Ischaemic optic neuropathy. The clinical profile and history.

Brain (1975) 98, 689-708

ISCH/EMIC OPTIC NEUROPATHY THE CLINICAL PROFILE AND NATURAL HISTORY BY

DAN R. BOGHEN AND JOEL S. GLASER1 (From the Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Florida)

HISTORICAL REVIEW AND DEFINITION OF TERMS

It is appropriate to begin with a brief historical discussion of clinical concepts of acute optic nerve infarction. The association of visual loss with giant-cell arteritis was first firmly established by Jennings in 1938. Ocular symptomatology had not been mentioned by Horton et al. (1932), in their original publications stressing headache patterns, but several authors in the 40s began reporting cases of optic nerve involvement in temporal arteritis, including Horton and associates at the Mayo Clinic (Johnson, 1943). Wagener, in 1946, classified cases of temporal arteritis into three ophthalmoscopically distinct groups, one of which he termed "ischasmic optic neuritis." This term was used for those cases of visual failure either with swelling of the optic nerve head or with normal discs, in which the lesion was presumed to be retrobulbar. The review by Bruce (1949) accounted for 84 cases of temporal arteritis, Reprintrequests:1638 N.W. 10th Avenue, Miami, Florida, 33152, USA (Dr. Glaser).

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INFARCTION of the anterior portion of the optic nerve in the absence of identifiable inflammation, demyelination, compression by mass lesion or hypoperfusion in the extracranial carotid system, is a poorly understood but well-recognized cause of sudden and often catastrophic loss of vision in middle and late life. Although an arteritic form of ischaemic optic neuropathy is definable by clinical and laboratory criteria, the non-arteritic idiopathic form is by far the more common. In contrast to demyelinative "optic neuritis," ischaemic neuropathy characteristically involves the pre-laminar portion of the optic nerve with a rather constant ophthalmoscopic appearance of disc swelling, "ischaemic papillopathy." Acute retrobulbar infarction without disc swelling must be considered a rare and somewhat tenuous diagnosis. The purpose of this report is to review the clinical profiles of 50 patients with ischaemic optic neuropathy, and to analyse and contrast data related to visual function, general morbidity and prognosis in non-arteritic versus arteritic cases.

690

DAN R. BOGHEN AND JOEL S. GLASER

MATERIAL AND METHODS

Patients in this study were examined at the Bascom Palmer Eye Institute of the University of Miami, between 1962 and 1972. Records were reviewed of all patients with a diagnosis of "ischaemic optic neuropathy," as well as those of patients over 40 years of age with a diagnosis of "optic neuritis." Cases were eliminated if there were insufficient data or if the diagnosis contained some element of doubt. A history of remissions and exacerbations of visual deficit or inconstant neurological signs and symptoms, or a temporally related history of sepsis or infectious disease, excluded patients from this study. Major considerations for admission to the study included: age of patient; temporal pattern of visual loss; visual field defect consistent with optic nerve disease; and funduscopic appearance. (All cases ultimately accepted into the study had swelling of the optic disc, either photographed or adequately described, and this factor may represent a bias of those clinicians responsible for diagnoses.) A questionnaire and appeal for re-examination was sent to those patients accepted for the study. Thirty-one patients were re-examined by at least one of the authors, and the following data were recorded: corrected visual acuity, applanation tonometry, Goldmann visual fields, brachial blood


with a 40 per cent incidence of ocular involvement, and Wagener and Hollenhorst (1958) lucidly described the course of arteritic ischaemic optic neuritis, including fundus characteristics, visual function and prognosis. As the concept of optic nerve involvement in giant-cell arteritis was becoming widely known, scattered reports appeared of ischsmic optic nerve disease in patients without arteritis. Kurz (1948) described under the name of "arteriosclerotic papillitis" two elderly patients who developed severe loss of vision first in one eye and then, over a period of several days, in the other. Swelling of the optic disc was present in both. In 1956, Francois et al. re-classified "vascular pseudo-papillitis," emphasizing the non-arteritic or "arteriosclerotic" form, and supported their contention with the work of Kurz (1948), Kreibig ("optico-malacia") (1953) and Kadlecova ("ischaemic papilloedema") (1951). Bonamour (1954) used the phrase "acute optic neuritis of hypertension," and Desvignes and Brun (1952) further confused the issue by describing surgical anatomy consisting of dilated and sclerotic ophthalmic arteries which "compressed" the nerves, evoking a "neurovascular reflex" which produced a pseudo-papillitis. Later papers by Lasco (1961), Francois et al. (1962) and others firmly established the non-arteritic clinical entity. A review in the American literature by Miller and Smith (1966), popularized still yet another perhaps more accurate synonym, ischcemic optic neuropathy. For the purposes of this report, ischaemic optic neuropathy is defined as: relatively acute loss of visual function, usually one eye involved in each episode, occurring in individuals at least in the fifth decade of life with little or no return of lost function; in addition, the fundus appearance is considered typical when sector or general pallid disc swelling is present at the onset of the visual symptoms. Since very few cases do not show some degree of disc oedema, "ischaemic papillopathy" is not an inappropriate alternative term. Idiopathic will be used herein to designate the nonarteritic (so-called "arteriosclerotic") form of ischaemic optic neuropathy, exclusive of optic nerve complications of readily definable clinical entities (e.g. acute massive blood loss, migraine, delayed radionecrosis, etc.; see Discussion).

ISC3LEMIC OPTIC NEUROPATHY

691

pressure, palpation and auscultation of the carotid arteries. In addition, colour fundus photographs and fluorescein angiographs were obtained. Patients who could not be personally re-examined returned a completed questionnaire. In those cases, other ophthalmologists' records were consulted and recent best corrected visual acuities obtained, as well as other clinical data. Only those cases personally examined (31) or those for whom reliable information was available (11), either from Institute records or from ophthalmologists in the community, are considered as "verified" follow-up. Cases in whom information was obtained only by questionnaire or by telephone (or both) are classified as "unverified follow-up." Verified follow-up data for both Eetiological groups were obtained in 42 cases (84 per cent), and the follow-up interval was three or more years in 95 per cent. Of the idiopathic group, 93 per cent had at least a three-year follow-up, and 79 per cent have been followed forfiveyears or more. TABLE I.—LENGTH OF FOLLOW-UP: VERIFIED DATA

No. of patients

Idiopathic 2 2 2 5 4 5 2 3 2 2 29

Arteritic — 7 3 1 — — 1 1 — 13

ANALYSIS OF DATA

Fifty cases of ischaemic optic neuropathy were studied, 37 of the "idiopathic" variety and 13 due to arteritis. The analysis of accrued data is as follows. Age/Sex Distribution The incidence with respect to age is displayed in fig. 1. In the idiopathic group, the largest number of patients are in the 56-70 years age group, with a range from 40 to 80 years; only 2 of the 37 patients were over 70 years of age at the time of onset. This is in contrast with the arteritis group, in which 12 of 13 patients were 70 years or older at the time of onset, the other patient being 67 years old. Our figures for age in arteritis are in agreement with larger series (Hamilton et al, 1971) which show the average age of involvement to be about 70 years. There was no statistically significant difference in sex incidence in either the idiopathic or arteritic groups, although Hamilton et al. (1971) has suggested a slight female preponderance in arteritis. Visual Symptoms at Onset Onset of visual deficit in the idiopathic group was rarely heralded by any premonitory symptoms, nor was it associated with any particular type of activity. Most patients experienced a sudden visual loss which prompted them to seek 46

BRAIN—VOL. xcvm


Interval (years) 2 and less 3 4 5 6 7 8 9 10 11

692


E23

Idiopathic Arteritis

12

12

• •1 1 II 1 5

3

3

JL

1

40-45 4&50

•

51-55 56-60 6165

66-70

5

n 71-75

5

7680

*Age at time of first eye involved.

