This document provides an overview of optic neuropathies. It begins by defining optic neuropathies as disorders of the optic nerve and describes their clinical presentations. It then discusses various mechanisms and types of optic neuropathies including ischemic, compressive, infiltrative, and hereditary. Specific conditions like anterior ischemic optic neuropathy (AION), giant cell arteritis, optic neuritis, and Leber's hereditary optic neuropathy are described. Diagnostic testing and treatment approaches are also summarized for different optic neuropathies.
2. Disorders of the optic nerve
are called optic
neuropathies.
Normal optic nerve -
Posterior /retrobulbar optic
neuropathies. (Fig a)
Optic nerve head swelling-
Anterior optic
neuropathies.(Fig b)
The optic nerve becomes
pale 4 to 6 weeks after the
onset of visual loss; even
after vision has recovered-
Optic atrophy (Fig c)
Introduction to Optic Neuropathies
3. Clinically, patients with optic neuropathies typically
present with:
Visual acuity loss
Visual field loss
Impaired colour vision
RAPD (in patients with unilateral or asymmetric
damage)
6. Ischemic optic neuropathies include :
Anterior ischemic optic neuropathy (AION) -always associated
with disc edema
Posterior ischemic optic neuropathy (PION)-optic nerve appears
normal acutely.
AION is more common than PION, accounting for 90% of cases
of optic nerve ischemia.
AION is subclassified as either arteritic anterior ischemic optic
neuropathy (AAION) -associated with vasculitis(GCA) or
nonarteritic anterior ischemic optic neuropathy (NAION)
The most important initial step in evaluating AION is to
distinguish between these two subtypes.
CLASSIFICATION
7. CLINICAL ANATOMY
The posterior ciliary arteries , originating from the ophthalmic artery ,
pial plexus provide the blood supply to the optic nerve.
Short posterior ciliary arteries supply the optic nerve head.
Long posterior ciliary arteries to the retrobulbar optic nerve
Only few vessels penetrate the nerve and extend to its central portion.
Hence, the center of the posterior optic nerve is relatively poorly
vascularized and is susceptible to ischemia.
Nonarteritic AION typically occurs in the setting of a disc-at-risk (small
crowded optic nerve with a small cup-to-disc ratio
8. Small cups are congenital and physiologic but represent the
most important contributing factor to nonarteritic anterior
ischemic optic neuropathy
The absence of a disc-at-risk in a patient with AION should
suggest giant cell arteritis or another underlying disorder.
In a patient with suspected ischemic optic neuropathy, the first
step should always be to consider giant cell arteritis
9. Optic nerve ischemia
often results in
superior (more often)
or inferior segmental
optic nerve atrophy.
There is pallor affecting
only the superior or
inferior half of the optic
nerve.
Hence, altitudinal
defects are common
with ischemic optic
neuropathies.
10. Occurs in patients older than 50 years.
C/F: Painless monocular vision loss that develops over
hours to days.
Visual field loss -Altitudinal and other variants of arcuate
defects are typical.
RAPD is present unless the optic neuropathy becomes
bilateral.
By definition, there is always ONH edema at onset, which
may precede the vision loss.
AION is subclassified as :
Arteritic anterior ischemic optic neuropathy (AAION)
Nonarteritic anterior ischemic optic neuropathy (NAION)
Anterior Ischemic Optic Neuropathy
11. Characteristics
Occurs in patients older than 50 years (mean age, 70 years).
Sudden, profound u/l vision loss with periocular pain.
Risk of rapid involvement of second eye(25%).
It is caused by inflammatory and thrombotic occlusion of the
short posterior ciliary arteries.
Systemic symptoms of GCA are usually present, including
headache, scalp tenderness, jaw claudication, malaise, anorexia,
weight loss, and fever.
25% of patients with vision loss from GCA have no systemic
symptoms (occult GCA).
Visual loss may be preceded by recurrent episodes of transient
monocular visual loss or transient diplopia.
Arteritic AION
12. Causes:
Giant cell arteritis
systemic vasculitis such as: systemic lupus
erythematosus, periarteritis nodosa, and Churg–
Strauss syndrome, RA
13. On examination:
Chalky-white pallid ONH edema (in NAION, the ONH is often
hyperemic)
Cotton-wool spots away from the ONH, which indicate concurrent
retinal ischemia (cotton- wool spots on or adjacent to the ONH
can be present in NAION)
Delayed choroidal filling on fluorescein angiographic studies
Normal or large cup in the fellow eye (in NAION, a small cup–disc
ratio is common)
Can have associated cilioretinal artery occlusion
14. Attack of AAION.
A: Right optic disc at the time of initial visual loss. Note pale optic disc
swelling, peripapillary hemorrhage, and cotton-wool spot.
