393:
fatigue and a subacute loss of vision. On the fundus, an objective sign was noted: a wedge defect of the temporal optic disc and the loss of the corresponding
Papillomacular bundle. Most of the patients reported high consumption of alcohol particularly homemade rum and smoking cigarettes. This was associated with severe deficiencies of protein and vitamin intake, in particular of vitamin B12 and folate. This picture of vitamin deficiencies was exacerbated by low levels of methanol present in homemade rum. It was thought that the Cuban epidemic may have been caused by the chronic accumulation of formate from methanol metabolism in a population with severe folic acid depletion and the accumulation of cyanide from cigarette smoke. This conclusion was supported by evidence of improvement in visual acuity on prompt and daily administration of cyanocobalamin (3 mg) and folate (250 mg) along with dietary supplementation.
78:
light. One would not expect to find an afferent pupillary defect because optic neuropathies are often bilateral and symmetric. The optic disc may appear mildly hyperemic with small splinter hemorrhages on or around the disc, or may appear nearly normal. Optic atrophy typically develops later and may appear mild. In later stages the optic atrophy can become severe, which indicates less opportunity for recovery.
589:
dysfunction, the patients history, examination, and radiological studies must be examined in order to determine the specific genetic tests required. For example, 90% of cases of Leber's
Hereditary Optic Neuropathy (LHON) are associated with three common mtDNA point mutations (m.3460G>A/MT-ND1, m.11778G>A/MT-ND4, m.14484T>C/MT-ND6) while a wider range of mtDNA mutations (MT-ND1, MT-ND5, MT-ND6;
605:, the most important course is to remove the offending agent if possible and to replace the missing nutritional elements, orally, intramuscularly, or intravenously. If treatment is delayed, the injury may be irreversible. The course of treatment varies with the congenital forms of these neuropathies. There are some drug treatments that have shown modest success, such as
1559:
Campuzano, V.; Montermini, L.; Molto, M. D.; Pianese, L.; Cossee, M.; Cavalcanti, F.; Monros, E.; Rodius, F.; Duclos, F.; Monticelli, A.; Zara, F.; Canizares, J.; Koutnikova, H.; Bidichandani, S. I.; Gellera, C.; Brice, A.; Trouillas, P.; De
Michele, G.; Filla, A.; De Frutos, R.; Palau, F.; Patel, P.
511:
As our understanding of mitochondrial diseases improves a degree of similarity and overlap are seen within this group of disorders. For example, in some OPA1 carriers, patients will develop neurological features indistinguishable from HSP while others develop a pattern of peripheral neuropathy with a
81:
The duration of onset can vary between immediate and insidious, owing to the specific etiology. Two key features may be helpful in distinguishing acquired from inherited optic neuropathies: absence of a family history and simultaneous involvement of both eyes; the former more commonly characterized
77:
The generalized, common presentation for this broad and inclusive group of diseases is painless, bilateral loss of visual acuity and pallor of the optic disc accompanied with varying degrees of dyschromatopsia and central/cecocentral scatomas. On examination the pupillary responses may be sluggish to
474:
HSP is marked by slowly progressive lower limb spasticity and weakness. HSP can be classified into pure and complicated forms, depending on whether additional clinical features are present besides spastic paraplegia, such as optic atrophy, ataxia, peripheral neuropathy, extrapyramidal deficits, and
247:
There is documentation of nutritional optic neuropathy among undernourished Allied prisoners of war of the
Japanese during World War II. After four months of food deprivation, some of the prisoners developed sub-acute vision loss in both eyes in addition to experiencing pain in their extremities and
208:
Months of depletion are usually necessary to deplete body stores of most nutrients and a nutritional optic neuropathy may be present in a patient with or without obvious evidence of under-nutrition. An individual suffering from starvation could be easily recognized as a person who is undernourished
489:
FA is an autosomal recessive disorder caused by pathological GAA trinucleotide repeat expansions in the FXN gene. The encoded protein frataxin is directed to the mitochondrial inner membrane and is involved in the assembly of iron-sulphur cluster, which are a critical component of the mitochondrial
459:
This disease is a heterogenous group of inherited neuropathies, stemming from a MFN2 mutation, in which both motor and sensory nerves are affected, resulting in distal limb weakness, sensory loss, decreased deep tendon reflexes, and foot deformities. Affected individuals develop progressive optic
383:
TAA is an old term for a constellation of elements that can lead to a mitochondrial optic neuropathy. The classic patient is a man with a history of heavy alcohol and tobacco consumption. Respectively, this combines nutritional mitochondrial impairment, from vitamin deficiencies (folate and B-12)
580:
A thorough history is essential and should cover family history, diet; drug/toxin exposure social history, including tobacco and alcohol use; and occupational background, with details on whether similar cases exist among coworkers. Treatment of any chronic disease such as pernicious anemia should
502:
Includes
