Optic Atrophy

Optic atrophy is the final common morphologic endpoint of any disease process that causes axondegeneration in the retinogeniculate pathway. Clinically, optic atrophy manifests as changes inthe color and the structure of the optic disc associated with variable degrees of visualdysfunction. Optic atrophy represents the permanent loss of retinal ganglion cell axons inconjunction with retinal ganglion cell death.

The axons possess a myelin sheath provided by oligodendrocytes. Once damaged, the axons donot regenerate. Light incident from the ophthalmoscope undergoes total internal reflectionthrough the axonal fibers, and subsequent reflection from the capillaries on the disc surface givesrise to the characteristic yellow-pink color of a healthy optic disc. Degenerated axons lose thisoptical property which explains the pallor in optic atrophy.

Alternatively, the loss of pial capillaries which supply the optic disc may be the cause of discpallor. The Kestenbaum index is the number of capillaries counted on the optic disc, whichnormally is around 10. Less than 6 capillaries indicates optic atrophy; more than 12 suggests dischyperaemia.

Histopathology changes in optic atrophy1

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

Classification

Optic atrophy is classified as pathologic, ophthalmoscopic, or etiologic1.

A. Pathologic classification

1) Anterograde degeneration (Wallerian degeneration): In conditions with anterogradedegeneration (e.g. toxic retinopathy, chronic simple glaucoma), deterioration begins in theretina and proceeds toward the lateral geniculate body (i.e., to the brain).

Axon thickness determines the rate of degeneration. Larger axons disintegrate more rapidly thansmaller axons. The essential feature is swelling and degeneration of the axon terminal in thelateral geniculate body (LGB), observed as early as 24 hours. Leukocytes rarely present inWallerian degeneration.

2. Retrograde degeneration: In conditions with retrograde degeneration (optic nervecompression by intracranial tumor), deterioration starts from the proximal portion of the axonand proceeds toward the optic disc (i.e., to the eye). The time course of this degeneration isapparently independent of the distance of the injury from the ganglion cell body. Thus, damageto the retrobulbar portion of the optic nerve, the optic chiasma, or the optic tract causespathologic and visible degeneration of the ganglion cell body simultaneously.

3. Trans-synaptic degeneration: In trans-synaptic degeneration, a neuron on one side of asynapse degenerates as a consequence of the loss of a neuron on the other side. This type ofdegeneration is observed in patients with occipital damage incurred either in utero or duringearly infancy.

B. Ophthalmoscopic classification

1. Primary optic atrophy: In conditions with primary optic atrophy (e.g. Pituitary tumor, opticnerve tumor, traumatic optic neuropathy, multiple sclerosis), optic nerve fibers degenerate in anorderly manner and are replaced by columns of glial cells without alteration in the architecture ofthe optic nerve head. The disc is chalky white and sharply demarcated, and the retinal vessels arenormal. Lamina cribrosa is well defined.

2. Secondary optic atrophy: In conditions with secondary optic atrophy (e.g., papilledema,papillitis), the atrophy is secondary to papilledema. Optic nerve fibers exhibit markeddegeneration, with excessive proliferation of glial tissue. The architecture is lost, resulting inindistinct margins. The disc is grey or dirty grey, the margins are poorly defined, and the laminacribrosa is obscured due to proliferating fibro glial tissue. Hyaline bodies (corpora amylacea) ordrusen may be observed. Peripapillary sheathing of arteries as well as tortuous veins may beobserved. Progressive contraction of visual fields may be seen as well. Optic atrophy followingpapilledema (secondary).

3. Consecutive optic atrophy: In consecutive optic atrophy (e.g., 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. Consecutive optic atrophyfollowing pan retinal photocoagulation (PRP).

4. Glaucomatous optic atrophy: Also known as cavernous optic atrophy, marked cupping ofthe disc is observed in glaucomatous optic atrophy. Characteristics include vertical enlargementof cup, visibility of the laminar pores (laminar dot sign), backward bowing of the laminacribrosa, bayoneting and nasal shifting of the retinal vessels, and Peripapillary halo and atrophy.Splinter hemorrhage at the disc margin may be observed

5. Temporal pallor: Temporal pallor may be observed in traumatic or nutritional opticneuropathy, and it is most commonly seen in patients with multiple sclerosis, particularly inthose with a history of optic neuritis. The disc is pale with a clear, demarcated margin andnormal vessels, and the physiologic pallor temporally is more distinctly pale.

C. 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.

1. Hereditary: This is divided into congenital or infantile optic atrophy (recessive or dominantform), Behr hereditary optic atrophy (autosomal recessive), and Leber optic atrophy.

2. Consecutive atrophy: Consecutive atrophy is an ascending type of atrophy (e.g.,chorioretinitis, pigmentary retinal dystrophy, cerebromacular degeneration) that usually followsdiseases of the choroid or the retina.

