C L I N I C A L P R O F I L E A N D L O N G - T E R M IMPLICATIONS O F ANTERIOR

I S C H E M I C OPTIC NEUROPATHY
M I C H A E L X. R E P K A , M . D . , P E T E R J. S A V I N O , M . D . , N O R M A N J. S C H A T Z , M.D.,
AND R O B E R T C. S E R G O T T , M.D.
Philadelphia, Pennsylvania

Of 196 patients with anterior ischémie optic neuropathy, 169 had the
nonarteritic form and 27 had the arteritic type. Visual acuities were
20/40 or better in 83 of 1S4 eyes with nonarteritic anterior ischémie
optic neuropathy but only eight of 45 eyes with the arteritic type. We
found systemic disease associations for hypertension and diabetes
mellitus only for patients with nonarteritic anterior ischémie optic
neuropathy who were between 45 and 64 years of age. After a mean
follow-up period of five years, 92 nonarteritic patients showed no
changes in the first affected eye; there was eventual involvement of the
second eye in 20 patients.

Anterior ischémie optic neuropathy is more years previously to determine the

frequently responsible for visual loss
after the age of 50 years. Previous reports
have described the acute clinical findings
in anterior ischémie optic neuropathy and
have noted trends in associated systemic
diseases. 1 ' 7 However, the small size of the
patient populations previously studied
has made statistically valid statements
regarding systemic disease associations
impossible.
We reviewed our experience with 196
patients with anterior ischémie optic neu­
ropathy in regard to the following: (1) the
demographic profile of patients without
giant cell arteritis (nonarteritic); (2) the
severity of visual loss at onset and follow-
up; (3) a survey of prevalent systemic
diseases; and (4) the percentage of pa­
tients with giant cell arteritis as a cause
(arteritic). We also recalled all 92 of our
patients with nonarteritic anterior isché­
mie optic neuropathy examined three or
Accepted for publication July 18, 1983.
From the Neuro-ophthalmology Service, Wills
Eye Hospital, Philadelphia, Pennsylvania.
Reprint requests to Peter J. Savino, M.D., Neuro-
ophthalmology Service, Wills Eye Hospital, Ninth
and Walnut Sts., Philadelphia, PA 19107.
478 ©AMERICAN JOURNAL OF OPHTHALMOLOGY 96:478-483, 1983
incidence of second eye involvement and
to evaluate subsequent morbidity and
mortality.
SUBJECTS AND METHODS
All the patients had been examined
here between January 1969 and March
1982. To be admitted into the study pa­
tients were required to be at least 45
years of age and to have experienced
sudden visual loss. Examination or photo­
graphic evidence of pallid optic disk
edema in the acute phase was mandatory.
The diagnosis of arteritic anterior ischém­
ie optic neuropathy required either a
positive temporal artery biopsy specimen
or an increased erythrocyte sedimenta­
tion rate with the classical symptoms of
giant cell arteritis. 1,8 · 9 To assess statistical­
ly the prevalence of systemic disease, we
compared our patients by chi-square
analysis with an age-matched population
drawn from Public Health Service Survey
data. 10
Of the 169 patients with acute
nonarteritic anterior ischémie optic neu­
ropathy, 92 had been examined before
January 1979. All of these patients were
recalled for examination so that we could
Vol. 96, NO. 4 ANTERIOR I S C H E M I C OPTIC NEUROPATHY
assess the long-term prognosis, but only
83 were reexamined, 58 here and 25 by
referring ophthalmologists. We obtained
systemic data for patients reexamined
elsewhere from the referring physicians
or by telephone interviews with the pa­
tient. All instances of involvement of the
second eye were documented by one of
us. The average follow-up period was five
years (range, three to 13 years).
During the follow-up period the inci­
dences of death and morbidity were sub­
jected to life-table analysis for construc­
tion of survival and freedom from disease
curves.11 We used two control groups.
Data for the first group were from a
Public Health Service survey10 of 61-year-
old subjects (same mean age as our pa­
tients). Data for the second control
group, composed of men 59 to 63 years
old, were from the Framingham study.12
We calculated cumulative standard errors
of the mean with the Greenwood approxi­
mation and plotted them with the life-
table data.13
RESULTS
Of the 196 patients with acute anterior
ischémie optic neuropathy, 169 (86%) had
nonarteritic optic neuropathy and 27
(14%) had optic neuropathy secondary to
!
SO -i
iLiL Lud
6/6
6/7
6/9
6/12
6/15
6/18
6/21
6/24
6/30
6/60 CF
6/120 HM
Fig. 1 (Repka and associates). Visual acuities of eyes with anterior ischémie optic neuropathy. CF, counting
fingers; HM, hand movements; LP, light perception; NLP, no light perception. Left, Nonarteritic type (184
eyes). Right, Arteritic type (45 eyes).
479
giant cell arteritis. The nonarteritic
group was composed of 92 men and 77
women with an average age of 64 years
(range, 42 to 88 years). Men were affected
at a slightly younger age than women.
The arteritic group contained nine men
and 18 women with a mean age of 70
years. The 2:1 female preponderance was
significant (P<.05).
Ocular findings—Our visual acuity and
perimetric data were derived from all
affected eyes (first eyes and subsequently
involved fellow eyes) for a total of 184
nonarteritic eyes and 45 arteritic eyes.
Visual acuities were 20/200 or worse in 77
of 184 affected eyes with nonarteritic
anterior ischémie optic neuropathy (42%)
and 20/40 or better in 83 of 184 eyes
(45%). In the patients with arteritic ante­
rior ischémie optic neuropathy, visual
acuities were 20/200 or worse in 26 of 45
affected eyes (58%) and 20/40 or better in
only eight of 45 eyes (18%). A proportion­
al analysis comparing the visual acuities
of nonarteritic patients with those of ar­
teritic patients with anterior ischémie
optic neuropathy showed that visual acui­
ties better than 20/30 were found signifi­
cantly more often in the nonarteritic pa­
tients than in the arteritic patients
(P<.001) (Fig. 1).
_ 3 0 -i
LP
NLP
6/6
6/7
6/9
6/12
6/15 6/21 6/60 CF
6/18 6/24 6/120 HM
6/30
LP
NLP
480 AMERICAN JOURNAL OF OPHTHALMOLOGY OCTOBER, 1983

