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Hereditary Optic Neuropathy

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Abstract

Hereditary optic neuropathies are a cluster of disorders that can present with sudden, subacute, or slowly progressive visual decline, typically affecting the central vision and color vision. While they can be inherited in autosomal dominant, autosomal recessive, or maternal patterns, they share a common mechanism of mitochondrial dysfunction. There are no proven treatments, but there are some accepted supportive measures, as well as the option for preimplantation genetic testing in combination with in vitro fertilization.

Keywords

  • Genetics
  • Hereditary
  • Idebenone
  • Optic neuropathy
  • Central scotoma
  • Dyschromatopsia

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Fig. 9.1

References

  1. Bocquet B, Lacroux A, Surget MO, et al. Relative frequencies of inherited retinal dystrophies and optic neuropathies in Southern France: assessment of 21-year data management. Ophthalmic Epidemiol. 2013;20(1):13–25. https://doi.org/10.3109/09286586.2012.737890.

    CrossRef  PubMed  Google Scholar 

  2. Eustace Ryan S, Ryan F, Barton D, O'Dwyer V, Neylan D. Development and validation of a novel PCR-RFLP based method for the detection of 3 primary mitochondrial mutations in Leber's hereditary optic neuropathy patients. Eye Vis (Lond). 2015;2:18. Published 2015 Oct 25.

    CrossRef  Google Scholar 

  3. Mascialino B, Leinonen M, Meier T. Meta-analysis of the prevalence of Leber hereditary optic neuropathy mtDNA mutations in Europe. Eur J Ophthalmol. 2012;22(3):461–5. https://doi.org/10.5301/ejo.5000055.

    CrossRef  PubMed  Google Scholar 

  4. Elliott HR, Samuels DC, Eden JA, Relton CL, Chinnery PF. Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet. 2008;83(2):254–60. https://doi.org/10.1016/j.ajhg.2008.07.004.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  5. Jiang P, Liang M, Zhang J, et al. Prevalence of mitochondrial ND4 mutations in 1281 Han Chinese subjects with Leber's hereditary optic neuropathy. Invest Ophthalmol Vis Sci. 2015;56(8):4778–88. https://doi.org/10.1167/iovs.14-16158.

    CAS  CrossRef  PubMed  Google Scholar 

  6. Ueda K, Morizane Y, Shiraga F, et al. Nationwide epidemiological survey of Leber hereditary optic neuropathy in Japan. J Epidemiol. 2017;27(9):447–50. https://doi.org/10.1016/j.je.2017.02.001.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  7. Abu-Amero KK, Bosley TM. Mitochondrial abnormalities in patients with LHON-like optic neuropathies. Invest Ophthalmol Vis Sci. 2006;47(10):4211–20.

    CrossRef  Google Scholar 

  8. Bosley TM, Abu-Amero KK. Assessing mitochondrial DNA nucleotide changes in spontaneous optic neuropathies. Ophthalmic Genet. 2010;31(4):163–72. https://doi.org/10.3109/13816810.2010.514015.

    CAS  CrossRef  PubMed  Google Scholar 

  9. Amaral-Fernandes MS, Marcondes AM, do Amor Divino Miranda PM, Maciel-Guerra AT, Sartorato EL. Mutations for Leber hereditary optic neuropathy in patients with alcohol and tobacco optic neuropathy. Mol Vis. 2011;17:3175–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Cullom ME, Heher KL, Miller NR, Savino PJ, Johns DR. Leber's hereditary optic neuropathy masquerading as tobacco-alcohol amblyopia. Arch Ophthalmol. 1993;111(11):1482–5. https://doi.org/10.1001/archopht.1993.01090110048021.

    CAS  CrossRef  PubMed  Google Scholar 

  11. Li JM, Rucker JC. Irreversible optic neuropathy in Wernicke encephalopathy and Leber hereditary optic neuropathy. J Neuroophthalmol. 2010;30(1):49–53. https://doi.org/10.1097/WNO.0b013e3181ce80c6.

  12. Pott JW, Wong KH. Leber's hereditary optic neuropathy and vitamin B12 deficiency. Graefes Arch Clin Exp Ophthalmol. 2006;244(10):1357–9. https://doi.org/10.1007/s00417-006-0269-7.

    CAS  CrossRef  PubMed  Google Scholar 

  13. Luca CC, Lam BL, Moraes CT. Erythromycin as a potential precipitating agent in the onset of Leber's hereditary optic neuropathy. Mitochondrion. 2004;4(1):31–6. https://doi.org/10.1016/j.mito.2004.05.002.

    CAS  CrossRef  PubMed  Google Scholar 

  14. Cardaioli E, Da Pozzo P, Gallus GN, et al. Leber's hereditary optic neuropathy associated with cocaine, ecstasy and telithromycin consumption. J Neurol. 2007;254(2):255–6. https://doi.org/10.1007/s00415-006-0351-4.

    CrossRef  PubMed  Google Scholar 

  15. Carelli V, Ross-Cisneros FN, Sadun AA. Optic nerve degeneration and mitochondrial dysfunction: genetic and acquired optic neuropathies. Neurochem Int. 2002;40(6):573–84. https://doi.org/10.1016/s0197-0186(01)00129-2.