B: Eight weeks after visual loss, the optic disc swelling has resolved,
and both the hemorrhage and the cotton-wool spot are resolving
C:Resultant optic atrophy and generalized attenuation of retinal arterioles.
15. Investigations:
Erythrocyte sedimentation rate (ESR) or C-
reactive protein (CRP)levels may be elevated.
CBC: elevated platelet count, anemia.
LFT :may be abnormal in GCA
Fluorescein angiography -Involvement of the
short posterior ciliary arteries in Arteritic AION.
Delayed filling of the optic disc and adjacent
choroid .
GCA is conɹrmed by a positive temporal artery
biopsy, ideally within 3 days of steroid therapy.
A negative biopsy, however, does not rule out
GCA.
Colour doppler – hyperechoic halo aroung the
arounf STA due to oedema in artery wall.
16. Treatment:
The primary goal of AAION therapy is to prevent
contralateral vision loss.
Untreated, the fellow eye becomes involved in up to 95% of
cases, within days to weeks. Intravenous
methylprednisolone (1 g/day for the first 3 days)
Thereafter, oral prednisone (1 mg/kg/day) tapered slowly
over 12 months or more depending on response.
Any significant symptomatic relapse- Treat aggressively
with IV methylprednisolone.
17. Characteristics
Compared with AAION, NAION is
more common (90%–95% of AION
cases).
Occurs in a relatively younger age
group (>50 years).
NAION is typically not associated
with any systemic symptoms
Related to compromised ONH
microcirculation in eyes with
structural “crowding” of the ONH.
Infarction within the scleral canal -
local compartment syndrome.
Non Arteritic AION
“DISC AT RISK”
18. Risk Factors:
Conditions that may predispose to decreased optic nerve
head perfusion via microvascular occlusion such as:
Structural crowding of the ONH (“disc at risk”)
Diabetes mellitus (particularly in young patients)
Systemic hypertension
Hyperlipidemia
Sleep apnea
Severe anemia.
Hypercoagulable disorders.
Acute intraocular hypertension (during ocular surgery, after
an intravitreal injection of steroids)
19. Clinical Presentation:
Loss of vision occurring over hours to days, less severe
visual loss than AAION.Not associated with pain.
Colour vision loss in NAION tends to parallel visual acuity
loss
Visual field -Altitudinal loss, usually inferior occurs most
commonly.
The ONH edema may be diffuse or segmental
Usually initially hyperemic
Peripapillary haemorrhage+
The ONH in the contralateral eye is typically small in
diameter and demonstrates a small or absent physiologic
cup
20. A ) Right NAAION
disc edema with small
peripapillary hemorrhages
B)a crowded optic nerve
disc-at-risk seen in the fellow eye
C) Disc edema has resolved,
there is segmental superior
atrophy of the optic nerve
E) Visual field.
Inferior altitudinal defect (RE)
21. Some patients develop “luxury
perfusion” of the ischemic optic
nerve head
Seen as dilated capillaries on
the disc edema, or adjacent to
the optic nerve pallor.
It is due to a vascular
autoregulatory response to
ischemia
Characterized by dilation of
blood vessels and increased
perfusion of tissues in a region
surrounding an infarct.
LUXURY PERFUSION
22. Course:
Static, in which case vision loss is stable from onset
May become progressive- stepwise decrements
or a steady decline of vision over a few days to weeks
before eventual stabilization.
The optic disc becomes atrophic,
either in a sectoral or diffuse pattern usually
within 4 to 6 weeks
Ischemic Optic Neuropathy Decompression Trial (IONDT)
43% of patients with a visual acuity worse than 20/64 at presentation
regained at least 3 lines of visual acuity on the Snellen eye chart within
6 months
Recurrences in the same eye are rare (< 5%).
Subsequent involvement of the fellow eye is about 15% at 5 years in
patients with a disc-at-risk.
Sectoral optic atrophy
23. Pseudo–Foster- Kennedy syndrome :
Occurrence of NAAION in the second eye produces the clinical
appearance of pseudo–Foster- Kennedy syndrome.
The previously affected ONH is atrophic and the currently
involved ONH is edematous.
True Foster- Kennedy syndrome
Secondary to intracranial mass
ONH is atrophic because of chronic compression by the mass
The other ONH is edematous because of elevated ICP
24. Diagnosis:
NAION must be differentiated from optic neuritis, especially in younger patients
Other important differential s include infltrative optic neuropathies, anterior orbital
lesions producing optic nerve compression, idiopathic forms of optic disc edema, and
diabetic papillopathy.
