atopy

1. Optic Atrophy
Resource person Dr Reshma Shrestha
Dr Madhu Thapa

2. INTRODUCTION
DEFINITION: optic atrophy represents the permanent loss of
retinal ganglion cell axons in conjunction with retinal ganglion
cell death.
 Final endpoint of any disease process causing axon
degeneration in retinogeniculate pathway
 Clinically, manifests as changes in the color & structure of
optic disc
 Variable degrees of visual dysfunction.
 Actually a misnomer
 Actually,atrophy refers to involution of a structure resulting
from prolonged disuse but optic atrophy refers to cell death.

3. OPTIC NERVE
 IInd cranial nerve
(neurosensory)
 Comprises approximately 1.2
million axons
 Originate at the ganglion cell
layer of the retina.
 The axons are myelinated by
oligodendrocytes,
 The axons do not regenerate.

4. The optic nerve is
divided into the following 4
parts:
1. Intraocular part =optic
nerve head (1 mm)
2. Intraorbital part (25 mm)
3. Intracanalicular part (5
mm)
4. Intracranial part (10 mm)

5. Visual pathway
 Unilateral atrophy
Lesion involving
anterior to optic
chiasm
 Bilateral atrophy
Lesion involving
chiasm &optic tract

6. FEATURES OF NORMAL OPTIC NERVE

7. •Thin pial strands divide
nerve into fascicles
400-600 fascicles – 2000
fibres
•smalll vessels run within
pial strands
•Axons are heavily
myelinated by
oligodendrocytes
•Meningeal sheath is closely
applied to optic nerve
(hematoxylin and eosin
staining).

8. Normal nerve fibre layer Optic nerve atrophy

9. Pathogenesis of Acquired Optic Disc Pallor
 When the optic nerve degenerates, its blood supply is
reduced
 smaller vessels that have been recognizable in the normal
nerve are no longer visible.
 Optic atrophy reflects this reduction of blood supply and
also the formation of reactive glial tissue.

10. Quigley and Anderson -
 thickness and the cytoarchitecture of fiber
bundles passing between glial columns
containing capillaries

11.  the transparent nerve
fibers act as fiberoptic
pathways in conducting
light.
 The light diffuses among
adjacent columns of glial
cells and capillaries and
acquires the pink color
of the capillaries.

12.  The axon bundles of an
atrophic optic disc have been
destroyed, and the remaining
astrocytes are arranged at
angles to the entering light.
 Thus, little light passes into the
disc substance to traverse the
capillaries
 The light reflected from
opaque glial cells does not pass
through capillaries, remains
white, and the optic disc
appears pale

13. Histopathologic changes in optic atrophy
 Immediately after injury, microglial cells tend to accumulate.
 Shrinkage of optic nerve due to loss of myelin and axis cylinders
 Widening of the pial septa
 Widening of the subarachnoid space with redundant dura
 Gliosis – astrocyte proliferation
 as remyelination occurs, number of oligodendroglia may also increase.
 Severed nerve leads to bulbous axonal swellings (Cajal end bulbs)

14. primary optic atrophy - absence of gliotic reaction on the
surface of the optic disc.
Secondary optic atrophy
 glial proliferation is seen on the surface and the edges
of the optic disc.
 Astrocytes are seen throughout the optic nerve head
and in heaps anterior to the disc.

15.  Histopathologic study of the retina reveals partial or complete
loss of retinal ganglion cells and their axons, which constitute
the nerve fiber layer.
 In contrast, the outer retinal layers are usually completely
normal.

16. Pathologic classification
ASCENDING OPTIC ATROPHY (ANTEROGRADE)
 degeneration of the retinal ganglion cell axons at the level of the
optic nerve head, secondary to retinal ganglion cell death
 Deterioration begins in the retina and proceeds toward the lateral
geniculate body - wallerian or ascending degeneration.
 rate of degeneration proportional to axon thickness- Larger axons
disintegrate more rapidly than smaller axons.
 The essential feature is swelling and degeneration of the axon
terminal in the lateral geniculate body (LGB), observed as early as
24 hours.
 Leukocytes rarely present in Wallerian degeneration.
 eg, toxic retinopathy, chronic simple glaucoma

17. Retrograde degeneration
 In conditions with retrograde degeneration (optic nerve
compression by intracranial tumor), deterioration starts from
the proximal portion of the axon and proceeds toward the
optic disc (ie, to the eye).
 The time course of this degeneration is apparently
independent of the distance of the injury from the ganglion
cell body.
 Thus, damage to the retrobulbar portion of the optic nerve,
the optic chiasma, or the optic tract causes pathologic and
visible degeneration of the ganglion cell body simultaneously.

