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Review

Non-arteritic anterior ischaemic optic neuropathy: A review and update


Nathan M. Kerr, Shenton S.S.L. Chew, Helen V. Danesh-Meyer
*
Department of Ophthalmology, Faculty of Medical and Health Sciences, Private Bag 92019, University of Auckland, Auckland Mail Centre, Auckland 1142, New Zealand
a r t i c l e i n f o
Article history:
Received 16 January 2009
Accepted 5 April 2009
Keyword:
Anterior ischemic optic neuropathy
a b s t r a c t
Non-arteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy
in people aged 50 years and older. The condition is caused by infarction of the laminar or retrolaminar
portion of the optic nerve head supplied by the short posterior ciliary arteries (SPCAs). The underlying
aetiology and pathophysiology is poorly elucidated. Factors that have been implicated include nocturnal
hypotension, impaired autoregulation of the microvascular supply, vasculopathic occlusion, and venous
insufciency. These factors are thought to result in axonal oedema causing a compartment syndrome in a
structurally crowded optic disc leading to axonal degeneration and loss of retinal ganglion cells via apop-
tosis. Clinically NAION is characterised by sudden, usually painless, loss of vision in one or both eyes.
Examination ndings include decreased visual acuity, a visual eld defect, decreased colour vision, a rel-
ative afferent pupillary defect, and optic disc swelling. Despite signicant research, treatment options for
NAION remain limited.
2009 Published by Elsevier Ltd.
1. Introduction
Non-arteritic anterior ischaemic optic neuropathy (NAION) is an
important cause of acute visual loss in the middle-aged and elderly
populations. However, many aspects of this disease remain poorly
understood. In particular the exact pathophysiology leading to
infarction of the optic nerve head remains to be elucidated. Fur-
thermore the efcacy of medical and surgical treatments for
NAION are yet to be proven. The purpose of this review is to syn-
thesise current knowledge on the clinical presentation, risk factors,
pathophysiology, and management of NAION.
2. Clinical features
The clinical picture may vary signicantly from the classic pre-
sentation of sudden, painless, unilateral visual loss, frequently no-
ticed on awakening from sleep (Table 1). It is now recognised that
approximately 12% of patients experience ocular pain or headache
which complicates the differentiation of NAION from optic neuri-
tis.
1
In over two-thirds of patients visual loss is noticed on awaken-
ing from sleep, or at the rst opportunity to use vision critically
after sleeping, suggesting that nocturnal arterial hypotension
may play an important role.
2
On clinical examination visual acuity in the affected eye may
vary widely, however no light perception is uncommon in NAION.
In the Ischemic Optic Neuropathy Decompression Trial (IONDT)
49% of patients on presentation had a visual acuity of better than
6/21 while 34% of patients had a visual acuity of 6/60 or worse.
3
In a study of the natural history of NAION the visual acuity at pre-
sentation was normal or near normal (6/5 to 6/9) in approximately
50% of patients.
4
Therefore the presence of normal visual acuity
does not rule out NAION.
There is often an acquired dyschromatopsia which is propor-
tional to the reduction in visual acuity. The most common
visual eld defect is a relative inferior altitudinal defect;
5
how-
ever, NAION may be associated with any pattern of visual eld
loss. Provided the contralateral eye is normal there will be a rel-
ative afferent pupillary defect (RAPD). The classic nding on
fundoscopy is that of a hyperaemic disc with segmental disc
swelling; however, in the IONDT study this nding was only
present in 25% of patients.
3
Typically, the unaffected eye has
a small or absent physiological cup reecting a disc-at-risk
(Table 2).
6
3. Epidemiology
NAION is the most common acute optic neuropathy in people
aged 50 years and over. The condition is estimated to affect be-
tween 2.3 and 10.3 people per 100 000 individuals per year.
7,8
Af-
fected individuals are typically between 60 and 70 years of age
although the condition is not uncommon in younger patients.
9
In
a retrospective study 23% of patients with NAION were under
50 years of age.
10
NAION is predominately a disease of Caucasian
people who account for nearly 95% of cases.
