Optic Atrophy – Causes, Symptoms, treatment

Optic atrophy is a pathological term referring to optic nerve shrinkage caused by the degeneration of retinal ganglion cell (RGC) axons. The term “optic atrophy” is regarded as a misnomer since atrophy implies disuse. Therefore, a better term for optic atrophy would be “optic neuropathy.” However, that term is also controversial since, in certain situations, such as primary optic atrophy or traumatic brain injury, optic neuropathy may not occur.[rx]

Optic atrophy is the end stage of a disease process affecting the retinogeniculate portion of the visual pathway, characterized by a non-specific sign of optic disc pallor. While the peripheral nervous system has an intrinsic ability for repair and regeneration, the central nervous system, for the most part, is incapable of such processes. The axons of the optic nerve are heavily myelinated by oligodendrocytes and reactive astrocytes, which express many inhibitory factors for axonal regeneration.[rx] Thus, the optic nerve, with its 1.2 million fibers, behaves more like a white matter tract rather than a true peripheral nerve. The optic nerve head is supplied by pial capillaries that undergo degeneration contributing to the pallor of the optic disc seen in optic atrophy. It is this neuro-vascular degeneration which forms the foundation for the development of optic atrophy.

Types of Optic Atrophy

Clinical Types

• Primary optic atrophy – occurs without any preceding swelling of the optic nerve head. The condition is caused by lesions in the anterior visual system extending from the RGCs to the lateral geniculate body (LGB). The etiology of primary optic atrophy varies from conditions such as pituitary or optic nerve tumors and aneurysms, hereditary- and traumatic- optic neuropathies, toxic- and nutritional-optic neuropathies, following retrobulbar neuritis to multiple sclerosis. In this condition, the axons degenerate in an orderly manner. Subsequently, the resolution is characterized by the laying down of columns of glial cells.
• Secondary optic atrophy – ensues optic disc swelling, such as that seen in papilledema, optic neuritis, or AION. The fibers of the optic nerve exhibit marked degeneration and profuse glial tissue proliferation. The optic nerve head architecture is lost, and disc margins become indistinct. The color of the disc is grey or dirty-grey. In this condition, the lamina cribrosa is not visible due to the filling of the cup by overlying proliferative microglial tissue. Hyaline bodies (corpora amylacea) or drusen may occur. Peripapillary sheathing of arteries, tortuous veins, and optociliary shunt vessels may be observed. Peripapillary retinochoroidal folds known as Paton Lines, especially temporal to the disc, may be present. Functional tests demonstrate progressive contraction of visual fields in these cases.
• Consecutive optic atrophy – is associated with diseases that affect the inner retina or its blood supply. Some of those conditions include retinitis pigmentosa, pathological myopia, following pan-retinal photocoagulation, extensive retinochoroiditis, and central retinal artery occlusion. In this type of optic atrophy, the optic nerve head is waxy pale with a normal disc margin, marked attenuation of arteries, and a normal physiologic cup. Clinical features of predisposing retino-choroidal conditions provide a clue to this type of optic atrophy.
• Glaucomatous optic atrophy – is a completely distinct entity. It is characterized by certain specific mechanical and vascular changes in the optic disc, such as an increase in the cup: disc ratio and changes in the blood vessels as well as thinning of surrounding RNFL. This type of optic atrophy will not be considered further in this article.

Pathological Types

• Ascending optic atrophy – is also known as Wallerian degeneration. This anterograde degeneration occurs as a consequence of injury to the retinal elements or ONH axons. The subsequent degeneration ascends towards the LGB and superior colliculus.[rx]
• Descending optic atrophy or retrograde optic atrophy – follows a higher-order lesion leading to neuronal death upstream in the pathway. Occipital lesions have been reported to cause bilateral optic atrophy. However, lesions beyond the LGB are unlikely to cause optic atrophy, since the second-order neurons (RGC axons) synapse in the LGB. More commonly, tumors involving the retrobulbar segments of the optic nerve or the chiasm may cause secondary optic atrophy of the descending type.

Classification based on the extent

Optic atrophy can also be classified depending upon the extent of the neural loss.

• Partial optic atrophy occurs when there is some preservation of neural elements, and the disc may show only mild changes. Visual acuity may range from moderate visual loss to counting fingers. Visual field analysis usually shows concentric contraction with tubular vision. In such cases, only the temporal side of the disc could be pale and known as temporal pallor. This appearance of the disc indicates atrophy of the papillomacular fibers. It can be seen in traumatic or nutritional optic atrophy and multiple sclerosis patients following optic neuritis. In retrobulbar optic neuritis, the optic disc appearance is normal. In suspicious cases, the disc appearance should not be regarded as normal temporal pallor seen in some healthy discs, and investigations performed to rule out any pathology. Another phenomenon is band atrophy or bow-tie atrophy. It is characterized by butterfly-shaped nasal as well as temporal optic disc atrophy. It is seen in lesions of the optic chiasm or optic tract.[rx]
• Total optic atrophy is characterized by the complete loss of the nerve fibers in the optic nerve. In such cases, the optic disc is completely pale, and vision is usually no perception-to-light.