3. Circulatory atrophy: Circulatory is an ischemic optic neuropathy observed when theperfusion pressure of the ciliary body falls below the intraocular pressure. Circulatory atrophy isobserved in central retinal artery occlusion, carotid artery occlusion, and cranial arteritis.

4. Metabolic atrophy: Metabolic atrophy is observed in disorders such as thyroidophthalmopathy, juvenile diabetes mellitus, nutritional amblyopia, toxic amblyopia, tobacco,methyl alcohol, and drugs (e.g., ethambutol, sulphonamides).

5. Demyelinating atrophy: Demyelinating atrophy is observed in diseases such as multiplesclerosis and Devic disease.

6. Pressure or traction atrophy: Pressure or traction atrophy is observed in diseases suchas glaucoma and papilledema.

7. Postinflammatory atrophy: Postinflammatory atrophy is observed in diseases such asoptic neuritis, perineuritis secondary to inflammation of the meninges, and sinus and orbitalcellulites.

8. Traumatic optic neuropathy: The exact pathophysiology of traumatic optic neuropathyis poorly understood, although optic nerve avulsion and transection, optic nerve sheathhematoma, and optic nerve impingement from a penetrating foreign body or bony fragment allreflect traumatic forms of optic nerve dysfunction that can lead to optic atrophy.

Epidemiology

Optic atrophy can be seen in any age group. There is no sex predisposition noted.

Differential diagnosis

Non-pathologic disc pallor is seen in axial myopia, myelinated nerve fibers, optic disc pit, tilteddisc, and disc drusen. Viewing the disc in a pseudophakic eye, or using a brighterophthalmoscope than usual can cause the disc to look paler.

Clinical Work-up

Visual acuity: It is measured using Snellen’s optotypes or using a Log MAR chart. Visual acuityis reduced, occasionally to no light perception.

Color vision: Color vision is more decreased in patients with optic nerve disorders than in thosewith retinal disorders especially in patients with ischemic and compressive optic neuropathy.Color vision may be assessed with pseudo isochromatic tests (e.g., Ishihara color blindness test,Hardy-Rand-Rittler polychromatic plates, and Dvorine plates) or the Farnsworth-Munsell 100Hues test or the Farnsworth panel D-15 test.

Pupillary evaluation: Pupil size should be noted, as well as the magnitude and the latency of thedirect and consensual responses to light and near stimulation. A relative afferent pupillary defect(RAPD) is a hallmark of unilateral or asymmetric afferent sensory abnormality. Occasionally itis the only objective sign elicited. RAPD can be quantitatively graded by balancing the defectusing neutral density filters. Clinically, it is graded as follows:

Initial constriction, but greater escape to a larger intermediate size than when the light isswung back to normal eye (trace).

No changes in initial pupillary size, followed by dilation of the pupils (1-2+) Immediate dilation of the pupil, instead of normal initial constriction (3-4+)

Contrast sensitivity test: This test measures the ability to perceive slight changes in luminancebetween regions that are not separated by definite borders, and is a sensitive test for optic nervefunction. It can be tested using Pelli-Robson contrast sensitivity chart, Cambridge low-contrastgrating test or Arden gratings.

Pulfrich phenomenon: In optic nerve damage, the transmission of impulses to the occipitalcortex is delayed. In patients with unilateral or markedly asymmetric optic neuropathy, when anoscillating small target in a frontal plane is viewed binocularly, the target appears to move in anelliptic path rather than in a to-and-fro path.

Extraocular movements: Restriction can be obtained in cases of compressive optic neuropathydue to either the mass effect or the involvement of the nerve supplying the muscle.

Cranial nerve examination: All cranial nerves are examined to rule out associated nerveinvolvement to help determine the site of the lesion.

Ophthalmoscopic features

Optic disc

Optic disc changes can present with temporal pallor, focal pallor or bow-tie pallor (as seen incompression of the optic chiasma), or cupping (glaucomatous damage). In the early stages of theatrophic process the optic disc loses its reddish hue. The substance of the disc slowly decreases,leaving a pale, shallow exposed lamina cribrosa. In the end stages of the atrophic process theretinal vessels of the normal caliber still emerge centrally through the otherwise avascular disc.Focal notching or diffuse obliteration of the neuroretinal rim with preservation of color of anyremaining rim tissue is characteristic of glaucoma.

Optic disc cupping also develops in patients in non-glaucomatous eyes due to ischemia,compression, inflammation, hereditary disorders or trauma.

Peripapillary retinal nerve fiber layer

Early focal loss of axons produces dark wedge shaped defects (best seen with a red-free filter onslit-lamp bio-microscopy) in the peripapillary retinal nerve fiber layer.

Retinal vessels

In most cases of optic atrophy, the retinal arteries are narrowed or attenuated. In cases of non-arteritic anterior ischemic optic neuropathy, the vessels may be focally narrowed or completelyobliterated.

Investigations

Visual field testing: In optic neuropathy, visual field changes can include enlargement of theblind spot, caecocentral scotoma, altitudinal defects (e.g. anterior ischemic optic neuropathy,optic neuritis), and bitemporal defects (e.g. compressive lesions, similar to optic chiasmatumors).