FIG. 1.—Age incidence of ischsemic papillopathy.

Medical Symptoms at Onset In the idiopathic group, 4 patients reported vague head and eye aches, ipsilateral to the side of visual loss in 3. Otherwise, as a group, these patients felt quite well.


immediate medical attention. In others, onset was characterized by a vague awareness of visual defect. Several patients complained of a "foreign body" sensation in the involved eye. Other terms used to describe the experience were: black "spots or dots" in the field of vision, "blurring" and looking through a "shade" or "grey veil"; one patient related an annoying persistence of "brightness" in the involved eye. Although not widely recognized, clinical progression may be a feature of ischsemic optic neuropathy (see case histories, in Visual Field Defects below). Deterioration of vision is likely to occur during the first week to ten days, but occasionally may occur as late as three to four weeks following onset. Where information was available, in the idiopathic group the deficit was maximal from the onset in 28 eyes and progressive to some degree in 11 eyes. Progression occurred over periods varying from twenty-four hours to four weeks, but in the majority was less than nine days. Both gradual and stepwise progressions were noted, but in no case was an intervening remission documented. In the arteritic group, two eyes progressed to no perception of light in two and five days. Prior to permanent deficits, transient visual loss with recovery in minutes to hours (similar to amaurosis fugax of carotid disease) was reported by 3 of 13 arteritis patients, as has been documented in other reports (Wagener and Hollenhorst, 1958). Such fleeting visual dysfunction was an uncommon feature of the histories in our idiopathic group (2 of 37 cases).

693

ISCHiEMIC OPTIC NEUROPATHY

In no instance was a history of pain on motion of the eyes elicited. By contrast, patients with arteritis had prominent symptoms which included: previous episodes of muscle aches, unexplained weight loss, sub-occipital neck pains, moderate to intense temporal headaches, scalp tenderness, masseter and temporomandibular joint ache precipitated by chewing and talking, and general malaise. One arteritis patient, at the time of visual loss, was being treated for a necrotic scalp lesion which had been diagnosed as zoster (!). Concurrent Medical Conditions {see Table II) Hypertension.—Patients were considered to be hypertensive either on the basis of appropriate past medical history or a diastolic pressure higher than 100 mmHg obtained at the time of examination, medical consultation or admission to hospital. In the idiopathic group, 15 of 34 patients (44 per cent) were found to have an accompanying hypertension, and 2 others had a raised diastolic pressure during follow-up periods. Only one arteritic patient could be identified as hypertensive, evidenced during the follow-up period.

Hypertension* 15 2 2 Diabetest definite equivocal 11 Arteriosclerotic heart disease Arrhythmia Angina pectoris 2 Myocardial infarct 1 Unspecified 1 Cerebrovascular disease 1 1 Transient ischxmic attacks 1 Stroke 2 Migraine 3 Retinal artery emboli 1 Deafness (vascuJar) 1 Gout 1 Glaucoma 1 Hyperthyroid Goitre 1 Trigeminal neuralgia 1 Allergy/asthma 2 Peptic ulcer 1 Rheumatoid arthritis 1 Ca. of vagina 1 Ca. of throat 1 Ca. of breast Herpes zoster (thoracic) 1 •Information available for 34 patients, tlnformation available

1 1 1 1

1

1

1

1 for 35 patients.


TABLE n.—CONCURRENT MEDICAL CONDITIONS—INITIAL AND SUBSEQUENT Idiopathic Arteritis Prior to During During Prior to follow-up onset follow-up onset

694


Systemic Prognosis and Mortality Six patients in the non-arteritic group developed symptomatic manifestations of vascular disease not recognized originally. There was no deterioration during followup in the status of those patients with vascular disease which was overt at the time of initial examination. With the exception of a death related to complications of thyroid surgery, no patient in the non-arteritic group has succumbed to date. Although the incidence of hypertension as defined above is greater than in the agematched population at large (Kannel et al., 1969), functional incapacity due to vascular disease was exceptional. Hypertension as a rule was benign and easily managed. Among those patients classified as having "heart disease," most were asymptomatic or had only occasional mild angina. Long-term follow-up of the non-arteritic patients showed them to be ambulant and self-sufficient. When present, incapacity was due primarily to visual deficits. Two of the arteritis patients, both 78 years old, died within four months of the onset of visual loss, one of myocardial infarction and the other in which the terminal event was not established. Although Hamilton et al. (1971) reports a low mortality rate in giant-cell arteritis, the present series is not large enough for a significant conclusion.


In comparing the patients with hypertension to those without, no significant differences as to age of onset or course of visual deficit were found. Thus, while hypertension in greater or lesser degree was present in about one-half of the cases of idiopathic ischaemic neuropathy, by no means was it a constant concomitant. Diabetes.—Adequate data were available on 35 patients in the idiopathic group. While 11 patients without previous medical history of diabetes demonstrated minimally abnormal glucose tolerance curves, only 2 patients were overtly diabetic requiring hypoglycaemic agents. In only a single case was diabetic retinopathy observed. It should be pointed out that many patients were being treated with oral steroids at the time of testing for hyperglycaania. However, if all such cases were uncritically accepted as "diabetic," the incidence of diabetes is no more than one-third. In addition, one patient with arteritis presented as an established diabetic. Cerebrovascular disease.—In the idiopathic group, 2 patients had experienced completed but minor strokes prior to eye symptoms, and an additional patient had an episode with fixed neurological deficit three years after ischaemic papillopathy. Two other patients reported transient ischaemic attacks, one prior to ischaemic optic neuropathy, the other during follow-up (see Diagnostic Procedures, Ophthalmodynamometry). Transient or fixed deficits were not encountered in the arteritic group, with the exception of an instance of hemiplegia occurring ten months after diagnosis (six months after cessation of steroid therapy). Certainly the incidence of transient or fixed neurological signs in this group of patients appears no higher than would be expected for an age-matched population without ischaemic neuropathy (Kannel et al., 1970).

695

ISCH^MIC OPTIC NEUROPATHY

Other Concomitant Disorders Various medical conditions were encountered in both groups of patients (Table II), but none was present to any significant degree, and all are considered statistically incidental. Three patients gave a history of migraine but this could not be causally associated with the onset of optic nerve disease {see McDonald and Sanders, 1971). No patient in the idiopathic group had chronic glaucoma, which contrasts sharplv with the incidence reported by Foulds (1969).