Mitochondrial Encephalitis Lactic Acidosis Seizures (MELAS), myoclonic epilepsy and ragged red fibers (MERRF), maternally inherited Leigh syndrome (MILS), and mitochondrial neurograstrointestinal encephalomyopathy (MNGIE), all of which can all develop optic neuropathies, although it is
149:
optic neuropathy. Patients may notice that colors are not as vivid or bright as before and that the color red is washed out. This normally occurs in both eyes at the same time and is not associated with any eye pain. They might initially notice a blur or fog, followed by a drop in vision. While
392:
Between 1992 and 1993, in the Cuban
Epidemic of Optic Neuropathy, nearly 50,000 people in Cuba were affected with optic neuropathy, sensory and autonomic peripheral neuropathy, neural deafness, and in a few cases, myelopathy. The most common pattern of symptoms consisted of severe weight loss,
415:
LHON, as the name suggests, is an inherited mutation that results in acute or subacute vision loss, displays incomplete penetrance and predominantly affects young males. Onset is usually between the 2nd and 4th decade of life, and usually presents with rapid vision loss in one eye followed by
588:
When the details of the examination and history indicate a familial history of similar ocular or systemic disease, whether or not there is evidence of toxic or nutritional causes for disease, certain genetic tests may be required. Because there are several congenital causes of mitochondrial
430:
DOA is an autosomal dominant disease caused by a defect in the nuclear gene OPA1. A slowly progressive optic neuropathy, usually presents in the first decade of life and is bilaterally symmetrical. Examination of these patients shows loss of visual acuity, temporal pallor of the optic discs,
493:
In a recent study of 26 patients with confirmed FA, all patients had evidence of optic nerve dysfunction, although only five were visually symptomatic. The optic neuropathy differed from that of LHON or DOA, displaying a pattern of retinal nerve fiber layer (RNFL) loss and no preferential
1970:
Newman, Nancy J.; Biousse, Valerie; David, Robert; Bhatti, M. Tariq; Hamilton, Steven R.; Farris, Bradley K.; Lesser, Robert L.; Newman, Steven A.; Turbin, Roger E.; Chen, Kuankuan; Keaney, Robert P. (2005). "Prophylaxis for Second Eye
Involvement in Leber Hereditary Optic Neuropathy: An
567:
relevance for optic neuropathies with primary or secondary involvement of mitochondria. Genetic mutations, toxic insult, and nutritional depletion can all have a negative impact on the structure and function of mitochondria within the optic system, resulting in this type of
584:
In most cases of nutritional/toxic optic neuropathy, the diagnosis may be obtained via detailed medical history and eye examination. Additionally, supplementary neurological imaging studies, such as MRI or enhanced CT, may be performed if the cause remains unclear.
256:
Toxic optic neuropathy refers to the ingestion of a toxin or an adverse drug reaction that results in vision loss from optic nerve damage. Patients may report either a sudden loss of vision in both eyes, in the setting of an acute intoxication, or an insidious
656:. We will refer to this as Toxic/Nutritional Optic Neuropathy, whereby nutritional deficiencies and toxic/metabolic insults are the simultaneous culprits of visual loss associated with damage and disruption of the RGC and optic nerve mitochondria.
384:
classically seen in alcoholics, with tobacco-derived products, such as cyanide and ROS. It has been suggested that the additive effect of the cyanide toxicity, ROS, and deficiencies of thiamine, riboflavin, pyridoxine, and b12 result in TAA.
416:
involvement of the second eye (usually within months). Visual acuity often remains stable and poor (below 20/200) with a residual central visual field defect. Patients with the m.14484/ND6 mutation are most likely to have visual recovery.
132:
between genetic and acquired mitochondrial optic neuropathies has been suggested and there are only a few case reports to support this phenomenon, requiring further research and demonstration of evidence to corroborate these findings
2042:
Yu-Wai-Man, Patrick; Griffiths, Philip G.; Burke, Ailbhe; Sellar, Peter W.; Clarke, Michael P.; Gnanaraj, Lawrence; Ah-Kine, Desiree; Hudson, Gavin; Czermin, Birgit; Taylor, Robert W.; Horvath, Rita; Chinnery, Patrick F. (2010).
244:(ROS). ROS are a natural bi-product of the mitochondrial production of ATP. As such, if they are allowed to accumulate without being neutralized, they could damage the very mitochondria from which they are being produced.
1746:
Gronlund, M A; Honarvar, A K S.; Andersson, S; Moslemi, A R; Oldfors, A; Holme, E; Tulinius, M; Darin, N (2010). "Ophthalmological findings in children and young adults with genetically verified mitochondrial disease".
2006:
Schaefer, Andrew M.; McFarland, Robert; Blakely, Emma L.; He, Langping; Whittaker, Roger G.; Taylor, Robert W.; Chinnery, Patrick F.; Turnbull, Douglass M. (2008). "Prevalence of mitochondrial DNA disease in adults".
109:
and then transported into the mitochondria. So it follows that, while an mtDNA point mutation are inherited through the mother, defects in nuclear DNA, even those affecting the mitochondria, will be transmitted in
1790:
Carelli, Valerio; La Morgia, Chiara; Valentino, Maria Lucia; Barboni, Piero; Ross-Cisneros, Fred N.; Sadun, Alfredo A. (2009). "Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders".
1378:
Sadun, Alfredo A.; Martone, James F.; Muci-Mendoza, Rafael; Reyes, Lillian; DuBois, Lindreth; Silva, Juan Carlos; Roman, Gustavo; Caballero, Benjamin (1994). "Epidemic Optic
Neuropathy in Cuba".
