Optic atrophy, or degeneration of the optic nerves, may lead to optic nerve disease which is associated with vision impairment and loss of sight.
Presentation
Most patients with optic atrophy will display visual impairment in one or both eyes that occurs gradually over time, although, certain genetic mutations lead to optic atrophy that causes abrupt visual impairment. Specific symptoms include blurred vision, acuity, impaired color vision, photophobia, headaches and vertigo. Damage to the macula will specifically impair central vision and ability to focus on small objects while no impairment in peripheral vision will be observed [8].
Entire Body System
- Pallor
(A) Bilateral temporal disc pallor; 26. Fig. (B) bilateral diffuse pallor 27. Thank You All [slideshare.net]
Moderate to severe temporal or diffuse pallor can be seen. The optic disc has been described as normal in 29% of documented carriers and 20% have no visual field defect. Pallor of the complete disc is found in only 10%. [disorders.eyes.arizona.edu]
CONCLUSIONS: Deeply buried ODD may be associated with NAION causing irreversible visual loss and optic disc pallor, a condition easily mistaken for atypical ON. [ncbi.nlm.nih.gov]
- Pain
Distention and pain in the sides or flanks Suffocating sensation in the chest Tendency to sigh Melancholy Depression Anxiety Irritability Inappropriate anger Anorexia Irregular menses Dysmenorrhea Irregular menstruation Breast distention and pain before [americandragon.com]
Ocular or orbital pain Ocular or orbital pain is associated with optic neuritis due to optic nerve edema. Ocular or orbital pain Ocular or orbital pain is associated with optic neuritis due to optic nerve edema. [medicaljoyworks.com]
(glaucoma) In an older patient temporal pain, jaw pain, scalp tenderness, weight loss, fatigue and myalgia is suggestive of (arteritic ischaemic optic neuropathy due to GCA) Drug history: drugs can be toxic to the optic nerve (e.g. ethambutol, amiodarone [medicaleducationleeds.com]
In a young patient, previous history of eye pain, paraesthesiae, ataxia or weakness suggest demyelination In an older patient, previous history of transient visual loss, diplopia, temporal pain, jaw claudication, fatigue, weight loss and myalgia suggests [patient.info]
- Falling
Audiological investigation in both siblings revealed abnormalities falling within the auditory neuropathy/dysynchrony spectrum. [ncbi.nlm.nih.gov]
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A key objective of the report is to establish the understanding for all the pipeline drugs that fall under Leber's Hereditary Optic Neuropathy (LHON) (Leber optic atrophy). [businesswire.com]
Fall is coming and you'll want to download our hunting and outdoors app to make searching for products even faster. But wait, there's more!!! You'll also need trail cameras, rifle scopes, red dot scopes and perhaps archery equipment as well. [opticsplanet.com]
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- Asymptomatic
After the secondary stage, there is a dormant (asymptomatic) stage, known as Latent Syphilis which may last for many years (even decades). All infections do not progress to the final (tertiary) stage. [dovemed.com]
The superior temporal disc pallor and sclerotic, occluded arteriole were due to an old asymptomatic branch retinal artery occlusion. His medical history was significant for controlled hypertension and hypercholesterolemia. [reviewofoptometry.com]
Thalassemia is known to be a hypercoaguable state with cases of asymptomatic brain damage attributable to thrombotic events. [18],[19] This may explain optic atrophy in this patient. [ijo.in]
Clinical Testing and Work-Up Consistent monitoring and surveillance of asymptomatic individuals with LHON-causing mutations is not necessary. [rarediseases.org]
- Anemia
The pattern... 77 Members Anemia Anemia (or anaemia), which literally means "without blood," is a deficiency of red blood cells and/or hemoglobin. [dailystrength.org]