18. Trans-synaptic degeneration
 In trans-synaptic degeneration, a neuron on one side of a
synapse degenerates as a consequence of the loss of a neuron on
the other side.
- Anterograde (more common)
- Retrograde

19. anterograde Transsynaptic atrophy of the lateral geniculate nucleus is
seen in long-standing severe ocular disease, such as absolute glaucoma,
or after trauma and enucleation of the eye
Retrograde Transsynaptic atrophy
 injury to the visual cortex or optic radiations may lead to retrograde
degeneration of lateral geniculate nucleus neurons.
 over considerable time, lead to degeneration of the retinal ganglion
cell and its axon, producing optic atrophy
 Seen only in cases with a long-standing cortical lesion - incurred either in
utero or during early infancy.

20. Etiologic classification
Hereditary
 Congenital or infantile optic atrophy (recessive or dominant form)
 Behr hereditary optic atrophy (autosomal recessive)
 Leber optic atrophy
Consecutive atrophy: following diseases of the choroid or the retina.
 Chorioretinitis,
 Pigmentary retinal dystrophy
 Cerebromacular degeneration
Circulatory atrophy:
 Central retinal artery occlusion,
 AION
 PION

21. Nutritional deficiency
 Vitamin B12
 Folte
 Thiamine
Toxic
 Ethambutol
 Isoniazide
 Chloramphenicol
 Hydroxyquinolone
 Cisplatin/ vincristine
 Amiadarone
 Methanol
Demyelinating atrophy
 multiple sclerosis
 Devic disease.

22. Pressure or traction atrophy
 glaucoma and
 papilledema.
Postinflammatory atrophy
 optic neuritis,
 perineuritis secondary to inflammation of the meninges, and
sinus and orbital cellulites.
Traumatic optic neuropathy:
 optic nerve avulsion and transection,
 optic nerve sheath hematoma, and
 optic nerve impingement from a penetrating foreign body or
bony fragment

23.  Band or "bow tie" optic atrophy
 Invovement of fibre entering optic disc nasally & temporally(sparing
superior & inferior portion)
 Unilateral visual defect.
 Chronic compression of the decussating visual
fibers of the chiasm
DIFFUSE
SECTORA
L

24.  The nature and the extent of optic nerve injury also affect disc appearance.
The optic disc atrophy may be slight, moderate, or severe, and it may be
diffuse or confined to one sector.
 In anterior ischemic optic neuropathy, the optic atrophy is often limited to the
upper or lower half of the disc.
 In chiasmal lesions, decussating fibers from the retina nasal to the fovea, and
hence both temporal and nasal to the optic disc are primarily involved, but
the superior and inferior arcuate bundles are relatively spared. This leads to
atrophy in both temporal and nasal portions of the optic disc, but the
superior and inferior regions remain pink.21 This so-called bow-tie or band
optic atrophy is also seen in the eye contralateral to a unilateral optic tract
lesion.3, 22, 23 Such a lesion also causes superior and inferior pallor of the
ipsilateral optic disc because it involves the temporal retinal ganglion cells
from that eye (see Chap. 297, Chiasmal Disorders).

25.  Associated with compressive lesions of the
pregeniculate post-chiasmal pathway (or)
 Congenital malformations of postgeniculate
radiations or cortex.
 The optic atrophy is strictly U/L
CAUSES
 After retrobulbar neuritis
 Tumour & aneurysms
 Hereditary optic neuropathies
 Toxic & nutritional optic neuropathies

26. Ophthalmoscopic classification
 Primary optic atrophy
 Secondary optic atrophy
 Consecutive optic atrophy
 Glaucomatous optic atrophy

27. PRIMARY OPTIC ATROPHY
optic nerve fibers degenerate in an orderly manner
and are replaced by columns of glial cells
without alteration in the architecture of the
optic nerve head.

28.  Disc is chalky white
 Well defined margins
 Lamina cribrosa is well
defined
 constriction of the
papillary or peripapillary
blood vessels
 Thinning of the nerve
fiber layer

29.  Kestenbaum sign
reduction in the number of
ophthalmoscopically
visible small blood
vessels crossing the disc
margin from about 10 in
normal down to less than
7

30. Causes of primary optic atrophy
Common causes
 anterior ischemic optic neuropathy,
 optic neuritis,
 compressive lesions of the optic nerve
( aneurisms, optic nerve sheath meningioma, olfactory groove
meningioma, pituitary adenoma)
Other causes
 posterior ischemic optic neuropathy,
 trauma,
 granulomatous inflammations of the optic nerve, and
 ophthalmic artery or other aneurysms that compress the optic
nerve.
 Glaucoma is the most common cause of optic atrophy

31. Secondary optic atrophy
 Optic atrophy occurs as
consequence of severe disc
edema or inflammation at the
optic nerve head
 Eg papilledema, papillitis
 Optic nerve fibers exhibit
marked degeneration with
excessive proliferation of
glial tissue.