150:
vision loss may be rapid, progression to blindness is unusual. These patients tend to have blind spots in the center of their vision with preserved peripheral vision. In most cases, the
1560:
I.; Di Donato, S.; Mandel, J.-L.; Cocozza, S.; Koenig, M.; Pandolfo, M. (1996). "Friedreich's Ataxia: Autosomal
Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion".
401:
The inherited optic neuropathies typically manifest as symmetric bilateral central visual loss. Optic nerve damage in most inherited optic neuropathies is permanent and progressive.
1167:
Cullom, Mary Ellen; Heher, Katrinka L.; Miller, Neil R.; Savino, Peter J.; Johns, Donald R. (1993). "Leber's
Hereditary Optic Neuropathy Masquerading as Tobacco-Alcohol Amblyopia".
934:
Bloomberg, Richard D.; Fleishman, Amy; Nalle, Jennifer E.; Herron, Daniel M.; Kini, Subhash (2005). "Nutritional Deficiencies following Bariatric Surgery: What Have We Learned?".
370:
supply or metabolism. It remains unknown as to why certain agents are toxic to the optic nerve while others are not and why particularly the papillomacular bundle gets affected.
1705:
Fortuna, F.; Barboni, P.; Liguori, R.; Valentino, M. L.; Savini, G.; Gellera, C.; Mariotti, C.; Rizzo, G.; Tonon, C.; Manners, D.; Lodi, R.; Sadun, A. A; Carelli, V. (2009).
547:, and distributed where they are needed. Efficient transportation of mitochondria depends on multiple factors, including their own energy production, the integrity of the
366:
can cause optic neuropathy, which is likely through buildup of toxic substances within the body. In most cases, the cause of the toxic neuropathy impairs the tissue's
652:) insult. It is worth mentioning that under-nutrition and toxic insult can occur simultaneously, so a third category may be understood as having a combined or mixed
90:
Because this grouping of diseases is of heterogenic origin, the causes can be singular or additive consequences of genetic, toxic, or nutritional stress.
141:
Nutritional deficiency may be the cause of a genuine optic neuropathy, sometimes associated with involvement of the peripheral nervous system, called
125:
medications, exposure to certain toxic chemicals, and situations that contribute to poor consumption or decreased absorption of nutrient-dense foods.
1202:
Román, GC (1994). "An epidemic in Cuba of optic neuropathy, sensorineural deafness, peripheral sensory neuropathy and dorsolateral myeloneuropathy".
157:
Again, the pathophysiological mechanisms involved in nutritional optic neuropathies is common to all mitochondrial optic neuropathies: it affects
735:
145:. Loss of vision is usually bilateral, painless, chronic, insidious and slowly progressive. Most often, they present as a non-specific
248:
hearing loss. Their visual loss did not correlate well with malnutrition and that not all prisoners experienced the loss of vision.
1829:
Carelli, Valerio; Ross-Cisneros, Fred N.; Sadun, Alfredo A. (2004). "Mitochondrial dysfunction as a cause of optic neuropathies".
1335:
Sadun, Alfredo A.; Martone, James F. (1994). "Cuba: response of medical science to a crisis of optic and peripheral neuropathy".
602:
410:
225:
and vitamin B12 deficiency can be seen amongst individuals who obtain adequate caloric input from foods low in nutritional and
1093:
636:
Of the acquired category, disease falls into further etiological distinction as arising from toxic (drugs or chemicals) or
1078:
454:
261:
loss of vision from an adverse drug reaction. The most important aspect of treatment is recognition and drug withdrawal.
977:
Briani, Chiara; Torre, Chiara; Citton, Valentina; Manara, Renzo; Pompanin, Sara; Binotto, Gianni; Adami, Fausto (2013).
1030:"Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space"
609:
used to treat LOHN. Often treatment is relegated to lifestyle alterations and accommodations and supportive measures.
117:
Optic neuropathies that are acquired can be the result of several processes. These include prolonged use of certain
512:
similar disease course to CMT, and still others will develop a prominent cerebellar syndrome consistent with FRDA.
1611:
Rouault, Tracey A.; Tong, Wing-Hang (2005). "Iron–sulphur cluster biogenesis and mitochondrial iron homeostasis".
445:
This is a rare autosomal recessive disorder characterized by early-onset optic atrophy, ataxia, and spasticity.
53:, or both. The three most common neuro-ophthalmic abnormalities seen in mitochondrial disorders are bilateral
1872:
Maresca, Alessandra; la Morgia, Chiara; Caporali, Leonardo; Valentino, Maria Lucia; Carelli, Valerio (2013).
754:
Pott, Jan Willem R.; Wong, Kwok H. (2006). "Leber's hereditary optic neuropathy and vitamin B12 deficiency".
520:
Even though dysfunction of the mitochondria can be either congenital or acquired, both causes share a common
469:
101:) is passed on from mother to child. Mitochondria, however, depend on other proteins that are encoded by
743:. 38th Annual NANOS Meeting. San Antonio, TX: North American Neuro-Ophthalmology Society. pp. 171–6.