0967-5868/$ - see front matter 2009 Published by Elsevier Ltd.
doi:10.1016/j.jocn.2009.04.002
* Corresponding author. Tel.: +64 9 373 7599x86254; fax: +64 9 367 7173.
E-mail address: h.daneshmeyer@auckland.ac.nz (H.V. Danesh-Meyer).
Journal of Clinical Neuroscience 16 (2009) 9941000
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience
j our nal homepage: www. el sevi er. com/ l ocat e/ j ocn
4. Aetiology
4.1. Small cup-to-disc ratio
Approximately 97% of people who develop NAION have a small
optic disc (less than 1.2 mm) with a small or absent physiological
cup (cup-to-disc disc ratio 6 0.2), a so-called disc-at-risk.
1116
It
is believed that crowding at the level of the lamina cribrosa predis-
poses to a compartment syndrome phenomenon whereby axoplas-
mic stasis and oedema following a microvascular ischaemic event
leads to further ischaemia through compression of capillaries
among nerve bre bundles due to crowding of the optic nerve
head.
12
4.2. Cardiovascular risk factors
Epidemiological studies have evaluated potential associations
between NAION and diseases that are associated with cardiovascu-
lar disease. Diabetes mellitus is a major risk factor in the develop-
ment of NAION
17
and is present in nearly 1 in 4 patients.
3
In a large
case control study diabetes mellitus was associated with an odds
ratio of 2.7 for the development of NAION.
17
The relationship between other diseases and NAION is less
clear. Hypertension may be a risk factor for the development of
NAION in younger patients.
3,18
However, other studies have found
no statistically signicant difference in the prevalence of hyperten-
sion between patients with NAION and age-matched controls.
10
Furthermore, hypertension has even been found to be protective
against NAION in one study.
17
There have been conicting reports on whether ischaemic heart
disease, cerebrovascular disease, and dyslipidaemia are associated
with increased rates of NAION.
9,17,19,20
Like hypertension, dyslip-
idaemia has been found to be associated with NAION in younger
patients.
21
The odds ratio of having an elevated blood cholesterol
with NAION is 3.3 and this likelihood increases when comparison
is restricted to non-diabetic patients.
21
Smoking however is not a
recognised risk factor for the development of NAION.
22
4.3. Prolonged surgical procedures, blood loss, and hypotension
NAION may complicate prolonged surgical procedures such as
spinal or cardiac bypass surgery in approximately 0.030.1% of
cases. In these settings NAION is frequently bilateral and simulta-
neous and results from a combination of hypovolaemia, hypoten-
sion, haemodilution, face-down positioning, and pre-existing
cardiovascular disease. Frequently the diagnosis is delayed due to
changes in the patients mental status post-operatively. NAION
may also be seen in the setting of severe blood loss and hypoten-
sion following trauma.
4.4. Obstructive sleep apnoea
There is a clear association between obstructive sleep apnoea
and NAION. In a case-control study there was evidence of obstruc-
tive sleep apnoea on polysomnography in 71% of patients with
NAION compared to 18% of controls.
23
These results are concordant
with a larger case-control study which found that patients with
NAION were signicantly more likely to report symptoms of
obstructive sleep apnoea on the Sleep Apnoea scale of the Sleep
Disorders Questionnaire (SA-SDQ) than controls.
24
The exact
mechanism by which obstructive sleep apnoea causes NAION is
unknown. However it is postulated that acute surges in blood pres-
sure, increased intracranial pressure, and nocturnal hypoxaemia
from apnoeic spells may result in ischaemia or hypoxia at the level
of the optic nerve head.
4.5. Medications
Two medications have been implicated in the development of
NAION PDE5 inhibitors and interferon-alpha.
There have been several case reports, including a rechallenge
case report,
25
describing NAION in users of PDE5 inhibitors. These
medications facilitate penile erection by potentiating the smooth
muscle relaxant properties of nitric oxide in the corpus caverno-
sum by preventing the breakdown of cyclic GMP (cGMP). It is
hypothesised that the mild hypotensive effect of PDE5 inhibitors
accentuates physiological nocturnal hypotension resulting in
ischaemia of the optic nerve head and a compartment syndrome
in a susceptible disc-at-risk.