Idnpothic, 49 eye* Arteritii, 17 oyw

2O/1S to 20/25

2O30 to 20/40

2IVJO

2O/«0 20-200 to 20/100

20400 to 20/400

Fro. 2.—Visual acuity after stabilization.

F.C. H.M.

L.P. NIP


Ophthalmological Findings Bilaterality.—In 14 patients in the idiopathic group (38 per cent) both eyes were eventually involved {see Cullen, 1967a, 15 per cent; Georgiades et al, 1966, 41 per cent). No patient in this series experienced simultaneous bilateral involvement, but such catastrophes have been reported (Georgiades et al, 1966; Calmettes et al., 1964; Legrande et al, 1957; Kurz, 1969; Ellenberger et al, 1973). The time interval between involvement of the two eyes ranged from five months to twenty-two years, but was less than one year in only one-third of bilateral cases. Only one of the bilateral cases examined at the Eye Institute was seen at the time of the first-eye involvement. The other 13 cases presented a rather typical picture of optic atrophy in one eye from previous nerve infarction, and a swollen nerve head in the acutely involved eye {see below, Fundus). No distinguishing features helpful in predicting bilaterality were found. Both eyes were involved in 4 patients with arteritis, in 2 cases simultaneously, and in 2 within a one-week interval. This interval is consistent with that found in other series (Crompton, 1959; Meadows, 1968; Cullen, 1967a) {see below, Efficacy of Treatment). Visual acuity.—Analysis of ultimate central visual function in idiopathic cases revealed no consistent differences between first and second eyes, or between normoand hypertensive cases. In the idiopathic group, visual acuity of 20/60 or better was retained in 45 per cent of eyes (fig. 2), whereas in the arteritic cases this level of vision

696


Visual Field Defects Adequate data for the analysis of visual fields were available in 34 of the patients considered to represent examples of non-arteritic ischaemic optic neuropathy. This material is summarized in Table IQ. Fourteen of these cases (41 per cent) had bilateral field involvement, but no instance of simultaneous onset was uncovered, as discussed above. A surprisingly high incidence of "stuttering" progression of visual defects occurred. Eleven patients (30 per cent) had progressive worsening over periods of several days to four weeks. The following documented instances are representative: Case H. N. A 61-year-old mildly hypertensive male presented with a four-day history of "hazy sensation," noted inferiorly in the field of the right eye. He attributed this phenomenon to sunbathing, but became concerned when his "eye was getting worse" two days after onset of symptoms.


was retained in only 4 of 17 involved eyes, with 7 eyes showing "bare" or no perception of light. Thus, though visual loss in the idiopathic group may be incapacitating, it tends to be less severe than in the arteritic group, in which devastating visual loss ("legal" blindness in 13 of 17 eyes) is an almost constant feature (see Meadows, 1968; Cullen, 19676). Although several authors (Kurz, 1969; Georgiades et al, 1966; Bardelli, 1964) have commented on different degrees of visual loss in first versus second eyes involved, bilateral cases in the present series demonstrated no discernible pattern. Course of visual acuity.—Where detailed histories were available, in the idiopathic group the earliest visual deficit was fixed and constant in 27 eyes, but was progressive in 12 eyes (see above, Visual Symptoms). Improvement in vision occurred in 2 eyes of the total series, in different patients. Initial vision of "finger-counting" function improved to 20/200 in nine weeks in one case, and in another improved to 20/20 over a seven-day interval, after an initial four-week period of very poor vision (patients described in Treatment section, below). With reference to subsequent visual loss in the same eye (Georgiades et al., 1966; Ellenberger et al., 1973), only one patient in the idiopathic group has experienced a clinically discernible second episode. In this instance, a 45-year-old physician's wife with a history of migraine felt the onset of a second field defect two years after the initial episode. Otherwise, in all patients with at least a three-year follow-up, visual acuity has been monotonously static. In the arteritis group, improvement in visual acuity (and field) from 20/50 to 20/25 occurred in one patient five days after onset, and a second patient with bilateral retrobulbar involvement recovered from finger-counting at 3 ft, and 20/400, to 20/40 and 20/50, on large doses of prednisone. However, while taking 30 mg prednisone a day for one week, a third patient suddenly lost vision in one eye to finger-counting levels. It is imperative to note that nerve infarction may occur in arteritis while the patient is on therapeutic levels of steroids. Despite reports that improvement may occur as long as one year after the acute phase (Schneider et al., 1971), vision in arteritic optic neuropathy is usually stationary.

ISCIWEMIC OPTIC NEUROPATHY

697

Seen initially on June 14,1971, examination revealed: visual acuity, 20/15, both eyes; pupils 4 mm and symmetrically briskly reactive (Gunn's afferent-defect pupil was categorically non-demonstrable); Goldmann perimetry (fig. 3A) revealed an inferior altitudinal defect which spared the central 15 degrees; the right optic disc (fig. 3B) was swollen in its superior aspect, but the inferior disc margin was distinct In the following week the patient noted worsening of visual function. Examination on June 22 revealed: visual acuity 20/40, right eye; the right pupil was sluggish and Gunn's pupil sign could now be elicited; repeat perimetry demonstrated that the inferior defect had ascended to include the horizontal meridian and fixational area; the right disc margin was totally obscured by oedematous nerve fibre layer (fig. 3c). Within the next week vision dropped to 20/400, and by July 6 wasfinger-countingat three feet, at which point the optic disc swelling was diminished, revealing pallor (fig. 3D). Visual acuity andfieldremainunchanged for over three years. Case G. V. A 63-year-old man was seen by his local ophthalmologist on March 30, 1971, complaining of "a blank spot toward the right of centre" in his right eye, which had occurred the preceding afternoon. Acuity was recorded as: right, 20/20; left, 20/400 (due to a dense posterior subcapsular cataract). Amsler grid was reported as demonstrating a defect in the right superior quadrant The right disc was "swollen on the temporal side." A diagnosis of "papillitis" was made and the patient started on prednisone 40 mg on alternate days. The patient noted rapid progression such that within one week acuity was 20/200. By April 8 vision was further reduced to finger-counting at 6 ft. At that time the nerve head was diffusely swollen. Visual acuity has remained at finger-counting for over four years. Downloaded from by guest on June 23, 2015

