504:
day for 24 weeks showed a slight improvement in visual acuity compared to the placebo group, though the difference was not statistically significant. But patients taking idebenone were protected from further vision loss, whereas the placebo group had a steady decline in visual acuity. Further, people taking idebenone demonstrated preservation of color vision and persistence of the effects of idebenone 30 months after discontinuing therapy. A retrospective analysis of 103 LHON patients by
Carelli et al. builds upon these results. This study highlighted that 44 subjects who were treated with idebenone within one year of onset of vision loss had better outcomes, and that these improvements persisted for years.
539:, and HRT were given together. Visual acuity improved much faster than is typically expected. The patient's vision returned to 20/40 and 20/60 from 20/60 and 20/200 in the right and left eyes respectively after only one month and was back normal by 8 months compared to the months to years timeframe seen in most cases. While the balance between risks and benefits of HRT remains controversial, the decision to start HRT requires an individualized approach based on the patient's context. While not applicable for all post-menopausal women, prophylactic (and therapeutic) HRT should be considered in all female carriers of a known LHON mutation given the substantial risk of vision loss associated with menopause.
81:
290:. Oxidative phosphorylation uses a series of four large multienzyme complexes, all embedded in the inner mitochondrial membrane, to convert oxygen and simple sugars to energy. Mutations in any of the genes disrupt this process to cause a variety of syndromes depending on the type of mutation and other factors. It remains unclear how these genetic changes cause the death of cells in the optic nerve and lead to the specific features of Leber hereditary optic neuropathy.
53:
208:. Both eyes become affected either simultaneously (25% of cases) or sequentially (75% of cases) with a median inter-eye delay of 8 weeks. Rarely, only one eye is affected. In the acute stage, lasting a few weeks, the affected eye demonstrates an oedematous appearance of the nerve fiber layer, especially in the arcuate bundles and enlarged or telangiectatic and tortuous peripapillary vessels (microangiopathy). The main features are seen on
197:, and then a few weeks to months later in the other. Onset is usually young adulthood, but age range at onset from 7-75 is reported. The age of onset is slightly higher in females (range 19–55 years: mean 31.3 years) than males (range 15–53 years: mean 24.3). The male-to-female ratio varies between mutations: 3:1 for 3460 G>A, 6:1 for 11778 G>A and 8:1 for 14484 T>C.
597:(1840–1917) in 1871. In a paper, Leber described four families in which a number of young men had abrupt loss of vision in both eyes either simultaneously or sequentially. This disease was initially thought to be X-linked but was subsequently shown to be mitochondrial. The nature of the causative mutation was first identified in 1988 by Wallace
529:
case series of various LHON pedigrees have described female carriers converting after menopause or cessation of hormone replacement therapies. Together, these form a shifting paradigm towards considering reduced estrogen states, such as menopause, as potential triggers of visual loss similar to smoking or excessive alcohol consumption.
2673:"Preliminary safety and tolerability results of intravitreal administration of GS010, a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing human wildtype mitochondrial NADH dehydrogenase 4 (ND4) gene in patients with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial DNA mutation"
508:
take 300 mg three times daily with meals. Idebenone is fat-soluble, and may be taken with a moderate amount of dietary fat in each meal to promote absorption. It is recommended that patients on idebenone also take vitamin C 500 mg daily to keep idebenone in its reduced form, as it is most active in this state.
1916:
Giordano, C.; Iommarini, L; Giordano, L; Maresca, A; Pisano, A; Valentino, M L; Caporali, L; Liguori, R; Deceglie, S; Roberti, M; Fanelli, F; Fracasso, F; Ross-Cisneros, F N; D'Adamo, P; Hudson, G; Pyle, A; Yu-Wai-Man, P; Chinnery, P F; Zeviani, M; Salomao, S R; Berezovsky, A; Belfort Jr, R; Ventura,
658:
Stealth BioTherapeutics is investigating the use of elamipretide (MTP-131), a mitochondrial protective agent, as a therapy for LHON. Elamipretide helps stabilize cardiolipin—an important component of mitochondrial inner membranes—and has been shown to reduce damaging reactive oxygen species in animal
654:
the functional version of ND4—the gene mutated in this variant of LHON—injected into one eye. A sham injection will be administered to the other eye for comparison. It is hypothesized that introduction of the viral vector may be able to rescue the function of the mutant gene. Preliminary results have
649:
Human clinical trials are underway at GenSight
Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in LHON. In these trials, participants affected by LHON with the G11778A mutation
409:
Avoiding optic nerve toxins is generally advised, especially tobacco and alcohol. Certain prescription drugs are potential risks, so all drugs should be treated with suspicion and checked before use by those at risk. Ethambutol, in particular, has been implicated as triggering visual loss in carriers
2115:
Hwang, T.J.; Karanjia, R; Moraes-Filho, M.N.; Gale, J; Show Tran, J.; Chu, E.R.; Salomao, S.R.; Berezovsky, A; Belfort Jr., R; Nunes Moraes, M; Sadun, F; DeNegri, A.M.; La Morgia, C; Barboni, P; Ramos, C.; Chicani, C.F.; Quiros, P.A.; Carelli, V; Sadun, A.A. (2017). "Natural
History of Conversion of
503:
Two large-scale studies have demonstrated the benefits of idebenone. The Rescue of
Hereditary Optic Disease Outpatient Study (RHODOS) evaluated the effects of idebenone in 85 patients with LHON who had lost vision within the prior five years. In this study, the group taking idebenone 900 mg per
499:
is a short-chain benzoquinone that interacts with the mitochondrial electron transport chain to enhance cellular respiration. When used in people with LHON, it is believed to allow electrons to bypass the dysfunctional complex I. Successful treatment with idebenone was initially reported in a small
507:
Idebenone, combined with avoidance of smoke and limitation of alcohol intake, is the preferred treatment protocol for people with LHON. Idebenone doses are prescribed to be taken spaced out throughout the day, rather than all at once. For example, to achieve a dose of 900 mg per day, patients
528:
In addition to the experimental evidence, clinical data also points towards the protective role of estrogens. Penetrance among female carriers is substantially lower (between 3 and 8 to 1 male to female ratios depending on the mutation) while average age at onset is significantly higher. Multiple
1099:
Shrader, W. D.; Amagata, A.; Barnes, A.; Enns, G. M.; Hinman, A.; Jankowski, O.; Kheifets, V.; Komatsuzaki, R.; Lee, E.; Mollard, P.; Murase, K.; Sadun, A. A.; Thoolen, M.; Wesson, K.; Miller, G. (2011). "Α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging".
572:
Additional factors may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may be involved, though studies of these factors have produced conflicting results. Researchers are also investigating whether changes in
488:"Three person in vitro fertilization" is a proof-of-concept research technique for preventing mitochondrial disease in developing human fetuses. So far, viable macaque monkeys have been produced. But ethical and knowledge hurdles remain before use of the technique in humans is established.
330:
in LHON cybrids have been shown to rescue LHON-affected retinal ganglion cells from apoptotic death. These experiments may in part explain the death of LHON-affected retinal ganglion cells in preference to other central nervous system neurons that also carry LHON-affected mitochondria.
519:
have been shown to have a protective role in the pathogenesis of LHON. Experiments using LHON cybrids have demonstrated that the estrogen receptor localizes to the mitochondria where it directly mediates mitochondrial biogenesis. Estrogens upregulate the antioxidant enzyme
524:
and mitochondrial DNA synthesis. These experiments helped to explain the mechanism behind the lower penetrance of disease among female carriers. While additional factors have been theorized, the protective role of estrogens appears to be a significant contributor.
1038:
Klopstock, T.; Yu-Wai-Man, P.; Dimitriadis, K.; Rouleau, J.; Heck, S.; Bailie, M.; Atawan, A.; Chattopadhyay, S.; Schubert, M.; Garip, A.; Kernt, M.; Petraki, D.; Rummey, C.; Leinonen, M.; Metz, G.; Griffiths, P. G.; Meier, T.; Chinnery, P. F. (2011).
364:
should be offered. Health and lifestyle choices should be reassessed, particularly in light of toxic and nutritional theories of gene expression. Vision aids assistance and work rehabilitation should be used to assist in maintaining employment.