26
An alternative explanation is that
these medications reduce optic nerve head perfusion or disrupt
autoregulation by potentiation of nitric oxide.
26
However to date
the incidence of NAION in users of PDE5 inhibitors has not ex-
ceeded that of the general population. In a retrospective cohort
study of male veterans aged 50 years and older the relative risk
of NAION in men prescribed a PDE5 inhibitor was only 1.02 (95%
condence interval 0.92 to 1.12).
27
Interferon-alpha may cause NAION through the deposition of
immune complexes in the optic disc circulation resulting in the
development of a bilateral, sequential NAION in some patients.
28,29
4.6. Cataract surgery
Patients who develop NAION following cataract extraction in
one eye are at a signicantly greater risk of developing NAION in
the fellow eye if cataract extraction is subsequently performed in
that eye.
30
It has been reported that the risk of NAION in the sec-
ond eye may be as high as 50% if the rst eye developed NAION
after cataract extraction.
31
In another study cataract extraction in
the fellow eye increased the risk of NAION occurrence in the fellow
eye by 3.6 times (P = 0.001).
30
In this study 9 of 17 NAION patients
(53%) who underwent cataract extraction in the fellow eye devel-
oped fellow eye NAION, compared to 59 of 308 NAION patients
(19%) who did not undergo cataract extraction in the fellow
eye.
30
The exact mechanism by which cataract surgery may precip-
itate NAION is not known and some authors believe the data do not
support a causal relationship.
32
4.7. Genetic predisposition
There have been reports of familial NAION suggesting that ge-
netic factors may be involved in the development of NAION.
3336
In a study of six affected individuals from a single pedigree the
G4132A mitochondrial variation was found in all six affected
family members but none of 1,585 control subjects.
34
In this
family all affected members were male and there was no evidence
Table 2
Signs of non-arteritic anterior ischaemic optic neuropathy
Decreased visual acuity
Reduced colour vision
Visual eld defect (typically inferior altitudinal)
Diffuse or segmental disc swelling
Flame-shaped haemorrhages
Small or absent physiological cup in the fellow eye
Table 1
Symptoms of non-arteritic anterior ischaemic optic neuropathy
Sudden monocular visual loss frequently noticed on awakening from sleep
Mild ocular pain or discomfort
N.M. Kerr et al. / Journal of Clinical Neuroscience 16 (2009) 9941000 995
of male-to-male transmission which would further suggest the
involvement of a mitochondrial gene.
34
Alternatively this pattern
of inheritance may be explained by an X-linked gene.
34
Supporting
the role of mitochondrial malfunction is a study that sequenced the
entire mitochondrial DNA coding region in 19 patients with NAION
and 100 controls.
37
The authors found that synonymous and
nonsynonymous nucleotide changes were signicantly more com-
mon in NAION patients compared to controls (P < 0.001).
37
Inter-
estingly four of the mitochondrial mutations identied have been
reported in patients with Leber hereditary optic neuropathy
(LHON).
38
Other studies have investigated genetic predisposition to
thrombosis. In a study of 61 patients with NAION, no association
was found between NAION and protein C, protein S, antithrombin
III, lupus anticoagulant, or three prothrombotic polymorphisms-
factor V G1691A, factor II G20210A, and methylenetetrahydrofo-
late reductase (MTHFR) C677T.
20
However, in a second study by
the same authors the presence of a platelet glycoprotein polymor-
phism (the VNTR B allele of glycoprotein Ib-alpha) was found to
confer a signicant risk for NAION and predispose affected patients
to second eye involvement.
39
Glucose-6-phosphate dehydrogenase (G6PD) deciency is one
of the most common human genetic abnormalities and has been
shown to be protective against ischemic heart, cerebrovascular dis-
ease, and retinal vein occlusion. It has recently been discovered
that G6PD deciency is also protective against NAION.
40
The mech-
anism by which G6PD deciency confers protection is unknown.