Contrast- enhanced MRI of the orbits (with fat suppression) can help in the
differentiation.
The affected optic nerve appears normal in NAION (95% of cases) but enhanced in
optic neuritis.
Evaluation for control of risk factors such as hypertension, diabetes, and
hyperlipidemia is essential.
25. Treatment:
There is no proven effective therapy for NAION.
The IONDT showed that ONSF had no benefit for NAION;
therefore, ONSF is no longer used.
Treatment with steroids or neuro-protective drugs is not
supported by any high- quality clinical studies.
There is also no proven prophylaxis for the fellow eye.
Avoidance of any potentially associated medications such as
phosphodiesterase-5 inhibitors or (controversially)
amiodarone.
26.
27. Acute ischemic damage to the retrobulbar
portion of the optic nerve .
Abrupt, severe vision loss with RAPD
Initially normal- appearing ONHs.
PION is rare and is a diagnosis of exclusion.
It occurs in 3 distinct scenarios:
1) perioperative (most commonly in spine,
cardiac, and head or neck procedures)
2) arteritic (especially from GCA)
3) nonarteritic (with risk factors and a clinical
course similar to those of NAION).
Posterior Ischemic Optic Neuropathy
29. Various lesions may compress or infiltrate the intraorbital,
intracranial, or prechiasmal optic nerves.
Anterior or large intraorbital lesions often produce optic
disc swelling .
Intracranial, intracanalicular, and posterior orbital
compressive lesions typically do not produce disc swelling
The lesions that most commonly produce optic neuropathy
include optic nerve sheath meningioma and optic nerve
glioma.
If an orbital compressive lesion is suspected,
neuroimaging is indicated.
30. Characteristics:
The clinical presentation
varies based on the type and
location of the mass:
Progressive unilateral optic
neuropathy (progressive
visual loss with abnormal
color vision, visual field
defect, and optic disc pallor
or disc edema).
Optociliary shunt vessels
may develop as a result of
optic nerve compression
1. Disc edema with optociliary shunt vessels
2. MRI with fat supression showing left optic nerve sheath
meningioma. Enhancement of optic nv sheath ( green arrow)
31. Intracranial lesions that may
produce vision loss in both
eyes (bilateral optic
neuropathies, bitemporal
hemianopia)
Usually, no associated pain .
Headache if raised intracranial
pressure (large tumor,
hydrocephalus) or involvement
of branches of the trigeminal
nerve (cavernous sinus).
Proptosis and diplopia
common in orbital lesions.
Cranial nerve palsies common
in lesions extending into the
cavernous sinus.
Compression of the right optic nerve by an
enlarged medial rectus muscle secondary
to thyroid eye disease
32. The optic nerve may also be compressed or infiltrated by
neoplasm/ inflammatory process.
Right optic nerve pallor in Pilocytic astrocytoma;
Axial T1-weighted magnetic resonance imaging of the orbits with contrast.
The right optic nerve is enlarged and is enhancing in its intraorbital and
intracranial portions (arrows)
34. Cupping of the optic
nerves can occur in
chronic
compression.
There is pallor of
the remaining rim;
unlike in
glaucomatous nerve
cupping, in which
the cups are large
with retained pink
rims.
OCT is abnormal in
chronic compressive
optic neuropathies
with optic atrophy
and thinning of
RNFL.
35. Causes of compressive optic neuropathy include :
Neoplastic.
Optic nerve sheath meningioma
Intraorbital tumor (hemangioma, lymphangioma,
metastasis, etc.)
Sphenoid meningioma.
Craniopharyngioma
Pituitary tumours
Nonneoplastic:
Thyroid eye disease
Orbital pseudotumor
Orbital hemorrhage.
37. Diagnosis and Management:
Based on clinical presentation and neuroimaging(MRI with fat
supression and gadolinium contrast).
Biopsy to obtain a definite diagnosis
Observation – if good vision and stable radiographic appearance.
Most show very slow progression over years and sometimes
show spontaneous regression.
Chemotherapy in patients with severe vision loss at presentation
or evidence of progression
.Surgical excision in patients with severe vision loss with
proptosis.
39. LHON is a rare ganglion cell degeneration that
typically affects the papillomacular bundle.
It is caused by mitochondrial DNA point mutations.
The condition typically affects males between the
ages of 15 and 35 years
In atypical cases it may affect females and present at
any age between 10 and 60 years.
