eMedicine Specialties > Ophthalmology > Optic Nerve

Optic Atrophy

Rashmin Gandhi, MBBS, FRCS(Edin), FRCS(Glasg), Faculty, Departments of Ocular Physiology and Neuro-ophthalmology, Elite School of Optometry; Faculty, CU Shah Ophthalmic Postgraduate Center, Consulting Staff, Department of Ophthalmology, Sankara Nethralaya Hospital
Gangaprasad Muthaiah Amula, MBBS, Trainee Ophthalmologist, Department of Ophthalmology, Sankara Nethralaya, India
Contributor Information and Disclosures

Updated: Jul 28, 2008

Introduction

Background

Optic atrophy is the final common morphologic endpoint of any disease process that causes axon degeneration in the retinogeniculate pathway. Clinically, optic atrophy manifests as changes in the color and the structure of the optic disc associated with variable degrees of visual dysfunction. Optic atrophy is actually a misnomer; in the strict histologic definition, atrophy refers to involution of a structure resulting from prolonged disuse.

Pathophysiology

The optic nerve comprises approximately 1.2 million axons that originate at the ganglion cell layer of the retina. The axons of the optic nerve are heavily myelinated by oligodendrocytes, and the axons, once damaged, do not regenerate. Thus, the optic nerve behaves more like a white matter tract rather than a true peripheral nerve.
 
The optic nerve is divided into the following 4 parts:

• Intraocular part (1 mm), also known as the optic nerve head
• Intraorbital part (25 mm)
• Intracanalicular part (5 mm)
• Intracranial part (10 mm)

The optic nerve head is 1 mm deep, 1.5 mm horizontally, 1.8 mm vertically at the retinal level, and a little wider posteriorly. The optic nerve head is a major transition between an area of high pressure to an area of low pressure (intracranial pressure). The optic nerve head comprises 4 types of cells, as follows: ganglion cell axons, astrocytes, capillary-associated cells, and fibroblasts. The optic nerve fibers pass through the lamina cribrosa (a sievelike structure with 200-300 holes that perforate the choroid and the sclera).
 
The optical property of normal axons of the optic disc is similar to fiber optic cable. The incident light originating from the ophthalmoscope undergoes total internal reflection through the axonal fibers and is reflected back by the capillaries on the disc surface, giving rise to the characteristic yellow-pink color of a healthy optic disc. The degenerated axons do not possess this optical property, leading to the atrophic disc’s pale appearance.

Pial capillaries arising from the circle of Zinn-Haller supply the optic disc. These capillaries exhibit autoregulation and are not leaky. According to another theory, the loss of capillaries in optic atrophy causes the pale-appearing disc.
 
The Kestenbaum count is the number of capillaries observed on the optic disc. The normal count is approximately 10. In optic atrophy, the number of these capillaries reduces to less than 6; in a hyperemic disc, the count is more than 12.  

Histopathologic changes in optic atrophy

• Shrinkage or loss of both myelin and axis cylinders
• Gliosis
• Deepening of the physiologic cup with barring of the lamina cribrosa
• Widening of the subarachnoid space with redundant dura
• Widening of the pial septa
• Severed nerve leads to bulbous axonal swellings (Cajal end bulbs); may be observed at the anterior cut end of the fibers

• Anterograde degeneration (Wallerian degeneration)
  • In conditions with anterograde degeneration (eg, toxic retinopathy, chronic simple glaucoma), deterioration begins in the retina and proceeds toward the lateral geniculate body (ie, to the brain).
  • Axon thickness determines the rate of degeneration. 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.
• 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.
• 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.
  • This type of degeneration is observed in patients with occipital damage incurred either in utero or during early infancy.

• Primary optic atrophy: In conditions with primary optic atrophy (eg, pituitary tumor, optic nerve tumor, traumatic optic neuropathy, multiple sclerosis), 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. The disc is chalky white and sharply demarcated, and the retinal vessels are normal. Lamina cribrosa is well defined.
• Secondary optic atrophy: In conditions with secondary optic atrophy (eg, papilledema, papillitis), the atrophy is secondary to papilledema. Optic nerve fibers exhibit marked degeneration, with excessive proliferation of glial tissue. The architecture is lost, resulting in indistinct margins. The disc is grey or dirty grey, the margins are poorly defined, and the lamina cribrosa is obscured due to proliferating fibroglial tissue. Hyaline bodies (corpora amylacea) or drusen may be observed. Peripapillary sheathing of arteries as well as tortuous veins may be observed.  Progressive contraction of visual fields may be seen as well.
• Consecutive optic atrophy: In consecutive optic atrophy (eg, retinitis pigmentosa, myopia, central retinal artery occlusion), the disc is waxy pale with a normal disc margin, marked attenuation of arteries, and a normal physiologic cup.
• Glaucomatous optic atrophy: Also known as cavernous optic atrophy, marked cupping of the disc is observed in glaucomatous optic atrophy. Characteristics include vertical enlargement of cup, visibility of the laminar pores (laminar dot sign), backward bowing of the lamina cribrosa, bayoneting and nasal shifting of the retinal vessels, and peripapillary halo and atrophy. Splinter hemorrhage at the disc margin may be observed.
• Temporal pallor: Temporal pallor may be observed in traumatic or nutritional optic neuropathy, and it is most commonly seen in patients with multiple sclerosis, particularly in those with a history of optic neuritis. The disc is pale with a clear, demarcated margin and normal vessels, and the physiologic pallor temporally is more distinctly pale.