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2951:
569:, severity of illness and probability of vision recovery in the affected. As a rule of thumb, a woman who harbors a homoplasmic primary LHON mutation has a ~40% risk of having an affected son and a ~10% risk of having an affected daughter.
1438:
Newman NJ, Biousse V, David R, et al. (September 2005). "Prophylaxis for second eye involvement in leber hereditary optic neuropathy: an open-labeled, nonrandomized multicenter trial of topical brimonidine purite".
343:
evaluation and blood testing for mitochondrial DNA assessment. It is important to exclude other possible causes of vision loss and associated syndromes such as heart electrical conduction system abnormalities.
2411:
Chinnery PF, Andrews RM, Turnbull DM, Howell NN (January 2001). "Leber hereditary optic neuropathy: Does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation?".
298:
The eye pathology is limited to the retinal ganglion cell layer, especially the maculopapillary bundle. Degeneration is evident from the retinal ganglion cell bodies to the axonal pathways leading to the
565:
More than 50% of males with a mutation and more than 85% of females with a mutation never experience vision loss or related medical problems. The particular mutation type may predict the likelihood of
641:(C) mutation at nucleotide 14484). These three mutations account for over 95% of cases: the 11778 mutation accounts for 50-70% of cases, the 14484 mutation for 10-15% and the 3460 mutation for 8-25%.
2753:"Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function"
1474:
Haroon MF, Fatima A, Schöler S, et al. (2007). "Minocycline, a possible neuroprotective agent in Leber's hereditary optic neuropathy (LHON): Studies of cybrid cells bearing 11778 mutation".
4724:
239:
LHON Plus is a rare variant of the disorder with eye disease together with other conditions. Its symptoms include loss of the brain's ability to control the movement of muscles, tremors, and
2546:
Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ, Nikoskelainen EK (December 1988). "Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy".
2018:
Pisano, A.; Preziuso, C; Iommarini, L; Perli, E; Grazioli, P; Campese, A.F.; Maresca, A; Montopoli, M; Masuelli, L; Sadun, A.A.; d'Amati, G; Carelli, V; Ghelli, A.M.; Giordano, C (2015).
360:
checks are advised for affected people. There is beneficial treatment for some cases of LHON, especially for early-onset disease, and experimental treatment protocols are in progress.
1969:
Giordano, C.; Montopoli, M; Perli, E; Orlandi, M; Fantin, M; Ross-Cisneros, F.N. L; Caparrotta, L; Martinuzzi, A; Ragazzi, E; Ghelli, A; Sadun, A.A.; d'Amati, G; Carelli, V (2011).
4820:
117:
that leads to an acute or subacute loss of central vision; it predominantly affects young adult males. LHON is transmitted only through the mother, as it is primarily due to
458:
Various treatment approaches have had early trials or been proposed, but so far none with convincing evidence of usefulness or safety for treatment or prevention, including
1881:
Mordente, A.; Martorana, G.E.; Minotti, G; Giardina, B (January 1998). "Antioxidant properties of 2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone (idebenone)".
535:(HRT) is emerging as an effective therapeutic target for female mutation carriers. In one recent case study where the affected female converted following cessation of HRT,
444:
has been shown in a small placebo-controlled trial to have modest benefit in about half of patients. People most likely to respond best were those treated early in onset.
4602:
4040:
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because of the lack of muscular control and the presence of demyelinating lesions in the CNS. It is therefore a subtype of MS, according to McDonald's definition.
3437:
1917:
D F; Moraes, M; Filho, M.M.; Barboni, P; Sadun, F; De Negri, A; Sadun, A.A.; Tancredi, A; Mancini, M; d'Amati, G; Polosa, P L; Cantatore, P; Carelli, V (2013).
633:
respiratory chain. The other two mutations known to cause this condition were identified in 1991 (G to A point mutation at nucleotide position 3460) and 1992 (
4703:
4661:
4109:
4035:
1554:
Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, Turnbull DM (May 2010).
1753:
Rudolph, G.; Dimitriadis, K.; BĂĽchner, B.; Heck, S.; Al-Tamami, J.; Seidensticker, F.; Rummey, C.; Leinonen, M.; Meier, T.; Klopstock, T. (March 2013).
832:
David
Bargiela, Patrick F Chinnery, Mitochondria in neuroinflammation – Multiple sclerosis (MS), leber hereditary optic neuropathy (LHON) and LHON-MS,
4825:
4619:
3049:
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The LHON ND4 G11778A mutation is the primary mutation in most of the world, with 70% of
Northern European cases and 90% of Asian cases. Due to a
4057:
693:
415:
411:
4595:
3917:
1176:
Oliveira, C. (2019). "Oliveira C. Toxic-Metabolic and
Hereditary Optic Neuropathies. Continuum (Minneap Minn). 2019 Oct;25(5):1265-1288".
2671:
Sahel, J.A.; Uretsky, S.; Combal, J.P.; Galy, A.; Thomasson, N.; Fitoussi, S.; Corral-Debrinsky, M.; Honnet, G.; Vignal, C. (June 2015).
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844:
4025:
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3479:
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For those who carry a LHON mutation, preclinical markers may be used to monitor progress. For example, fundus photography can monitor
311:
of retinal ganglion cells. Also, experiments suggest that normal, non-LHON-affected retinal ganglion cells produce less of the potent
4632:
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2857:
1340:
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1422:
3745:
2425:
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1420:
Sadun, A et al. "EPI-743 alters the natural history of progression of Leber hereditary optic neuropathy". AOS meeting. May 2011
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additional genes, particularly genes on the X chromosome, contribute to the development of signs and symptoms. The degree of
3740:
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may have overlaps with LHON in symptoms, mitochondrial mechanisms of disease and management. And when a patient with LHON or
1538:
3833:
3724:
3590:
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The prognosis for those left untreated is almost always continued significant visual loss in both eyes. Regular corrected
2702:
Birk, A.V.; Liu, S.; Soong, Y.; Mills, W.; Singh, P.; Warren, J.D.; Seshan, S.V.; Pardee, J.D.; Szeto, H.H. (July 2013).
1517:
916:"Use of mitochondrial antioxidant defenses for rescue of cells with a Leber hereditary optic neuropathy-causing mutation"
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4231:
3922:
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373:
106:
61:
2495:
Leber T. Ueber hereditaere und congenital angelegte sehnervenleiden (1871) Graefes Arch Clin Exp
Ophthalmol. 17:249–291
547:
In
Northern European populations about one in 9,000 people carries one of the three primary LHON mutations. There is a
3119:
3077:
3042:
532:
2449:"Clinical Expression of Leber Hereditary Optic Neuropathy Is Affected by the Mitochondrial DNA–Haplogroup Background"
2892:
Carelli V, Ross-Cisneros FN, Sadun AA (January 2004). "Mitochondrial dysfunction as a cause of optic neuropathies".
1373:"Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy?"
1280:
Carelli V, Ross-Cisneros FN, Sadun AA (January 2004). "Mitochondrial dysfunction as a cause of optic neuropathies".
960:"Protection against oxidant-induced apoptosis by exogenous glutathione in Leber hereditary optic neuropathy cybrids"
4752:
4047:
3843:
3817:
3775:
3770:
3635:
3508:
3496:
3452:
300:
4679:
4114:
3513:
137:. Men cannot pass on the disease to their offspring. LHON is usually due to one of three pathogenic mitochondrial
4226:
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3867:
3712:
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2364:"Identification of an X-Chromosomal Locus and Haplotype Modulating the Phenotype of a Mitochondrial DNA Disorder"
683:
431:
287:
182:
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Karanjia, R.; Sadun, A.A. (2015). "Advances in therapeutic strategies for Leber's hereditary optic neuropathy".
3765:
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1137:"Subclinical carriers and conversions in Leber hereditary optic neuropathy: A prospective psychophysical study"
389:
2704:"The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin"
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3990:
3790:
3310:
3303:
2751:
Thomas, D.A.; Stauffer, C.; Zhao, K.; Yang, H.; Sharma, V.K.; Szeto, H.H.; Suthanthiran, M. (January 2007).
