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Ischemic Optic Neuropathy

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 Seminars in Ophthalmology, 25(4), 130–135, 2010
Copyright © 2010 Informa Healthcare USA, Inc.
ISSN: 0882-0538 print/ 1744-5205 online
DOI: 10.3109/15368378.2010.499849

Ischemic Optic Neuropathy

Alberto Gonzalez-Garcia,1 Carlos E. Mendoza-Santiesteban,2
Enrique A. Mendoza-Santiesteban,1 Daniel Lopez Felipe,2
Odelaisys Hernandez Echavarria,2 Rosaralis Santiesteban-Freixas,1 and
Thomas R. Hedges III3
The Institute of Neurology and Neurosurgery “Dr. Rafael Estrada González,” Havana, Cuba
1
Semin Ophthalmol Downloaded from informahealthcare.com by Bascom Palmer Eye Institute on 08/10/10

2
Departments of Neuro-ophthalmology at The Cuban Ophthalmology Institute “Ramon Pando Ferrer,” Havana, Cuba
3
The New England Eye Center, Tufts Medical Center, Boston, Massachusetts, USA

Abstract
Anterior ischemic optic neuropathy (AION) is a common cause of visual loss in patients over
50 years of age. Optical coherence tomography has provided new information which may have
implications regarding future approaches to management.
Keywords:  ischemic optic neuropathy; subretinal fluid; optical coherence tomography
For personal use only.

INTRODUCTION PREDISPOSING FACTORS

Ischemic optic neuropathy (ION) includes a group
of ischemic disorders of the optic nerve.1 This entity
can be classified as anterior (AION) characterized by
relative afferent pupilary defect, visual field defect
(Figure 1), optic disc edema (Figure 2), and posterior
(PION) with no disc edema.2,3 AION can be further
classified as arteritic (aAION) associated with tem-
poral or giant cell arteritis (GCA) and nonarteritic
(nAION). The optic disc edema of nAION tends to be
sectorial (Figure 3), whereas diffuse and severe optic
disc edema is more typical of aAION.
ION constitutes the most prevalent non-
­glaucomatous optic neuropathy in patients older
than 50 years of age4, 5 and nAION is the main cause
of loss of vision from optic neuropathy in this age
group. The incidence is 2.3 to 10.2 per 100 000 people.6
NAION is a multifactorial condition with no single
factor explaining the phenomenon by itself. These
associated factors can be divided into two major
groups: predisposing factors (local and systemic) and
precipitating factors.
Correspondence: Carlos Ernesto Mendoza Santiestaban, MD,
Director de Neuro-oftalmologia, Instituto Nacional de Oftalmol-
gia, “Ramon Pando Ferrer” Calle E/31 Y 41, Marianao Ciudad
de la Habana Cuba, Codigo Postal 10 400. E-mail: cm121270@
gmail.com
130
The factors listed in Table 1 are associated with optic
nerve susceptibility to ischemia. Among them, optic
disc crowding is the most common (Figure 4).
Arteriosclerosis/atherosclerosis has been consid-
ered the main cause of nAION. Although a consider-
able amount of patients with hyperlipidemia suffer
from nAION,7 this condition by itself does not explain
the nature of the ischemic process.
GCA is the main cause of aAION and should be
ruled out in all ION patients 55 years old or older.1
Vasospasm may have several causes and it can
happen during infection or with autoimmune
disorders and may cause ION, even in presum-
ably normal subjects. This phenomenon could be
divided into primary and secondary vasospasm
syndromes. Primary vasospasm occurs in the pres-
ence of cold or emotional stress. The secondary
could be associated with multiple sclerosis, lupus,
and GCA.8 Hayreh and co-workers found evidence
of vasospasm in the posterior short ciliary arter-
ies caused by white-cell-released serotonin at the
atheromatous plaques.9
NAION has been associated with hematologic
disorders, including anemia of several etiologies,
massive gastrointestinal and external hemorrhage,10
as well as uremia.11 Antiphospholipid syndrome was
found more commonly in ION patients than in a
 Ischemic Optic Neuropathy    131
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For personal use only.

FIGURE 1  Characteristic altitudinal visual field defect of an AION (Humphrey

30-2, Allergan, Irvine, CA).

FIGURE 3  Red-free fundus photograph showing superior

FIGURE 2  Fundus photograph of pale optic disc edema pallor and sectoral optic disc edema associated with axonal
associated with AION. survival during a nAION attack.

© 2010 Informa Healthcare USA, Inc.