Neuro-imaging: Neuro-imaging is indicated to find the cause of atrophy.

Ultrasonography is recommended when orbital tumor is suspected. For post-traumatic optic neuropathy a noncontrast CT scan is preferred. In optic neuritis or multiple sclerosis, a gadolinium-enhanced MRI/fluid-attenuated

inversion recovery (FLAIR) sequence is useful to detect hyper intense areas ofdemyelination.

Electroretinogram (ERG)

Abnormal electroretinogram (ERG) results that can be seen are as follows: Subnormal: Potential less than 0.08 microvolts; seen in toxic neuropathy Negative: a preserved a-wave but absent b-wave. It May be seen in arteritic AION or

central retinal artery occlusion. Extinguished ERG: seen in complete optic atrophy. N95:P50 ratio in pattern ERG is low in optic neuropathy and normal in maculopathy.

Visually evoked potential (VEP)

In optic neuritis the VEP has an increased latency period as compared to the normal eye whichpersists even after visual recovery. Compressive optic lesions tend to reduce the amplitude andcause waveform changes of the VEP.

Unexplained optic atrophy

As optic atrophy is a sign of end-stage optic nerve damage, and not a diagnosis in itself, furtherinvestigation is required if the above tests do not reveal its cause.

Clinical features of optic atrophy

Loss of vision: may be sudden or gradual onset (depending upon the cause of opticatrophy) and partial or total (depending upon the degree of atrophy).

Pupil is semi dilated and direct reflex is very sluggish or absent. Swinging Flash light testdepicts Marcus Gunn pupil.

Ophthalmoscopic appearance of the disc varies with type of optic atrophy. Visual field loss varies with the distribution of the fibers that have been damaged. In

general the field loss is peripheral in systemic infections, central in focal optic neuritisand eccentric when the nerve or tracts are compressed. Paracentral, caecocentral orcentral scotomas may be present.

Treatment

No proven treatment exists to reverse optic atrophy. At present, the best defense is earlydiagnosis. If specific treatment of the cause is initiated before the development of optic atrophy,useful vision may be salvaged. For example, early diagnosis and prompt treatment can help incompressive and toxic neuropathies. Neuro-protective agents like gingko biloba have been triedwith anecdotal success. Research in stem cell therapy may provide answers in the not-too-distantfuture. Low-vision aids should be considered for occupational rehabilitation.

Low Vision Management

Magnification at both distance and near with the use of low vision devices must be consideredfor the patients with reduced visual acuity due to optic atrophy. For distance too, telescopes arevery useful (Handheld versus spectacle mounted clip-on). Direct illumination along withmagnification & Reading stand quite helpful for performing near tasks.

Excessive lighting should be avoided for these patients.

Sun lenses, tints and filters should be used to eliminate glare both outdoor and indoor.

Non optical systems should be demonstrated and let them follow in their dailies.

Orientation and mobility management techniques and devices can be demonstrated for thepatients with low vision. Sighted guide technique, canes, dog guides and electronic travel aidscan be given to the patients for mobility.

Eccentric viewing if central vision is affected. Patients with central scotoma often have to useeccentric viewing to function more effectively. When a person has a large scotoma, being able toeffectively use an eccentric point can be more difficult with optical magnification. Eccentricviewing may be easier with an assistive technology device.7

Additionally, as fixation moves further from the fovea, the impact of crowding increases. Usingdifferent types of text presentation can lessen the effects of visual crowding7. For example,studies have reported that using text stretching to increase the spacing between letters and wordscan reduce crowding and may be beneficial for the person trying to read with a central scotoma

Peak cap and Sunglasses prove to be helpful for outdoors to tackle photophobia.

A patient with severe contrast sensitivity loss may functions better using reverse contrast, whichcan only be achieved with electronic magnification assistive technology7.

Bold line paper, Black ink with felt tipped pen for writing.

When color perception is impacted, a person may have difficulty with color contrasts, which maymake text or objects on a colored background more difficult to see. Using electronicmagnification, colors can be converted to black and white, and if necessary, contrast can also beenhanced. In addition, if a person has problems with color identification, assistive technologycan offer solutions.

Genetic counseling is must for the case of heredodegenerative forms of optic atrophy2.

References:

1. Optic Atrophy-A major review by Dr. Devendra V. Venkatramani, Dr. Gangaprasad

Muthaiah Amula, Dr. Rashmin A. Gandhi

2. Richard L.Brilliant.Essentials of Low Vision Practice

3. The Lighthouse Ophthalmology Resident training manual by Eleanor, Benjamin Freed, KarenR. Seidman, Michael Fischer.

4. Wolff’s anatomy of eye and orbit Eighth edition.

5. Comprehensive Ophthalmology bu A K Khurana

6. lowvision.preventable blindness.org

7. website of lighthouse international

Raju Kaiti

M. Optometry (Practioner)

Amity University