393:
304:
178:
2333:"X-Inactivation patterns in females harboring mtDNA mutations that cause Leber hereditary optic neuropathy"
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2020:"Targeting estrogen receptor β as preventive therapeutic strategy for Leber's hereditary optic neuropathy"
673:
2066:"Hormone replacement therapy in Leber's hereditary optic neuropathy: Accelerated visual recovery in vivo"
4719:
4611:
4448:
4124:
2284:"A "Fille du Roy" Introduced the T14484C Leber Hereditary Optic Neuropathy Mutation in French Canadians"
1919:"Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy"
340:
110:
1611:
Haefeli RH, Erb M, Gemperli AC, Robay D, Courdier Fruh I, Anklin C, Dallmann R, Gueven N (March 2011).
609:(A) mutation at nucleotide position 11778 in nine families. This mutation converts a highly conserved
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419:
1613:"NQO1-dependent redox cycling of idebenone: effects on cellular redox potential and energy levels"
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metabolite, has had some success in small open-label trials in reversing early onset vision loss.
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3405:
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1201:
764:"Leber's "plus": neurological abnormalities in patients with Leber's hereditary optic neuropathy"
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244:
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259:. Although most DNA is packaged in chromosomes within the nucleus, mitochondria have a distinct
219:
may be visible in the acute stage as well. Examination reveals decreased visual acuity, loss of
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4002:
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3003:
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69:
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2125:
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1990:
1982:
1938:
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1890:
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1068:
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971:
927:
883:
873:
783:
775:
734:
726:
3022:
1556:"Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease"
1041:"A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy"
52:
4335:
4299:
4263:
3882:
3707:
3694:
3628:
3585:
3503:
3315:
3247:
3167:
3152:
1542:
1524:
1426:
1755:"Effects of idebenone on color vision in patients with Leber hereditary optic neuropathy"
1706:"Persistence of the treatment effect of idebenone in Leber's hereditary optic neuropathy"
2801:"Reduction of early reperfusion injury with the mitochondria-targeting peptide bendavia"
2559:
1971:"Oestrogens ameliorate mitochondrial dysfunction in Leber's hereditary optic neuropathy"
1628:
1571:
1419:
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than other normal central nervous system neurons. Viral vector experiments that augment
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1995:
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1153:
1136:
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1040:
888:
861:
739:
714:
555:
403:
142:
2632:"An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy"
2218:
2193:
788:
763:
376:
can be used for more detailed study of retinal nerve fiber layer thickness. Red green
4809:
4485:
4340:
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3822:
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1205:
688:
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205:
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74:
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2194:"The Epidemiology of Leber Hereditary Optic Neuropathy in the North East of England"
2192:
Man PY, Griffiths PG, Brown DT, Howell N, Turnbull DM, Chinnery PF (February 2003).
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Ghelli A, Porcelli AM, Zanna C, Martinuzzi A, Carelli V, Rugolo M (February 2008).
630:
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3162:
3114:
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471:
463:
459:
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406:(a form of B12) should be avoided as it may lead to blindness in LHON patients.
327:
2082:
1113:
932:
915:
833:
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4357:
4345:
4289:
4250:
4156:
4092:
4071:
3961:
3320:
3185:
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2591:"A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy"
1487:
1452:
1000:
582:
566:
548:
312:
212:
146:
2816:
2243:"Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland"
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2004:
1986:
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demonstrated tolerability of the injections in a small number of subjects.
303:. Experimental evidence reveals impaired glutamate transport and increased
2884:
2657:
2616:
2575:
2532:
2331:
Hudson G, Carelli V, Horvath R, Zeviani M, Smeets HJ, Chinnery PF (2007).
1902:
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2019:
1259:
976:
959:
678:
638:
610:
516:
475:
467:
170:
118:
2943:
2426:
10.1002/1096-8628(20010122)98:3<235::AID-AJMG1086>3.0.CO;2-O
2169:
2152:
1672:"Idebenone treatment in patients with Leber hereditary optic neuropathy"
1579:
339:
Without a known family history of LHON the diagnosis usually requires a
282:
genes cause Leber hereditary optic neuropathy. These genes code for the
4387:
4330:
3872:
3679:
3610:
3580:
3570:
3177:
602:
578:
427:
275:
255:
Leber hereditary optic neuropathy is a condition related to changes in
224:
166:
162:
158:
154:
150:
1894:
762:
Nikoskelainen EK, Marttila RJ, Huoponen K, et al. (August 1995).
4774:
4490:
3392:
3369:
3089:
2955:
2589:
Huoponen K, Vilkki J, Aula P, Nikoskelainen EK, Savontaus ML (1991).
559:
279:
271:
267:
134:
122:
1802:
Carelli V; La Morgia C; Valentino ML; et al. (September 2011).
17:
2507:"Leber's optic atrophy, a possible example of maternal inheritance"
2464:
2379:
2299:
2209:
4760:
4462:
715:"More evidence for non-maternal inheritance of mitochondrial DNA?"
618:
558:, the LHON ND6 T14484C mutation accounts for 86% of LHON cases in
2865:
193:
Clinically, there is an acute onset of visual loss, first in one
3542:
3104:
2986:
2241:
Puomila A, Hämäläinen P, Kivioja S, et al. (October 2007).
862:"Differential production of superoxide by neuronal mitochondria"
848:
174:
126:
114:
4584:
4547:
3943:
3346:
3075:
3031:
1355:
Clinical
Idebenone trial recruiting at Newcastle University UK
2362:
Hudson G, Keers S, Yu Wai Man P, et al. (December 2005).
1371:
Mashima Y, Kigasawa K, Wakakura M, Oguchi Y (September 2000).
138:
27:
Mitochondrially inherited degeneration of retinal nerve cells
1804:"Idebenone treatment in Leber's hereditary optic neuropathy"
914:
Qi X, Sun L, Hauswirth WW, Lewin AS, Guy J (February 2007).
581:, may play a role. Patterns of mitochondrial alleles called
2447:
Hudson G, Carelli V, Spruijt L, et al. (August 2007).
2153:"Oestrogen, ocular function and low-level vision: a review"
2866:"Clinical spectrum of Leber's hereditary optic neuropathy"
2799:
Brown DA; Hale SL; Baines CP; et al. (January 2014).
2064:
Fantini, M.; Asanad, S; Karanjia, R; Sadun, A.A. (2019).
1356:
400:
blood markers may predict conversion to affected status.
286:
protein involved in the normal mitochondrial function of
1219:
Vasavada A, Sanghavi D. . StatPearls Publishing (2021).
1135:
Sadun AA, Salomao SR, Berezovsky A, et al. (2006).
713:
Bandelt HJ, Kong QP, Parson W, Salas A (December 2005).
1704:
Klopstock T; Metz G; Yu-Wai-Man P; et al. (2013).
593:
LHON was first described by the German ophthalmologist
109:(transmitted from mother to offspring) degeneration of
2933:
2151:
Hutchinson, C.V.; Walker, J.A.; Davidson, C (2014).
4738:
4712:
4670:
4641:
4618:
4514:
4461:
4426:
4386:
4298:
4249:
4214:
4155:
4123:
4091:
4070:
4011:
3956:
3852:
3693:
3653:
3609:
3550:
3541:
3391:
3368:
3359:
3284:
3246:
3213:
3176:
3097:
3088:
2937:
2282:Laberge AM, Jomphe M, Houde L, et al. (2005).
1670:Eng, J.G.; Aggarwal, D.; Sadun, A.A. (April 2009).
422:as a possible complication of the disease process,
215:, just before or after the onset of visual loss. A
88:
68:
40:
35:
1964:
1962:
1841:
1839:
577:, the percentage of mitochondria that have mutant
4036:arteritic anterior (AAION or arteritic AION)
1033:
1031:
1029:
243:. Many cases of LHON plus have been compared to
1366:
1364:
430:) should not be used, due to increased risk of
173:, respectively in the ND4, ND1 and ND6 subunit
1094:
1092:
384:may be diminished. There could be an abnormal
4596:
3043:
2059:
2057:
2055:
8:
4821:Disorders of optic nerve and visual pathways
4110:Chronic progressive external ophthalmoplegia
1102:Bioorganic & Medicinal Chemistry Letters
953:
951:
834:https://doi.org/10.1016/j.neulet.2017.06.051
235:LHON with demyelinating lesions or LHON Plus
3438:Thygeson's superficial punctate keratopathy
1243:: CS1 maint: numeric names: authors list (
999:Yu-Wai-Man P, Chinnery PF (June 23, 2016).