617:
Those diseases understood as congenital in origin could either be specific to the ocular organ system (
425:
258:
49:
consisting of metabolic and/or structural damage as a consequence of genetic mutations, environmental
1415:"Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome"
525:
1145:
241:
633:). It is estimated that these inherited optic neuropathies in the aggregate affect 1 in 10,000
529:
484:
66:
1921:
Man, P.Y.W.; Griffiths, P.G.; Brown, D.T.; Howell, N.; Turnbull, D.M.; Chinnery, P.F. (2003).
2098:
142:
676:
Biousse, Valérie; Newman, Nancy J. (2001). "Neuro-ophthalmology of Mitochondrial Diseases".
601:
Treatment is dependent upon diagnosis and the stage at which the diagnosis is secured. For
1569:
797:
Rizzo, Joseph F. (1995). "Adenosine triphosphate deficiency: a genre of optic neuropathy".
22:
are a heterogenous group of disorders that present with visual disturbances resultant from
714:
8:
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1180:
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2044:
1898:
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Oostra, R J; Bolhuis, P A; Wijburg, F A; Zorn-Ende, G; Bleeker-Wagemakers, E M (1994).
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1005:
978:
959:
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884:
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822:
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645:
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593:) have been associated with overlapping phenotypes of LHON, MELAS, and Leigh syndrome.
186:
1947:
1922:
1529:
1109:
Kerrison, J (2004). "Optic neuropathies caused by toxins and adverse drug reactions".
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centrocecal scotomas with peripheral sparing, and subtle impairments in color vision.
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Metabolic disorders may also cause this version of disease. Systemic problems such as
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320:
2045:"The Prevalence and Natural History of Dominant Optic Atrophy Due to OPA1 Mutations"
1923:"The Epidemiology of Leber Hereditary Optic Neuropathy in the North East of England"
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685:
166:
54:
1581:
1516:
Harding, A.E. (1983). "Classification of the hereditary ataxias and paraplegias".
1469:"Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies"
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usually a secondary feature overshadowed by more prominent neurological features.
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1804:
622:
521:
363:
341:
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deficiency from poor absorption. The optic neuropathy associated with pernicious
62:
58:
1263:
1247:"Epidemic Optic Neuropathy in Cuba — Clinical Characterization and Risk Factors"
1246:
1045:
840:
Orssaud, C.; Roche, O.; Dufier, J.L. (2007). "Nutritional optic neuropathies".
359:
214:
174:
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1984:
1971:
Open-Labeled, Nonrandomized Multicenter Trial of Topical Brimonidine Purite".
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853:
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111:
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Mitochondria are maternally inherited, so a genetic defect in mitochondrial
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appearance. However, a not so obvious individual may be the recipient of a
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23:
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Yu-Wai-Man, Patrick; Griffiths, Philip G.; Chinnery, Patrick F. (2011).
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271:
202:
194:
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182:
2020:
995:
1874:"The optic nerve: A 'mito-window' on mitochondrial neurodegeneration"
1293:"Acquired mitochondrial impairment as a cause of optic nerve disease"
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30:
979:"Cobalamin Deficiency: Clinical Picture and Radiological Findings"
1871:
556:
552:
129:
1789:
1745:
1707:"Visual system involvement in patients with Friedreich's ataxia"
1088:(3rd ed.). Lippincott Williams & Wilkins. p. 451.
1558:
1086:
Walsh & Hoyt's Clinical Neuro-Ophthalmology: The Essentials
1077:
Miller, Neil R.; Subramanian, Prem; Patel, Vivek, eds. (2015).
540:
222:
198:
27:
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1704:
306:(taken for serious infections not helped by other antibiotics)
1412:
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933:
626:
404:
151:
98:
1654:
Stemmler, T. L.; Lesuisse, E.; Pain, D.; Dancis, A. (2010).
756:
Graefe's Archive for Clinical and Experimental Ophthalmology
373:
240:, substances critical to preventing the damaging effects of
1466:
618:
544:
310:
2005:
1653:
1146:"Toxic and Nutritional Optic Neuropothy: First, Undo Harm"
709:
707:
590:
1828:
1028:
Han, Derick; Williams, Everett; Cadenas, Enrique (2001).
563:
of the axons. Any dysfunction of these systems may be of
419:
264:
Among the many causes of TON, the top 10 toxins include:
94:
1969:
1920:
1166:
976:
704:
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within the mitochondria, which leads to a decrease of
463:
1297:
Transactions of the American Ophthalmological Society
387:
497:
448:
236:
Additionally, nutrient-poor diet may also be low in
1793:
Biochimica et Biophysica Acta (BBA) - Bioenergetics
1656:"Frataxin and Mitochondrial FeS Cluster Biogenesis"
1027:
839:
378:
1245:Cuba Neuropathy Field Investigation Team (1995).
737:Mitochondrial Optic Neuropathies: Toxic/Metabolic
251:
136:
2090:
396:
1824:
1822:
1462:
1460:
1458:
1286:
1284:
1282:
543:of the retinal ganglion cell, transported down
539:These mitochondria are made within the central
460:nerve dysfunction starting later in childhood.