In the first instance, retrobulbar injection of triamcinolone (Kenalog, Squibb) 60 mg, on June 14, 22, and 30 did not prevent progression of the visual defect. The second case had been using warfarin (Panwarfin, Abbott) for the preceding four years following a myocardial infarction, and was considered "adequately anticoagulated" by his physician. Patterns of field defects (Table HI).—The visual field defects in 48 eyes of 34 patients are organized in tabular form in order to conveniently display the data. This technique necessitates a somewhat arbitrary classification of defects with which other clinicians may disagree. Altitudinal defects (so-called, "altitudinal hemianopias" or incomplete nasalquadrantanopias) comprise the most common pattern (33 of 48 fields) of visual field loss (see Georgiades et al., 1966; Kurz, 1969). There was a three-to-one preferential involvement of the inferior half-field In this "altitudinal" group, the fixational area (that is central acuity) was spared at least as often as it was involved. An interesting finding was the occurrence of central scotomata as the predominant field defect in six eyes (12-5 per cent). In this group, acuity ranged from 20/25 to 8/200. Other field defects ranged from mild generalized constriction to no perception of light. In no instance was the temporal hemi-field predominantly involved. In fact, the nasalfieldappears especially vulnerable, typically inferiorly. Even by confrontation testing techniques, therefore, confusion with chiasmal or homonymous hemianopic defects should not arise. In a smaller series (21 eyes in 19 patients), Cullen (1967a) reported 5 instances of central scotoma, and 6 eyes with an inferior altitudinal hemianopsia or quadrantanopsia. Ellenberger et al. (1973) reviewed a series of 48 patients over 35 years of age, characterized by sudden onset of optic nerve disease (excluding

698

DAN R. BOGHEN AND JOEL S. GLASER TABLE HI.—VISUAL FIELD DEFECTS IN NON-ARTERITIC ISCH^MIC OPTIC NEUROPATHY 48 EYES IN 34 PATIENTS

ALTITUDIHAL "HEKLABOPBIA"

ARCUATE FIELD LOES

JJ> BROAD

15

U MARROW

SVC--"

CE))TBAL SCOTOHi

£

MILD (ACUITY

2 20/25-40)

SEVERE (ACU1TT

4 20/200-8/200)

3

X \

V

1 INFERIOR (GOOD ACUITY

12 8)

"QUADRANTANOFSIA" (COOD ACUITY

12

5)

MISCELLANEOUS

8

NO LIGHT PEKCEPTIOB FIHCER COUNT 1-4 F T . GEHERAL CONSTRICTION SUPEROHASAL REMNANT SOPEBONA3AL DEPRESSION

4 3)

(GOOD ACUITY

3 1)

possible cases of demyelinating disease, but including 3 recognized cases of arteritis); arcuate defects, including altitudinal hemianopias, were found in 51 of 64 visual fields, inferior defects being twice as common as superior; central scotomata were found in 8 eyes or about 12-5 per cent. We are in complete agreement with Cullen (1967a) that the visual deficits in arteritic ischaemic neuropathy tend to be more severe than with the non-arteritic variety. In the present series of arteritis patients, one of every 3 involved eyes had no light perception and the percentage was even greater (18 of 34 eyes) in the report by Cullen. Ophthalmoscopic Findings Fundus photographs of 31 patients with idiopathic ischaemic papillopathy were available for review. Narrowing and attenuation of the retinal arteriolar tree was present in about one-half of these patients, these changes occurring primarily in the clinically hypertensive group, as might be anticipated. During the acute phase of disc infarction, there was no significant difference in generalized vessel attenuation when the fundus of the symptomatic eye was compared to the normal eye. However, in the bilateral cases the eye with long-standing optic atrophy showed greater vessel attenuation than in the eye with acute disc infarction. No doubt the accentuated narrowing of vessels in eyes with evolved optic atrophy simply reflects attrition in the nerve fibre layer. Not all patients were seen immediately at the time of onset of the visual symptoms, but those eyes observed in the relatively acute phase showed variable degrees of optic


SUPERIOR (GOOD ACUITI

ISCHiEMIC OPTIC NEUROPATHY

699


disc swelling. In most instances, the more extensive the disc swelling, the greater the visual deficit (taking into account the delay between onset of symptoms and date of photographic documentation). Several patients presented with massively swollen nerve heads simulating well-developed papilloedema associated with increased intracranial pressure (fig. 4A, B). In others, disc swelling was often modest and confined to one sector of the nerve head (fig. 4c). Small, single or multiple "flame" haemorrhages almost constantly accompanied disc swelling, often confined to the same area of sectoral oedema. With the exception of the occasional clear-cut superior or inferior altitudinal disc swelling, it was not possible to predict by ophthalmoscopy the pattern of the field defect. After the acute episode of disc swelling, optic atrophy ensued, leaving the appearance of sectoral or diffuse disc pallor (fig. 4D). The retinal arterioles rapidly become narrowed and segmentally constricted (figs. 3D, 5A, B). These vessels may also appear "sheathed." Haemorrhages absorbed slowly, the smaller "flames" disappearing in three to five weeks. Thirteen patients showed a fundus appearance of acutely swollen disc in one eye and optic atrophy in the other, a "pseudo-Foster-Kennedy syndrome." Of course, in this situation (sudden visual loss) the disc swelling is not due to increased intracranial pressure but rather to acute infarction of disc tissue. Pallor in the contralateral eye is evidence of previous disc infarction. Schatz and Smith (1967) have stressed the importance of recognizing this clinical situation and have pointed out that this "missed diagnosis" has led to unnecessary arteriography, pneumoencephalography and even craniotomy. We would stress again here that acute loss of visual function {acuity or field) is exceedingly rare with swollen disc due to increased intracranial pressure, and these visual symptoms categorically point to disc inflammation or infarction. Although none of the cases included in this series showed simultaneous bilateral disc swelling, one of us (J. S. G.) has subsequently seen such a patient, who presented with typical symptomatic ischaemic optic neuropathy with acute loss of vision in the right eye. The right disc was moderately swollen with "flame" haemorrhages noted inferiorly. The asymptomatic left eye showed a diffusely swollen disc and a fluorescein pattern compatible with "papilloedema" (fig. 6A, B). TWO weeks later, vision dropped drastically in the left eye. A complete haematological investigation, including antinuclear factor and immuno-globulins, was negative. Carotid arteriography performed prior to consultation was reviewed and considered normal. Foulds (1969) has stated that "it is our experience that the signs of ischaemic optic neuropathy may occur before the symptoms," but this postulate is otherwise not substantiated. Regarding bilateral, simultaneous disc swelling, Georgiades et al. (1966) recorded 4 cases in a review of 17 patients with "arteriosclerotic vascular pseudo-papillitis," and Kurz (1969) includes 5 cases of bilateral "papilloedema" in a series of 38 patients. Apparently, the cases of Kurz had simultaneous symptoms, but the 4 cases of Georgiades had unilateral visual defects when first observed, 3 subsequently developing defects in two to six months (that is, the asymptomatic disc swelling became symptomatic). Sanders (1971) has also recorded a complicated case

700


of ischaemic papillopathy occurring in a 44-year-old syphilitic with bilateral disc oedema, the oedema on one side preceding subjective visual impairment. In the arteritis group, thirteen fundi of 10 patients were photographed during the period of acute loss of vision (hours to twelve days). In one instance, an 80-year-old man presented with sudden bilateral loss of vision (RE 3/200; LE 20/400) and normal optic discs. On large doses of prednisone vision ultimately recovered to 20/40 and 20/50. This is considered an instance of simultaneous bilateral retrobulbar ischaemia due to arteritis. Another patient presented with severe visual loss (light perception in one eye, no light perception in the other) with a ten-day interval between eyes, and a funduscopic appearance of pale-white, swollen discs, including retinal infarction in the distribution of a cilio-retinal artery. A total of nine fundi showed this picture of pallid infarction without haemorrhages. One patient presented with a fundus appearance compatible with central retinal artery occlusion (see Cullen, 19676). Hayreh (1974a) has also pointed out the peculiar chalk-white appearance of the disc, likely to signify underlying arteritis.