551:of between 1:30,000 to 1:50,000 in Europe.
4603:
4589:
4581:
4544:
4308:
4097:
4088:
3966:
3953:
3940:
3547:
3365:
3356:
3343:
3094:
3085:
3072:
3050:
3036:
3028:
2934:
326:or LHON animal models or use of exogenous
79:
60:Leber's hereditary optic neuropathy has a
51:
32:
2824:
2768:
2727:
2647:
2606:
2522:
2472:
2387:
2307:
2258:
2217:
2168:
2091:
2081:
2035:
1994:
1942:
1819:
1778:
1729:
1646:
1636:
1587:
1388:
1152:
1072:
975:
931:
887:
877:
787:
738:
585:may also affect expression of mutations.
860:Hoegger MJ, Lieven CJ, Levin LA (2008).
412:toxic and nutritional optic neuropathies
2853:Leber's hereditary optic neuropathy
1516:Clinical Curcurmin trial recruiting at
705:
2630:Johns DR, Neufeld MJ, Park RD (1992).
2116:Leber's Hereditary Optic Neuropathy".
1236:
694:Toxic and nutritional optic neuropathy
200:This typically evolves to very severe
1699:
1697:
1327:Parkland Manual of Inpatient Medicine
7:
3918:Familial exudative vitreoretinopathy
909:
907:
4041:non-arteritic anterior (NAION)
3878:Leber's hereditary optic neuropathy
1323:Katz, Jason; Patel, Chetan (2006).
1001:"Leber Hereditary Optic Neuropathy"
845:Online Mendelian Inheritance in Man
121:in the mitochondrial (not nuclear)
99:Leber's hereditary optic neuropathy
36:Leber's hereditary optic neuropathy
3913:Persistent tunica vasculosa lentis
2511:American Journal of Human Genetics
416:toxic/nutritional optic neuropathy
25:
3641:Polypoidal choroidal vasculopathy
4826:Diseases named after discoverers
3746:Central retinal artery occlusion
2906:10.1016/j.preteyeres.2003.10.003
2070:Journal of Current Ophthalmology
1390:10.1097/00041327-200020030-00006
1331:. Dallas, TX: FA Davis. p.
1294:10.1016/j.preteyeres.2003.10.003
768:J. Neurol. Neurosurg. Psychiatry
4686:Mitochondrial encephalomyopathy
3751:Branch retinal artery occlusion
3480:Terrien's marginal degeneration
2864:Kerrison JB, Newman NJ (1997).
822:Mayo Clinic: Multiple Sclerosis
3781:Bietti's crystalline dystrophy
3741:Central retinal vein occlusion
3470:Pellucid marginal degeneration
1848:Expert Opinion on Orphan Drugs
1178:Continuum (Minneapolis, Minn.)
45:Leber hereditary optic atrophy
1:
3834:Vitelliform macular dystrophy
3725:Posterior vitreous detachment
3591:Persistent pupillary membrane
3023:NCBI Genetic Testing Registry
1860:10.1517/21678707.2015.1098531
1536:Wisconsin near infrared trial
4321:Leber's congenital amaurosis
4232:Internuclear ophthalmoplegia
3923:Vogt-Koyanagi-Harada disease
3908:Persistent fetal vasculature
3839:Leber's congenital amaurosis
2677:Invest. Ophthalmol. Vis. Sci
2649:10.1016/0006-291x(92)90479-5
2130:10.1016/j.ophtha.2017.01.002
1771:10.1097/WNO.0b013e318272c643
1638:10.1371/journal.pone.0017963
1190:10.1212/CON.0000000000000769
964:Invest. Ophthalmol. Vis. Sci
849:LEBER OPTIC ATROPHY - 535000
512:Estrogen replacement therapy
374:Optical coherence tomography
204:and a permanent decrease of
3120:Meibomian gland dysfunction
2805:J Cardiovasc Pharmacol Ther
533:Hormone replacement therapy
380:testing may detect losses.
4842:
3844:Birdshot chorioretinopathy
3818:Central serous retinopathy
3636:Focal choroidal excavation
3509:Corneal neovascularization
3326:Subconjunctival hemorrhage
2636:Biochem Biophys Res Commun
2083:10.1016/j.joco.2018.10.003
1518:ClinicalTrials.nlm.nih.gov
1114:10.1016/j.bmcl.2011.04.085
933:10.1001/archopht.125.2.268
4791:
4556:
4543:
4311:
4227:Convergence insufficiency
4100:
3969:
3952:
3939:
3868:Primary juvenile glaucoma
3713:Cytomegalovirus retinitis
3355:
3342:
3128:
3084:
3071:
3062:Diseases of the human eye
1676:Invest Ophthalmol Vis Sci
1488:10.1016/j.nbd.2007.07.021
1453:10.1016/j.ajo.2005.03.058
684:Ischemic optic neuropathy
301:lateral geniculate nuclei
288:oxidative phosphorylation
183:oxidative phosphorylation
145:. These mutations are at
107:mitochondrially inherited
62:mitochondrial inheritance
59:
50:
4781:Mohr–Tranebjærg syndrome
3737:Ocular ischemic syndrome
2817:10.1177/1074248413508003
2505:Erickson RP (May 1972).
2157:Journal of Endocrinology
2024:Human Molecular Genetics
390:visual evoked potentials
229:visual field examination
4753:Kjer's optic neuropathy
4620:Carbohydrate metabolism
4237:One and a half syndrome
3991:Foster Kennedy syndrome
2860:Genetics Home Reference
2568:10.1126/science.3201231
2260:10.1038/sj.ejhg.5201828
1141:Trans Am Ophthalmol Soc
731:10.1136/jmg.2005.033589
396:and axonal heavy chain
394:Neuron-specific enolase
305:reactive oxygen species
185:chain in mitochondria.
4816:Mitochondrial diseases
4796:mitochondrial proteins
4612:Mitochondrial diseases
4476:Argyll Robertson pupil
3276:Periorbital cellulitis
2770:10.1681/asn.2006080825
2720:10.1681/ASN.2012121216
674:Dominant optic atrophy
522:superoxide dismutase 2
341:neuro-ophthalmological
111:retinal ganglion cells
4449:Scintillating scotoma
4115:Kearns–Sayre syndrome
4058:Toxic and nutritional
4031:posterior (PION)
3514:Kayser–Fleischer ring
1357:http://lhon.ncl.ac.uk
879:10.1186/1471-2202-9-4
780:10.1136/jnnp.59.2.160
4222:Conjugate gaze palsy
4093:Paralytic strabismus
4026:anterior (AION)
3808:Retinitis pigmentosa
3803:Macular degeneration
3576:Intermediate uveitis
3492:Keratoconjunctivitis
1987:10.1093/brain/awq276
1935:10.1093/brain/awt343
1821:10.1093/brain/awr180
1722:10.1093/brain/aws279
1057:10.1093/brain/awr170
977:10.1167/iovs.07-0880
500:number of patients.
434:in response to this
432:optic nerve ischemia
382:Contrast sensitivity
320:superoxide dismutase
261:mitochondrial genome
92:1:30,000 to 1:50,000
4527:Childhood blindness
4506:Parinaud's syndrome
4076:Extraocular muscles
3864:Ocular hypertension
3828:Epiretinal membrane
3813:Retinal haemorrhage
3668:Congenital cataract
2560:1988Sci...242.1427W
2170:10.1530/JOE-14-0349
1629:2011PLoSO...617963H
1580:10.1038/nature08958
1572:2010Natur.465...82C
601:who discovered the
420:hypertensive crisis
263:composed of mtDNA.