Drug-induced ONA Amiodarone, PDE5 inhibitors (e.g., sildenafil), ethambutol, vincristine, linezolid, streptomycin ONA secondary to medication-induced PTC (isotretinoin, oral contraceptive pills, tetracyclines) Nutritional ONA Vitamin B12 (pernicious anemia [unboundmedicine.com]
Hallucinations Hallucination Sensory hallucination [ more ] 0000738 Hemiparesis Weakness of one side of body 0001269 Horizontal nystagmus 0000666 Hypogonadism Decreased activity of gonads 0000135 Hypothyroidism Underactive thyroid 0000821 Macrocytic anemia [rarediseases.info.nih.gov]
Degeneration of the disc may also accompany arteriosclerosis, diabetes, glaucoma, hydrocephalus, pernicious anemia, and various neurological disorders. [medical-dictionary.thefreedictionary.com]
This condition can be caused by any of the following: demyelinating diseases (e.g., multiple sclerosis, postinfectious encephalomyelitis); systemic infections (viral or bacterial); nutritional and metabolic diseases (e.g., diabetes, pernicious anemia, [tedmontgomery.com]
Cardiovascular
- Thrombosis
Thus OPA1 plays an essential role in regulating platelet mitochondrial function, platelet activation and thrombosis in males but not in females. [circ.ahajournals.org]
[…] pressure (ICP) transmitted to the ganglion cell axons of the optic nerve Tumor (e.g., pituitary adenoma, optic nerve meningioma) Aneurysm Hydrocephalus Pseudotumor cerebri (PTC): idiopathic elevated ICP, often in obese young females Cortical venous sinus thrombosis [unboundmedicine.com]
[…] arthritis--it is an inflammatory disease that causes joints, cartilage or other fibrous tissue (such... 196 Members Antiphospholipid Syndrome Antiphospholipid syndrome (or antiphospholipid antibody syndrome) is a disorder of coagulation which causes thrombosis [dailystrength.org]
[…] permanent vision loss; however, multiple episodes can result in both. papilledema “Papilledema” is edema or swelling of the optic disc (papilla), most commonly due to an increase in intracranial pressure (often from a tumor), malignant hypertension, or thrombosis [tedmontgomery.com]
Skin
- Acne Vulgaris
The most common form of acne is known as "acne vulgaris", meaning "common acne." [dailystrength.org]
Ears
- Hearing Impairment
Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. [ncbi.nlm.nih.gov]
Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus and psychiatric disease. Human Mutation. 2003;22:275-87. Yu G, Yu M, Wang J, et al. [medigraphic.com]
0030515 Morning glory anomaly 0025514 Ophthalmoplegia Eye muscle paralysis 0000602 Sensorimotor neuropathy Nerve damage causing decreased feeling and movement 0007141 Sensorineural hearing impairment 0000407 Temporal optic disc pallor 0012511 5%-29% [rarediseases.info.nih.gov]
Causative variants in WFS1 are implicated in autosomal recessive WS (Rendtorff et al. 2011) and autosomal dominant low frequency sensorineural hearing impairment. [preventiongenetics.com]
Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. Am. J. Med. Genet. [journal.frontiersin.org]
- Progressive Hearing Loss
Dominant optic nerve atrophy with progressive hearing loss and chronic progressive external ophthalmoplegia (CPEO). [ncbi.nlm.nih.gov]
Eyes
- Visual Impairment
PURPOSE: To search for WFS1 mutations in patients with optic atrophy (OA) and assess visual impairment. DESIGN: Retrospective molecular genetic and clinical study. [ncbi.nlm.nih.gov]
In addition ethambutol toxicity may also contribute to visual impairment. Sub-clinical visual impairment can be detected by visual evoked potentials [ 11 ]. [omicsonline.org]
The effects of ONA have a broad range dependent on the adequacy of visual messages sent from the eyes to the brain, from little or no visual impairment to near-total blindness. The condition may affect one or both eyes. [familyconnect.org]
- Blurred Vision
Danish Retinablødning, synsforstyrrelser (ikke yderligere specificeret), sløret syn, fotofobi, chromatopsia, cyanopsia, øjenirritation, blodsprængte øjne / røde øjne English Retinal haemorrhage, visual disturbance NOS, blurred vision, photophobia, chromatopsia [mymemory.translated.net]