Causes of Optic Atrophy

The risk factors for the development of optic atrophy have been denoted by the mnemonic: VIN DITTCH MD. This mnemonic denotes the following conditions= V: Vascular; I: Inflammatory and infectious; N: Neoplastic or compressive; D: Primary demyelinating disease or idiopathic optic neuritis; T(2): Toxic and traumatic; C: Congenital; H: Hereditary; M: Metabolic and endocrine causes; D: Degenerative.[rx]

A retrospective case series of non-glaucomatous optic atrophy in Malaysia found the main etiologies to be: space-occupying intracranial lesions (26%), congenital/hereditary diseases (13%), hydrocephalus (12%), trauma (12%) and vascular causes (12%).

Optic atrophy can be classified based on the various causes which may lead to this condition. Various conditions in which optic atrophy may occur can be classified as follows:

• Congenital optic neuropathies:

  • Isolated: These include dominant and recessive optic atrophy, Leber’s hereditary optic neuropathy, and Behr’s hereditary optic atrophy.
  • Optic atrophy associated with systemic disease or neurological conditions.
• Extrinsic compression: Pituitary adenoma, intracranial meningioma, aneurysms, craniopharyngioma, mucoceles, papillomas, metastasis.
• Intrinsic optic nerve tumors: Optic nerve glioma, optic nerve sheath meningioma, and lymphoma.
• Vascular disease: Arteritic and non-arteritic anterior ischemic optic neuropathy (AION, NAION), central retinal artery occlusion, carotid artery occlusion, cranial arteritis.
• Inflammatory disease: Demyelinating optic neuritis (Multiple sclerosis, Devic’s disease), sarcoidosis, systemic lupus erythematosus, polyarthritis nodosa, Churg-Strauss syndrome, meningitis, orbital cellulitis.
• Infection: Syphilis, tuberculosis, Lyme disease, Aspergillosis, Cryptococcus, chickenpox, measles, mumps.
• Toxic and nutritional optic neuropathies: Nutritional amblyopia, toxic amblyopia, thyroid ophthalmopathy, juvenile diabetes, tobacco, methyl alcohol, and drug addiction. Optic atrophy due to toxic or nutritional causes is usually symmetrical and insidious in onset.
• Trauma: To optic nerve, optic nerve sheath hematoma, damage due to orbital fracture or foreign body.
• Swollen optic nerve: Papilledema, anterior ischemic optic neuropathy (AION).
• Retinal disease: Retinitis pigmentosa, macular dystrophies.

Symptoms of Optic Atrophy

The main symptom of optic atrophy is vision loss. Any other symptoms are attributable to the underlying process that caused the disc damage (such as pain with angle-closure glaucoma).

Optic atrophy is a sign and typically is noted as optic nerve pallor. This is the end stage of a process resulting in optic nerve damage.  Because the optic nerve fiber layer is thinned or absent the disc margins appear sharp and the disc is pale, probably reflecting the absence of small vessels in the disc head.

The symptoms of optic atrophy relate to a change in vision, specifically:

• Blurred vision.
• Difficulties with peripheral (side) vision.
• Difficulties with color vision.
• A reduction in sharpness of vision.

Symptoms of optic atrophy are a change in the optic disc and a decrease in visual function. This change in visual function can be a decrease in sharpness and clarity of vision (visual acuity) or decreases in side (peripheral) vision. Color vision and contrast sensitivity can also be affected.

Diagnosis of Optic Atrophy

In optic atrophy, certain histopathological changes can be seen. These include the widening of the pial septa and subarachnoid space with a redundancy of the dura. In case of trauma, the anterior severed ends of the nerve show bulbous swellings known as Cajal end bulbs.

History and Physical

Patients who develop optic atrophy often complain of loss of vision with the segmental or diffuse blurring of the visual field. History should be directed to the suspected cause of visual impairment. Certain important points in history include the nature of the presenting illness; visual and ocular history; family, medical and surgical history; medication and social history; and hospital or institutional admission history. History of systemic infections and diseases such as diabetes and thyroid disorders, dietary disturbances, addictions to alcohol, tobacco or recreational drugs, trauma, and other factors should be elicited.

Optic neuritis is an important cause of optic atrophy. It usually occurs in individuals between 10-50 years of age. Patients typically present with sudden, usually severe visual loss associated with pain on ocular movements. AION occurs in individuals above 50 years of age with headache and tenderness of the temporal artery. In optic atrophy due to tumors, there is an insidious history of slowly progressive visual impairment. However, hemorrhage within or due to the tumor eroding surrounding vessels would cause a sudden visual loss. Reduced color saturation or contrast sensitivity may develop before the occurrence of defective vision. Red color desaturation is seen in optic neuritis. While defects in identifying blue-yellow color may be an early sign of dominant optic atrophy, the normal linear association between stereo acuity and Snellen visual acuity could also be lost in optic atrophy.