45:. These disturbances are multifactorial, their
1330:
1328:
671:
669:
675:
1819:
1455:
1334:
1279:
882:
729:
727:
1610:
1325:
715:Toxic/Nutritional Optic Neuropathy~clinical
666:
478:
532:production and a simultaneous increase in
405:Leber's Hereditary Optic Neuropathy (LHON)
313:that fails to respond to other treatments)
2068:
1946:
1897:
1722:
1681:
1671:
1492:
1438:
1308:
1262:
1053:
1004:
994:
910:
900:
724:
506:
374:Combined Mitochondrial Optic Neuropathies
1108:
753:
603:toxic and nutritional optic neuropathies
1515:
1079:"Epidemic Nutritional Optic Neuropathy"
883:Sharma, Reena; Sharma, Pradeep (2011).
734:Sadun, Alfredo A. (February 13, 2012).
154:continue to respond normally to light.
2091:
1927:The American Journal of Human Genetics
1143:
1111:Ophthalmology Clinics of North America
494:involvement of papillomacular bundle.
420:Autosomal Dominant Optic Atrophy (DOA)
217:surgery, a procedure that may lead to
26:dysfunction within the anatomy of the
1613:Nature Reviews Molecular Cell Biology
1290:
1201:
796:
733:
72:
1831:Progress in Retinal and Eye Research
1473:Progress in Retinal and Eye Research
1392:10.1001/archopht.1994.01090170139037
1204:Journal of the Neurological Sciences
1181:10.1001/archopht.1993.01090110048021
842:Journal of the Neurological Sciences
165:energetic production, correction of
1878:Molecular and Cellular Neuroscience
464:Hereditary spastic paraplegia (HSP)
411:Leber's hereditary optic neuropathy
13:
515:
434:
388:Cuban Epidemic of Optic Neuropathy
14:
2110:
1973:American Journal of Ophthalmology
498:Mitochondrial encephalomyopathies
449:Charcot Marie Tooth disease (CMT)
1843:10.1016/j.preteyeres.2003.10.003
1749:British Journal of Ophthalmology
1485:10.1016/j.preteyeres.2010.11.002
20:Mitochondrial optic neuropathies
2035:
1999:
1963:
1914:
1865:
1783:
1739:
1698:
1660:Journal of Biological Chemistry
1647:
1604:
1552:
1509:
1406:
1371:
1251:New England Journal of Medicine
1238:
1195:
1160:
1137:
1102:
1070:
1021:
889:Indian Journal of Ophthalmology
612:
379:Tobacco Alcohol Ambylopia (TAA)
970:
927:
876:
833:
790:
747:
309:Isoretinoin (taken for severe
252:Toxic optic neuropathies (TON)
137:Nutritional optic neuropathies
1:
1582:10.1126/science.271.5254.1423
1530:10.1016/S0140-6736(83)92879-9
659:
490:respiratory chain complexes.
470:Hereditary spastic paraplegia
397:Hereditary Optic Neuropathies
338:, and some cleaning products)
2061:10.1016/j.ophtha.2009.12.038
1805:10.1016/j.bbabio.2009.02.024
1216:10.1016/0022-510x(94)90130-9
596:
575:
7:
1419:Journal of Medical Genetics
1337:International Ophthalmology
1264:10.1056/NEJM199511023331803
1144:Stuart, Annie (July 2014).
455:Charcot–Marie–Tooth disease
173:. Specific deficiencies of
10:
2115:
482:
467:
452:
438:
423:
408:
348:and hydraulic brake fluid)
197:, and other proteins with
1985:10.1016/j.ajo.2005.03.058
1890:10.1016/j.mcn.2012.08.004
1380:Archives of Ophthalmology
1169:Archives of Ophthalmology
1123:10.1016/j.ohc.2004.05.005
1046:10.1042/0264-6021:3530411
854:10.1016/j.jns.2007.06.038
768:10.1007/s00417-006-0269-7
526:oxidative phosphorylation
85:
16:Group of visual disorders
948:10.1381/0960892053268264
885:"Toxic optic neuropathy"
479:Friedreich's ataxia (FA)
286:(tuberculosis treatment)
2055:(8): 1538–46, 1546.e1.
1761:10.1136/bjo.2008.154187
1673:10.1074/jbc.R110.118679
902:10.4103/0301-4738.77035
591:http://www.mitomap.org/
426:Kjer's optic neuropathy
242:reactive oxygen species
209:due to their cachectic
82:by these two features.
581:always be elucidated.
559:, etc.), and adequate
507:Overlapping phenotypes
296:infections, including
67:pigmentary retinopathy
678:Seminars in Neurology
161:pathways involved in
143:peripheral neuropathy
105:, constructed in the
1724:10.1093/brain/awn269
1431:10.1136/jmg.31.4.280
690:10.1055/s-2001-17945
2009:Annals of Neurology
1574:1996Sci...271.1423C
1034:Biochemical Journal
811:10.1212/WNL.45.1.11
524:: an impairment of
485:Friedreich's ataxia
475:cognitive decline.
334:(component of some
1349:10.1007/BF00930318
1117:(3): 481–8, viii.
646:vitamin deficiency
631:multiple sclerosis
73:Signs and Symptoms
2021:10.1002/ana.21217
1291:Sadun, A (1998).
1095:978-1-4963-1873-2
996:10.3390/nu5114521
356:diabetes mellitus
321:immunosuppressant
205:may play a role.