Jing -Well points of Six Hand Channels, needle DU-20, DU-26, GB-20, GB-34, KI-1, KI-3, LIV-2, LIV-3, PC-8, UB-18, UB-23 Clinical Manifestations Blindness Dryness in both eyes Facial complexion pale and sallow Both cheeks slightly red Dizziness Dry eyes Blurred [americandragon.com]
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. [my.clevelandclinic.org]
Symptoms Blurred vision Abnormal side vision Abnormal color vision Decreased brightness in one eye relative to the other The symptoms described above may not necessarily mean that you have optic atrophy. [umkelloggeye.org]
- Photophobia
An individual with photophobia may benefit from specialized sunglasses (amber-tinted lenses), use of a brimmed hat while outdoors as well as shutting blinds while indoors if glare is present. [familyconnect.org]
Danish Retinablødning, synsforstyrrelser (ikke yderligere specificeret), sløret syn, fotofobi, chromatopsia, cyanopsia, øjenirritation, blodsprængte øjne / røde øjne English Retinal haemorrhage, visual disturbance NOS, blurred vision, photophobia, chromatopsia [mymemory.translated.net]
Specific symptoms include blurred vision, acuity, impaired color vision, photophobia, headaches and vertigo. [symptoma.com]
[…] have reported that using text stretching to increase the spacing between letters and words can 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 [slideshare.net]
- Visual Acuity Decreased
Answer and interpretation Visual acuity — decreased Colour vision — decreased Visual fields — patchy defects may be present, often arcuate or central Pupils — a Marcus-Gunn pupil (a relative afferent pupilary defect or RAPD) may be present. [lifeinthefastlane.com]
acuity Moderate visual impairment 0030515 Morning glory anomaly 0025514 Ophthalmoplegia Eye muscle paralysis 0000602 Sensorimotor neuropathy Nerve damage causing decreased feeling and movement 0007141 Sensorineural hearing impairment 0000407 Temporal [rarediseases.info.nih.gov]
Patient V.1, a female born in 1967, first had a decrease in visual acuity at the age of 12. At age 18, visual acuity was 4/10 in each eye. [jmg.bmj.com]
Neurologic
- Papilledema
Outer retinal changes were present in 20 of 151 glaucoma eyes (13.2%) (12 prior intraocular surgery, 5 uveitis, 3 primary retinopathy) and 6 of 76 nonglaucomatous optic atrophy eyes (7.9%) (1 retinal vasculitis, 3 papilledema, 2 infiltrative optic neuropathy [ncbi.nlm.nih.gov]
Optical coherence tomography (OCT) can be used to establish and monitor retinal nerve fiber layer (RNFL) thickness, but can be confounding in cases of optic atrophy due to papilledema, where RNFL thinning may mimic resolution of papilledema. [morancore.utah.edu]
These factors include increased pressure on the optic nerve, glaucoma, papilledema, inflammation (eg. [symptoma.com]
Optic atrophy following papilledema (secondary). [emedicine.medscape.com]
- Stroke
Repeat neuroimaging demonstrated reversibility of the findings in 1 sibling and persistent metabolic stroke in the other. [ncbi.nlm.nih.gov]
Stroke of the optic nerve, known as anterior ischemic optic neuropathy. A tumor that is pressing on the optic nerve. Optic neuritis, an inflammation (swelling) of the optic nerve caused by multiple sclerosis. [my.clevelandclinic.org]
Causes of ONA include heredity, trauma (including stroke), a tumor, decrease in oxygen or blood supply, infections, or disorders. [familyconnect.org]
- Headache
Figure 1: Funduscopy in a 36-year-old man with headaches and loss of vision. (A) Edema of the optic disk (arrows) in the chronic phase (“champagne cork”) is visible in the right fundus, with venous tortuosity and dilatation (arrowheads). [cmaj.ca]
2, LIV-3, LIV-4, LIV-5, LIV-13, LIV-14, PC-6, SJ-6, SP-6, UB-18 Clinical Manifestations Commonly seen in children Both eyes affected Deviation of the eyes and mouth enlarged pupils Anxiety Rigidity Dizziness and vertigo to the point of falling over Headache [americandragon.com]
Nausea, vomiting, headaches, emotional lability and impaired memory Foster Kennedy syndrome is a condition associated with clinical triad of optic atrophy in one eye, papilledema in the contralateral eye, and anosmia. [medicaljoyworks.com]