40
Human leukocyte antigen (HLA) class may be a predisposing
factor. In one study HLA-A29 was found to be a risk factor for the
development of NAION.
41
4.8. Prothrombotic states
There have been reports of NAION occurring in patients with
prothrombotic risk factors such as hyperhomocysteinaemia, lupus
anticoagulant, anticardiolipin antibodies, factor V Leiden muta-
tions, and deciencies in protein C, protein S, and antithrombin
III.
20,4247
However, as yet routine thrombophilia screening in pa-
tients presenting with NAION is not indicated.
5. Pathophysiology
The exact pathophysiology of NAION is unclear and highly con-
troversial. It is generally accepted that the site of the infarction is
located in the retrolaminar portion of the optic nerve head which
is supplied by the short posterior ciliary arteries (SPCAs) as this
has been demonstrated histologically.
48
Doppler studies have also
corroborated these ndings by showing reduced blood ow in the
SPCAs.
49
The location of impaired blood ow has been further re-
ned by uorescein and indocyanine green angiographic studies.
These studies demonstrate delayed optic disc lling without
impairment of the choroidal circulation suggesting that the vascu-
lopathy is located in the para-optic branches of the SPCA after their
branching from the choroidal branches rather than in the short cil-
iary arteries themselves.
50,51
There is also agreement that the nal common pathway leads
to a compartment syndrome with axonal oedema occurring in
a structurally crowded optic disc
12
and subsequent axonal
degeneration and loss of retinal ganglion cells via apoptosis.
52
However, the mechanisms that lead to the axonal oedema
remain controversial and unsubstantiated. Theories that have
been suggested include a reduction in blood ow from a combi-
nation of nocturnal hypotension,
53
impaired autoregulation of
the microvascular supply,
54
vasculopathic occlusion, and venous
insufciency.
55
5.1. Nocturnal hypotension
It has been suggested that nocturnal hypotension, in the pres-
ence of other vascular risk factors, may reduce optic nerve head
blood ow below a critical level leading to ischaemia of the optic
nerve head. This may be important as oral hypotensive therapy
may aggravate nocturnal hypotension, especially when adminis-
tered before bed.
53
However, in a case-control study of 24 patients
with NAION and 24 control subjects matched for age, gender, med-
ical diagnoses, and medications there was no statistically signi-
cant difference in blood pressure on ambulatory diurnal blood
pressure monitoring.
56
Although patients with NAION did have a
less steep and more irregular rise of blood pressure on awakening
in the morning.
56
5.2. Impaired autoregulation
The human optic nerve head exhibits efcient blood ow auto-
regulation, probably due to an increase in vascular capacitance.
57
However various diseases impair these autoregulatory mecha-
nisms.
53
For example, in systemic hypertension these autoregulato-
ry mechanisms may be lost.
53
Additionally humoral mechanisms
may result in vasospasm leading to transient impairment of blood
ow.
54
Hayreh et al. showed that in atherosclerotic monkeys sero-
tonin produced transient occlusion or delayed lling of the poster-
ior ciliary artery and/or central retinal artery in 9 eyes of 9
animals.
54
This is supported by human studies showing proximal
constriction of retinal arterioles in 19 of 28 eyes (68%) with NAION
compared to only 11 of 206 control eyes (5%).
58
One potential
humoral factor is endothelin-1 (ET-1).
59
Animal studies have
shown that intravenous administration of ET-1 causes a reduction
in optic nerve head blood ow and that this is reversed with the
administration of a calcium channel blocker.
59
5.3. Vasculopathic occlusion
Diseases such as diabetes mellitus, hypertension, and dyslipida-
emia may predispose to occlusion of the microvasculature supply-
ing the optic nerve head; however, histopathological studies have
failed to conrm this.
5.4. Venous insufciency
It has been suggested that NAION results from venous insuf-
ciency secondary to closure of the tributary venules that receive
blood from the optic nerve capillaries and drain into the central
retinal vein.
55
This theory is based on the observed differences
between NAION and arteritic anterior ischaemic optic neuropathy
(AAION), the latter being well recognised to result from arterial
insufciency due to occlusion of the posterior ciliary arteries.