4053:Leber's hereditary
3720:Retinal detachment
3673:Childhood cataract
3485:Post-LASIK ectasia
3266:Orbital cellulitis
3215:Lacrimal apparatus
2894:Prog Retin Eye Res
2247:Eur. J. Hum. Genet
2037:10.1093/hmg/ddv396
1541:2008-05-15 at the
1523:2009-02-13 at the
1425:2011-09-04 at the
1282:Prog Retin Eye Res
650:will have a virus
623:NADH dehydrogenase
410:of LHON. In fact,
362:Genetic counseling
284:NADH dehydrogenase
245:multiple sclerosis
241:cardiac arrhythmia
223:and a cecocentral
189:Signs and symptoms
4803:
4802:
4713:No primary system
4578:
4577:
4574:
4573:
4539:
4538:
4535:
4534:
4481:Marcus Gunn pupil
4457:
4456:
4378:Visual impairment
4245:
4244:
4151:
4150:
4138:Fourth-nerve (IV)
4066:
4065:
4003:Optic disc drusen
3935:
3934:
3931:
3930:
3649:
3648:
3537:
3536:
3443:Corneal dystrophy
3338:
3337:
3334:
3333:
3209:
3208:
3018:
3017:
2554:(4884): 1427–30.
2453:Am. J. Hum. Genet
2414:Am. J. Med. Genet
2368:Am. J. Hum. Genet
2288:Am. J. Hum. Genet
2198:Am. J. Hum. Genet
2030:(24): 6921–6931.
1981:(Pt 1): 220–234.
1929:(Pt 2): 335–353.
1895:10.1021/tx970136j
1854:(12): 1439–1446.
1759:J Neuroophthalmol
1441:Am. J. Ophthalmol
1377:J Neuroophthalmol
1260:"Things to avoid"
1108:(12): 3693–3698.
811:cardiac arrythmia
436:anti-hypertensive
386:electroretinogram
370:nerve fiber layer
266:Mutations in the
257:mitochondrial DNA
113:(RGCs) and their
96:
95:
30:Medical condition
16:(Redirected from
4833:
4730:Pearson syndrome
4605:
4598:
4591:
4582:
4545:
4309:
4300:Vision disorders
4259:Refractive error
4201:Brown's syndrome
4157:Other strabismus
4143:Sixth-nerve (VI)
4133:Oculomotor (III)
4105:Ophthalmoparesis
4098:
4089:
4080:Binocular vision
4013:Optic neuropathy
3979:optic papillitis
3967:
3954:
3941:
3830:(Macular pucker)
3548:
3529:Band keratopathy
3366:
3357:
3344:
3271:Orbital lymphoma
3158:Blepharophimosis
3148:Blepharochalasis
3095:
3086:
3073:
3052:
3045:
3038:
3029:
2935:
2925:
2888:
2870:
2869:(IFOND reprints)
2839:
2838:
2828:
2796:
2790:
2789:
2787:
2785:
2772:
2757:J Am Soc Nephrol
2748:
2742:
2741:
2731:
2708:J Am Soc Nephrol
2699:
2693:
2692:
2690:
2688:
2668:
2662:
2661:
2651:
2642:(3): 1551–1557.
2627:
2621:
2620:
2610:
2601:(6): 1147–1153.
2586:
2580:
2579:
2543:
2537:
2536:
2526:
2502:
2496:
2493:
2487:
2486:
2476:
2444:
2438:
2437:
2408:
2402:
2401:
2391:
2359:
2353:
2352:
2328:
2322:
2321:
2311:
2279:
2273:
2272:
2262:
2238:
2232:
2231:
2221:
2189:
2183:
2182:
2172:
2148:
2142:
2141:
2112:
2106:
2105:
2095:
2085:
2061:
2050:
2049:
2039:
2015:
2009:
2008:
1998:
1966:
1957:
1956:
1946:
1913:
1907:
1906:
1883:Chem Res Toxicol
1878:
1872:
1871:
1843:
1834:
1833:
1823:
1814:(Part 9): e188.
1799:
1793:
1792:
1782:
1750:
1744:
1743:
1733:
1701:
1692:
1691:
1689:
1687:
1667:
1661:
1660:
1650:
1640:
1608:
1602:
1601:
1591:
1551:
1545:
1533:
1527:
1514:
1508:
1507:
1471:
1465:
1464:
1435:
1429:
1417:
1411:
1410:
1392:
1368:
1359:
1353:
1347:
1346:
1330:
1320:
1314:
1313:
1277:
1271:
1270:
1268:
1266:
1255:
1249:
1248:
1242:
1234:
1216:
1210:
1209:
1184:(5): 1265–1288.
1173:
1167:
1166:
1156:
1132:
1126:
1125:
1096:
1087:
1086:
1076:
1051:(9): 2677–2686.
1035:
1024:
1023:
1021:
1019:
996:
990:
989:
979:
955:
946:
945:
935:
920:Arch. Ophthalmol
911:
902:
901:
891:
881:
857:
851:
842:
836:
830:
824:
819:
813:
808:
802:
801:
791:
759:
753:
752:
742:
710:
217:pupillary defect
149:positions 11778
84:
83:
55:
33:
21:
4841:
4840:
4836:
4835:
4834:
4832:
4831:
4830:
4806:
4805:
4804:
4799:
4787:
4734:
4708:
4666:
4637:
4614:
4609:
4579:
4570:
4552:
4531:
4510:
4453:
4422:
4382:
4336:Color blindness
4302:
4294:
4241:
4215:Other binocular
4210:
4147:
4119:
4082:
4078:
4074:
4062:
4007:
3960:
3948:
3927:
3883:Ocular hypotony
3848:
3708:Chorioretinitis
3689:
3645:
3629:Chorioretinitis
3605:
3586:Rubeosis iridis
3564:
3533:
3504:Corneal opacity
3460:Corneal ectasia
3387:
3351:
3330:
3316:Pseudopterygium
3280:
3242:
3205:
3172:
3168:Ankyloblepharon
3124:
3080:
3067:
3066:
3056:
3019:
3014:
3013:
2946:
2932:
2891:
2868:
2863:
2848:
2846:Further reading
2843:
2842:
2798:
2797:
2793:
2783:
2781:
2750:
2749:
2745:
2701:
2700:
2696:
2686:
2684:
2670:
2669:
2665:
2629:
2628:
2624:
2588:
2587:
2583:
2545:
2544:
2540:
2504:
2503:
2499:
2494:
2490:
2446:
2445:
2441:
2410:
2409:
2405:
2361:
2360:
2356:
2330:
2329:
2325:
2281:
2280:
2276:
2253:(10): 1079–89.
2240:
2239:
2235:
2191:
2190:
2186:
2150:
2149:
2145:
2114:
2113:
2109:
2063:
2062:
2053:
2017:
2016:
2012:
1968:
1967:
1960:
1915:
1914:
1910:
1880:
1879:
1875:
1845:
1844:
1837:
1801:
1800:
1796:
1752:
1751:
1747:
1703:
1702:
1695:
1685:
1683:
1669:
1668:
1664:
1610:
1609:
1605:
1566:(7294): 82–85.
1553:
1552:
1548:
1543:Wayback Machine
1534:
1530:
1525:Wayback Machine
1515:
1511:
1473:
1472:
1468:
1437:
1436:
1432:
1427:Wayback Machine
1418:
1414:
1370:
1369:
1362:
1354:
1350:
1343:
1322:
1321:
1317:
1279:
1278:
1274:
1264:
1262:
1257:
1256:
1252:
1235:
1218:
1217:
1213:
1175:
1174:
1170:
1134:
1133:
1129:
1098:
1097:
1090:
1037:
1036:
1027:
1017:
1015:
1007:. Genereviews.