Diagnostic Procedures Erythrocyte sedimentation rate (ESR).—In 25 patients with idiopathic papillopathy the ESR was measured at least once, and only 4 cases had rates of 40 mm/hr or above (negative histories, physical signs and benign clinical follow-up in all; 2 with negative biopsies). By contrast, all but 2 patients with arteritis had ESRs greater than 40 mm (range: 36-115 mm; average 68 mm). Cullen (1967a), in comparing arteritic versus "arteriosclerotic" ischaemic optic neuropathy, found only 3 of 19 patients in the latter group with ESR greater than 30 mm (mean 26 mm), while only 3 of 25 patients with biopsy-positive arteritis had ESRs of 50 mm and below (mean 84 mm; 70 mm or above in 80 per cent). Cullen (1963) has also pointed out the rare occurrence of arteritis with normal ESR. Eagling et al. (1974) included 2 cases of biopsy-positive arteritis with normal sedimentation rates. In a series of 31 cases of temporal arteritis with severe visual impairment, Palm (1958) reported the mean of the highest ESR values to be 96 mm with a range of 50-145 mm. In an extensive and excellent monograph on "Polymyalgia Arteritica," Bengt Hamrin (1972) found mean ESR values of 106 mm (51 biopsypositive patients) and 99 mm (42 biopsy-negative patients); for the entire series of 93 cases, mean ESR was 103 ± 26-5 mm/hr (range 47-155 mm). It is clear from the papers of Wilhelm and Tillisch (1951), Boyd and Hoffbrand (1966), and Milne and Williamson (1972), that ESR increases with age and is "elevated" (>20 mm/hr) in apparently healthy elderly subjects. In the last-named paper, it was demonstrated that in at least 50 per cent of persons with an ESR greater than 50 mm, no cause was found. Furthermore, taking 20 mm as upper limit of normal, bacteriuria, ischasmic heart disease, and chronic respiratory symptoms show no consistent association with a raised ESR. We are in agreement with the above authors and personally accept 35-40 mm/hr (Westergren) as the upper limit of normal for the ESR in the elderly.

ISCILEMIC OPTIC NEUROPATHY

701

Temporal artery biopsy.—Biopsy was performed in 9 cases of the idiopathic group and was negative for arteritic changes in all. Artery biopsy was obtained in all cases of arteritis and demonstrated pathological changes typical for that disease in 11 instances. Of the 2 patients with negative biopsy, one was believed to have polyarteritis and the other had ESR of 73 mm/hr, a history compatible with giant-cell arteritis and a positive temporal arteriogram. Ophthalmodynamometry.—Ophthalmic artery pressures were determined by the Bailliart technique in 15 of the idiopathic cases and no significant pressure difference was found in 12. In 3 cases a lower pressure was demonstrated ipsilateral to the symptomatic eye. In the series reported by Ellenberger et al. (1973) systolic and diastolic values were bilaterally equal in all 33 patients on whom ophthalmodynamometry was performed.


Efficacy of Treatment Systemic steroid administration has been the treatment of choice in giant-cell arteritis, and detailed accounts of efficacy may be found in the literature (Meadows, 1968; Hamilton, 1971). There seems little doubt that high dosages (for example, 80 mg prednisone per day) are indicated initially, and may be tapered if symptoms and sedimentation rate abate. We cannot draw firm conclusions from our small series, but it is of passing interest that in one of the present cases, three days of 80 mg prednisone did not abort transient obscurations of vision which progressed to total blindness. Similar instances were reported by Meadows (1968). For idiopathic ischa?mic optic neuropathy, no successful remedy has emerged. In desperation, steroids have been used, both by systemic or orbital routes, but results have been disappointing. Foulds (1969) has reported improvement in vision with large doses of prednisolone in a non-randomized, small heterogeneous group of patients (acute blood loss, diabetes, malignancy, glaucoma, etc.). Recently, Hayreh (19746) has reported that systemic corticosteroids have a beneficial effect in patients with non-arteritic ischaemic optic neuropathy; he suggests that the visual fields are a better guide in assessing improvement than central visual acuity alone. Unfortunately, the only case elaborated upon in Hayreh's publication is that of a 46-year-old hypothyroid, unstable diabetic. Ideally, details of the other 5 cases with "improvement" should have been included in support of alleged efficacy of corticosteroids in this controversial area. In our series, corticosteroids administered systemically in large doses at two days to three weeks following onset did not prevent visual deterioration in 3 cases, and 10 remained unchanged. Eight patients were treated with early administration of steroids by injection into the sub-tenon or retrobulbar space, with subsequent deterioration in two eyes (see above, Case H. N.) and no change in six. Prednisone 100 mg per day was initiated in one case three weeks after loss of vision, and function concomitantly improved from 18/200 to 20/40 within four days. One patient, completely blind in the right eye after a previous episode of ischaemic optic neuropathy, presented with a four-day history of finger-counting vision in the left

702


Pathology and Pathogenesis

The elucidation of the pathology in non-arteritic ischaemic optic neuropathy suffers from a striking lack of well-studied material. Similarly, the relationship of nerve ischemia and subsequent production of field defects is speculative and for the most part inferred from experimental studies. It is profitable to consider what is known to occur in the arteritic form of ischasmic optic neuropathy. This subject has been reviewed by Henkind et al. (1970), who found 14 histologjcally studied cases of giant-cell arteritis. Henkind's case demonstrated infarction of the optic nerve within and behind the lamina cribrosa, and the authors pointed out the similarity to the photograph published by Cogan (1966) showing retrolaminar opticomalacia in a case of non-arteritic ischaemic optic neuropathy. According to Henkind, most of the orbital vessels, including the ophthalmic artery, posterior ciliary group and intraneural central retinal artery may be involved by the arteritic process, but actual arteritis of intraocular vessels of the choroid and retina is probably quite rare {see RodenhSuser, 1964). This phenomenon may be related to absence of an internal elastic lamina in intraocular vessels. Henkind suggests that involvement of the posterior ciliary arteries plays the dominant role in retrolaminar infarction of the nerve, with occlusion of the end-arteries of the circle of Zinn which supply the lamina cribrosa. Francois (1956) considered disc infarction to follow occlusion of the central artery of the optic nerve, or one of its branches. This explanation, although adopted by most European clinicians, has been refuted by authors who believe this artery to be a rare anatomical variant which, when present, does not supply the area of the lamina cribrosa and disc substance (Hayreh, 1970; Henkind et al., 1970).


eye. She was placed on prednisone 100 mg per day by mouth, and heparin. Within seven days vision in the left eye recovered to 20/20. Another similar case, however, had progressive visual loss despite high doses of steroids and adequate anticoagulation, instituted on the fourth day of symptoms. Case G. V. (cited above) developed progressive ischaemic papillopathy while on an anti-coagulant, while another patient apparently improved, although this point is not well documented. The inconsistencies and vagaries of thesefindingsraise grave doubts regarding the efficacy of steroids or anti-coagulants, or combinations. Other agents have been employed (Georgiades et al, 1966; Francois et al, 1962; Kurz, 1969) but results have been uniformly unsatisfactory. Currently under trial are Diamox (acetazolamide), which reduces intraocular pressure, hopefully improving perfusion of the optic nerve head (Sanders, 1971), and Dilantin (diphenylhydantoin) which has been shown experimentally to partially reverse effects of anoxia on nerve conduction (Keltner et al., 1972). Neither of these treatments has yet been shown to be effective, and the efficacy of corticosteroids in uncomplicated ischsemic optic neuropathy (without arteritis, collagenosis, syphilis or other inflammatory conditions) is not adequately established (Foulds, 1969; Hayreh, 19746; Eagling et al., 1974, notwithstanding).