Goldmann perimetry disclosed a TABLE 1

marked prevalence of inferior visual field VISUAL FIELD DEFECTS IN ANTERIOR ISCHEMIC
defects in patients with nonarteritic ante­ OPTIC NEUROPATHY
rior ischémie optic neuropathy. The most
Nonarteritic
frequently plotted defect was inferior al- Type Arteritic Type
titudinal (79 of 172 defects; 46%) but Defect (172 Eyes) (23 Eyes)
other partial inferior defects also oc­
curred (27 of 172 defects; 16%). Isolated Altitudinal
Inferior 79 13
central scotomas occurred in 34 patients Superior 29 0
(20%). Patients with arteritic anterior is­ Central scotoma 34 7
chémie optic neuropathy displayed pat­ Interior quandrantic 14 0
Inferior arcuate 14 2
terns similar to those of nonarteritic Other 2 1
patients but showed a more striking
compromise of central fixation (Table 1).
Systemic findings—The most common
systemic diseases accompanying nonar­ 64 years) of nonarteritic patients had sig­
teritic anterior ischémie optic neuropathy nificantly increased prevalences (P<.05)
were hypertension, diabetes mellitus, of both hypertension (37 of 102 patients;
and coronary artery disease. When we 36%) and diabetes mellitus (20 of 102
compared the prevalence ratios for these patients; 20%). In patients more than 64
diseases and cerebrovascular disorders years of age, no diseases occurred signifi­
with expected prevalence values from cantly more often than in the general
Public Health Service data10 (Table 2), we population. Ischemic heart disease and
found that the younger group (aged 45 to cerebrovascular disease did not occur at

TABLE 2
PREVALENCE OF SYSTEMIC DISEASE IN ANTERIOR ISCHEMIC OPTIC NEUROPATHY

Age of Patients
Systemic Disease (yrs) Observed Ratio Control Value*

Nonarteritic "type (169 Patients)

Hypertension 45 to 64 37 of 102 = .36+ .21
65 and older 28 of 67 = .42 .38
Diabetes mellitus 45 to 64 20 of 102 = .20+ .06
65 and older 6 of 67 = .09 .08
Heart disease 45 to 64 9 of 102 = .09 .13
65 and older 17 of 67 = .25 .27
Cerebrovascular disease 45 to 64 3 of 102 = .03 .02
65 and older 2 of 67 = .03 .05

Arteritic Type (27 Patients)

Hypertension 45 to 64 Oof 9 = 0 .21
65 and older 10 of 18 = .56 .38
Diabetes mellitus 45 to 64 l o f 9 = .11 .06
65 and older 3 of 18 = .17 .08
Heart disease 45 to 64 l o f 9 = .11 .13
65 and older 5 of 18 = .28 .27
Cerebrovascular disease 45 to 64 Oof 9 = 0 .02
65 and older 3 of 18 = .17 .05

*Data from the National Health Interview Survey.