Leber hereditary optic neuropathy
40. Symptoms.
Acute ,severe painless unilateral
(50%) loss of central vision occurs.
The fellow eye becomes involved
within weeks or months.
Signs
Acute stage -the disc may be entirely
normal.
Colour vision is affected and RAPD +
In typical cases there is disc
hyperaemia with obscuration of the
disc margins (A)
Dilated capillaries on the disc
surface, which may extend onto
adjacent retina (telangiectatic
microangiopathy) (B)
41. Swelling of the peripapillary nerve fibre layer (pseudooedema).
Dilatation and tortuosity of posterior pole vasculature.
Subsequently, severe optic atrophy is seen ( C )
Investigations:
Genetic testing to look for mutations in MT-ND4 gene
OCT: Peripapillary retinal thinning
Visual field -central or centrocaecal scotomas, with preserved
peripheral vision.
FA shows no leakage from the disc or microangiopathic vessels
Treatment is generally ineffective and prognosis is poor.
42. Inheritance is autosomal dominant
This is the most common hereditary
optic neuropathy
Presentation is typically, in childhood
with insidious visual loss. There is
usually a family history
Optic atrophy - temporal or diffuse
with enlargement of the cup.
Prognosis is variable
Very slow progression over decades
is typical.
Systemic abnormalities: 20 % develop
sensorineural hearing loss.
Dominant optic atrophy
(Kjer type optic atrophy, optic
atrophy type 1)
43. Inheritance is AR
Pesentation is in early childhood with reduced vision.
Optic atrophy is diffuse.
Prognosis is variable, with moderate to severe visual
loss and nystagmus.
Systemic abnormalities include spastic gait, ataxia
and mental handicap.
Behr syndrome
44. Inheritance: Three genetic forms due to mutations in
WFS1, with inheritance being AR, AD or mitochondrial.
Presentation is usually between the ages of 5 and 21 years.
Diabetes mellitus is typically the first manifestation,
followed by visual problems.
Optic atrophy is diffuse and severe and may be associated
with disc cupping.
Prognosis is typically poor
Systemic abnormalities (apart from DIDMOAD) may
include anosmia, ataxia, seizures,short stature, endocrine
abnormalities .
Wolfram syndrome -DIDMOAD
(diabetes insipidus, diabetes mellitus,
optic atrophy and deafness).
46. Introduction:
optic neuropathy (tobacco-alcohol amblyopia) is acquired
optic neuropathy.
Mechanism: Deficient mitochondrial function,
papillomacular bundle is preferentially affected.
Typically affects individuals with high alcohol and tobacco
consumption.
Deficiency in the B-complex vitamins, particularly
cyanocobalamin (B12) and thiamine (B1)
A similar clinical picture may be seen due to toxicity from
medication or environmental (e.g. occupational) toxins.
47. Diagnosis:
Symptoms:Insidious onset of painless bilateral central blurring
associated with abnormal colour vision.
Signs :VA is very variably affected.
The discs at presentation are normal in most cases, but
some patients show subtle temporal pallor, splinter-shaped
haemorrhages on or around the disc, or minimal oedema.
The pupil reactions are often normal
Colour vision testing. A reduction in colour vision is
disproportionate to the reduction in acuity.
Red desaturation is likely to be present.
48. Investigations:
Visual field defects are bilateral, relatively symmetrical,
centrocaecal scotomas.
OCT may show peripapillary RNFL thickening and will help
to exclude macular pathology.
Fundus autofluorescence (FAF) to exclude macula changes
secondary to a cone or cone-rod dystrophy
Blood tests. B12 (cobalamin) and folate (serum and red
cell) ,other vitamin, CBC, Peripheral smear.
VEP. The P100 amplitude is markedly reduced but with
normal or near-normal latency.
MRI to rule out intracranial pathology
Prognosis is good in early cases provided patients comply
with treatment although visual recovery may be slow.
49. Visual field
cecocentral scotoma
on the left and a
relative central
scotoma on the
right.
Fundus appearance
shows
mild temporal optic
atrophy
50. Treatment:
Dietary revision
Abstention from alcohol and tobacco is a priority,
A daily multivitamin preparation, plus thiamine (100 mg
twice daily) and folate (1 mg daily).
Intramuscular hydroxocobalamin (vitamin B12) injections.
Hydroxocobalamin injections improve vision in tobacco-
alcohol amblyopia, by reversing cyanide toxicity
Regimens range from 1 mg weekly for 8 weeks to monthly
for several months. Injections every 3 months are typically
continued for life.