ISCH^MIC OPTIC NEUROPATHY

703


Based primarily on the work of Singh Hayreh (1969) and Anderson (1970), evidence is overwhelming that the blood supply of the optic disc and laminar portion of the nerve is derived fromchoroidal circulation, that is, branches of posterior ciliary arteries and arterial anastomotic plexuses (arterial circle of Zinn-Haller). Pial branches from the ophthalmic artery supply the posterior portion of the intraorbital optic nerve; the anterior segment is supplied axially by intraneural branches of the central retinal artery, and a peripheral pial complex supplied by the arterial circle of Zinn-Haller, branches of the ophthalmic artery and pial anastomoses from branches of the central retinal artery. The surface vessels of the disc are derived from the central retinal artery and from pre-papillary capillary loops (Henkind, 1967). By means of fluorescein angiography of the ocular fundus, Hayreh (1970, 1972) has demonstrated that the posterior ciliary arteries irrigate more or less well-demarcated segments of the choroid and optic nerve head. He has proposed that posterior ciliary artery occlusions may infarct the optic disc and adjacent retrolaminar nerve, with resultant nerve fibre bundle defects, altitudinal hemianopsias and vertical hemianopsias. (It must be noted that vertical "hemianopsias" with the border of the defect passing through the blind-spot must be extraordinarily rare, if they exist at all.) Sanders (1971) has suggested that the small vessel circulation of the optic disc must be a relatively high pressure capillary system to compensate for the high extraneural pressure exerted by intraocular tension, and that there also exists a marginal perfusion zone between retinal and choroidal circulation. These factors may contribute to a special susceptibility to infarction, which may be further exacerbated by oedematous swelling in the rigid confines of the scleral canal. Thus, occlusion of a relatively small vessel may result in a progressive infarction out of proportion to the territory initially insulted. Although micro-embolization from carotid atheromatous disease to retinal circulation is well established (Zimmerman, 1965; Wolter and Ryan, 1972), we are unaware of histological confirmation of ischaemic optic neuropathy occurring as a result of atheromatous embolization of the arterial circulation of the lamina cribrosa or nerve head. Although the anticipated relationship between extracranial carotid occlusive disease and ischasmic optic neuropathy would provide a convenient and facile explanation, the actual pathophysiological mechanisms of nerve infarction are inconclusive. Clinical features such as reduced ophthalmic artery pressures, abnormal carotid angiography or concomitant ipsilateral hemispheral signs or symptoms, by their absence fail to incriminate the carotid system. The complicated case reported by Knox and Duke (1971) is controversial and somewhat speculative, although ipsilateral carotid occlusive disease was demonstrated at autopsy. In the present series, one patient died twelve days after onset of right visual loss, death occurring as a complication of a thyroid operation (case reported by Schatz and Smith, 1967). There was oedema of the nerve fibre layer of the right nerve head and superficial haemorrhages. There was mild swelling and gliosis of the left disc, but no other abnormalities were noted in multiple cross-sections of the nerves. The blood

704


SUMMARY AND CONCLUSION

The clinical situation of acute optic disc infarction in middle-aged and senescent patients is not uncommon, yet with the exception of those instances due to giant-cell arteritis, pathophysiological mechanisms remain obscure. In hopes of elucidating this syndrome, the clinical profile and natural history of 37 cases of non-arteritic ischaemic optic neuropathy were reviewed. For contrast, 13 cases of arteritic optic neuropathy were surveyed. The salient features of idiopathic optic neuropathy may be summarized as follows: (1) the syndrome occurs primarily in 55-70-year-old patients who, for the most part, are otherwise well; (2) mild hypertension is present in about half of the cases, but does not determine a separate variant of the disorder; (3) there is no significant association with extracranial carotid occlusive disease;


vessels of the nerve were quite normal. However, neither the posterior ciliary arteries nor the carotid system was examined. Recently, Carroll (1973) has again called attention to a form of ischsemic optic papillopathy occurring after uncomplicated cataract extraction, with sudden visual loss from four weeks to fifteen months post-operatively. Carroll cautions that 50 per cent of patients with first eye involvement may anticipate visual loss following surgery on the second eye. Two additional points regarding pathophysiology are worth noting: 3 patients were in their 50s {see also bilateral case of O'KeefTe and Choudhury, 1960); the syndrome occurs with both retrobulbar or general anzesthesia. In Carroll's series, no patient experienced a loss of vision in a second eye unless subjected to cataract extraction, and therefore Carroll speculates that "there is at least a localized occlusive vascular process involving the blood supply to the optic nerve," and that the operative procedure "tends to increase the occlusive disease over a period of weeks or months." Carroll also concluded that neither corticosteroids nor anticoagulants are effective remedies. It would seem that optic neuropathy following cataract extraction represents a distinct variant of the ischaemic syndrome, characterized by a circumscribed time course and high incidence of bilaterality when the second eye is operated upon (even in the sixth decade), to the point of predictability. This special situation sheds no light on pathophysiological mechanisms. Ellenberger and Netsky (1968) studied histologically 40 optic nerves from 20 cadavers, all over 45 years of age. They found diffuse but minimal intimal thickening in the posterior ciliary arteries and thickening of the walls of the arterioles in the pia and within the substance of the nerves. They interpreted these changes as a demonstration that the arterial vessels supplying the optic nerve are subject to athero- and arteriolosclerosis. At the present time neither the pathophysiology nor anatomical background of primary, non-arteritic ischasmic optic neuropathy is completely understood. There is no conclusive evidence either from previous reports or from the present study to implicate the extracranial carotid system, and the roles of arteriosclerotic vascular disease and hypertension are uncertain.