Migraine headache Migraine headaches [ more ] 0002076 Myalgia Muscle ache Muscle pain [ more ] 0003326 Nystagmus Involuntary, rapid, rhythmic eye movements 0000639 Pes cavus High-arched foot 0001761 Progressive external ophthalmoplegia 0000590 Proximal [rarediseases.info.nih.gov]
- Intracranial Hemorrhage
hemorrhage leads to optic nerve compression or hydrocephalus-related ONA) Iatrogenic (e.g., surgical) Infectious causes of optic atrophy Syphilis, Lyme disease, tuberculosis (TB) Postmeningitis (e.g., viral, bacterial, fungal, cryptococcal) Postintraocular [unboundmedicine.com]
Of these 133 patients, 20 (15%) had preterm delivery, 94 (71%) had history of delayed developmental milestones with one or more episodes of seizures, 7 (5%) had microcephaly, 2 (2%) had a history of intracranial hemorrhage, 1 (1%) underwent laser therapy [ijo.in]
Workup
Optic atrophy can be diagnosed using imaging studies and functional tests specific for the etiology of disease. In patients with orbital tumors ultrasonography should be used. Patients who are affected with papilledema that is causing optic atrophy should be imaged using an optical ultrasound which can be utilized to identify dilatation of the sheath. Optic atrophy caused by a fracture should be imaged using computed tomography without contrast. Patients with optic atrophy caused by multiple sclerosis will have hyperechoic areas which should be imaged using magnetic resonance imaging with gadolinium followed by fluid attenuated inversion recovery [9]. Functional optic nerve tests to determine optic atrophy include visual acuity test (eg. Snellen test), color vision tests (eg. Farnswoth-Munsell tests, Pseudoisochromatic tests, Holmgren wool tests and lantern tests), sensitivity to contrast tests (eg. Arden grantings test, Cambridge low contrast grating tests and Pelli-Robson contrast sensitivity tests), pupillary tests to detect a relative afferent pupillary defect along with other tests to determine the presence and severity of optic nerve damage.
Treatment
There are no standard treatments that can cure optic atrophy to restore lost vision. However, timely diagnosis and treatment may prevent the progression of optic atrophy and save vision that is yet to be lost. Both ischemic optic neuropathy and optic neuritis are shown to benefit from steroid administration intravenously. Recent studies have indicated that idebenone, which has minimal side effects, is effective in preventing the progression of Leber's hereditary optic neuropathy in patients with visual acuities due to its effects on ATP synthesis and free radicals [10]. Traditionally, it was thought that optic nerves have no regenerative capacity. However, recent studies in animals have demonstrated that regeneration and retina remapping are possible and factors are now being identified that can improve and speed up this process [11] [12]. Furthermore, stem cell therapies for neuropathies are showing great promise and it may one day be possible to deliver stem cells that can regenerate the optic nerve to cure patients with optic atrophy.
Prognosis
If serious direct destruction of the optic nerve has occurred, due to trauma, the resulting blindness is often irreversible. Similarly, optic nerve atrophy caused by toxins, degenerative or vascular disease may also be irreversible. On the other hand, if optic atrophy occurs secondary to pressure caused by a tumor improvement of sight to normal is likely. Severity of the inherited form of optic atrophy varies widely and greatly depends on the underlying mutation as well as other known and unknown environmental factors. There is no cure for optic atrophy, although physicians may be able to prevent further nerve damage by removing the cause of degeneration which may allow patients to preserve adequate vision and in some cases return to normal vision.
Etiology
The most common causes of optic atrophy are genomic mutations. Dysfunctional mitochondria, resulting from genomic abnormalities, lead to an inability of nerve cells in the retina to fight off oxidative stress caused by the free radicals produced when light enters the retina [3]. This amplified oxidative stress leads to injury and death of nerve cells.