998:
997:
993:
957:
956:
949:
913:
912:
905:
859:
858:
854:
843:
839:
831:
827:
820:
816:
809:
805:
761:
760:
756:
712:
711:
707:
702:
665:
647:
591:
545:
514:
494:
479:light treatment
350:
337:
296:
294:Pathophysiology
253:
237:
191:
143:point mutations
125:, and only the
78:
31:
28:
23:
22:
15:
12:
11:
5:
4839:
4837:
4829:
4828:
4823:
4818:
4808:
4807:
4801:
4800:
4792:
4789:
4788:
4786:
4785:
4784:
4783:
4771:
4770:
4769:
4767:HUPRA syndrome
4757:
4756:
4755:
4742:
4740:
4736:
4735:
4733:
4732:
4727:
4722:
4716:
4714:
4710:
4709:
4707:
4706:
4701:
4700:
4699:
4694:
4682:
4676:
4674:
4668:
4667:
4665:
4664:
4659:
4654:
4648:
4646:
4644:nervous system
4639:
4638:
4636:
4635:
4630:
4624:
4622:
4616:
4615:
4610:
4608:
4607:
4600:
4593:
4585:
4576:
4575:
4572:
4571:
4569:
4568:
4566:Onchocerciasis
4563:
4557:
4554:
4553:
4548:
4541:
4540:
4537:
4536:
4533:
4532:
4530:
4529:
4524:
4518:
4516:
4512:
4511:
4509:
4508:
4503:
4498:
4493:
4488:
4483:
4478:
4473:
4467:
4465:
4459:
4458:
4455:
4454:
4452:
4451:
4446:
4441:
4436:
4430:
4428:
4424:
4423:
4421:
4420:
4418:Quadrantanopia
4415:
4414:
4413:
4408:
4403:
4392:
4390:
4384:
4383:
4381:
4380:
4367:
4366:
4365:
4363:Oguchi disease
4355:
4354:
4353:
4348:
4343:
4333:
4328:
4323:
4318:
4312:
4306:
4296:
4295:
4293:
4292:
4287:
4278:
4273:
4272:
4271:
4266:
4255:
4253:
4247:
4246:
4243:
4242:
4240:
4239:
4234:
4229:
4224:
4218:
4216:
4212:
4211:
4209:
4208:
4206:Duane syndrome
4203:
4198:
4193:
4192:
4191:
4186:
4176:
4171:
4161:
4159:
4153:
4152:
4149:
4148:
4146:
4145:
4140:
4135:
4129:
4127:
4121:
4120:
4118:
4117:
4112:
4107:
4101:
4095:
4086:
4068:
4067:
4064:
4063:
4061:
4060:
4055:
4050:
4045:
4044:
4043:
4038:
4033:
4028:
4017:
4015:
4009:
4008:
4006:
4005:
4000:
3995:
3994:
3993:
3983:
3982:
3981:
3974:Optic neuritis
3970:
3964:
3950:
3949:
3944:
3937:
3936:
3933:
3932:
3929:
3928:
3926:
3925:
3920:
3915:
3910:
3905:
3903:Phthisis bulbi
3900:
3895:
3890:
3885:
3880:
3875:
3870:
3856:
3854:
3850:
3849:
3847:
3846:
3841:
3836:
3831:
3825:
3820:
3815:
3810:
3805:
3800:
3799:
3798:
3793:
3788:
3786:Coats' disease
3783:
3778:
3776:of prematurity
3773:
3768:
3763:
3753:
3748:
3743:
3734:
3729:
3728:
3727:
3717:
3716:
3715:
3710:
3699:
3697:
3691:
3690:
3688:
3687:
3685:Ectopia lentis
3682:
3677:
3676:
3675:
3670:
3659:
3657:
3651:
3650:
3647:
3646:
3644:
3643:
3638:
3633:
3632:
3631:
3621:
3615:
3613:
3607:
3606:
3604:
3603:
3598:
3593:
3588:
3583:
3578:
3573:
3567:
3565:
3563:
3562:
3557:
3551:
3545:
3543:Vascular tunic
3539:
3538:
3535:
3534:
3532:
3531:
3526:
3521:
3516:
3511:
3506:
3501:
3500:
3499:
3489:
3488:
3487:
3482:
3477:
3472:
3467:
3457:
3456:
3455:
3450:
3440:
3435:
3430:
3429:
3428:
3426:Photokeratitis
3423:
3418:
3413:
3408:
3397:
3395:
3389:
3388:
3386:
3385:
3380:
3374:
3372:
3363:
3353:
3352:
3347:
3340:
3339:
3336:
3335:
3332:
3331:
3329:
3328:
3323:
3318:
3313:
3308:
3307:
3306:
3299:Conjunctivitis
3296:
3290:
3288:
3282:
3281:
3279:
3278:
3273:
3268:
3263:
3258:
3252:
3250:
3244:
3243:
3241:
3240:
3235:
3233:Dacryocystitis
3230:
3225:
3223:Dacryoadenitis
3219:
3217:
3211:
3210:
3207:
3206:
3204:
3203:
3198:
3193:
3188:
3182:
3180:
3174:
3173:
3171:
3170:
3165:
3160:
3155:
3150:
3145:
3140:
3135:
3129:
3126:
3125:
3123:
3122:
3117:
3112:
3107:
3101:
3099:
3092:
3082:
3081:
3076:
3069:
3068:
3065:
3064:
3058:
3057:
3055:
3054:
3047:
3040:
3032:
3026:
3025:
3016:
3015:
3012:
3011:
3000:
2989:
2978:
2963:
2947:
2942:
2941:
2939:
2938:Classification
2931:
2930:External links
2928:
2927:
2926:
2889:
2879:(5): 295–301.
2873:Clin. Neurosci
2861:
2847:
2844:
2841:
2840:
2811:(1): 121–132.
2791:
2763:(1): 213–222.
2743:
2714:(8): 1250–61.
2694:
2663:
2622:
2595:Am J Hum Genet
2581:
2538:
2497:
2488:
2465:10.1086/519394
2439:
2403:
2380:10.1086/498176
2374:(6): 1086–91.
2354:
2323:
2300:10.1086/432491
2274:
2233:
2210:10.1086/346066
2184:
2143:
2124:(6): 843–850.
2107:
2076:(1): 102–105.
2051:
2010:
1958:
1908:
1873:
1835:
1794:
1745:
1693:
1662:
1603:
1546:
1528:
1509:
1466:
1430:
1412:
1360:
1348:
1341:
1315:
1272:
1250:
1225:. StatPearls.
1222:Cyanocobalamin
1211:
1168:
1127:
1088:
1025:
991:
947:
903:
852:
837:
825:
814:
803:
754:
725:(12): 957–60.
704:
703:
701:
698:
697:
696:
691:
686:
681:
676:
671:
664:
661:
646:
643:
590:
587:
556:Founder effect
544:
541:
513:
510:
493:
490:
404:Cyanocobalamin
349:
346:
336:
333:
307:(ROS) causing
295:
292:
252:
249:
236:
233:
190:
187:
94:
93:
90:
86:
85:
72:
66:
65:
57:
56:
48:
47:
42:
38:
37:
29:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
4838:
4827:
4824:
4822:
4819:
4817:
4814:
4813:
4811:
4798:
4797:
4790:
4782:
4779:
4778:
4777:
4776:
4772:
4768:
4765:
4764:
4763:
4762:
4758:
4754:
4751:
4750:
4749:
4748:
4744:
4743:
4741:
4737:
4731:
4728:
4726:
4723:
4721:
4718:
4717:
4715:
4711:
4705:
4702:
4698:
4695:
4693:
4690:
4689:
4688:
4687:
4683:
4681:
4678:
4677:
4675:
4673:
4669:
4663:
4660:
4658:
4655:
4653:
4652:Leigh disease
4650:
4649:
4647:
4645:
4640:
4634:
4631:
4629:
4626:
4625:
4623:
4621:
4617:
4613:
4606:
4601:
4599:
4594:
4592:
4587:
4586:
4583:
4567:
4564:
4562:
4559:
4558:
4555:
4551:
4546:
4542:
4528:
4525:
4523:
4520:
4519:
4517:
4513:
4507:
4504:
4502:
4499:
4497:
4494:
4492:
4489:
4487:
4486:Adie syndrome
4484:
4482:
4479:
4477:
4474:
4472:
4469:
4468:
4466:
4464:
4460:
4450:
4447:
4445:
4442:
4440:
4437:
4435:
4432:
4431:
4429:
4425:
4419:
4416:
4412:
4409:
4407:
4404:
4402:
4399:
4398:
4397:
4394:
4393:
4391:
4389:
4385:
4379:
4375:
4371:
4368:
4364:
4361:
4360:
4359:
4356:
4352:
4349:
4347:
4344:
4342:
4341:Achromatopsia
4339:
4338:
4337:
4334:
4332:
4329:
4327:
4324:
4322:
4319:
4317:
4314:
4313:
4310:
4307:
4305:
4301:
4297:
4291:
4288:
4286:
4282:
4281:Anisometropia
4279:
4277:
4274:
4270:
4267:
4265:
4262:
4261:
4260:
4257:
4256:
4254:
4252:
4248:
4238:
4235:
4233:
4230:
4228:
4225:
4223:
4220:
4219:
4217:
4213:
4207:
4204:
4202:
4199:
4197:
4194:
4190:
4187:
4185:
4182:
4181:
4180:
4177:
4175:
4172:
4170:
4166:
4163:
4162:
4160:
4158:
4154:
4144:
4141:
4139:
4136:
4134:
4131:
4130:
4128:
4126:
4122:
4116:
4113:
4111:
4108:
4106:
4103:
4102:
4099:
4096:
4094:
4090:
4087:
4085:
4084:Accommodation
4081:
4077:
4073:
4069:
4059:
4056:
4054:
4051:
4049:
4046:
4042:
4039:
4037:
4034:
4032:
4029:
4027:
4024:
4023:
4022:
4019:
4018:
4016:
4014:
4010:
4004:
4001:
3999:
3998:Optic atrophy
3996:
3992:
3989:
3988:
3987:
3984:
3980:
3977:
3976:
3975:
3972:
3971:
3968:
3965:
3963:
3959:
3955:
3951:
3947:
3942:
3938:
3924:
3921:
3919:
3916:
3914:
3911:
3909:
3906:
3904:
3901:
3899:
3898:Keratomycosis
3896:
3894:
3893:Globe rupture
3891:
3889:
3886:
3884:
3881:
3879:
3876:
3874:
3871:
3869:
3865:
3861:
3858:
3857:
3855:
3851:
3845:
3842:
3840:
3837:
3835:
3832:
3829:
3826:
3824:
3823:Macular edema
3821:
3819:
3816:
3814:
3811:
3809:
3806:
3804:
3801:
3797:
3794:
3792:
3789:
3787:
3784:
3782:
3779:
3777:
3774:
3772:
3769:
3767:
3764:
3762:
3759:
3758:
3757:
3754:
3752:
3749:
3747:
3744:
3742:
3738:
3735:
3733:
3732:Retinoschisis
3730:
3726:
3723:
3722:
3721:
3718:
3714:
3711:
3709:
3706:
3705:
3704:
3701:
3700:
3698:
3696:
3692:
3686:
3683:
3681:
3678:
3674:
3671:
3669:
3666:
3665:
3664:
3661:
3660:
3658:
3656:
3652:
3642:
3639:
3637:
3634:
3630:
3627:
3626:
3625:
3622:
3620:
3619:Choroideremia
3617:
3616:
3614:
3612:
3608:
3602:
3599:
3597:
3596:Iridodialysis
3594:
3592:
3589:
3587:
3584:
3582:
3579:
3577:
3574:
3572:
3569:
3568:
3566:
3561:
3558:
3556:
3553:
3552:
3549:
3546:
3544:
3540:
3530:
3527:
3525:
3524:Arcus senilis
3522:
3520:
3519:Haab's striae
3517:
3515:
3512:
3510:
3507:
3505:
3502:
3498:
3495:
3494:
3493:
3490:
3486:
3483:
3481:
3478:
3476:
3473:
3471:
3468:
3466:
3463:
3462:
3461:
3458:
3454:
3451:
3449:
3446:
3445:
3444:
3441:
3439:
3436:
3434:
3433:Corneal ulcer
3431:
3427:
3424:
3422:
3419:
3417:
3414:
3412:
3411:acanthamoebic
3409:
3407:
3404:
3403:
3402:
3399:
3398:
3396:
3394:
3390:
3384:
3381:
3379:
3376:
3375:
3373:
3371:
3367:
3364:
3362:
3361:Fibrous tunic
3358:
3354:
3350:
3345:
3341:
3327:
3324:
3322:
3319:
3317:
3314:
3312:
3309:
3305:
3302:
3301:
3300:
3297:
3295:
3292:
3291:
3289:
3287:
3283:
3277:
3274:
3272:
3269:
3267:
3264:
3262:
3259:
3257:
3254:
3253:
3251:
3249:
3245:
3239:
3238:Xerophthalmia
3236:
3234:
3231:
3229:
3226:
3224:
3221:
3220:
3218:
3216:
3212:
3202:
3199:
3197:
3194:
3192:
3189:
3187:
3184:
3183:
3181:
3179:
3175:
3169:
3166:
3164:
3161:
3159:
3156:
3154:
3151:
3149:
3146:
3144:
3143:Lagophthalmos
3141:
3139:
3136:
3134:
3131:
3130:
3127:
3121:
3118:
3116:
3113:
3111:
3108:
3106:
3103:
3102:
3100:
3096:
3093:
3091:
3087:
3083:
3079:
3074:
3070:
3063:
3060:
3059:
3053:
3048:
3046:
3041:
3039:
3034:
3033:
3030:
3024:
3021:
3020:
3010:
3006:
3005:
3001:
2999:
2995:
2994:
2990:
2988:
2984:
2983:
2979:
2977:
2973:
2972:
2968:
2964:
2962:
2958:
2957:
2953:
2949:
2948:
2945:
2940:
2936:
2929:
2923:
2919:
2915:
2911:
2907:
2903:
2899:
2895:
2890:
2886:
2882:
2878:
2874:
2867:
2862:
2859:
2855:
2854:
2850:
2849:
2845:
2836:
2832:
2827:
2822:
2818:
2814:
2810:
2806:
2802:
2795:
2792:
2780:
2776:
2771:
2766:
2762:
2758:
2754:
2747:
2744:
2739:
2735:
2730:
2725:
2721:
2717:
2713:
2709:
2705:
2698:
2695:
2682:
2678:
2674:
2667:
2664:
2659:
2655:
2650:
2645:
2641:
2637:
2633:
2626:
2623:
2618:
2614:
2609:
2604:
2600:
2596:
2592:
2585:
2582:
2577:
2573:
2569:
2565:
2561:
2557:
2553:
2549:
2542:
2539:
2534:
2530:
2525:
2520:
2516:
2512:
2508:
2501:
2498:
2492:
2489:
2484:
2480:
2475:
2470:
2466:
2462:
2459:(2): 228–33.
2458:
2454:
2450:
2443:
2440:
2435:
2431:
2427:
2423:
2420:(3): 235–43.
2419:
2415:
2407:
2404:
2399:
2395:
2390:
2385:
2381:
2377:
2373:
2369:
2365:
2358:
2355:
2350:
2346:
2342:
2338:
2334:
2327:
2324:
2319:
2315:
2310:
2305:
2301:
2297:
2293:
2289:
2285:
2278:
2275:
2270:
2266:
2261:
2256:
2252:
2248:
2244:
2237:
2234:
2229:
2225:
2220:
2215:
2211:
2207:
2203:
2199:
2195:
2188:
2185:
2180:
2176:
2171:
2166:
2163:(2): R9–R18.
2162:
2158:
2154:
2147:
2144:
2139:
2135:
2131:
2127:
2123:
2119:
2118:Ophthalmology
2111:
2108:
2103:
2099:
2094:
2089:
2084:
2079:
2075:
2071:
2067:
2060:
2058:
2056:
2052:
2047:
2043:
2038:
2033:
2029:
2025:
2021:
2014:
2011:
2006:
2002:
1997:
1992:
1988:
1984:
1980:
1976:
1972:
1965:
1963:
1959:
1954:
1950:
1945:
1940:
1936:
1932:
1928:
1924:
1920:
1912:
1909:
1904:
1900:
1896:
1892:
1888:
1884:
1877:
1874:
1869:
1865:
1861:
1857:
1853:
1849:
1842:
1840:
1836:
1831:
1827:
1822:
1817:
1813:
1809:
1805:
1798:
1795:
1790:
1786:
1781:
1776:
1772:
1768:
1764:
1760:
1756:
1749:
1746:
1741:
1737:
1732:
1727:
1723:
1719:
1715:
1711:
1707:
1700:
1698:
1694:
1681:
1677:
1673:
1666:
1663:
1658:
1654:
1649:
1644:
1639:
1634:
1630:
1626:
1623:(3): e17963.
1622:
1618:
1614:
1607:
1604:
1599:
1595:
1590:
1585:
1581:
1577:
1573:
1569:
1565:
1561:
1557:
1550:
1547:
1544:
1540:
1537:
1532:
1529:
1526:
1522:
1519:
1513:
1510:
1505:
1501:
1497:
1493:
1489:
1485:
1482:(3): 237–50.