OPTIC NEUROPATHY

705

(4) over long follow-up periods there appears to be no increased incidence of stroke; (5) the syndrome should be easily recognized on clinical grounds, consisting of sudden or rapidly progressive monocular visual deficit associated with optic disc swelling, with stable visual defects of variable degree; (6) after an interval of months to many years, the second eye is involved in about 40 per cent of cases (old optic atrophy coupled with contralateral fresh disc infarction may be confused with the Foster-Kennedy syndrome); (7) no form of therapy has proved efficacious; (8) pathophysiological mechanisms remain speculative. It is the responsibility of the physician, be he ophthalmologist or neurologist, to distinguish the patient with occult arteritis (history, physical examination, sedimentation rate, arterial biopsy) and institute immediate high-dosage corticosteroid therapy. It is also incumbent upon the clinician to desist from unnecessary and unrewarding diagnostic procedures, in particular cerebral angiography, when confronted with an instance of non-arteritic ischaemic optic neuropathy. ACKNOWLEDGMENTS

REFERENCES ANDERSON, D. R. (1970) Vascular supply of the optic nerve of primates. Am. J. Ophthal., 70, 341-351. BARDELLI, A. M. (1964) Pseudopapilliti vascolari. Minerva Oftal., 6, 1-4. BONAMOUR, G. (1954) Les atrophies optiques chez les hypertendus arteriels. Bull. Soc. Ophtal. Fr. (1), 120-122. BOYD, R. V., and HOFFBRAND, B. I. (1966) Erythrocyte sedimentation rate in elderly hospital in-patients. Br. med. J., 1, 901-902. BRUCE, G. M. (1949) Temporal arteritis as a cause of blindness: Review of literature and report of a case. Trans. Am. ophthal. Soc., 47, 300-316. CALMETTES, L., DEODATI, F., GAYRAL, L., and BECHAC, G. (1964) Pseudopapillite vasculaire bilaterale.

Revue Oto-Neuro-Ophtal., 36, 371-373. CARROLL, F. D. (1973) Optic nerve complications of cataract extraction. Trans. Am. Acad. Ophth. Otol., TJ, 623-629. COOAN, D. G. (1966) "Neurology of the Visual System." Springfield: Thomas, p. 186. CROMFTON, M. R- (1959) The visual changes in temporal (giant-cell) arteritis. Brain, 82, 377-390. CULLEN, J. F. (1963) Occult temporal arteritis. Trans, ophthal. Soc. UJC., 88, 725-736. (1967a) Ischemic optic neuropathy. Trans, ophthal. Soc. U.K., 87, 759-774. (19676) Occult temporal arteritis. A common cause of blindness in old age. Br. J. Ophthal., 51, 513-525. DESVKJNES, P., and BRUN, M. (1952) Nevrite optique aigug avec arteriosclerose de l'artere ophtalmique. Bull. Soc. Ophtal. Fr. (65), 110-113.


This investigation was supported in part by Public Health Service Training Grant No. EY-OOO28 from the National Eye Institute, National Institutes of Health, Bethesda, Md. 20014, and the Canadian National Institute for the Blind by means of A. Baker Foundation Grant for the Prevention of Blindness, and H. K. Detweiler travelling fellowship of the Royal College of Canada.

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EAGLTNO, E. M., SANDERS, M. D., and MILLER, S. J. H. (1974) Ischsemic papillopathy. Clinical and fluorescein angiographic review of forty cases. Br. J. Ophthal., 58, 990-1008. ELLENBEROER, C , and NETSKY, M. D. (1968) Infarction in the optic nerve. / . Neurol. Neurosurg. Piychiat., 31,606-611. , KELTNER, J. L., and BURDE, R. M. (1973) Acute optic neuropathy in older patients. Neurol., Chicago, 28, 182-185.

Archs

FOULDS, W. S. (1969) Visual disturbances in systemic disorders. Optic neuropathy and systemic disease. Trans ophthal. Soc. UJC., 89, 125-146. FRANCOIS, J., VERRIEST, Q., and BARON, A. (1956) Pseudo-papillites vasculaire. Bull. Soc. Ophtal. Fr. (69), 36-57. ,

, NEETENS, A., DE ROUCK, A , and HANSSENS, M. (1962) Pseudo-papillites vasculaire.

Annls Oculist, 195, 830-885. GEOROIADES, G., KONSTAS, P., and STANGOS, N. (1966) Reflexions issues de l'etude de nombreux cas de pseudo-papillite vasculaire. Bull. Soc. Ophtal. Fr. (79), 506-536. HAMILTON, C. R-, SHELLEY, W. M., and TUMULTY, P. A. (1971) Giant cell arteritis: including temporal arteritis and polymyalgia rheumatica. Medicine, Baltimore, 50,1-27. HAMRIN, B. (1972) Polymyalgia arteritica. Ada med. stand. Supplement 533. HAYREH, S. S. (1969) Blood supply of the optic nerve head and its role in optic atrophy, glaucoma, and oedema of the optic disc. Br. J. Ophthal., 53, 721-747.

(1974a) Anterior ischaemic optic neuropathy, n . Fundus on ophthalmoscopy and fluoresccin angiography. Br. J. Ophthal., 58, 964-980. (19746) Anterior ischsmic optic neuropathy. diagnosis. Br. J. Ophthal., 58, 981-989.

HL Treatment, prophylaxis, and differential

, and BAINES, J. A. B. (1972) Occlusion of the posterior ciliary artery, Parts I, n , m . Br. J. Ophthal., 56, 719-764. HENKTND, P. (1967) The radial peripapillary capillaries of the retina. I. Anatomy, human and comparative. Br. J. Ophthal., 51,115-123. , CHARLES, N. C , and PEARSON, J. (1970) Histopathology of ischemic optic neuropathy. Am. J. Ophthal., 69, 78-90. HORTON, B. T., MAOATH, T. B., and BROWN, G. E. (1932) An undescribed form of arteritis of the temporal vessels. Proc. Staff. Meet. Mayo Clin., 7, 700-701. JENNINGS, G. H. (1938) Arteritis of temporal arteries. Lancet, 1, 424-428. JOHNSON, R. H., HARLEY, R. B., and HORTON, B. T. (1943) Arteritis of temporal vessels associated with loss of vision: Report of two cases. Am. J. Ophthal., 26, 147-151. KADLECOVA, V. (1951) (Edema papilla ischaanicum. Cslka Oftal., 7, 388-394. KANNEL, W. B., SCHWARTZ, M. J., and MCNAMARA, P. M. (1969) Blood pressure and risk of coronary heart disease. The Framingham study. Dis. Chest, 56, 43-52. ,

WOLD, P. A., WESTER, J., and MCNAMARA, P. M. (1970) Epidemiologic assessment of the role of

blood pressure in stroke. The Framingham study. J. Am. med. Ass., 214, 301-310. KELTNER, J. L., BECKER, B., GAY, A. J., and PODOZ, S. M. (1972) Effect of diphenylhydantoin in ischemic

optic neuritis. Trans. Am. Ophthal. Soc, 70, 113-130. KNOX, D. L., and DUKE, J. R. (1971) Slowly progressive ischemic optic neuropathy. A clinicopathologk: case report. Trans. Am. Acad. Ophthal. Otol., 75,1065-1068.


(1970) Pathogenesis of visual field defects. Role of the ciliary circulation. Brit. J. Ophthal., 54,289-311.