Aside from genomic abnormalities, optic atrophy may be caused by a number of environmentally acquired factors. These factors include increased pressure on the optic nerve, glaucoma, papilledema, inflammation (eg. Graves disease and Sarcoidosis), direct and indirect trauma, infections (eg. syphilis, tuberculosis and meningitis), hypoperfusion of the optic nerve, drugs (eg. chloroquine, amiodarone, ethambutol, isotretinoin, vincristine, linezolid, oral contraceptive pills, streptomycin and PDE-5 inhibitors), vitamin deficiency, toxins (eg. heavy metals, cyanide, alcohols and tobacco) and oxygen deficiency during pregnancy and labor (congenital).
Epidemiology
Of individuals who are blind, approximately 0.8-0.12% of the condition is caused by optic atrophy and around 0.04% of individuals may attribute their partial blindness to optic atrophy [4] [5]. Since optic atrophy may be associated with or even caused by a plethora of other conditions, the morbidity rates are highly dependent on the cause of optic atrophy.
Pathophysiology
Optic atrophy affects the optic nerve, which is made up of over one million highly myelinated neurons that do not express regenerative capabilities like other peripheral nerves. There are four distinct regions of the optic nerve which include the intracranial, intracanalicular, intraorbital and intraocular parts. A healthy optic nerve internally reflects the light of an ophthalmoscope to the capillaries and back to the disk surface producing a pinkish-yellow color. Once damage occurs to the optic nerve the axons lose their reflective properties resulting in a pale color. Furthermore, in optic atrophy the Kestenbaum count (total quantity of optic disk capillaries) reduces from around 10 to fewer than 6, which may also contribute to the pale appearance upon examination of the optic disk.
Optic atrophy may be classified based on the origin and direction of degeneration. During anterograde degeneration, the origin of degeneration is the retina which progresses in the direction of the brain. In this type of optic atrophy the bigger axons degenerate faster than the smaller axons. Conversely, during retrograde degeneration, the origin of degeneration is the region of the axon closer to the brain which progresses in the direction of the eye. Finally, during trans-synaptic degeneration, which occurs in the womb or in infancy, the destruction of an optic neuron leads to the degeneration of another optic neuron on the opposite side of the synapse.
Another way to classify optic atrophy is through the cause of nerve damage. Optic nerve or pituitary tumors, trauma and multiple sclerosis may cause primary optic atrophy, which is characterized by ordered degeneration of nerves that does not result in changes to the structure of the optic nerve. Papilledema may cause secondary optic atrophy, which is characterized by obvious nerve degeneration leading to a buildup of glial tissue. Retinal artery occlusion, myopia and retinitis pigmentosa may cause consecutive optic atrophy, which is characterized by a pale waxy disk with shrunken arteries but no change in margins or physiologic cup. Glaucoma may cause glaucomatous optic atrophy, which is characterized by severe cupping of the optic disk. Vitamin deficiency, trauma and multiple sclerosis may cause temporal pallor. Disease classification is usually established through functional tests of the optic nerve.
The different types of inherited optic atrophy include ADOA, AROA, Behr optic atrophy and Leber optic atrophy [6] [7]. The mutation responsible for ADOA is found within the mitochondrial dynamin like GTPase (OPA1) gene located at position q29 on chromosome 3. A mutation in the OPA2 gene found on the X chromosome causes X-linked optic atrophy and AROA is caused by a mutation in the 3-methylglutaconic aciduria, type 3 (OPA3) gene found at location q13.32 on chromosome 19.
Prevention
The majority of factors that cause optic atrophy are unavoidable, however, there are some things that can be done to prevent this disease. Since high blood pressure is one factor that promotes optic atrophy, patients should closely monitor and try to maintain a healthy blood pressure. Any practices that reduce the risk of face injuries, including seat belt usage while driving, will help to lower the chances of developing optic atrophy. Regular glaucoma exams are also recommended to prevent optic atrophy. Methanol, which is linked to optic nerve damage and present in some homemade alcohols, should be avoided.
