Transcript Ischemic optic neuropathy (ION)

Ischemic optic neuropathy (ION)
Nasr Esfahani MD
Ischemic optic neuropathy
 ION reflecting ischemic damage to different part of
optic nerve with different etiologies
Types of ION
 two types:







anterior ION = AION
posterior ION = PION
AION
arteritic AION
(A-AION: due to giant cell arteritis)
non-arteritic AION (NA-AION: due to other causes).
PION
arteritic PION
(A-PION: due to giant cell arteritis)
non-arteritic PION (NA-PION: due to other causes)
surgical PION
(a complication of several systemic
surgical procedures).
VASCULAR ANATOMY
 The optic nerve head (ONH) consist of
prelaminar and
laminar portion
supplied by
15 to 20 short posterior ciliary arteries and
circle of Zinn-Haller.
 circle of Zinn-Haller itself is made by
the short posterior ciliary arteries(major part)
pial branches , and
choroidal vessels .
In summary:
PCA is the main source of blood supply to the ONH.
the rest of the optic nerve is supplied from other sources
and not PCA
Pathogenesis of NA-AION
 NA-AION is two types:
 the most common is caused by transient nonperfusion
or hypoperfusion of the ONH circulation;
 the second, and rarer one, is due to embolism to the
arteries/arterioles feeding the ONH.
Nonarteritic Anterior ISchemic
Optic Neuropathy (NAION)
 90-95% of AION cases
 In younger age groups (mean age 60yr)
 Related to compromise of optic disc microcirculation
 ↓ VA On awakening,related to noctural systemic
Hypotension
 Systemic symptoms are absent
DIAGNOSIS
 — The diagnosis of NAION in the majority of patients
is clinical, based upon age, presence of vasculopathic
risk factors, the pattern of visual loss, and the
appearance of the swollen disc.
EXAMINATION FINDINGS
 Reduced visual acuity
 Dyschromatopsia
 Afferent pupillary defect
 Optic disc edema
 Peripapillary splinter hemorrhage
 Small optic cup, nerve fiber crowding in the unaffected
eye
 A relative afferent pupillary defect
 Types of ↓VA(initial V.A > 20/200 in over 60% of cases)





static
progressive (22-37 %)
episodic
stepwise
steady decline over weeks to months
VF
An altitudinal visual field defect is the classically described field defect seen in
NAION, but among reported case series, its prevalence varies from 25 to 79
percent
. In one series of perimetry studies in 312 eyes, a variety of visual field defects were
observed, with an absolute inferior altitudinal defect observed in only 8 percent .
The single most commonly observed defect was an absolute inferior nasal defect,
found in 22 percent.
Other common defects included central, centrocecal and arcuate scotomas, as
well as generalized depression
Fundus finding
 Optic disc edema (segmental or diffuse)
 Diffuse hyperemia
 Palor is less common
 Flame shaped Hx.
 Optic disk in other eye is small and with small or
absent cup.↦ noted in 82 percent of patients
 Retinal arterial narrowing
Figure 7
Right fundus photograph showing optic disc
edema and hyperemia, with a splinter
hemorrhage (arrow) during the acute phase
of NA-AION
Figure 5
Fundus photographs of left eye of a 53-year-old man: (a) Normal disc before
developing NA-AION, (b) with optic disc edema and hyperemia during the active
phase of NA-AION, and (c) after resolution of optic disc edema and development of
sectorial edema
FA
 Delayed optic disc filling in 75% of NAION
 Normal choroidal filling
 In the acute phase of NAION there is delayed filling of
the prelaminar layers of the edematous optic disc .
Poor or absent filling of the choroid is not typical of
NAION and suggests giant cell arteritis [
Further testing in such patients may include
fluorescein angiography.
22].
Contrast-enhanced magnetic re
FA in acute non-arteritic AION
Localized hyperfluorescence
Increasing localized
hyperfluorescence
Generalized hyperfluorescence
Risk Factors of NAION
 Systemic and ocular
 Optic disc drusen
 Small optic disc: Crowding of disk (disk at risk)↦