 132    A. Gonzalez-Garcia et al.

felt that there was a lack of evidence of IOP influence

on ONH flow except in the case of marked and sudden
IOP elevation.1, 18
Some drugs have been associated with the genesis
of ION. The causal effect of sildenafil is controversial.
Some authors have found a relationship,19 and others
have not.20 Other drugs linked to ION include amio-
darone21 and amphetamine.22

Precipitating Factors

Precipitating factors include conditions that may tip

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the balance, as it were, during the acute onset of ONH

FIGURE 4  Crowded disc without cupping in the fellow
eye of patient eye in Figure 2.
TABLE 1 
Predisposing Factors (systemic)
Hypertension
Diabetes Mellitus
Stroke
Myocardial Infarction
Thyroid disorders
For personal use only.
Predisposing Factors (local)
Crowded optic disc
ONH edema (from other
causes, e.g., papilledema)
ONH drusen
Ocular hypertension (OHT)
ischemia. Nocturnal hypotension could play a role in
the genesis of nAION given the large series of nAION
patients with this condition.23 This may be worsened
by the use of beta-blocker drugs.24
ANCILLARY TESTS OF FUNCTION
AND STRUCTURE
Various clinical tests may help in the diagnosis and

Arteriosclerosis ONH congenital anomalies
Atherosclerosis Watershed choroidal infacts
Internal carotid artery disease
GCA
Vasculitis
Nocturnal hypotension
Migraine
Cardiac valvulopathy
Massive hemorrhage
Hyperhomocistinemia
Sleep apnea
Drugs
control group.12 The altered hematologic parameters
in ION include increased hematocrit, fibrinogen, blood
viscosity, and aggregation indices often higher than
normal subjects.13
Hyperhomocysteinemia constitutes a risk factor
for cardiac vaso-occlusive disease. A recent study
suggests that high level of plasma homocysteine may
cause endothelial dysfunction, directly or by increase
in oxidative stress due to disorders of nitric oxide
metabolism.14 Anther study demonstrated a relation-
ship between hyperhomocysteinemia and ION.15
Optic nerve head blood flow may be influenced by
perfusion pressure and flow resistance.16 In recent stud-
ies, patients with glaucoma have been found to have
lower mean ocular perfusion pressure than normal
individuals, demonstrating the important influence of
IOP on ONH blood flow regulation.17 However, this
observation was questioned by another author, who
classification of ION. Routine blood tests (hemoglobin,
lipid, etc.) may be done in patients with ION in order
to identify possible related risk factors.25 Elevated
erythrocyte sedimentation rates have been helpful in
identifying aAION, although a large series showed
positive temporal artery biopsies with normal erythro-
cyte sedimentation rates. Most authors advise combin-
ing an erythrocyte sedimentation rate with C reactive
protein as a stronger predictor of temporal arteritis as
the cause of AION.26
Fluorescein angiography shows profuse leakage of
dye in the edematous areas of the ONH in patients with
AION (Figure 5).27 In arteritic AION, delayed choroidal
filling may be present. Doppler ultrasound has shown
abnormalities in eyes with ION.28 Peak systolic veloc-
ity, final diastolic velocity, and mean maximum veloc-
ity are the Doppler parameters most altered in ONH
with ION.29 However, both tests are not used routinely
in most cases.
Magnetic resonance imaging (MRI) helps to differ-
entiate between AION and ONH edema due to demy-
elinating optic neuritis. Electrophysiology (e.g., visual
evoked potential recording) may differentiate ischemic
optic neuropathy from optic neuritis.32 The rare occur-
rence of optic disc edema due to optic nerve sheath
tumors, particularly optic nerve sheath meningioma,
can be identified by MRI or computed tomography
(CT).30, 31
AION in some respects resembles papilledema from
increased intracranial pressure. In addition to obvious
distortion of the normal anatomy of the optic disc, in

