This document provides information on anterior ischemic optic neuropathy (AION), which is the most common cause of acute optic neuropathy in older age groups. It can be divided into two types: arteritic AION, which is due to giant cell arteritis; and non-arteritic AION, which makes up most cases. Both types present with sudden painless vision loss and optic disc swelling. Arteritic AION carries a worse prognosis and requires high-dose steroid treatment to prevent loss of vision in the fellow eye. Non-arteritic AION has a variable course but generally a poor rate of recovery without any proven effective treatments.

1. Jagdish Dukre

2. INTRODUCTION
 Anterior ischemic optic neuropathy (AION) is the most
common cause of acute optic neuropathy in older age
groups.
 AION is a potentially blinding disorder.
 Field defects typical of ischemic optic neuropathy were
first described by Knapp in 1875.
 Miller and Smith first used the term ʺischemic optic
neuropathyʺ in 1966, and Hayreh later added the term
ʺanterior.ʺ
 In 1924, Uhthoff first described severe visual loss, with
field defects and swollen optic discs.

3. Clinical Features
 AION presents with rapid onset of painless, unilateral visual
loss manifested by decreased visual acuity, visual field, or
both.
 The level of visual acuity impairment varies widely, from
minimal loss to no light perception, and the visual field loss
may conform to any pattern of deficit related to the optic
disc.
 An altitudinal field defect is most common, but generalized
depression, broad arcuate scotomas, and cecocentral
defects also are seen.
 A relative afferent pupillary defect invariably is present with
monocular optic neuropathy.

4.  The optic disc is edematous at onset, and edema
occasionally precedes visual loss by weeks to months.
 Although pallid edema has been described as the hallmark
of AION, it is common to see hyperemic swelling,
particularly in the nonarteritic form.

5.  The disc most often is swollen diffusely, but a segment of
more prominent involvement frequently is present, and
either focal or diffuse surface telangiectasia is not unusual
and may be quite pronounced.
 Commonly, flame hemorrhages are located adjacent to the
disc, and the peripapillary retinal arterioles frequently are
narrowed.

6. Clinical Classification of
AION
Depending upon the underlying cause, AION is of two
types
1) Arteritic : This is the most serious type and is due to
giant cell arteritis.
2) Non-arteritic: This is the most common one, and
consists of all cases other than those due to giant
cell arteritis.

7. Arteritic Anterior Ischemic Optic
Neuropathy
AAION

8. Pathogenesis
 AAION results from short posterior ciliary artery
(SPCA) vasculitis and the resultant optic nerve head
infarction.
 Human autopsy studies of acute AAION show
 optic disc edema
 with ischemic necrosis of the prelaminar, laminar, and
retrolaminar portions of the nerve and
 infiltration of the SPCAs by chronic inflammatory cells.
 Segments of these vessels in some cases were
occluded by inflammatory thickening and thrombus.

9.  Fluorescein angiographic data support the
histopathological evidence of involvement of the
SPCAs in AAION.
 Delayed filling of the optic disc and choroid is a
consistent feature
 extremely poor or absent filling of the choroid has
been depicted as a characteristic of AAION
 It has been suggested as one useful factor by which
to differentiate AAION from NAION.
 Delayed completion of choroidal fluorescein filling
that averages 30–69seconds has been reported in
AAION, compared with a mean of 5–13seconds in
NAION.

10. Ocular Manifestations
 Typically, AAION develops in elderly patients, with a
mean age of 70years, with severe visual loss (visual
acuity < 6/60 in the majority).
 AAION is almost three times more common in women
than in men.
 It may be preceded by transient visual loss similar to that
of carotid artery disease and when present, is highly
suggestive of arteritis.
 Pallor, which may be severe, chalky-white, is associated
with the edema of the optic disc more frequently in
AAION than in the nonarteritic form.

11.  Choroidal ischemia may be associated with the optic
neuropathy and produces peripapillary pallor and edema
deep to the retina.
 The disc of the fellow eye is of normal diameter most
frequently, with a normal physiological cup.

12.  In 5–10% of cases, AION may occur as a manifestation
of the vasculitis associated with temporal arteritis.
 Patients with the arteritic form usually note other
symptoms of the disease –
 headache (most common),
 jaw claudication, and
 temporal artery or scalp tenderness
 Malaise, anorexia, weight loss, fever, proximal joint
arthralgia, and myalgia also are noted commonly.

13.  However, the disease occasionally manifests with
visual loss in the absence of overt systemic
symptoms, so-called occult temporal arteritis.
the superficial
temporal artery is pulseless,
nodular and thickened

14. Diagnosis
 The most important early step in the management of AION is
the differentiation of the arteritic from the nonarteritic form of
the disease.
 Active temporal arteritis usually is associated with an elevation
of ESR to 70–120mm/hour, and in acute AION that is
associated with other typical features, this finding suggests the
arteritic form.
 Abnormally high readings occur normally with increasing age
and with other diseases, most commonly occult malignancy,
other inflammatory disease, and diabetes.
 Measurement of serum C-reactive protein (CRP), another
acute-phase plasma protein, may aid in diagnosis.
 Hayreh et al. reported 97% specificity for temporal arteritis in
cases of AION in which both ESR >47mm/hour and CRP
>2.45mg/dL were found.