AAION results in severe visual loss and pale optic disc swelling
whereas NAION causes variable visual loss and hyperaemic disc
swelling. Furthermore, the morphology of the NAION infarct is
not consistent with the vascular bed of any known artery
60
and
known arterial risk factors such as ischaemic heart disease, cere-
brovascular disease, and smoking are not recognised risk factors
for NAION.
55
Neuroimaging modalities may allow further investigation of
this hypothesis. If NAION is precipitated by venous disease, then
the anterior optic nerve would demonstrate imaging characteris-
tics of venous infarction, not arterial infarction in the acute
phase. In venous occlusion, cytotoxic oedema is rapidly followed
by vasogenic oedema.
61
In arterial infarction there is primarily
cytotoxic oedema. Vasogenic oedema can be differentiated from
cytotoxic oedema by a greater apparent diffusion coefcient on
MRI.
62
996 N.M. Kerr et al. / Journal of Clinical Neuroscience 16 (2009) 9941000
High-resolution imaging of the apparent diffusion coefcient in
the small volume of the optic nerve is currently impractical but
should be possible in future years with higher eld strength mag-
nets and improved techniques.
6. Differential diagnosis
6.1. Arteritic anterior ischaemic optic neuropathy
It is important that NAION is differentiated from AAION (Table
3) due to the propensity of the latter to cause profound bilateral vi-
sual loss without expeditious systemic corticosteroid treatment.
Unlike NAION, which is not uncommon in patients under the age
of 60 years, AAION almost exclusively affects patients 60 years of
age or older. AAION typically presents with sudden, profound, vi-
sual loss and may become bilateral over hours to days; usually in
the setting of delayed diagnosis. In AAION amaurosis fugax may
precede visual loss in approximately 718% of patients
63
and the
majority of patients will have systemic symptoms of giant cell
arteritis (GCA). The main symptom is headache and is present in
two-thirds of patients. It is characteristically temporal in location
although it may be frontal, parietal, or occipital. The temporal ar-
tery is frequently tender and classically patients report pain asso-
ciated with hair brushing. Jaw claudication is highly specic for
GCA and is described as a muscular cramping that increases with
continued chewing or talking and is relieved by rest. Claudication
may also affect the muscles of the tongue. Approximately 40
60% of patients with GCA will have symptoms of polymyalgia
rheumatica (PMR) proximal muscle pain and stiffness that is
characteristically worse in the morning, arthralgia, night sweats,
weight loss, anorexia, fatigue, and malaise. However, approxi-
mately 20% of patients with biopsy proven GCA will have no symp-
toms other than visual loss, therefore the absence of systemic
symptoms does not rule out the diagnosis of AAION.
On examination there is usually profound visual loss. In 6080%
of patients visual acuity in the affected eye is less than 6/60 and
20% have no light perception.
5,9,64
The classic nding on fundos-
copy is a pale chalky white swollen optic nerve head. Nerve bre
layer haemorrhages are not uncommon as are cotton wool spots.
Cilioretinal artery occlusion may be present in up to 21% of cases.
65
6.2. Optic neuritis
Optic neuritis typically affects younger patients and is associ-
ated with pain on eye movement. However, it should be remem-
bered that 12% of patients with NAION will report pain or
headache.
1
The majority of patients with optic neuritis have a ret-
robulbar neuritis and therefore do not have disc swelling. When
optic disc swelling is present in optic neuritis the swelling is more
diffuse whereas in NAION segmental optic disc swelling is more
common.
6.3. Compressive optic neuropathy
Compressive optic neuropathy may mimic NAION. Unlike
NAION the onset of visual loss tends to be slowly progressive.
However, some patients may suddenly notice the visual loss in
one eye leading to potential confusion with NAION. The optic nerve
head more commonly appears pale rather than swollen. Other fea-
tures which suggest a compressive process include proptosis and
optociliary shunt vessels around the optic disc (small vessels that
shunt blood from the retinal circulation to the choroidal circula-
tion). However, if the optic nerve is compressed close to the poster-
ior aspect of the globe (such as often occurs in optic nerve
meningiomas) then optic nerve swelling may be present. In these
circumstances, the optic nerve swelling may be monitored. If the
optic nerve swelling does not resolve within weeks then the pa-
tient should undergo neuroimaging to evaluate the possibility of
an underlying compressive lesion.