32.  disc is grey or dirty grey,
 margins poorly defined
 lamina cribrosa obscured due
to proliferating fibroglial
tissue.
 Hyaline bodies or drusen
may be observed.
 Peripapillary sheathing of
arteries
 tortuous veins
 reduced Kestenbaum's
number

33. CONSECUTIVE OPTIC
ATROPHY
 Associated with lesions of retina & choroid.
 In chorioretinitis & primary pigmentary
degeneration of the retina.
 Inflammatory / degenerative lesions.
 Ascending type
OPHTHALMOSCOPICALLY
 Yellowish waxy disc
 Attenuated retinal vessels
 Changes in the surrounding
retina
Optic atrophy in Retinitis pigmentosa

34. GLAUCOMATOUS OPTIC
ATROPHY
 slowly progressive visual field loss –
arcuate and peripheral
 Marked excavation of optic disc
remaining neuroretinal rim appearing
relatively normal, without evidence of
pallor
 diffuse thinning of the retinal nerve
fiber layer
 Focal notching at superior and inferior
pole
 Pallor develops only with relatively
advanced damage
 Nasal shift of blood vessels

35.  loss of visual field long before they experience loss of
central vision
 Patients with glaucoma develop visual field defects only
after there is extensive damage to the optic disc.
 Color vision deficits are typically of the blue-yellow
type

36. Excavation may be seen in:
 Compressive neuropathy
 Lebers hereditary optic neuropathy
 AAION
 Compressive lesion- temporal rather than nasal or arcuate visual
field defect
 LHON-central and cecocentral loss
 Earlier and more prominent pallor with less severe excavation
and notching than in glaucoma
 central vision and colour vision reduced early

37. Optic neuritis
 Loss of vision over hrs to days
 18-45yrs
 Orbital pain with eye movement
 Preceeding flu like symptoms
 Altered perception of moving object (pulfrich phenomenon)
 Worsening of symptoms with exercise or raised body temp.
 Central, cecocentral, arcuate or altitudinal visual field defect
 APD, altered colour and contrast sensitivity
 Optic atropy following recurrent attack

38. 38
Post neuritic OA
 Optic disc dirty white
 Gliosis with blurred edges of disc
 Cup obliterated
 Lamina cribrosa not visible
 Attenuated vessels with or without sheathing

39. AION
 > 50years age
 Painless monocular visual loss over hours to days
 Headache , jaw claudication scalp tenderness
 Altitudinal visual field defect
 Pale or segmental disc edema
 Peripapillary fame shaped hemorrhage, retinal arteriolar
narrowing
 Optic disc becomes visibly atropic within 4-8 weeks
 FFA- delayed optic disc swelling

40. Compressive optic neuropathy
 Slowly prgressive visual loss
 Central visual field defect
 Signs of orbital disease like
Proptosis, restricted motility, lid lag/
retraction
 Optic nerve glioma: usual < 20yrs ,
associated neurofribromatosis
 Optic nerve meningioma: usually
adult women
 Optociliary shunt vessels
 choroidal folds

41. Toxic/ nutritional optic neuropathy
 Gradually progressive bilaterally symmetrical painless
visual loss affecting central vision
 Central/centrocecal scotoma
 Signs of poor nutrition, alcoholism and tobacco use
 Methanol toxicity- rapid onset severe visual loss with
prominent disc edema
 Optic atrophy if cause not corrected
 Early reversal of inciting cause-> gradual visual
recovery over 3-9 months

42. HEREDITARY
INFANTILE HEREDITARY OPTIC
ATROPHY
 Recessive inheritence
 Loss of vision
 Constricted visual field
 Nystagmus
INFANTILE HEREDITARY
ATROPHY
BEHR’S
DISEASE
LEBER’S
DISEASE

43. Behr’s optic atrophy
 Begins in infancy
 Autosomal recessive
 Incomplete bilateral optic atrophy with temporal
pallor of both disc
 Associated with neurological
abnormalities:cerebellar ataxia,spasticity,
Pyramidal tract abnomality

44. Leber’s optic atrophy
 Bilateral
 Recessive X-linkage
mitochondrial DNA mutation
11778
 In adolescent males
 Present with acute severe Unilateral visual
loss followed by involvement of other eye
within days-months
 Optic disc sweling, peripapillary
telangiectasia, FFAno leakage
 eventually followed by optic atrophy
 Central or cecocentral visual field defect
Telangiectic microangiopathy
Severe optic atrophy