15.  Confirmation of the diagnosis of temporal arteritis is by
superficial temporal artery biopsy.
 Positive biopsy findings, such as intimal thickening, internal
limiting lamina fragmentation, and chronic inflammatory
infiltrate with giant cells, provide support for long-term systemic
corticosteroid therapy.
 A negative biopsy result, however, does not rule out arteritis;
both discontinuous arterial involvement (“skip lesions”) and
solely contralateral temporal artery inflammation may result in
false-negative results.

16. Treatment
 Early treatment of AAION is essential and must be
instituted immediately in any suspected case of temporal
arteritis.
 High-dose systemic corticosteroids are standard.
 intravenous methylprednisolone at 1g/day for the first 3
days has been recommended for AAION when the patient
is in the acute phase of severe involvement.
 Oral prednisone in the range of 60–100mg/day may be
used initially and for follow-up to intravenous pulse therapy.

17.  alternate day regimens do not suppress the
disease effectively.
 Treatment usually reduces systemic symptoms
within several days.
 A positive response is so typical that if it does not
occur, an alternate disease process should be
considered.
 Treatment is usually continued at high dose for
several months before beginning taper.

18. Course and Outcome
 The major goal of therapy in AAION is to prevent visual
loss in the fellow eye.
 Untreated, such involvement occurs in 54–95% of cases,
typically within 4months.
 With corticosteroid therapy, the rate of such
breakthrough is reduced to an estimated 13%.
 Prognosis for visual recovery in the affected eye that has
treatment generally is poor, but
 Recent reports suggest a 15–34% improvement rate,
which is higher with intravenous than with oral therapy.
 Worsening of vision in spite of therapy has been
reported in 9–17% of cases.

19. Nonarteritic Anterior
Ischemic Optic Neuropathy
(NAION)

20. Pathogenesis
 The rapid onset, stable course with generally poor
recovery, association with vasculopathic risk factors,
and similarity to AAION have implied a vascular cause
for NAION as well, but the direct evidence remains
limited.
 Several histopathological reports document laminar and
retrolaminar infarction, but cases of uncomplicated
NAION are rare, and none has confirmed vasculopathy
within the SPCAs or their distal branches.
 The most commonly proposed pathogenic theory states
that insufficiency of the optic disc circulation,
exacerbated by structural crowding of nerve fibers and
supporting structures at the nerve head, eventually
reaches a point at which inadequate oxygenation
produces ischemia and swelling of the disc.

21.  These features may be mild and subclinical (no visual
loss), reversible to some degree, or irreversible
(infarction).
 In some cases, a cycle of ischemia, axonal swelling,
microvascular compression, and further ischemia may
lead to progressive nerve damage.
 Knox et al. have recently documented cavernous
degeneration within ischemic regions of the optic nerve
head, with distortion of adjacent axons, theorizing that
this process may be responsible for the progressive
course in some cases.
 Periodic nocturnal systemic hypotension and the location
of the optic disc in a watershed zone between
distributions of lateral and medial SPCAs may be
contributing factors.

22.  Fluorescein angiographic studies in NAION also suggest
impaired optic disc perfusion.
 Detailed quantitative analysis of prelaminar optic disc and
peripapillary choroidal filling in NAION confirms
significantly delayed disc filling when compared with age-matched
controls.
 Delay in a segment of disc by at least 5 seconds, was
present in 75.6% of such cases.
FFA (AAION) early AV phase.
The temporal portion of the optic
disc fills normally (small arrows),
but the remaining sectors
demonstrate markedly delayed
filling (large arrows)
approximately 10 seconds later.

23.  In contrast, peripapillary choroidal filling was not delayed
consistently and not significantly more than the degree of
segmental delay often found in normal subjects.
 These findings suggest that the impaired flow to the optic
nerve head in NAION is distal to the SPCAs themselves,
possibly at the level of the paraoptic branches that supply
the optic nerve head directly
FFA (AAION) early AV phase.
The temporal portion of the optic
disc fills normally (small arrows),
but the remaining sectors
demonstrate markedly delayed
filling (large arrows)
approximately 10 seconds later.

24. Ocular Manifestations
 In 90–95% of cases, AION is unrelated to temporal
arteritis.
 The nonarteritic form of the disease occurs in a relatively
younger age group (mean age of 60years) and usually is
associated with less severe visual loss.
 Frequently, visual impairment is reported upon
awakening, possibly related to nocturnal systemic
hypotension.
 The initial course of visual loss may be
a) static (with little or no fluctuation of visual level after the
initial loss) or
b) progressive (with either episodic or visual loss that
declines steadily over weeks to months prior to eventual
stabilization).