Seminars in Ophthalmology

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FIGURE 5  Fluorescein angiogram showing hyperfluores-
cence of the optic nerve head in nAION.
For personal use only.
FIGURE 6  Foveal subretinal fluid in a left eye with
nAION.
both conditions there is evidence of axoplasmic flow
stasis in the optic nerve head. Some patients with
papilledema develop sub-retinal fluid that accumulates
in the peripapillary region33 and under the macula.34
We have identified evidence of sub-retinal fluid accu-
mulation in patients who underwent optical coherence
tomography (OCT) soon after developing nAION.
Most often this occurred in the peripapillary subreti-
nal regions but, most notably, there was evidence of
subfoveal fluid in a subgroup of patients (Figure 6).35
The frequency of subfoveal edema in AION that we
found in 10% is an estimate since OCTs have not been
done routinely in the same manner prospectively in all
patients. Some degree of subretinal fluid accumulation
in the peripapillary region appears to occur in more
than half of patients with nAION. No specific addi-
tional risk factors were more prevalent in the patients
with more extensive subretinal fluid accumulation.35
Fluid in the peripapillary sub-retinal space may
accumulate due to vertical forces generated by the
optic disc edema, creating a negative pressure which
may draw fluid from neighboring edematous tissue. A
disruption of the glial tissues that make up the interme-
diary tissue of Kuhnt could be another cause of fluid
© 2010 Informa Healthcare USA, Inc.
Ischemic Optic Neuropathy    133
in the peripapillary sub-retinal space.36 This is where
tracer material has been found to extend from the optic
nerve head into the sub-retinal space in experimental
papilledema.37 Perhaps a similar phenomenon occurs
in some patients with nAION, particularly if the infarct
involves the temporal portion of the optic disc. In this
situation, sub-retinal fluid may escape from the peri-
papillary choroid into the sub-retinal space and, in
some cases, track into the macular region. Futhermore,
fluorescein angiography does not show accumulation
of dye in the macular region, indicating that the fluid
did not arise from retinal blood vessels or directly
from the choroid. In patients with sub-retinal fluid
from papilledema, fluorescein angiography also has
not shown subretinal staining or leakage directly into
the subfoveal region.34 In a previous study of fundus
fluorescein angiography in nAION, retinal exudates
have been described, but such exudates were in the
retinal nerve fiber layer and not under the retina.38
In patients reported with sub-retinal fluid associated
papilledema there was correlation between the amount
of sub-retinal fluid and visual acuity.34 In patients with
AION visual acuity improved substantially as the sub-
retinal fluid resolved. In some patients with AION the
visual loss may be progressive, and in a significant
number of individuals visual acuity may improve
spontaneously.39 If sub-retinal fluid is present in such
cases, the pattern of progression and improvement of
vision in AION might be explained by progressive and
reversible effects on the macula by sub-retinal fluid
independent of the optic disc damage.
MANAGEMENT
Currently there is no specific treatment for nAION.
However, some steps can be taken to rescue ganglion
cells in a damaged optic nerve or to prevent future ipsi-
lateral or fellow eye attacks. No isolated treatment can
achieve benefit to a multifactorial disease like nAION;
it may be prudent to use different approaches to treat
nAION.
Aspirin usage in nAION remains controversial.
Some authors in a retrospective study found aspirin
to reduce the risk of fellow eye nAION involvement.40
On the other hand, in a prospective study aspirin
seemed to have no effect on nAION natural history.41
These different results may be due to study design,
racial distribution, and the well-known idiosyncratic
aspirin effect.
Large doses of steroid remain the best option for
arteritic AION.1 Prompt treatment of aAION with
steroids can lead to improvement of visual acuity in
some cases. Intravenous steroids may offer a greater
prospect of improvement compared with oral steroids,
 134    A. Gonzalez-Garcia et al.
but a prospective trial comparing intravenous with oral
steroids would be necessary to validate this option.42
There is no surgical treatment for AION. Optic nerve
sheath decompression improved visual acuity but had
little effect on overall visual function in patients with
progressive nAION. Optic nerve sheath decompres-
sion did not improve visual field or acuity in patients
with static nAION.43
Vascular endothelial growth factor (VEGF) results
in a rapid and reversible increase in vascular permea-
bility.44 Inhibition of VEGF signaling, therefore, may
provide a way for reducing vasogenic edema in a
nAION, preserving axonal integrety. AntiVEGF treat-
Semin Ophthalmol Downloaded from informahealthcare.com by Bascom Palmer Eye Institute on 08/10/10
ment has been used in one case of nAION and was
apparently associated with more rapid resolution of
the optic disc edema and recovery of visual acuity.45 We
have applied this to five cases of progressive nAION in
Cuba, and the visual loss appeared to stabilize in all.
Further controlled trials of antiVEGF treatment seem
warranted.
CONCLUSION
For personal use only.
Anterior ischemic optic meuropathy (AION) is a
commonly seen neuro-ophthalmological disease
with a tendency to increase in frequency and affect
younger patients as some of the risk factors became
prevalent in modern society. It is important to dif-
ferentiate between the arteritic and the non-arteritic
form of the disease because of the urgency required to
treat arteritic AION before the second eye is affected.
OCT has been proven to be useful to determine if the
visual loss is due to optic nerve damage or secondary
to subretinal fluid present in some patients. Although
there is no specific treatment for nAION, there is some
evidence that antiVEGF treatment could be useful in
some patients.
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