Optic atrophy can be classified using different parameters. These can be clinical, pathological, and those based upon the extent and etiology.[rx]

Evaluation

In a case of optic atrophy, a number of investigations can be tailored according to the suspected etiology of the condition.

• Visual field tests – should be done whenever possible to help in diagnosis as well as follow-up of the patient’s condition. The 30-2 program is most useful in the investigation of optic atrophy. Visual field changes can include enlargement of the blind spot and paracentral scotoma, altitudinal defects (as seen in AION and optic neuritis), and bitemporal defects (seen in compressive lesions, similar to optic chiasma tumors).
• Magnetic Resonance Imaging (MRI) – of the brain and orbits with contrast is useful in the diagnosis and should be done in all patients with optic atrophy, if possible. Imaging techniques may demonstrate space-occupying lesions, sinusitis, hyperpneumatized sinuses, fibrous dysplasia, and fractures.
• On MRI images – multiple sclerosis plaques are typically seen located in the infratentorial region, in the deep white matter, periventricular, juxtacortical, or mixed white matter-grey matter lesions. The lesions appear iso- or hypointense on T1 images (T1 black holes), while, on T2 images, they are hyperintense. FLAIR sequence also shows hyperintense lesions. Other sequences, such as T1-weighted post-contrast (gadolinium), MR spectroscopy, and Double-inversion recovery (DIR), can also be used.
• In suspected fractures – a non-contrast computed tomography (CT) scan is preferable.
• Optical coherence tomography (OCT) – can be done to demonstrate the thinning of the retinal nerve fiber layer.
• Ultrasonography (B-scan) – is recommended for orbital tumors. B-scan in papilledema may demonstrate nerve sheath dilatation.
• Blood glucose level – Useful for diagnosis of diabetes mellitus as well as before initiating steroid therapy as the baseline.
• Blood pressure, cardiovascular examination – To look for vascular causes.
• Carotid Doppler ultrasound study – Carotid occlusion may need to be ruled out in selected cases.
• Vitamin B-12 levels – Nutritional causes of optic atrophy need to be ruled out when suggestive. However, a nutritional etiology may be obvious from history and systemic examination.
• Laboratory tests – may be required when indicated. These investigations include Venereal Disease Research Laboratory (VDRL)/Treponema pallidum hemagglutination (TPHA) tests, Antinuclear antibody levels, Angiotensin-Converting Enzyme assay, Homocysteine levels, Antiphospholipid antibodies, Enzyme-linked immunosorbent assay (ELISA) for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus (TORCH panel).

• Electroretinography (ERG) – results may show abnormalities such as:

  • Subnormal: Potential less than 0.08 microvolts, seen in toxic neuropathy.
  • Negative: When a large a-wave is seen, it may be due to giant cell arteritis, central retinal artery occlusion, or central retinal vein occlusion.
  • Extinguished: The response was seen in complete optic atrophy.
• Visually evoked response (VER)/ Visually evoked potential (VEP) – In optic neuritis, VER/VEP has increased latency period and decreased amplitude when compared to the normal eye. Compressive optic lesions tend to reduce the amplitude of VER/VEP while producing a minimal shift in the latency.
• Fundus fluorescein angiography (FFA) – It can be performed in cases of retinal-choroiditis, diabetic retinopathy to look for areas of capillary drop-out, neovascularization, and other defects. In optic disc drusen, FFA shows fundus autofluorescence.

Treatment of Optic Atrophy

The ideal treatment for optic atrophy would involve neuroregeneration. Unfortunately, such modalities are still not available for clinical use. Pharmacological treatment for optic atrophy has also been largely ineffective. The only focus in management is treating the exact cause before the development of significant damage to salvage useful vision. Once the condition is stabilized, low vision aids can be tried in selected individuals.

Pulse intravenous methylprednisolone has been used in conditions such as optic neuritis, arteritic anterior ischemic optic neuropathy, and traumatic optic neuropathy with successful outcomes. The optic neuritis treatment trial recommended doses of 500-1000 mg/day of IV methylprednisolone for three days, followed by oral prednisolone 1 mg/Kg BW for 11 days. Beta-interferons and glatiramer acetate have been used in the treatment of multiple sclerosis and related optic neuritis to reduce the occurrence of clinical lesions seen on MRI as well as the number of recurrences.[rx][rx]

Stem cell treatment may prove to be key in the future treatment of neuronal disorders. Neural progenitor cells can be delivered to the vitreous from where they can integrate into the ganglion cell layer of the retina. These cells would turn on neurofilament genes, and migrate into the host optic nerve to stimulate the regeneration of neural elements.[rx]

References