6.4. Amiodarone optic neuropathy
Amiodarone optic neuropathy should also be considered in
the differential diagnosis. The diagnosis of amiodarone optic
neuropathy is a clinical one. Amiodarone may produce bilateral
insidious visual loss with optic disc swelling that may persist for
months despite withdrawal of the drug. In contrast, NAION is
characterised by acute unilateral visual loss with resolution of
discoedema over several weeks. However, unilateral cases of
amiodarone optic neuropathy have been reported. Patients with
unilateral disc oedema should be evaluated for atypical features
Table 3
Comparison of NAION and other common optic neuropathies
NAION AAION Compressive optic
neuropathy
Amiodarone optic
neuropathy
Optic neuritis
Patient
demographics
Typically occurs in patients
4060 years of age
Typically occurs in patients
60 years of age or older
May occur at any age May occur at any age in
patients taking amiodarone
Typically occurs in patients
1845 years of age
Symptoms Sudden monocular
visual loss
Sudden painless visual loss
Initially unilateral but may
Slowly progressive visual
loss
Insidious onset unilateral or
bilateral visual impairment
Loss of vision over hours to
days
Mild ocular pain or
discomfort
rapidly become bilateral
May be preceded by
amaurosis fugax
Symptoms of giant cell
arteritis
Pain on eye movement
Focal neurologic symptoms
Symptoms may be worse
with exercise or increased
body temperature
Signs Variable visual loss Profound visual loss Reduced visual acuity Reduced visual acuity Subtle to profound visual
Reduced colour vision
Visual eld defect (typically
Pale (chalky white) optic
disc swelling
Visual eld defect
Normal, swollen, or pale
Visual eld defect
Bilateral optic disc swelling
loss
Decreased colour vision
inferior altitudinal)
Diffuse or segmental disc
Flame-shaped
haemorrhages
optic disc Visual eld defects
Optic disc swelling (more
swelling
Flame-shaped
haemorrhages
Small or absent
physiological cup in the
fellow eye
Progressive cupping
following resolution of
oedema
Small choroidal-retinal
shunt vessels around the
optic disc
Proptosis
common in children)
Normal optic disc (more
common in adults)
Posterior vitreous cells
AAION = Arteritic anterior ischaemic optic neuropathy, NAION = non-arteritic anterior ischaemic optic neuropathy.
N.M. Kerr et al. / Journal of Clinical Neuroscience 16 (2009) 9941000 997
of NAION such as insidious onset of symptoms, relatively mild
optic nerve dysfunction, and a generous cup-to-disc ratio in the fel-
low eye. The presence of a crowded fellow disc is so characteristic
of NAION that its absence should cast some doubt on the diagnosis.
Systemic symptoms consistent with amiodarone toxicity increase
the suspicion that the patients optic neuropathy is secondary to
amiodarone. Finally, prolonged duration of disc oedema that does
not resolve is not typical for NAION and should suggest another
underlying pathology.
66,67
The exact cause of the optic neuropathy is not known. Lipid
inclusions characteristic of amiodarone have been found in a histo-
pathologic study of the optic nerve in a patient treated with amio-
darone.
68
Intraneuronal accumulation of this material may lead
directly to axonal swelling or, alternatively, deposition in glial cells
with subsequent swelling of these cells may secondarily obstruct
axonal transport.
7. Investigations
The diagnosis of NAION is predominately clinical and no specic
investigations are required to conrm the diagnosis. However, in
younger patients it can be difcult to differentiate the 12% of pa-
tients with NAION who experience pain from patients with optic
neuritis. In this situation MRI can be helpful as the optic nerve is
frequently normal with NAION in contrast to optic neuritis. In
one study optic nerve abnormalities were present on MRI in 31
of 32 patients with optic neuritis compared to only 5 out of 32 pa-
tients with NAION.