169:and quenching of
2106:
2083:
2082:
2072:
2039:
2033:
2032:
2003:
1997:
1996:
1967:
1961:
1960:
1950:
1918:
1912:
1911:
1901:
1869:
1863:
1862:
1826:
1817:
1816:
1787:
1781:
1780:
1743:
1737:
1736:
1726:
1717:(Pt 1): 116–23.
1702:
1696:
1695:
1685:
1675:
1666:(35): 26737–43.
1651:
1645:
1644:
1608:
1602:
1601:
1568:(5254): 1423–7.
1556:
1550:
1549:
1524:(8334): 1151–5.
1513:
1507:
1506:
1496:
1464:
1453:
1452:
1442:
1410:
1404:
1403:
1375:
1369:
1368:
1332:
1323:
1322:
1312:
1288:
1277:
1276:
1266:
1242:
1236:
1235:
1199:
1193:
1192:
1164:
1158:
1157:
1141:
1135:
1134:
1106:
1100:
1099:
1083:
1074:
1068:
1067:
1057:
1025:
1019:
1018:
1008:
998:
974:
968:
967:
931:
925:
924:
914:
904:
880:
874:
873:
837:
831:
830:
794:
788:
787:
751:
745:
744:
742:
731:
722:
711:
702:
701:
673:
625:) or syndromic (
167:oxidative stress
55:optic neuropathy
2114:
2113:
2109:
2108:
2107:
2105:
2104:
2103:
2089:
2088:
2087:
2086:
2040:
2036:
2004:
2000:
1968:
1964:
1919:
1915:
1870:
1866:
1827:
1820:
1788:
1784:
1744:
1740:
1703:
1699:
1652:
1648:
1625:10.1038/nrm1620
1609:
1605:
1557:
1553:
1514:
1510:
1465:
1456:
1411:
1407:
1376:
1372:
1333:
1326:
1289:
1280:
1257:(18): 1176–82.
1243:
1239:
1200:
1196:
1165:
1161:
1142:
1138:
1107:
1103:
1096:
1081:
1075:
1071:
1040:(Pt 2): 411–6.
1026:
1022:
989:(11): 4521–39.
975:
971:
936:Obesity Surgery
932:
928:
881:
877:
848:(1–2): 158–64.
838:
834:
795:
791:
752:
748:
740:
732:
725:
712:
705:
674:
667:
662:
615:
599:
578:
522:pathophysiology
518:
516:Pathophysiology
509:
500:
487:
481:
472:
466:
457:
451:
443:
437:
435:Behr’s syndrome
428:
422:
413:
407:
399:
390:
381:
376:
364:thyroid disease
342:Ethylene glycol
304:Chloramphenicol
254:
139:
88:
75:
59:ophthalmoplegia
17:
12:
11:
5:
2112:
2102:
2101:
2085:
2084:
2034:
1998:
1962:
1939:10.1086/346066
1913:
1884:(100): 62–76.
1864:
1818:
1782:
1738:
1697:
1646:
1603:
1551:
1508:
1454:
1405:
1370:
1324:
1278:
1237:
1194:
1175:(11): 1482–5.
1159:
1136:
1101:
1094:
1069:
1020:
969:
926:
875:
832:
789:
762:(10): 1357–9.
746:
723:
703:
664:
663:
661:
658:
614:
611:
598:
595:
577:
574:
517:
514:
508:
505:
499:
496:
483:Main article:
480:
477:
468:Main article:
465:
462:
453:Main article:
450:
447:
439:Main article:
436:
433:
424:Main article:
421:
418:
409:Main article:
406:
403:
398:
395:
389:
386:
380:
377:
375:
372:
360:kidney failure
352:
351:
350:
349:
339:
326:
325:
324:
314:
307:
301:
287:
253:
250:
215:gastric bypass
175:cyanocobalamin
138:
135:
87:
84:
74:
71:
15:
9:
6:
4:
3:
2:
2111:
2100:
2097:
2096:
2094:
2080:
2076:
2071:
2066:
2062:
2058:
2054:
2050:
2049:Ophthalmology
2046:
2038:
2030:
2026:
2022:
2018:
2014:
2010:
2002:
1994:
1990:
1986:
1982:
1979:(3): 407–15.
1978:
1974:
1966:
1958:
1954:
1949:
1944:
1940:
1936:
1932:
1928:
1924:
1917:
1909:
1905:
1900:
1895:
1891:
1887:
1883:
1879:
1875:
1868:
1860:
1856:
1852:
1848:
1844:
1840:
1836:
1832:
1825:
1823:
1814:
1810:
1806:
1802:
1799:(5): 518–28.
1798:
1794:
1786:
1778:
1774:
1770:
1766:
1762:
1758:
1754:
1750:
1742:
1734:
1730:
1725:
1720:
1716:
1712:
1708:
1701:
1693:
1689:
1684:
1679:
1674:
1669:
1665:
1661:
1657:
1650:
1642:
1638:
1634:
1630:
1626:
1622:
1619:(4): 345–51.
1618:
1614:
1607:
1599:
1595:
1591:
1587:
1583:
1579:
1575:
1571:
1567:
1563:
1555:
1547:
1543:
1539:
1535:
1531:
1527:
1523:
1519:
1512:
1504:
1500:
1495:
1490:
1486:
1482:
1479:(2): 81–114.