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KRHBIG, W. (1953) Optikomalazie, die Folge cincs Gefassverschlusses im retrobulb&ren Abschnitt des Sehnerven. Kiln. Mbl Augenheilk., V22, 719-731. KURZ, O. (1948) Uber Papillitis arteriosclerotica. Ophthalmologica, 116, 281-285. (1969) Vascular opticopathy. Doc. Ophthalmol, 26, 582-591. LASCO, F. (1961) Les affections vasculaires du nerf optique et leurs manifestations clinique. Opthalmologica, 142, 429-445, 500-509. LEORANDE, J., BARON, A., BIOA, S., and BILLET, R. (1957) A propos de trois cas d'eedeme papillaire.

Bull. Soc. Ophial. Fr. (4), 235-240. MCDONALD, W. I., and SANDERS, M. D. (1971) Migraine complicated by ischaemic papillopathy. Lancet, 2, 521-523. MEADOWS, S. P. (1968) Temporal or giant-cell arteritis, ophthalmic aspects. In: "Neuro-Ophthalmology, IV. Symposium of the University of Miami." Edited by J. L. Smith. St Louis: Mosby, pp. 148-157. MILLER, G. R,, and SMITH, J. L. (1966) Ischemic optic neuropathy. Am. J. Ophthal., 62, 103-115. MILNE, J. S., and WILLIAMSON, J. (1972) The ESR in older people. Geront. din., 14, 36-42. OTCEEFFE, D., and CHOUDHURY, K. C. (1960) Bilateral optic neuritis following cataract extraction. Br. J. Ophthal., 50, 608-609.

RODENHAUSER, J. H. (1964) Uber pathologisch-anatomische Augenveranderungen bei generalisierter Riesenzellarteriitis. Klin. Mbl Augenheilk., 145, 414-429. SANDERS, M. D. (1971) Ischsmic papillopathy. Trans, ophthal. Soc. U.K., 91, 363-386. SCHATZ, N. J., and SMITH, J. L. (1967) Non-tumor causes of the Foster-Kennedy syndrome. / . Neurosurg., 27, 37-44. SCHNEIDER, H. A., WEBER, A. A., and BALLGN, P. H. (1971) The visual prognosis in temporal arteritis. Ann. Ophthal., 3,1215-1230. WAGENER, H. P. (1946) Temporal arteritis and loss of vision. Am. J. med. ScL, 111, 225-228. , and HOLLENHORST, R. W. (1958) The ocular lesions of temporal arteritis. Am. J. Ophthal., 45, 617-630. WILHELM, F., and TILUSCH, J. H. (1951) Relationship of sedimentation rate to age. Med. Clins N. Am., 35,1209-1211. WOLTER, J. R., and RYAN, R. W. (1972) Atheromatous embolism of the central retinal artery. Archs Ophthal. N.Y., 87, 301-304. ZIMMERMAN, L. E. (1965) Embolism of central retinal artery. Archs Ophthal. N. Y., 73, 822-826. {Received July 2, 1975)

LEGENDS FOR PLATES PLATE LXVTJ Flo. 3.—Case H. N. A, Visual field June 14, demonstrates inferior altitudinal defect with spared acuity, B, Right optic disc June 14; superior aspect swollen but inferior margin distinct, c, Right optic disc June 22; oedema now involves entire disc including peripapillary retina (arrows), D, Right disc July 6; diffuse optic atrophy and segmental narrowing of retinal arteries. 47

BRAIN—VOL. XCVm


PALM, E. (1958) The ocular crisis of the temporal arteritis syndrome (Horton). Ada ophthal., 36, 208-243.

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DAN R. BOGHEN AND JOEL S. GLASER PLATE LXVIH

Fro. 4.—Ischaemic papillopathy. A, Marked diffuse disc swelling simulating papilloedema of increased intracranial pressure, B, Moderate disc oedema simulating early stage of papilloedema; note also venous engorgement, c, Inferior sectoral disc swelling with small flame hEemorrhagcs (arrow), D, Superior sectoral atrophy associated with inferior altitudinal field defect; note also arteriolar constriction and attenuated retinal nerve fibre layer (compare with appearance of nerve fibre layer of inferior aspect of fundus). PLATE LXIX FIG. 5.—A, Acute disc infarction; note swelling extending into retinal nerve fibre layer inferiorly and subretinal haemorrhage at nasal aspect of disc (arrows), B, One month later disc is diffusely pale and arterioles markedly attenuated, with focal constrictions. FIG. 6.—Fundi of 63-year-old woman, otherwise fit, with sudden loss of vision of right eye. All studies, including cerebral angiography, were normal, A, Right disc shows diffuse swelling and flame haemorrhage inferiorly (acuity, finger-counting), B, Asymptomatic left eye shows diffuse disc swelling with capillary telangiectasia (acuity, 20/25). One month later, sudden loss of field and acuity were noted in left eye and the disc swelling was replaced by pallor. Downloaded from by guest on June 23, 2015

PLATE LXVII


FIG. 3.

To illustrate article by Dan R. Boghen and Joel S. Glaser.

PLATE LXVIII


FIG.

4.


PLATE LXIX

FIG. 6.



FIG. 5.


The natural history of non-arteritic anterior ischaemic optic neuropathy.

Anti-phospholipid antibodies and ischaemic optic neuropathy.

Anterior ischaemic optic neuropathy and intraocular pressure.

Influence of clinical history on MRI interpretation of optic neuropathy.

Antiphospholipid antibodies in the aetiology of ischaemic optic neuropathy.

Late onset Leber's optic neuropathy: a case confused with ischaemic optic neuropathy.

Incipient non-arteritic anterior ischaemic optic neuropathy: a distinct clinical entity, the Singapore scene 3.

Bilateral Simultaneous Nonarteritic Anterior Ischaemic Optic Neuropathy: Case Report.

Graves' disease presenting as unilateral anterior ischaemic optic neuropathy.

Optic neuritis and ischemic optic neuropathy. Overlapping clinical profiles.

Unusual optic disc infarction in a case of arteritic anterior ischaemic optic neuropathy (AAION).

Dominant optic atrophy. The clinical profile.

Microvascular study of the retrolaminar optic nerve in man: the possible significance in anterior ischaemic optic neuropathy.

Changes in macular layers in the early course of non-arteritic ischaemic optic neuropathy.

Intravitreal dexamethasone implant [Ozurdex] for the treatment of nonarteritic anterior ischaemic optic neuropathy.

Anterior ischaemic optic neuropathy. Differentiation of arteritic from non-arteritic type and its management.

Haemorheological parameters in patients with retinal artery occlusion and anterior ischaemic optic neuropathy.

Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation.

Effect of enhanced extracorporeal counterpulsation in patients with non-arteritic anterior ischaemic optic neuropathy.

Bilateral sequential non-arteritic anterior ischaemic optic neuropathy following repeat influenza vaccination.

Posterior Pole Retinal Thickness for Detection of Structural Damage in Anterior Ischaemic Optic Neuropathy.

Ischaemic optic neuropathy induced sudden blindness as an initial presentation of acute lymphoblastic leukemia.

Twenty-four-hour rhythm of ocular perfusion pressure in non-arteritic anterior ischaemic optic neuropathy.

Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy : preparation for gene therapy clinical trial.