent fine vessels on the disc (like neovascularization), some pefipapillary retinal hemorrhages and engorged veins but no other evidence of diabetic retinopathy in the rest of the fundus. He was treated with systemic cortico-steroids which produced resolution of both fundi to normal (b) and normal visual acuity and visual fields. Now followed for 4 years with normal optic discs, fundi and vision, and stable diabetes.
Fig. 10. Fluorescein fundus angiogram of left eye of a 64 year old man with bare counting finger vision in a small temporal island, which was plotted with V 4 only of the Goldmann perimeter, AION of 12 days duration, ESR 5 mm/hour, no evidence of temporal arteritis, swollen optic disc, and showing f'flling defect in the pefipapillary choroid and the optic disc. He was treated with systemic corticosteroids-the visual acuity recovered to 6/12 - 6/15 and normal peripheral visual fields with 12 of Goldmann perimeter and small central scotoma.
16 Apart from the ocular findings there may be systemic abnormalities indicative of the causative systemic disease. Thus it is essential to do systemic evaluation o f the patient to find out the cause o r l O N .
Diagnosis In a patient with ION, the first important step is to rule out the presence o f temporal arteritis because of the potential danger of bilateral total b l i n d n e s s observance o f this fact can prevent many tragic blindnesses. This can be done by doing an emergency estimation of the erythrocyte sedimantation rate (ESR) in these patients. The question of normal ESR in elderly persons is highly controversial. In m y series of patients with AION and confirmed temporal arteritis (on biopsy of the superficial temporal artery) the ESR has varied from 21 to 135 (mean 85) m m / hour by the Westergren method although in extremely rare instances some authors have reported an ESR as low as 13, 12 and even 6 m m / h o u r (2, 3, 4, 17, 20). In m y patients with AION and a negative temporal artery biopsy for temporal arteritis, the ESR varied from 1 to 115 (mean 22) mm/hour. This indicates that while elevated ESR is highly suggestive of temporal arteritis, a normal ESR in the elderly does not rule out temporal arteritis. Small and Gavrillescu (23) showed the presence of serum C-reactive the ESR has varied from 21 to 135 (mean 85) m m / hour by the Westergren m e t h o d although in extremely rare instances some authors have reported an ESR as low as 13, 12 and even 6 ram/hour (2, 3, 4, 17, 20). and in assessing the activity of the disease. This requires further exploration. Biopsy o f the superficial temporal artery should be performed in all cases suspected of temporal arteritis to establish the diagnosis; since temporal arteritis is in fact a systemic disease, general symptoms (e.g., malaise, weakness, muscular and joint pains, anorexia, fever, etc.) and headache, particularly in the temporal region, may be helpful in suggesting the disease. The presence of euphoria in these patients or of the occult variety of the disease may mislead the physician. Recently some investigators have indicated the presence of normal areas in a superficial temporal artery otherwise involved by giant cell arteritis, so that a section through the nor-
Sohan Singh Hayreh mal segment would give a false negative result (1, 18); in m y series of about a hundred patients with AION so far I have had no reasons to believe that there has been a false negative temporal artery biopsy. As a result of this, I am of the opinion that in patients with temporal arteritis and AION, the chances of having a false negative temporal artery biopsy are extremely small. It has been suggested by some observers that carotid angiography should be performed in these patients (21). I feel there is no need to subject the vast majority of patients with AION to such a procedure, because the chances of finding any helpful information from it are so small that it does not justify the hazards involved; it should only be done if there is an evident carotid artery abnormality clinically. O p h t h a l m o d y n a m o m e t r y routinely has also been suggested in these patients (21). It is not only an unreliable and unreproducible test but also does not give any useful information in the vast majority about the state of circulation in the PCAs, because AION is not due to occlusion of the central retinal artery but to involvement of the P C A s - a normal ophthalmic artery pressure does not rule out PCA and small optic nerve vessel disease and vice versa. As mentioned earlier, a systemic evaluation of a patient with ION is extremely important, for both diagnosis and management of these patients.