a process similar to that of a compartment syndrome
Systemic hypertension
Diabetes (young)
Smoking,
hyperlipidemia
Hyperhomocysteinemia, platelet polymorphism,
Phosphodiestrase inhibitors (sildenafil or viagra) ??
Nocturnal hypotension
Sleep apnea ͢ prolonged hypoxia
a 58-year-old woman with bilateral
NA-AION and on no medication
Differential Diagnosis of NAION
 Optic neuritis
 Infiltrative optic neuropathies
 Anterior orbital lesion
 Diabetic papillopathy
NAION
Optic neurtis
Age
>50
<40
pain
Unusual
92%+
Pupil
APD+
APD+
VF
Altitudinal
Central
Optic disk
Edema 100%
pale
Common
Edema 33%
hyperemic
Unusual
Delayed disk
filling
No optic nereve
enhancement
No delayed
Retinal
hemorrhage
F.A.
MRI
enhancement
summary
Age
60 yr
Sex
F=M
Symptoms
None
VA
>20/200 60%
Fundus
ESR
Small cup
Hyperemic edema
Mean 20-40mm/hr
C.R.P.
Normal
Natural history
31% improved
12-19% fellow eye
treatment
None proven
PROGNOSIS
 vision may deteriorate in some patients over the first few days or




weeks.
After this most patients stabilize or improve;
25 to 40 percent of patients can have significant improvement in
visual acuity [3,5]. Continued progression is unusual; progressive
worsening should prompt investigation into alternative causes of
vision loss.
No specific demographic factor or comorbidity (eg, age, gender,
diabetes, hypertension) has been associated with visual outcome
Disc edema typically resolves over two to three months, and is
followed by optic atrophy [8]. At six months, the disc appears
pale, usually in a diffuse, but sometimes sectoral, pattern
Mortality and other vascular
events
 — Patients with NAION do not appear to have a
higher mortality or risk for stroke or cardiovascular
disease than would otherwise be expected on the basis
of their underlying comorbidities
Treatment of NAION
 Untreated case remain stable but recovery of 3 lines




31% after 2 years
Recurrence unusual 6.4%
No proven therapy, surgery no benefit
No proven prophylaxis
the effect of aspirin in reducing incidence of fellow eye
involvement is unclear
TREATMENT
 — There is no known effective therapy for NAION to
ameliorate the degree of visual impairment
Aspirin
 Aspirin therapy does not appear to influence visual
outcomes of acute NAION.
 In a retrospective case-control study, 23 patients
treated with aspirin before and during the course of
NAION were compared to 55 patients with NAION
who did not use aspirin [25].
 Visual outcomes (visual acuity and mean deviation on
automated perimetry) were similar in the two groups
Blood pressure
 NAION in the setting of severe hypotension ↦
prompt efforts to reverse hypotension,
 Patients with acute HTN should have their blood
pressure lowered incrementally rather than abruptly,
as this has been described as precipitating NAION in
at least one case report
Corticosteroids
 — The evidence supporting the use of corticosteroid therapy in NAION is
limited
 . Corticosteroids are sometimes used in NAION, particularly when there is
concern that giant cell arteritis has not been excluded, but also in cases of
severe bilateral vision loss as can occur in the perioperative or dialysis setting
 Some anecdotal reports suggest that corticosteroids may have some benefit in
NAION [30-32].
 One retrospective study examined outcomes in 613 patients with NAION, 312 of
whom were treated with corticosteroids [33]. Treated patients were somewhat
younger and less likely to have hypertension or diabetes. After a median
followup of 3.8 years, a benefit for treatment was observed in the subgroup of
70 eyes with initial acuity of 20/70 or worse, who were treated within two weeks
of onset; 70 percent improved two or more lines compared with 41 percent in
the untreated group. In this subgroup, visual field defects were also more likely
to improve in the treated compared with the untreated group (40 versus 25
percent). the author concluded that early (within two weeks) treatment with
corticosteroids leads to improvement in both visual acuity and visual fields,
Surgical therapies
 Optic Nerve Sheath Decompression —
 two or more slits or a window in the optic nerve sheath
are created reducing the pressure surrounding the
optic nerve. Compression of the optic nerve sheath is
possibly pathogenic in NAION
.
 The conclusions of IONDT were that Optic Nerve
Sheath Decompression appears to be of no value to
most patients with NAION and could potentially cause
further visual deterioration.
Optic neurotomy
 — This investigational surgical procedure relaxes the
scleral ring surrounding the prelaminar and laminar
regions of the optic nerve head, with the goal of
reducing constriction and preventing necrosis of
underperfused nerve fibers.
 surgical manipulation of the optic nerve head has the
potential to further damage nerve fibers and blood
vessels, potentially causing devastating loss of vision
[37].
Vitrectomy
 — A case series of 16 patients with NAION had
findings on optical coherence tomography and
ultrasound that were consistent with partial posterior
vitreous detachment
 elevation of the optic nerve head from traction of the
posterior vitreous may have disrupted the
microcirculation and axoplasmic flow leading to optic
nerve edema and visual dysfunction.
 Surgical release of epipapillary vitreous traction
 this study raises the possibility of a role of vitreous
traction in the pathogenesis of NAION
Other investigational medications
 medications that may have