52. Traumatic optic neuropathy follows ocular, orbital or head trauma
Patients present with sudden ,severe visual loss
It occurs in up to 5% of facial fractures.
Classification :
Direct, due to blunt or sharp optic nerve damage from agents
such as displaced bony fragments, or local haematoma.
Indirect, may occur even with relatively minor head injury. The
trauma involves the frontal or maxillary bone, and the transmitted
forces damage the optic nerve at the orbital apex. Avulsion of the
nerve may also occur. ( more common)
The pathophysiology involves shear forces on the nerve which
comprimises vascular supply in the optic canal.
53. Left orbital trauma with
enophthalmos.
There is a left relative
afferent pupillary defect
Computed tomographic
scan of the brain and
orbits without contrast
(bone window) showing
an extensive fracture of
the left medial wall of the
orbit, involving the optic
canal.
54. Presentation:
RAPD
The optic nerve head and
fundus are initially normal
Pallor develops over
subsequent days and weeks
It is important to exclude
reversible causes of traumatic
visual loss such as
compressive orbital
haemorrhage.
55. Investigation:
CT for bony abnormalities such as optic canal fracture
MRI is for soft tissue changes (e.g. haematoma).
With either modality very thin sections are recommended.
Treatment.
Spontaneous visual improvement occurs in up to about half of patients
with an indirect injury.
Steroids (intravenous methylprednisolone) in patients with severe
visual loss .They should be started within the first 8 hours
2 g methylprednisolone intravenous and then 0.4 g for 48 hours in a
20 mL/hour infusion
Their use remains controversial- no proven benefit.
In a trial of high-dose corticosteroid treatment of patients with acute
brain injury (CRASH study) patients receiving steroids were at higher risk
of death.
Optic nerve surgery If there is progressive visual deterioration despite
steroids. It may be necessary but may not affect the prognosis for the
optic nerve.
57. Optic atrophy refers to the late stage changes that
take place in the optic nerve resulting from axonal
degeneration
Manifests with disturbance in visual function and in
the appearance of the optic nerve head.
Trypes: Primary, Secondary, consecutive ,
glaucomatous
Introduction
58. Primary optic atrophy occurs without antecedent
swelling of the optic nerve head.
It may be caused by lesions affecting the visual
pathways at any point from the retrolaminar portion
of the optic nerve to the lateral geniculate body.
Lesions anterior to the optic chiasm result in
unilateral optic atrophy, whereas those involving the
chiasm and optic tract will cause bilateral change
1. Primary optic atrophy
59. Causes:
Optic neuritis.
Compression by tumours and aneurysms.
Hereditary optic neuropathies.
Toxic and nutritional optic neuropathy, which may
give temporal pallor, particularly in early/milder cases
when the papillomacular fibres are preferentially
affected.
Trauma
60. Flat white disc with clearly delineated
margins .
Reduction in the number of small blood
vessels on the disc surface.
Attenuation of peripapillary blood vessels
and thinning of the retinal nerve fibre
layer (RNFL).
The atrophy may be diffuse or sectoral
depending on the cause and level of the
lesion.
Temporal pallor of the optic nerve head
may indicate atrophy of fibres of the
papillomacular bundle.
Signs:
61. Secondary optic atrophy is preceded by longstanding
swelling of the optic nerve head.
Causes :
chronic papilloedema
anterior ischaemic optic neuropathy
apillitis
Secondary optic atrophy
62. Signs vary according to the cause and
its course.
Slightly or moderately raised white or
greyish disc with poorly delineated
margins due to gliosis
Obscuration of the lamina cribrosa.
Reduction in the number of small blood
vessels on the disc surface.
Peripapillary circumferential
retinochoroidal folds (Paton lines)
Sheathing of arterioles and venous
tortuosity may be present
63. Consecutive optic atrophy is caused by disease of the
inner retina or its blood supply.
Causes:
extensive retinal photocoagulation
retinitis pigmentosa
prior central retinal artery occlusion
O/e: The disc appears waxy, with reasonably
preserved architecture
Consecutive optic atrophy
64. Chronic open-angle glaucoma is the most common cause of
progressive bilateral optic neuropathy.
This disorder is characterized by slowly progressive peripheral visual
field loss, elevated intraocular pressures ,and cupping of the optic
disc
Central visual acuity is preserved until very late in the course of the
disease
A vertically enlarged cup with nasal displacement of the vessels and
the absence of pallor of the retained rim of neural tissue are highly
suggestive of glaucoma.
Glaucomatous Optic Neuropathy