Differential diagnosis It depends upon whether the patient is seen soon after onset of AION (i.e., with optic disc edema) or late (i.e., with optic atrophy). If an elderly individual is seen with a history of sudden loss of vision and optic disc related visual field defects with (i) unilateral optic disc edema, or (ii) optic disc edema in one eye and optic atrophy in the fellow eye, or (ii) bilateral optic atrophy, the diagnosis is AION unless proved otherwise. A lack of appreciation of these facts has resulted in not only wrong diagnosis but also unnecessary, hazardous, time consuming and expensive neuro-surgical investigations. In diabetics of any age, if the disc is swollen and there are disc related visual field defects, AION must be considered as a most probable cause; diabetics get a particularly rough deal from ophthalmologists because
Ischemic optic neuropathy
any visual loss in them tends to be attributed to diabetic retinopathy and the patient tragically may be treated with panretinal photocoagulation under the erroneous impression that the prominent vessels on the optic disc represent neovascularization. In collagen vascular diseases, a sudden loss of vision with a normal fundus during the early stages must be considered due to PION unless proved otherwise. It is beyond the scope of this paper to go into any more details on the differential diagnosis of ION.
Treatment The management of ION can be divided into the following categories: 1. 1ON due to temporal arteritis: This is an ocular emergency. If in doubt, AION in persons over the age of 60 years should be regarded as due to temporal arteritis, particularly if a patient suddenly develops attacks of transient altitudinal hemianopic amaurosis or sudden complete blindness in an eye preceded b y attacks of transient amaurosis. The treatment is to institue therapy immediately with systemic corticosteroids in adequately high doses, e.g., prednisone 80-100 mg or even more daily. The object of the treatment is to prevent the loss of vision in the second eye. Occasionally the treatment may produce some visual recovery which tends to be insignificant. Dosage and duration of therapy is guided by the ESR level. These patients require prolonged steroid therapy, usually for years, and suddenly reducing or stopping the drug prematurely may produce visual symptoms in the normal eye and a rise of ESR. 2. I O N due to collagen vascular disease: These patients should be treated by high doses of systemic corticosteroids during the initial stages of the disease. In m y experience there is a significant recovery of visual function in some of these patients after an early and adequate corticosteroid therapy. 3. A I O N with diabetes mellitus: There is no weUestablished treatment available for this category. In m y experience so far there has been a significant recovery of visual function on treatment with high doses of systemic corticosteroids during the initial stages of the disease when the disc is edematous. The steroids aggravate the diabetes and these patients require very stringent inpatient control o f their dia-
17 betes by a diabetes specialist-without such strict control this therapy should not be given. 4. A I O N due to causes other than vasculitis: Most of the patients with AION fall in this category, where, apart from arteriosclerosis and atherosclerosis, there is no evident abnormality. Their management is highly controversial. Most physicians do not treat them, and dismiss them with a philosophical advice to accept blindness as an 'act of God'. However, there are some reports suggesting that systemic corticosteroids in high doses during the initial stages of the disease (i.e., with optic disc edema) have a beneficial effect in a significant number of these patients (5, 7, 15, 16).
I would like to emphasize very strongly that if systemic corticosteroid therapy is to show beneficial effect in categories 2, 3 and 4 above, the treatment must be instituted as early as possible, while the optic disc still shows a fair amount o f edema, starting with at least 80 mg prednisone daily and maintained on adequate doses (not less than 40 mg. daily) so long as the disc shows edema (which lasts at the maximum for 4-8 weeks from its onset). Once the disc has become atrophic, no treatment is worthwhile. Since the treatment is given for not more than 4-6 weeks at the maximum, none of the serious sideeffects associated with long-term steroid therapy are seen in the vast majority except those with diabetes meUitus (see above). Since the whole of this treatment is somewhat controversial, we are at present conducting a double masked randomized therapeutic trial with systemic corticosteroids versus placebo to evaluate further the role of this therapy in AION. In addition to this, I feel every attempt should be made to reduce the intraoccular pressure to as low a level as possible in patients with AION, with a view improve perfusion pressure in the optic disc vessels (Perfusion pressure = Mean Blood pressure minus intraocular pressure).
Prophylactic measures against ION Since ION, particularly in temporal arteritis, is a blinding disease with poor prognosis for recovery o f vision, and with a high risk of the second eye being involved after the first, it is worthwhile to consider the possible preventive measures that could
18 be taken to lower the incidence of blindness due to ION. These are discussed at length elsewhere (16). Briefly these consist of early diagnosis of temporal arteritis, i.e., before ocular symptoms develop, and, if a patient has ION in one eye, therapy should be started immediately even if the diagnosis of temporal arteritis is not conclusive.