neuroprotective effects,

meliorate disc edema and pressure surrounding the
optic nerve head, and

improve blood flow to areas of ischemia.
Levodopa
 — A potential role for dopamine in the treatment of
NAION is based on its putative neuroprotective and
neuromodulatory effects in the retina, optic nerve,
and/or brain, or its activity as a neurotransmitter in
the retina.
 The benefit of levodopa in NAION is not established.
Brimonidine
 — Brimonidine is an alpha-2 agonist that lowers
intraocular pressure and is used in the treatment of
glaucoma.
 There have been promising reports from animal
studies suggesting that topical brimonidine may have
a neuroprotective effect on retinal ganglion cells and
reduce optic nerve injury after ischemia
 However, a randomized placebo controlled trial found
no therapeutic effect of brimonidine 0.2 percent in 36
patients with acute NAION
Citicoline
 — Citicoline is a putative neuroprotective agent that
has been evaluated
 in the treatment of acute cerebral infarction.
 In a randomized pilot study, 14 patients with NAION
were treated with citicoline 1600 mg per day for 60
days.
 After 60 and 180 days, these treated patients
demonstrated overall improvement in visual acuity
compared to baseline, while untreated patients did not
Intravitreal agents
 — Intravitreal administration of medications offers
the promise of delivering targeted medications directly
to the source of pathology. However, this route of
administration is not without risks, including a small
risk of infectious endophthalmitis, retinal
detachment, and traumatic cataract estimated at
about 0.15 percent [54]. None of the agents discussed
below is currently recommended in the treatment of
NAION.
Triamcinolone
 — Intravitreal triamcinolone acetonide (IVTA), a corticosteroid,
has been administered to patients with NAION. In one case
series of four patients, treatment was associated with marked,
early resolution of optic disc swelling, disappearing by week
three in all eyes, in contrast to persistence of disc edema in a
control group of six patients [55]. Mean improvements in visual
acuity also appeared better with treatment compared with
controls; however, treatment was not clearly associated with
visual field improvement. In two other small case series of three
and four patients, respectively, IVTA was administered with
some observed gains in visual acuity, but these case series were
not controlled [56,57]. In one case, treatment was complicated
by increase in intraocular pressure requiring anti-glaucoma
treatment, a complication that occurs in up to 25 percent of
patients when IVTA is administered for other indications
[58,59].
Anti-vascular endothelial growth
factor (VEGF) agents
 decreasing optic nerve head edema and secondary tissue
injury.
 A recent report described visual improvement in four eyes
of four patients after single intravitreal injection of
ranibizumab [60].
 Another case report describes rapid resolution of vision
loss and disc edema in a patient with NAION treated with
intravitreal bevacizumab [61].
 However, there have been two reports of NAION occurring
after intravitreal injection of bevacizumab (for nonNAION indications) at one week and two weeks postinjection [
Erythropoietin
 — In one case series, 31 patients with NAION received
unilateral intravitreal erythropoietin injection (2000
units), within one month of onset of NAION [64].
Visual acuity improvement occurred in 61 percent of
patients within the first month. Vision continued to
improve up to three months and then deteriorated,
but remained significantly better than baseline at the
last, six month, follow-up examination
Fibrinogen/LDL apheresis
 — Fibrinogen/LDL apheresis, also known as heparin-
induced extracorporeal LDL/fibrinogen precipitation
(HELP) removes fibrinogen, total cholesterol, low
density lipoproteins and triglycerides from plasma and
has shown promise in the treatment of microvascular