45. Differential Diagnosis
 Axial myopia
 Optic nerve hypoplasia- double ring sign
 Brighter-than-normal luminosity
- indirect ophthalmoscope -2000 lux
- direct ophthalmoscope -900 lux
 Optic nerve pit
 Myelinated nerve fibers
 Scleral crescent – devoid of RPE
 Optic disc drusen
 Tilted disc
Optic nerve pit
Temporal crescent

46. WORK-UP OF OPTIC ATROPHY
 Visual acuity
 Colour vision
 Color vision is more decreased in patients with optic nerve disorders than in those with
retinal disorders.
 Color vision is profoundly decreased compared to visual acuity in patients with ischemic
and compressive optic neuropathy
 Contrast sensitivity test

47.  Pupillary evaluation
 Pupil size
 RAPD
 Edge-light pupil cycle time
-900 milliseconds per cycle
 Photostess recovery test
 Pulfrich phenomenon
 Cranial nerve examination
 Extraocular movements -
compressive optic neuropathy
PULFRICH PHENOMENON

48.  Visual field
 enlargement of the blind spot and paracentral scotoma (eg, optic
neuropathy),
 altitudinal defects (eg, anterior ischemic optic neuropathy, optic
neuritis)
 bitemporal defects (eg, compressive lesions, similar to optic
chiasma tumors).

49. BILATERAL OPTIC ATROPHY WITH
CENTROCECAL SCOTOMAS
 Hereditary (dominant,
Leber’s)
 Toxic (medications,
methanol, heavy
metals)
 Nutritional (folate, B12)
 Demyelinating (optic
neuritis, multiple
sclerosis)
CENTROCECAL SCOTOMAS

50.  EEG
 Visually evoked response
 optic neuritis- increased latency period and a decreased
amplitude
 Compressive optic lesions tend to reduce the amplitude of the
VER, while producing a minimal shift in the latency

51.  Imaging technique
 B-scan,- For tumors located in the orbit, in
papilledema to look for optic sheath dilatation
CT scan
Gadolinium enhanced MRI - multiple sclerosis
MRI in multiple sclerosis

52. OTHER INVESTIGATIONS
 Blood glucose level
 Blood pressure, cardiovascular examination
 Carotid Doppler ultrasound study
 Vitamin B-12 levels
 Venereal Disease Research Laboratory (VDRL)/Treponema pallidum
hemagglutination (TPHA) tests
 Antinuclear antibody levels
 Sarcoid examination
 Homocysteine levels
 Antiphospholipid antibodies
 Enzyme-linked immunosorbent assay (ELISA) for toxoplasmosis, rubella,
cytomegalovirus, herpes simplex virus (TORCH panel)

53. Treatment
Medical Care
 No proven treatment exists for optic atrophy.
 Treatment initiated before the development of optic atrophy
can be helpful
 The role of intravenous steroids is proven in a case of
 optic neuritis
 arteritic anterior ischemic optic neuropathy.
 Idebenone, a quinone analog is on trial Leber hereditary optic
neuropathy to ameliorate the net ATP synthesis
 Stem cell treatment :future treatment of neuronal disorders.
 At present, the best defense is an early diagnosis

54. PREVENTION
 Early detection of inflammations
 Some doctors recommend vitamin C, vitamin E,
coenzyme Q10, or other antioxidants,
 Avoid tobacco / alcohol
 Avoiding toxin exposure
 Avoid nutritional deficiency
 Early diagnosis and prompt treatment of compressive &
toxic neuropathies
 Genetic counselling in hereditary disease

55. Vitamin, Water Soluble
Essential to normal metabolism and DNA
synthesis.
Cyanocobalamin (Nascobal)
 Deoxyadenosylcobalamin and hydroxocobalamin
are active forms of vitamin B-12.
 Vitamin B-12 synthesized by microbes
 Required for healthy neuronal functions and
normal functions of rapidly growing cells.

56. Dosing
Adult
 Vitamin B-12 deficiency: 1000 mcg PO once a day
Pernicious anemia or other causes that decrease oral absorption,
administer
parenteral injection of 30 mcg IM/Sc once a day for 5-10 d,
then 100-200 mcg IM/SC once a month
 Intranasal gel: 500 mcg in one nostril once a wk
Pediatric
 Oral administration:
<12 years: Not established
>12 years: Administer as in adults

Alternatively,
100 mcg IM/SC once a day for 10-15 d (total dose of 1-1.5 mg),
then 60-100 mcg IM/SC once or twice weekly for several month
 Intranasal gel: Not established

57. Further Outpatient Care
 Low-vision aids for occupational rehabilitation.
PROGNOSIS
 Early and intensive treatment of cause provide
patients with near-normal vision

58. THANK
YOU