Summary
Optic atrophy is a genetic disease that can be autosomal dominant or autosomal recessive. The autosomal dominant form of optic atrophy (ADOA) requires only one copy of the defective gene in order for a patient to be affected, whereas, the autosomal recessive form (AROA) requires both copies of the defective gene to be present [1]. Therefore, individuals carrying one copy of the AROA gene will not display symptoms. A maternally inherited form of optic atrophy known as Leber's hereditary optic neuropathy (LHON) primarily affects men and is leading to blindness from the ages of 20 to 30 years of age [2]. The etiology of LHON is not well established and is thought to be caused by a combination of genetic and environmental factors. Some patients with LHON may regain sight for unexplained reasons and LHON is linked to other neuropathies, such as Alzheimer disease, glaucoma and Parkinson's disease. Along with genetic factors, acquired factors include local inflammation, papilledema, increased local pressure (from a tumor, glaucoma or aneurysm), retinal disease, other neurological disorders, diabetes and hypoperfusion or injury of the optic nerve. Lifestyle choices including consuming high levels of alcohol and smoking are also associated with optic atrophy. Additionally, vitamin deficiency, specific blood pressure drugs and antibiotics have been shown to be linked to the development of optic atrophy.
Patient Information
Optic atrophy is degeneration of the optic nerve which causes impairment in vision (central, peripheral and color) and potentially blindness. The causes of optic atrophy include genetic, local and systemic factors that cause optic nerve damage such as inherited dominant or recessive gene mutations, injuries, infection, ischemia, tumors, poisons and hydrocephalus. This disease may begin at any age and is associated with symptoms that include blurry vision, impaired color and peripheral vision and decreased visual acuity. Diagnosis of optic atrophy can be achieved through eye exams, medical imaging procedures or nerve function tests. Patients with optic atrophy will display a pale white optic nerve instead of the classic pink appearance upon inspection with an ophthalmoscope. Other simple tests that can be done to verify optic atrophy include assessment of pupils, acuity, color vision and peripheral vision. In some cases, imaging studies, such as computed tomography and magnetic resonance imaging, are performed to verify location and extent of nerve damage. Currently, optic atrophy is an irreversible condition. Physicians will try to protect the optic nerve from further damage in order to prevent further impairment of vision. The type of treatment will depend on the cause of optic atrophy and aim at resolving the causative factors.
References
- Votruba M, Fitzke FW, Holder GE, et al. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch Ophthal. 1998; 116: 351-358.
- Yu-Wai-Man P, Griffiths PG, Hudson G, et al. Inherited mitochondrial optic neuropathies. J Med Genet. 2009; 46: 145-158.
- Cullom ME, Heher KL, Miller NR, et al. Leber's hereditary optic neuropathy masquerading as tobacco-alcohol amblyopia. Arch Ophthal. 1993; 111: 1482-1485.
- Tielsch JM, Javitt JC, Coleman A, et al. The prevalence of blindness and visual impairment among nursing home residents in Baltimore. N Engl J Med. 1995; 332(18):1205-9.
- Munoz B, West SK, Rubin GS, et al. Causes of blindness and visual impairment in a population of older Americans: The Salisbury Eye Evaluation Study. Arch Ophthalmol. 2000; 118(6):819-25.
- Lenaers G, Hamel CP, Delettre C, et al. Dominant optic atrophy. Orphanet J Rare Dis. 2012; 7(1):46.
- Nakaso K, Adachi Y, Fusayasu E, Doi K, et al. Leber's Hereditary Optic Neuropathy with Olivocerebellar Degeneration due to G11778A and T3394C Mutations in the Mitochondrial DNA. J Clin Neurol. 2012; 8(3):230-4.
- Votruba M, Fitzke FW, Holder GE, et al. T. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch Ophthal. 1998; 116: 351-358.
- Phillips PH, Vaphiades M, Glasier CM, et al. Chiasmal enlargement and optic nerve enhancement on magnetic resonance imaging in Leber hereditary optic neuropathy. Arch Ophthal. 2003; 121: 577-579.
- Klopstock T, Yu-Wai-Man P, Dimitriadis K, et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain. 2011; 134:2677-86.
- Keirstead SA, Rasminsky M, Fukuda Y, et al. Electrophysiologic responses in hamster superior colliculus evoked by regenerating retinal axons. Science. 1989; 246(4927):255-7.
- Fischer D, Heiduschka P, Thanos S. Lens-injury-stimulated axonal regeneration throughout the optic pathway of adult rats. Exp Neurol. 2001; 172(2):257-72.