1478:
1474:
1470:
1463:
1461:
1459:
1450:
1446:
1441:
1436:
1432:
1428:
1424:
1420:
1416:
1409:
1401:
1397:
1393:
1389:
1385:
1381:
1374:
1366:
1362:
1358:
1354:
1350:
1346:
1342:
1338:
1331:
1329:
1320:
1316:
1311:
1306:
1302:
1298:
1294:
1287:
1285:
1283:
1274:
1270:
1265:
1260:
1256:
1252:
1248:
1241:
1233:
1229:
1225:
1221:
1217:
1213:
1209:
1205:
1198:
1190:
1186:
1182:
1178:
1174:
1170:
1163:
1155:
1151:
1147:
1140:
1132:
1128:
1124:
1120:
1116:
1112:
1105:
1097:
1091:
1087:
1080:
1073:
1065:
1061:
1056:
1051:
1047:
1043:
1039:
1035:
1031:
1024:
1016:
1012:
1007:
1002:
997:
992:
988:
984:
980:
973:
965:
961:
957:
953:
949:
945:
942:(2): 145–54.
941:
937:
930:
922:
918:
913:
908:
903:
898:
895:(2): 137–41.
894:
890:
886:
879:
871:
867:
863:
859:
855:
851:
847:
843:
836:
828:
824:
820:
816:
812:
808:
804:
800:
793:
785:
781:
777:
773:
769:
765:
761:
757:
750:
739:
738:
730:
728:
721:
717:
716:
710:
708:
699:
695:
691:
687:
684:(3): 275–91.
683:
679:
672:
670:
665:
657:
655:
651:
647:
643:
639:
634:
632:
628:
624:
620:
610:
608:
604:
594:
592:
586:
582:
573:
571:
566:
562:
558:
554:
550:
546:
542:
537:
535:
531:
527:
523:
513:
504:
495:
491:
486:
476:
471:
461:
456:
446:
442:
441:Behr syndrome
432:
427:
417:
412:
402:
394:
385:
371:
369:
365:
361:
357:
347:
343:
340:
337:
333:
330:
329:
328:Acute Toxins
327:
322:
319:(widely used
318:
315:
312:
308:
305:
302:
299:
295:
291:
288:
285:
281:
277:
273:
270:
269:
267:
266:
265:
262:
260:
249:
245:
243:
239:
238:anti-oxidants
234:
232:
229:density (see
228:
227:micronutrient
224:
220:
216:
212:
206:
204:
200:
196:
192:
188:
184:
180:
176:
172:
171:free radicals
168:
164:
160:
155:
153:
148:
144:
134:
131:
126:
124:
120:
115:
113:
108:
104:
103:nuclear genes
100:
96:
91:
83:
79:
70:
68:
64:
60:
56:
52:
48:
44:
40:
36:
33:Cells (RGC),
32:
29:
25:
24:mitochondrial
21:
2099:Eye diseases
2052:
2048:
2037:
2012:
2008:
2001:
1976:
1972:
1965:
1933:(2): 333–9.
1930:
1926:
1916:
1881:
1877:
1867:
1837:(1): 53–89.
1834:
1830:
1796:
1792:
1785:
1755:(1): 121–7.
1752:
1748:
1741:
1714:
1710:
1700:
1663:
1659:
1649:
1616:
1612:
1606:
1565:
1561:
1554:
1521:
1517:
1511:
1476:
1472:
1425:(4): 280–6.
1422:
1418:
1408:
1386:(5): 691–9.
1383:
1379:
1373:
1343:(6): 373–8.
1340:
1336:
1300:
1296:
1254:
1250:
1240:
1210:(1): 11–28.
1207:
1203:
1197:
1172:
1168:
1162:
1153:
1149:
1139:
1114:
1110:
1104:
1085:
1072:
1037:
1033:
1023:
986:
982:
972:
939:
935:
929:
892:
888:
878:
845:
841:
835:
802:
798:
792:
759:
755:
749:
736:
713:
681:
677:
635:
616:
613:Epidemiology
600:
587:
583:
579:
565:pathological
555:components (
549:cytoskeleton
538:
519:
510:
501:
492:
488:
473:
458:
444:
429:
414:
400:
391:
382:
353:
344:(present in
284:streptomycin
268:Medications
263:
255:
246:
235:
207:
201:-containing
156:
140:
127:
123:tuberculosis
116:
92:
89:
80:
76:
39:optic chiasm
19:
18:
2015:(1): 35–9.
1303:: 881–923.
1156:(7): 37–42.
805:(1): 11–6.
638:nutritional
561:myelination
346:anti-freeze
317:Ciclosporin
292:(taken for
231:Food desert
219:vitamin B12
203:amino acids
159:biochemical
147:retrobulbar
128:A possible
119:antibiotics
43:optic tract
35:optic nerve
660:References
570:neuropathy
272:Ethambutol
259:asymmetric
195:folic acid
191:pyridoxine
183:riboflavin
983:Nutrients
799:Neurology
720:eMedicine
642:metabolic
607:Idebenone
597:Treatment
576:Diagnosis
336:moonshine
298:pneumonia
294:bacterial
290:Linezolid
280:isoniazid
130:synergism
114:fashion.