disorders, including peripheral artery disease and
sudden hearing loss of vascular origin [65,66]. In a
small, randomized, controlled study, 40 patients with
recent-onset NAION, were assigned to treatment with
HELP or to hemodilution therapy [67]. There was no
significant difference in visual outcomes between the
two groups.
Hyperbaric oxygen
 — While case reports have suggested a possible
benefit for hyperbaric oxygen in the treatment of
NAION, these findings have not been confirmed in
well-designed studies [68].
 A nonrandomized study compared hyperbaric oxygen
treatment in 20 patients with acute NAION with 27
untreated patients and found
 no significant difference in visual acuity or visual field
outcomes in the groups
SECONDARY PREVENTION
 — There is no known effective therapy proven to
prevent NAION in the fellow eye [1,23]. Most patients
with NAION are treated with daily aspirin and risk
factor management.
 Patients taking medications implicated in the
pathogenesis of NAION (eg, phosphodiesterase
inhibitors, amiodarone, interferon alpha,
sympathomimetics) should be counseled about a
possible association and consider alternative
medications if available.
Aspirin
 — Four retrospective studies have evaluated the role
of aspirin in the prevention of NAION in the fellow eye
with somewhat mixed results:
 The largest study compared outcomes in 153 patients
who had received aspirin following the development of
unilateral NAION and 278 who had not [14]. After five
years. the cumulative probability of NAION in the
fellow eye was similar in the aspirin and no-aspirin
groups (17 and 20 percent respectively
Vascular risk factor management
 — Medical control of underlying vasculopathic risk factors
(eg, hypertension, diabetes, and smoking) is indicated in
the primary prevention of cardiovascular disease and
stroke; it is not known whether such interventions
decrease the risk of NAION recurrence.
 Over-aggressive control of systemic arterial hypertension
may produce nocturnal hypotension, which is believed to
be a risk factor for NAION [76]. Morning administration of
blood pressure medications should be considered.
Patients with acutely elevated blood pressure should have
their blood pressure lowered incrementally rather than
abruptly.
Pathogenesis of A-AION
 When a patient is diagnosed as having AION, the first
crucial step in patients aged 50 and over is to identify
immediately whether it is arteritic or non-arteritic
 In the eye, GCA has a special predilection to involve
the PCA, resulting in its thrombotic occlusion
AAION
 Is less frequent 5-10%
 Affects about 25% of untreated patients with giant
cell arteritis
 Older patients (mean 70yr)
 Inflammatory and thrombotic occlusion post. Cilliary
artery
 Systemic symptoms
Fundus photograph of right eye with AAION, showing chalky white optic disc
edema during the initial stages
AAION
 Sever visual loss
 Pale edema
 Cotton wool spot
 F.A. delayed choroidal filling
 Normal cup.
Systemic Findings of GCA
 Are usually present
 Headache, temporal and scalp tenderness
 Jaw claudication
 Malaise, anorexia, weight loss, fever, joint & muscle pain
 Ear pain
Superficial temporal arteritis
Presentation
•
•
•
•
•
•
•
Age - 65-80 years
Scalp tenderness
Headache
Jaw claudication
Polymyalgia rheumatica
Superficial temporal arteritis
Acute visual loss
Special investigations
•
ESR - often > 60, but normal in 20%
C-reactive protein - always raised
•
Temporal artery biopsy
•
Histology of giant cell arteritis
•
Granulomatous cell infiltration
•
Disruption of internal elastic lamina
•
Proliferation of intima
•
Occlusion of lumen
•
High-magnification shows giant cells
Age
summary
Mean 70 yr
60 yr
Sex
F>M
F=M
Symptoms
Headache …
None
VA
<20/200 60%
>20/200 60%
Fundus
Normal cup pale
edema
ESR
Mean 70mm/hr
Small cup
Hyperemic edema
Mean 20-40mm/hr
C.R.P.
Elevated
Normal
Natural history
Rarely improved 31% improved
54-95% fellow
12-19% fellow eye