69
Other ndings on MRI in NAION include a
small optic nerve and chiasm volume compared to normal subjects
which may reect axonal loss.
70
Visual evoked potentials (VEP) may also assist in the differenti-
ation of NAION from optic neuritis. In NAION VEP amplitude is re-
duced while latency is normal.
71
This is in comparison to optic
neuritis where latency is increased.
72
Furthermore in optic neuritis
the uninvolved eye is frequently abnormal. There are also differ-
ences in the N95 component of the pattern electroretinogram. In
ischaemic optic neuropathy the N95 amplitude is decreased
whereas in optic neuritis N95 latency is decreased.
72
8. Management
Currently there is no effective treatment for NAION. Optic nerve
decompression surgery has been investigated however the results
have been disappointing. The IONDT study was a randomized, sin-
gle-masked, multicenter trial that investigated the safety and ef-
cacy of optic nerve decompression surgery compared with careful
follow-up alone in patients with NAION. While the study was
underpowered to determine whether progressive NAION beneted
from such intervention, it did establish that the non-progressive
form did not.
73
The authors concluded that optic nerve decom-
pression surgery for NAION was not effective, may be harmful,
and should be abandoned.
74
Also based on the assumption that NAION is a scleral outlet
compartment syndrome, transvitreal optic neurotomy has been
trialled in an attempt to relax the scleral ring and reduce constric-
tion of salvageable but underperfused nerve bres. In a non-
masked, non-randomized study of optic neurotomy in patients
with severe vision loss from NAION there was visual improvement
in six of seven patients.
75
However, due to the design of this study
it was not possible to discern whether visual improvement was the
consequence of surgery or simply the natural history of the dis-
ease. In a subsequent randomised clinical trial comparing optic
neurotomy to observation alone there was improvement in visual
acuity in six of eight patients treated with optic neurotomy com-
pared to one of eight patients who were observed.
76
However
baseline visual acuity was signicantly lower in cases compared
to controls and this may be a signicant source of bias.
76
Various medical therapies for NAION have been investigated
including systemic corticosteroids, anticoagulants, antiplatelet
agents, diphenylhydantoin, and levodopa.
77
To date none of these
treatments have been found to be effective.
77
Brimonidine,
7881
oestrogen,
82
and citicoline
83
have been trialled as neuroprotective
agents however the results have been poor. Visual Restoration
Therapy (VRT) is a computer technique that claims to stimulate
areas of residual vision in patients with visual eld defects. The
benet of such treatment remains highly controversial and more
studies are necessary to evaluate its efcacy.
84,85
9. Prognosis
Over 6 to 12 weeks the optic disc swelling subsides leaving a
pale and atrophic optic disc. Unlike AAION there is no signicant
enlargement of the cup-to-disc ratio.
86
In a longitudinal study of
the natural history of NAION there was improvement in 41% of pa-
tients who had a visual acuity of 6/21 or better at presentation.
4
The prognosis for visual recovery is better for patients less than
50 years of age.
10
Although it should be remembered that apparent
improvements in visual acuity may simply be an adaptation to the
visual eld defect or eccentric xation.
9
The risk of recurrence in the same eye is approximately 38%
over three years
87
while the risk of involvement in the contralat-
eral eye is between 1524% over 5 years. The risk is greater for pa-
tients with diabetes or a baseline visual acuity of 6/60 or worse in
the rst eye.
88
It is unclear whether aspirin reduces the risk of second eye
involvement. In one retrospective study aspirin reduced the risk
of second eye involvement by 37% at 2 years.
89
However another
study found no signicant difference at 5 years.
90
10. Conclusion
NAION is an important cause of acute visual loss in the middle-
aged and elderly populations. Multiple medical and surgical treat-
ments have been investigated; however to date the results have
been disappointing primarily because of the lack of understanding
of the underlying pathophysiology. Application of improved neuro-
imaging modalities may allow a greater understanding into the
underlying pathophysiology of NAION. Further areas of research
should focus on the mechanisms of neurodegeneration following
ischaemic injury to the optic nerve head and potential for neuro-
protection strategies.
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