112:Mendelian
107:cytoplasm
51:stressors
47:aetiology
2093:Category
2079:20417570
2029:17886296
1993:16083844
1957:12518276
1908:22960139
1859:15862778
1851:14766317
1813:19268652
1769:20385529
1733:18931386
1692:20522547
1641:26934988
1633:15803140
1598:20303793
1503:21112411
1365:11575498
1319:10360310
1232:34940462
1131:15337202
1064:11139407
1015:24248213
956:15802055
921:21350283
870:40934548
862:17707410
827:24524494
784:22682385
776:16523300
698:11641818
654:etiology
650:diabetes
551:and its
368:vascular
332:Methanol
276:rifampin
211:corporal
179:thiamine
121:or anti-
31:Ganglion
2070:4040407
1899:3629569
1777:9342345
1683:2930671
1590:8596916
1570:Bibcode
1562:Science
1546:6780732
1538:6133167
1494:3081075
1449:8071952
1440:1049799
1400:8185530
1357:7642340
1310:1298416
1273:7565972
1224:7699385
1189:8240101
1055:1221585
1006:3847746
964:1310334
912:3116542
819:7824099
557:tubulin
553:protein
28:Retinal
2077:
2067:
2027:
1991:
1955:
1948:379226
1945:
1906:
1896:
1857:
1849:
1811:
1775:
1767:
1731:
1690:
1680:
1639:
1631:
1596:
1588:
1544:
1536:
1518:Lancet
1501:
1491:
1447:
1437:
1398:
1363:
1355:
1317:
1307:
1271:
1230:
1222:
1187:
1150:EyeNet
1129:
1092:
1062:
1052:
1013:
1003:
962:
954:
919:
909:
868:
860:
825:
817:
782:
774:
696:
541:somata
362:, and
223:anemia
199:sulfur
189:, and
187:niacin
152:pupils
86:Causes
65:, and
63:ptosis
41:, and
1855:S2CID
1773:S2CID
1711:Brain
1637:S2CID
1594:S2CID
1542:S2CID
1361:S2CID
1228:S2CID
1082:(PDF)
960:S2CID
866:S2CID
823:S2CID
780:S2CID
741:(PDF)
627:MELAS
545:axons
99:mtDNA
61:with
2075:PMID
2025:PMID
1989:PMID
1953:PMID
1904:PMID
1847:PMID
1809:PMID
1797:1787
1765:PMID
1729:PMID
1688:PMID
1629:PMID
1586:PMID
1534:PMID
1499:PMID
1445:PMID
1396:PMID
1353:PMID
1315:PMID
1269:PMID
1220:PMID
1185:PMID
1127:PMID
1090:ISBN
1060:PMID
1011:PMID
952:PMID
917:PMID
858:PMID
815:PMID
772:PMID
694:PMID
619:LHON
311:acne
163:cell
2065:PMC
2057:doi
2053:117
2017:doi
1981:doi
1977:140
1943:PMC
1935:doi
1894:PMC
1886:doi
1839:doi
1801:doi
1757:doi
1719:doi
1715:132
1678:PMC
1668:doi
1664:285
1621:doi
1578:doi
1566:271
1526:doi
1489:PMC
1481:doi
1435:PMC
1427:doi
1388:doi
1384:112
1345:doi
1305:PMC
1259:doi
1255:333
1212:doi
1208:127
1177:doi
1173:111
1119:doi
1050:PMC
1042:doi
1038:353
1001:PMC
991:doi
944:doi
907:PMC
897:doi
850:doi
846:262
807:doi
764:doi
760:244
718:at
686:doi
623:DOA
534:ROS
530:ATP
233:).
95:DNA
2095::
2073:.
2063:.
2051:.
2047:.
2023:.
2013:63
2011:.
1987:.
1975:.
1951:.
1941:.
1931:72
1929:.
1925:.
1902:.
1892:.
1882:55
1880:.
1876:.
1853:.
1845:.
1835:23
1833:.
1821:^
1807:.
1795:.
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1753:94
1751:.
1727:.
1713:.
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1662:.
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1615:.
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1564:.
1540:.
1532:.
1520:.
1497:.
1487:.
1477:30
1475:.
1471:.
1457:^
1443:.
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1421:.
1417:.
1394:.
1382:.
1359:.
1351:.
1341:18
1339:.
1327:^
1313:.
1301:96
1299:.
1295:.
1281:^
1267:.
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1226:.
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1009:.
999:.
985:.
981:.
958:.
950:.
940:15
938:.
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893:59
891:.
887:.
864:.
856:.
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803:45
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778:.
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758:.
726:^
706:^
692:.
682:21
680:.
668:^
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621:,
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536:.
358:,
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274:,
193:,
185:,
181:,
177:,
69:.
57:,
37:,
2081:.
2059::
2031:.
2019::
1995:.
1983::
1959:.
1937::
1910:.
1888::
1861:.
1841::
1815:.
1803::
1779:.
1759::
1735:.
1721::
1694:.
1670::
1643:.
1623::
1617:6
1600:.
1580::
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1451:.
1429::
1402:.
1390::
1367:.
1347::
1321:.
1275:.
1261::
1234:.
1214::
1191:.
1179::
1133:.
1121::
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1044::
1017:.
993::
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872:.
852::
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809::
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766::
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688::
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644:(
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300:)
97:(
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.