eye
Systemic steroids None proven
treatment
Major Goals of Therapy
 Prevent contralateral visual loss
 Fellow eye involved 95% days or weeks
 Affected eye improve somewhat
 Avoid systemic vascular complication
 Risk of recurrence is 7% so tapering must be slow and
careful
Treating AAION
 Immediate therapy is critical
 Temporal artery biopsy may delayed treat
 IV prednisolone 1 g/day for 3-5 days
 Then oral prednisolone 100 mg/day tapered 3-12
month or more
Intravitreal Bevacizumab for Treatment of Non-Arteritic
Anterior Ischemic Optic Neuropathy
Dan Rootman, Harmeet Gill, Edward Margolin
University of Toronto, Toronto, ON, Canada
Conclusion:
The use of intravitreal bevacizumab for the treatment of acute NAION may reduce optic nerve
swelling, leading toimproved visual acuity and visual field outcomes.
.
Patients with NA-AION, when treated
with systemic corticosteroid therapy
within first 2 weeks of onset, had
significantly better visual outcome
than untreated ones.
PION
 There are three distinct etiologic categories that
account for the majority of patients with PION:
perioperative,
 arteritic,
 and nonarteritic (idiopathic) PION. (See 'Etiologies
and pathogenesis' above.)
Perioperative PION
 is most often described in the setting of spinal
surgeries and radical neck dissection, although a wide
range of operative procedures have been implicated.
Hypotension and blood loss are the most universal risk
factors for this complication. Localized venous
hypertension resulting from prolonged use of the
prone position in spine surgery and from internal
jugular venous ligation in neck dissections are believed
to contribute to PION in these cases. (See
'Perioperative PION' above
 PION is an infrequent complication of giant cell
arteritis, a condition occurring exclusively in older
adults (>50 years) and associated with a prodrome of
polymyalgia rheumatica. (See 'Arteritic PION' above.)
 More than half of PION cases are classified as
nonarteritic, idiopathic. Associated comorbidities in
these patients suggest that nonarteritic PION is a
manifestation of systemic vascular disease. (See
'Nonarteritic (idiopathic) PION' above.)
 Most patients with PION present with abrupt,
painless, monocular vision loss. About half of patients
with perioperative PION will have bilateral vision loss,
while patients with arteritic PION are at risk for
rapidly sequential vision loss affecting first one eye
then the next. Vision loss is usually severe in patients
with perioperative and arteritic PION, but is more
variable in patients with nonarteritic PION.
PION is a diagnosis of exclusion.
 The most urgent diagnostic imperative is to diagnose or exclude GCA
with ESR and CRP and/or a temporal artery biopsy. Patients also
require ophthalmologic examination and a contrast-enhanced
magnetic resonance imaging study that focuses on the optic nerves.
(See 'Diagnosis' above.)
 Patients with PION and GCA are treated with corticosteroids. While
significant visual recovery is unlikely, treatment is aimed at preventing
vision loss in the other eye. (See 'Prognosis and treatment' above.)
 Patients with perioperative PION do not usually experience significant
visual recovery, while up to one-third of patients with nonarteritic
(idiopathic) PION may improve. There is no treatment for
perioperative or nonarteritic PION. Patients with nonarteritic PION
may experience a subsequent episode in the other eye over the next
months and years, but interventions (such as atherosclerosis risk factor
management and aspirin) are not known to prevent this. (See
'Prognosis and treatment' above.)
PION
 SUMMARY AND RECOMMENDATIONS — PION is
believed to result from an infarction of the retrobulbar
optic nerve. While there is much overlap, the vascular
anatomy, etiologies, and clinical presentation of PION
are distinct from those of anterior ischemic optic
neuropathy, which is more common and affects the
optic nerve head
THANK YOU