25.  The progressive form has been reported in 22% to 37%
of NAION cases.
 Usually, no associated systemic symptoms occur,
although periorbital pain is described occasionally.
 Fellow eye involvement is estimated to occur in 12–19%
by 5years after onset.
 Recurrent episodes of visual loss that result from
NAION in the same eye are unusual and occur most
often in younger patients.

26.  The optic disc edema in NAION may be diffuse or
segmental, hyperemic or pale, but pallor occurs less
frequently than it does in AAION.
 A focal region of more severe swelling often is seen but
it does not correlate consistently with the sector of
visual field loss.
The hyperemic disc edema
is more prominent
superiorly.
Focal surface telangiectasia
of disc vessels is seen
superotemporally (arrows).

27.  Diffuse or focal telangiectasia of the edematous disc may
be present, occasionally prominent enough to resemble a
vascular mass or neovascularization.
 This finding may represent microvascular shunting from
ischemic to nonischemic regions of the optic nerve head,
so-called luxury perfusion.
The hyperemic disc edema
is more prominent
superiorly.
Focal surface telangiectasia
of disc vessels is seen
superotemporally (arrows).

28.  The optic disc in the contralateral eye typically is small in
diameter and demonstrates a small or absent physiological
cup.
 The disc appearance in such fellow eyes has been described
as the disc at risk, with postulated structural crowding of the
axons at the level of the cribriform plate, associated mild disc
elevation, and disc margin blurring without overt edema
Fellow eye in AAION.
The optic disc is small in
diameter, with absent
physiological cup and slight
blurring of the nasal margin.

29. Systemic Associations
 NAION has been reported in association with a number of
diseases that could predispose to reduced perfusion
pressure or increased resistance to flow within the optic
nerve head.
 In NAION patients 47% of patients have hypertension and
24% have diabetes.
 Repka et al. indicated that the prevalences of both
hypertension and diabetes are increased over those of the
control population in NAION patients in the age range 45–
64years, but that in patients over 64years of age, no
significant difference exists from those of the general
population.
 Diabetics in particular show a predisposition to NAION at a
young age.

30.  Also, NAION has been reported in association with
multiple forms of vasculitis, acute systemic hypotension,
migraine, optic disc drusen, and idiopathic vaso-occlusive
diseases.
 Other risk factors, such as hyperopia, smoking, the
presence of HLA A29, and hyperlipidemia have been
proposed.
 Among these, nocturnal arterial hypotension (i.e. fall of
blood pressure during sleep) seems to play a very
important role in the development of non-arteritic AION
and is often considered a precipitating factor.
 Recent reports of the association of hyperhomocystinemia
with AION, particularly in patients under 50, are
inconclusive.
 Prothrombotic risk factors, such as protein C and S and
antithrombin III deficiencies, factor V Leiden mutation, and
cardiolipin antibodies, do not seem to be associated with
AION

31. Treatment
 There is no proven effective therapy for NAION.
 Oral corticosteroids at standard dosage (1mg/kg per day)
are not beneficial, and megadose intravenous therapy has
not been evaluated systematically.
 Optic nerve sheath decompression (ONSD) surgery has
been attempted,
 It was based on the theory that reduction of perineural
subarachnoid cerebrospinal fluid pressure might improve
local vascular flow or axoplasmic transport in the optic
nerve head, and thus reduce tissue injury in reversibly
damaged axons.

32.  The Ischemic Optic Neuropathy Decompression Trial
compared ONSD surgery in 119 patients with no treatment in
125 controls.
 The study revealed no significant benefit for treatment and; it
was recommended that ONSD not be performed
 Hyperbaric oxygen, by marked elevation of the dissolved
oxygen content in the blood, provides increased tissue
oxygenation that might reduce damage in reversibly injured
axons.
 A controlled clinical pilot study of hyperbaric oxygen in 22
patients who had acute NAION, however, has shown no
beneficial effect.
 Neuroprotective agents have shown a beneficial effect in
animal models of optic nerve damage, but are not proven to
be effective in NAION.
 The effect of aspirin in reducing risk of fellow eye
involvement is unclear.

33. Course and Outcome
 The course of untreated NAION varies considerably.
 Reports indicate that 24–43% of cases demonstrate
spontaneous improvement of visual acuity by three
Snellen lines or more.
 Even in the progressive form, improvement has
been reported to occur in roughly 30%.
 Whether NAION is static or progressive, visual
acuity and field stabilize after several months.

34.  Within 6weeks, occasionally sooner, the optic disc
becomes visibly atrophic, either in a sectorial or diffuse
pattern.
 Further progression or recurrent episodes are extremely
rare after 2months and, if present, should prompt
evaluation for another cause of optic neuropathy.
2 months after onset of inferior visual field loss, is segmentally atrophic superiorly
(arrows), with sparing and resolving edema inferiorly.