Etiologic classification

Regardless of etiology, optic atrophy is associated with variable degrees of visual dysfunction, which may be detected by one or all of the optic nerve function tests (see Other Tests). 

• Hereditary
  • Congenital or infantile optic atrophy (recessive or dominant form)
  • Behr hereditary optic atrophy (autosomal recessive)
  • Leber optic atrophy
• Consecutive atrophy: Consecutive atrophy is an ascending type of atrophy (eg, chorioretinitis, pigmentary retinal dystrophy, cerebromacular degeneration) that usually follows diseases of the choroid or the retina.
• Circulatory atrophy: Circulatory is an ischemic optic neuropathy observed when the perfusion pressure of the ciliary body falls below the intraocular pressure. Circulatory atrophy is observed in central retinal artery occlusion, carotid artery occlusion, and cranial arteritis.
• Metabolic atrophy is observed in disorders such as thyroid ophthalmopathy, juvenile diabetes mellitus, nutritional amblyopia, toxic amblyopia, tobacco, methyl alcohol, and drugs (eg, ethambutol, sulphonamides).
• Demyelinating atrophy is observed in diseases such as multiple sclerosis and Devic disease.
• Pressure or traction atrophy is observed in diseases such as glaucoma and papilledema.
• Postinflammatory atrophy is observed in diseases such as optic neuritis, perineuritis secondary to inflammation of the meninges, and sinus and orbital cellulites.
• Traumatic optic neuropathy: The exact pathophysiology of traumatic optic neuropathy is poorly understood, although optic nerve avulsion and transection, optic nerve sheath hematoma, and optic nerve impingement from a penetrating foreign body or bony fragment all reflect traumatic forms of optic nerve dysfunction that can lead to optic atrophy.

Frequency

United States

According to Tielsch et al, the prevalence of blindness attributable to optic atrophy was 0.8%.¹ 

According to Munoz et al, the prevalence of visual impairment and blindness attributable to optic atrophy was 0.04% and 0.12%, respectively.²

Mortality/Morbidity

Optic atrophy is not a disease but a sign of many disease processes. Thus, morbidity and mortality in optic atrophy depends on the etiology.

Race

Optic atrophy is more prevalent in African Americans (0.3%) than in whites (0.05%).

Sex

There is no sexual predisposition noted.

Age

Optic atrophy is seen in any age group.

Clinical

History

See Physical.

Physical

When examining a patient with a pale disc, determine primarily if the pallor is physiologic. Nonpathologic disc pallor is observed in the following:

• Axial myopia: The optic disc has a segmental whitish appearance due to an oblique angle of insertion of the optic nerve and nasal displacement of the optic nerve contents.
• Myelinated nerve fibers: Feathery margins are due to the superficial location, usually adjacent to the disc.
• Optic nerve pit: Small colobomas are most often located in the inferotemporal portion of the disc.
• Tilted disc can cause confusion.
• Optic nerve hypoplasia has a double ring sign, and the inner ring is actually the optic disc margin.
• Scleral crescent areas are devoid of retinal pigment epithelium.
• Optic disc drusen
• Fundus viewing through an intraocular lens implant
• Brighter-than-normal luminosity: The luminosity of an indirect ophthalmoscope is approximately 2000 lux and that of a direct ophthalmoscope is up to 900 lux. A disc appears pale if the luminosity of the instrument is brighter than normal.

Optic atrophy in young individuals

Hereditary and congenital optic atrophy generally presents in the first or second decade of life. They can be broadly classified into the following 3 major groups:

• Optic atrophy with generalized white matter disease (eg, adrenoleukodystrophy)
• Optic atrophy with seemingly unrelated systemic features (generally associated with OPA1 gene mutation)
• Isolated optic atrophy (may be autosomal  dominant or recessive mitochondrial inheritance; eg, Leber hereditary optic neuropathy)

Unexplained optic atrophy
 
Optic atrophy that does not fit into the aforementioned groups requires further investigation. A typical investigation protocol is as follows: 

• Visual fields 30-2 and full field
• MRI of the brain and orbits with contrast
• CT scanning of the brain and orbits with contrast (in addition to space-occupying lesion [SOL], look for sinusitis, hyperpneumatized sinuses, fibrous dysplasia) 
• 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)

Causes

See Pathophysiology.

References

• Axial myopia
• Brighter-than-normal luminosity
• Myelinated nerve fibers
• Optic disc drusen
• Optic nerve hypoplasia
• Optic nerve pit
• Scleral crescent
• Tilted disc