+
P < .05.
Vol. 96, NO. 4
rates different from those of control sub­
jects in any age group. In the arteritic
patients, no other systemic disease oc­
curred at rates different from those in the
control groups.
Of the 92 patients who had had acute
episodes of nonarteritic anterior ischémie
optic neuropathy at least three years pre­
viously, nine did not respond to our re­
quest for reexamination. Thus, the
follow-up group consisted of 83 patients
(51 men and 32 women with a mean age of
61.2 years). The mean follow-up period
was five years, the median period, 4.3
years, and the range, three to 13 years.
None of the 83 patients showed a change
of more than two Snellen lines and only
three had changed visual fields (Fig. 2).
These three patients had new deficits
compatible with a second ischémie event
in the same eye occurring between two
and 60 months after the initial episode.
Involvement of the second eye was
present in 20 of 83 patients with nonar­
teritic anterior ischémie optic neuropa­
thy. The second eyes of four patients
become involved within the first two
weeks, and ten fellow eyes were affected
at least one year after the initial episode.
The mean interval between involvement
of the first eye and involvement of the
Ï 20
β/β β/ί β/15 β/21 β/βθ
β/7.5 β/12 β/1β 6/24 β/120
β/30
Fig. 2 (Repka and associates). Visual acuities of
eyes with nonarteritic anterior ischémie optic neu­
ropathy at first examination and after a mean follow-
up period of five years.
ANTERIOR ISCHEMIC OPTIC NEUROPATHY 481
fellow eye was 2.9 years. Of 15 arteritic
patients followed up over a similar peri­
od, six have had second eye involvement.
The prevalence of systemic disease was
not significantly different at the time of
the last follow-up examination. Eight pa­
tients had died: five of heart disease, one
of neoplasm, one of a stroke, and one of
unknown causes. These mortality data
were identical to those for the two com­
parable control groups for death from all
causes (Fig. 3). However, patients with
anterior ischémie optic neuropathy died
of ischémie heart disease more often than
expected, but this was not statistically
significant (Fig. 4).
Four patients had nonfatal myocardial
infarcts, and two had strokes. Combining
all the morbidity and mortality data, we
plotted freedom from heart disease vs
time curves. Again, the incidence of
heart disease seemed to be increased in
the nonarteritic patients but not in a
statistically significant manner.
DISCUSSION
Nonarteritic anterior ischémie optic
neuropathy can be defined as sudden loss
of vision associated with pallid optic disk
Framingham 61 yo males
US Population 61 yo
INITIAL SO a y · ·
FOLLOW UP 7 8 a y · · AION
CF LP
ΗΜ NLP
Years
Fig. 3 (Repka and associates). Fraction of patients
surviving vs time for nonarteritic anterior ischémie
optic neuropathy (AION). Comparison with the two
control groups shows no difference in mortality.
482 AMERICAN JOURNAL OF OPHTHALMOLOGY
• Framingham 6 1 y o mala»
A AION N o n - a r t a r l t i c
Ï .90
3
Years
Fig. 4 (Repka and associates). Fraction of patients
free of ischémie heart disease vs time for nonarteritic
anterior ischémie optic neuropathy (AION).
edema and no evidence of temporal arte-
ritis. The goal of our study was to supple­
ment the clinical information about this
entity. Ellenberger, Keltner, and Bürde 4
described 45 patients with nonarteritic
anterior ischémie optic neuropathy with
an average age of 60 years and an equal
sex incidence. Boghen and Glaser's 1 37
patients had an approximate mean age of
61 years with no apparent sex difference.
Eagling, Sanders, and Miller 14 described
33 patients with an average age of 57
years. Hayreh and Podhajsky15 described
97 patients between 15 and 88 years of
age with nonarteritic anterior ischémie
optic neuropathy. Bronner and associ­
ates 3 described 36 patients with an aver­
age age of 60 years. No sex incidence was
reported. The average age of our 169
patients at the onset of nonarteritic ante­
rior ischémie optic neuropathy was 64
years (range, 45 to 88 years), with males
and females being equally affected.
We found that arteritic anterior isché­
mie optic neuropathy occurred in an
older group (mean age, 69.3 years) than