References
1. Albert, D.M., M.C. Ruchman & J.L. Keltner. Skip areas in temporal arteritis. Arch. Ophthal. (Chicago) 94: 2072-2077 (1976). 2. Bethlenfalvay, N.C. & M.L. Nusynowitz. Temporal arteritis, a rarity in the young adult. Arch. Inter. Med. 114:487-489 (1964). 3. Cullen, J.F. Occult temporal merits. Trans. Ophthal. Soc. U.K. 83:725-736 (1963). 4. Eagling, E.M., M.D. Sanders & S.J.H. Miller. Ischaemic papillopathy. Br. J. Ophthal. 5 8 : 9 9 0 - 1 0 0 8 (1974). 5. Foulds, W.S. Visual disturbances in systemic disorders - optic neuropathy and systemic disease. Trans. Ophthal. Soe. U.K. 89:125-146 (1969). 6. Francois, J. Les pseudo-papillites vasculalres. Rapport Soc. fran~. Ophtal. (1956). 7. Georgiades, G., N. Stangos &E. lliadelis. The anterior ischemic opticopathy or vascular pseudothilitis. Ophthal. Chron. (Athens) 13:32-56 (1976). 8. Hayreh, S.S. A study of the central artery of the retina in human beings. Thesis for Master of Surgery. Panjab University, India (1958). 9. Hayreh, S.S. The ophthalmic artery - III. Branches. Br. J. Ophthal. 46:212-247 (1962). 10. Hayreh, S.S. Blood supply in the optic nerve head and its role in optic atrophy, glaucoma and oedema of the optic disc. Br. J. Ophthal. 53:721-748 (1969). 11. Hayreh, S.S. Pathogenesis of visual field defects - role of the ciliary circulation. Br. J. Ophthal. 54: 289311 (1970). 12. Hayreh, S.S. Anatomy and physiology of the optic nerve head. Trans. Am. Acad. Ophthal. Otolaryng. 7 8 : 0 P - 2 4 0 - 2 5 4 (1974a). 13. Hayreh, S.S. Anterior ischaemic optic neuropathy -I. Temainology and pathogenesis. Br. J. Ophthal. 58: 955-963 (1974h). 14. Hayreh, S.S. Anterior isehaemic optic neuropathy-lI. Fundus on ophthalmoscopy and fluorescein angiography. Br. J. Ophthal. 58:964-980 (1974c). 15. Hayreh, S.S. Anterior ischaemic optic neuropathy-III. Treatment, prophylaxis, and differential diagnosis. Br. J. Ophthal. 58: 981-989, (1974 d). 16. Hayreh, S.S. Anterior ischemie optic neurophaty. Springer-Verlag, New York (1975). 17. Kansu, T., J. Corbett, P. Savino & N. Schatz. Giant cell arteritis with normal sedimentation rate. Arch. Neurol. (Chicago) 34: 624-625 ( 1977 ). 18. Klein, R.G., R.J. CampveU, G.G. Hunder & J.A. Carney. Skip lesions in temporal arteritis. Mayo Clin. Proc. 51:504-510 (1976).
Sohan Singh Hayreh 19. Lancet. Editorial on 'C-reactive protein or E.S.R.?' Lancet 2:1166 (1977). 20. Permin, H., F. Juhl, A. Wiik & J. Balslov. Immunoglobniin deposits in the dermo-epidermal junction zones in patients with systemic lupus erythematosus. Rheumatoid arthritis and temporal arteritis compared by serological testing including a2 -macroglobniin. Scand. J. Rheum 6:105-110 (1977). 21. Sanders, M.D.s Neurol. Sci. 31:308 (1977). 22. Singh, S. & R. Dass. The central artery of the retina. II. A study of its distribution and anastomoses. Br. d. OphthaL 44: 280-229, (1960). 23. Small, J.M. & K. Gavrilescu. The serum protein changes in giant cell arteritis. J. Neurol. Neurosurg. Psychiat. 26:257-261 (1963). Author's address: University of Iowa Hospitals and Clinics Iowa City, Iowa 52242 USA