1481:
1477:
1476:Neurobiol Dis
1470:
1467:
1462:
1458:
1454:
1450:
1447:(3): 407–15.
1446:
1442:
1434:
1431:
1428:
1424:
1421:
1416:
1413:
1408:
1404:
1400:
1396:
1391:
1386:
1383:(3): 166–70.
1382:
1378:
1374:
1367:
1365:
1361:
1358:
1352:
1349:
1344:
1342:9780803613973
1338:
1334:
1329:
1328:
1319:
1316:
1311:
1307:
1303:
1299:
1295:
1291:
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719:J. Med. Genet
716:
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690:
689:Optic atrophy
687:
685:
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667:
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632:
631:mitochondrial
628:
625:subunit 4 of
624:
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595:Theodor Leber
588:
586:
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476:near infrared
473:
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426:(trade name:
425:
424:nitroprusside
421:
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398:neurofilament
395:
391:
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354:visual acuity
347:
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206:visual acuity
203:
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4372: /
4351:Monochromacy
4283: /
4179:Heterophoria
4167: /
4052:
3877:
3866: /
3862: /
3766:hypertensive
3739: /
3560:Ciliary body
3475:Keratoglobus
3383:Episcleritis
3261:Enophthalmos
3256:Exophthalmos
3201:Trichomegaly
3196:Distichiasis
3098:Inflammation
3002:
2991:
2980:
2965:
2950:
2900:(1): 53–89.
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1974:
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575:heteroplasmy
571:
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543:Epidemiology
531:
527:
515:
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495:
487:
485:techniques.
483:viral vector
457:
451:-quinone, a
446:
440:
408:
402:
378:color vision
367:
351:
338:
297:
265:
254:
238:
221:color vision
199:
192:
131:mitochondria
129:contributes
102:
98:
97:
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4739:Chromosomal
4501:Cycloplegia
4444:Photophobia
4439:Hemeralopia
4396:Hemianopsia
4374:Vision loss
4285:Aniseikonia
4276:Astigmatism
4196:Cyclotropia
4174:Hypertropia
3986:Papilledema
3958:Optic nerve
3791:Sickle cell
3771:Purtscher's
3756:Retinopathy
3624:Choroiditis
3465:Keratoconus
3286:Conjunctiva
3163:Xanthelasma
3115:Blepharitis
2343:: 2339–43.
1716:(2): e230.
621:340 in the
472:glutathione
464:minocycline
460:brimonidine
449:Tocotrienol
328:glutathione
213:examination
41:Other names
4810:Categories
4672:Myopathies
4642:Primarily
4550:Infections
4471:Anisocoria
4434:Asthenopia
4427:subjective
4411:homonymous
4406:bitemporal
4358:Nyctalopia
4346:Dichromacy
4290:Presbyopia
4251:Refraction
4072:Strabismus
3962:Optic disc
3321:Pinguecula
3186:Trichiasis
3004:DiseasesDB
700:References
652:expressing
583:haplogroup
567:penetrance
562:, Canada.
549:prevalence
372:swelling.
322:2 in LHON
313:superoxide
165:and 14484
147:nucleotide
4794:see also
4522:Nystagmus
4496:Mydriasis
4370:Blindness
4316:Amblyopia
4304:Blindness
4264:Hyperopia
4189:Exophoria
4184:Esophoria
4169:Exotropia
4165:Esotropia
3703:Retinitis
3401:Keratitis
3378:Scleritis
3311:Pterygium
3191:Madarosis
3138:Ectropion
3133:Entropion
3110:Chalazion
2784:March 22,
2687:March 22,
2683:(7): 1088
1686:March 22,
1239:cite book
1206:203660987
1147:: 51–61.
1065:0006-8950
669:Amaurosis
635:thymidine
627:complex I
615:histidine
607:adenosine
537:idebenone
517:Estrogens
497:Idebenone
492:Idebenone
453:vitamin E
442:Idebenone
358:perimetry
348:Treatment
335:Diagnosis
309:apoptosis
179:complex I
119:mutations
89:Frequency
70:Specialty
4561:Trachoma
4326:Diplopia
4021:Ischemic
3946:Pathways
3860:Glaucoma
3761:diabetic
3663:Cataract
3601:Synechia
3453:Meesmann
3421:Exposure
3406:herpetic
3304:allergic
3294:Chemosis
3228:Epiphora
2922:15862778
2914:14766317
2835:24288396
2779:17151329
2738:23813215
2483:17668373
2434:11169561
2398:16380918
2349:18199976
2337:Mol. Vis
2318:15954041
2269:17406640
2228:12518276
2179:25143633
2138:28196731
2102:30899856
2046:26410888
2005:20943885
1953:24369379
1868:74119548
1830:21810891
1789:23263355
1740:23388409
1657:21483849
1617:PLOS ONE
1598:20393463
1539:Archived
1521:Archived
1504:30986663
1496:17822909
1461:16083844
1423:Archived
1407:22247204
1399:11001192
1310:15862778
1302:14766317
1231:32310424
1198:31584537
1163:17471325
1122:21600768
1083:21788663
1013:20301353
986:18235013
942:17296905
898:18182110
847:(OMIM):
749:15923271
679:Glaucoma
663:See also
659:models.
645:Research
639:cytosine
611:arginine
468:curcumin
251:Genetics
141:(mtDNA)
64:pattern.
4401:binasal
4388:Anopsia
4331:Scotoma
4125:palsies
3888:Red eye
3873:Floater
3680:Aphakia
3611:Choroid
3581:Hyphema
3571:Uveitis
3178:Eyelash
2998:D029242
2885:9292259
2826:4103197
2729:3736700
2658:1417830
2617:1674640
2608:1683111
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2556:Bibcode
2548:Science
2533:5063796
2524:1762279
2474:1950812
2389:1285165
2309:1224533
2093:6407313
1996:3025718
1944:3914475
1903:9477226
1780:3658961
1731:3572931
1648:3069029
1625:Bibcode
1589:2875160
1568:Bibcode
1154:1809912
1074:3170530
889:2266764
798:7629530
740:1735965
637:(T) to
629:of the
605:(G) to
603:guanine
589:History
579:alleles
428:Nipride
324:cybrids
316:radical
276:MT-ND4L
225:scotoma
181:of the
157:, 3460
133:to the
105:) is a
4775:TIMM8A
4491:Miosis
4269:Myopia
4048:Kjer's
3796:photic
3695:Retina
3448:Fuchs'
3416:fungal
3393:Cornea
3370:Sclera
3153:Ptosis
3090:Eyelid
3078:Adnexa
2987:535000
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280:MT-ND6
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272:MT-ND4
268:MT-ND1
210:fundus
135:embryo
123:genome
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4761:SARS2
4725:MNGIE
4697:MERRF
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4463:Pupil
3853:Other
3497:sicca
3349:Globe
3248:Orbit
2961:H47.2
2918:S2CID
1975:Brain
1923:Brain
1864:S2CID
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1710:Brain
1500:S2CID
1403:S2CID
1306:S2CID
1202:S2CID
1045:Brain
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175:genes
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4662:NARP
4657:LHON
4633:PDHA
3655:Lens
3555:Iris
3105:Stye
3009:7340
2993:MeSH
2982:OMIM
2971:9-CM
2910:PMID
2881:PMID
2831:PMID
2786:2016
2775:PMID
2734:PMID
2689:2016
2654:PMID
2613:PMID
2572:PMID
2529:PMID
2479:PMID
2430:PMID
2394:PMID
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2175:PMID
2134:PMID
2098:PMID
2042:PMID
2001:PMID
1949:PMID
1899:PMID
1826:PMID
1785:PMID
1736:PMID
1688:2016
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1594:PMID
1492:PMID
1457:PMID
1395:PMID
1337:ISBN
1298:PMID
1267:2021
1245:link
1227:PMID
1194:PMID
1159:PMID
1118:PMID
1079:PMID
1061:ISSN
1020:2018
1009:PMID
1005:NCBI
982:PMID
938:PMID
894:PMID
794:PMID
745:PMID
466:,
356:and
103:LHON
18:LHON
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4680:KSS
4628:PCD
2967:ICD
2952:ICD
2902:doi
2858:NLM
2856:at
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2765:doi
2724:PMC
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2603:PMC
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