nonarteritic anterior ischémie optic neu­
ropathy. Additionally, the patient was
twice as likely to be female. Boghen and
Glaser 1 did not find this in their study of
OCTOBER, 1983
14 cases of ocular giant cell arteritis, but
19 of 23 patients with arteritis studied by
Hayreh and Podhajsky 15 were women.
Such a female preponderance agreed
with two other studies 8 ' 9 of giant cell
arteritis. No other systemic disease oc­
curred in the arteritic patients at fre­
quencies different from those of the con­
trol groups.
Visual acuities were 20/200 or worse in
77 of our 184 eyes with nonarteritic ante­
rior ischémie optic neuropathy and 20/40
or better in 83. Ellenberger, Keltner,
and Bürde 4 noted visual acuities of 20/100
or worse in 25 of 60 eyes and Boghen and
Glaser 1 reported visual acuities of 20/200
or worse in 23 of 49 eyes with nonarteritic
anterior ischémie optic neuropathy. Hay­
reh and Podhajsky 15 found visual acuities
of 20/200 or worse in 39 of 127 patients
and 20/40 or better in 67. In our study,
inferior visual field defects, usually altitu-
dinal, were present in 106 eyes, agreeing
with previous reports. 1,3,4,15 Our 27 arte­
ritic patients also had predominantly in­
ferior defects.
Hypertension and diabetes mellitus
have been assumed to be important in the
pathogenesis of anterior ischémie optic
neuropathy, 1,5,7 although this hypothesis
has yet to be statistically validated. Our
nonarteritic patients in the age group
between 45 and 64 years had significantly
increased prevalences of both hyperten­
sion (37 of 102 patients) and diabetes
mellitus (20 of 102 patients) compared
with a control population (P<.05). How­
ever, no comparable difference could be
demonstrated for patients older than 65
years. Ellenberger, Keltner, and Bürde 4
reported that 18 of 48 patients had diabe­
tes mellitus and 12 of 48 had hyperten­
sion. Boghen and Glaser 1 reported that 15
of 34 patients had hypertension. Hayreh
and Podhajsky 15 found diabetes mellitus
in 40 of their patients but they did not
state how many had hypertension.
Vol. 96, NO. 4 ANTERIOR ISCHEMIC OPTIC NEUROPATHY
Foulds 16 found hypertension and heart
disease in one third of his 24 patients. In
our study, the prevalences of ischémie
heart disease, cerebrovascular disease,
and vasculitis were not increased.
Long-term ocular follow-up data are
available for two small groups totaling 69
patients with nonarteritic anterior isché­
mie optic neuropathy. 1 , 4 A third group 15
has been described but the length of
follow-up was not specified. Ellenberger,
Keltner, and Bürde 4 reported improved
visual acuities in one third of 40 patients
after a mean follow-up of 2.9 years.
Boghen and Glaser, 1 after a mean follow-
up of 6.4 years, noted "monotonously
static" visual deficits in 29 patients. Our
83 patients had a mean follow-up of five
years. We observed no improvement or
deterioration in their visual acuities or
visual fields. In only three instances did a
second ischémie event affect an eye with
previous anterior ischémie optic neuropa­
thy. This agreed well with previous clini­
cal observations, suggesting that a second
event rarely occurs in previously affected
eyes.
The prognosis for the uninvolved eye is
critically important to the patient and the
clinician. We found subsequent contralat­
eral ocular involvement in 20 of 83 pa­
tients with nonarteritic anterior ischémie
optic neuropathy. Previous reports have
varied, but recurrence rates usually have
been higher than ours (Cullen, 6 15%;
Georgiades, Konstas, and Stangos, 2 4 1 % ;
Ellenberger, Keltner, and Bürde, 4 48%;
Boghen and Glaser, 1 4 1 % ; Hayreh and
Podhajsky, 15 36%).
During the follow-up period we found
no change in the prevalence of any sys­
temic disease over the ratios noted at the
outset except coronary artery disease,
which appeared to be responsible for
most of the mortality and morbidity in
483
our patients. Survival curve analysis sug­
gested that coronary artery disease may
be developing more rapidly in patients
with nonarteritic anterior ischémie optic
neuropathy than in controls. Only further
follow-up can confirm this hypothesis.
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