    CAS  CrossRef  PubMed  Google Scholar 

  16. Lüke C, Cornely OA, Fricke J, Lehrer E, Bartz-Schmidt KU. Late onset of Leber's hereditary optic neuropathy in HIV infection. Br J Ophthalmol. 1999;83(10):1204–5. https://doi.org/10.1136/bjo.83.10.1194k.

    CrossRef  PubMed  Google Scholar 

  17. Mackey DA, Fingert JH, Luzhansky JZ, et al. Leber's hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus. Eye (Lond). 2003;17(3):312–7. https://doi.org/10.1038/sj.eye.6700362.

    CAS  CrossRef  Google Scholar 

  18. Warner JE, Ries KM. Optic neuropathy in a patient with AIDS. J Neuroophthalmol. 2001;21(2):92–4. https://doi.org/10.1097/00041327-200106000-00006.

    CAS  CrossRef  PubMed  Google Scholar 

  19. Luzhansky JZ, Pierce AB, Hoy JF, Hall AJ. Leber's hereditary optic neuropathy in the setting of nucleoside analogue toxicity. AIDS. 2001;15(12):1588–9. https://doi.org/10.1097/00002030-200108170-00022.

    CAS  CrossRef  PubMed  Google Scholar 

  20. Oliveira C. Toxic-metabolic and hereditary optic neuropathies. Continuum (Minneap Minn). 2019;25(5):1265–88. https://doi.org/10.1212/CON.0000000000000769.

    CrossRef  Google Scholar 

  21. Dotti MT, Plewnia K, Cardaioli E, et al. A case of ethambutol-induced optic neuropathy harbouring the primary mitochondrial LHON mutation at nt 11778. J Neurol. 1998;245(5):302–3. https://doi.org/10.1007/s004150050223.

    CAS  CrossRef  PubMed  Google Scholar 

  22. Ikeda A, Ikeda T, Ikeda N, Kawakami Y, Mimura O. Leber's hereditary optic neuropathy precipitated by ethambutol. Jpn J Ophthalmol. 2006;50(3):280–3. https://doi.org/10.1007/s10384-005-0308-7.

    CrossRef  PubMed  Google Scholar 

  23. Fortuna F, Barboni P, Liguori R, et al. Visual system involvement in patients with Friedreich's ataxia. Brain. 2009;132(Pt 1):116–23. https://doi.org/10.1093/brain/awn269.

    CrossRef  PubMed  Google Scholar 

  24. Han J, Lee YM, Kim SM, Han SY, Lee JB, Han SH. Ophthalmological manifestations in patients with Leigh syndrome. Br J Ophthalmol. 2015;99(4):528–35. https://doi.org/10.1136/bjophthalmol-2014-305704.

    CrossRef  PubMed  Google Scholar 

  25. Åkebrand R, Andersson S, Seyedi Honarvar AK, et al. Ophthalmological characteristics in children with Leigh syndrome – A long-term follow-up. Acta Ophthalmol. 2016;94(6):609–17. https://doi.org/10.1111/aos.12983.

    CAS  CrossRef  PubMed  Google Scholar 

  26. Bosley TM, Brodsky MC, Glasier CM, Abu-Amero KK. Sporadic bilateral optic neuropathy in children: the role of mitochondrial abnormalities. Invest Ophthalmol Vis Sci. 2008;49(12):5250–6. https://doi.org/10.1167/iovs.08-2193.

    CrossRef  PubMed  Google Scholar 

  27. Orssaud C. Cardiac disorders in patients with Leber hereditary optic neuropathy. J Neuroophthalmol. 2018;38(4):466–9. https://doi.org/10.1097/WNO.0000000000000623.

    CrossRef  PubMed  Google Scholar 

  28. Govindaraj P, Rani B, Sundaravadivel P, et al. Mitochondrial genome variations in idiopathic dilated cardiomyopathy. Mitochondrion. 2019;48:51–9. https://doi.org/10.1016/j.mito.2019.03.003.

    CAS  CrossRef  PubMed  Google Scholar 

  29. Zhang Z, Liu M, He J, Zhang X, Chen Y, Li H. Maternally inherited coronary heart disease is associated with a novel mitochondrial tRNA mutation. BMC Cardiovasc Disord. 2019;19(1):293. Published 2019 Dec 16. https://doi.org/10.1186/s12872-019-01284-4.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  30. Bosley TM, Constantinescu CS, Tench CR, Abu-Amero KK. Mitochondrial changes in leukocytes of patients with optic neuritis. Mol Vis. 2007;13:1516–28. Published 2007 Aug 29.

    CAS  PubMed  Google Scholar 

  31. Bargiela D, Chinnery PF. Mitochondria in neuroinflammation – Multiple sclerosis (MS), Leber hereditary optic neuropathy (LHON) and LHON-MS. Neurosci Lett. 2019;710:132932. https://doi.org/10.1016/j.neulet.2017.06.051.

  32. Matthews L, Enzinger C, Fazekas F, et al. MRI in Leber's hereditary optic neuropathy: the relationship to multiple sclerosis. J Neurol Neurosurg Psychiatry. 2015;86(5):537–42. https://doi.org/10.1136/jnnp-2014-308186.

    CrossRef  PubMed  Google Scholar 

  33. Frye RE. Leber's hereditary optic neuropathy mutations associated with infantile-onset myoclonic epilepsy. J Child Neurol. 2011;26(6):782–5. https://doi.org/10.1177/0883073810391531.

    CrossRef  PubMed  Google Scholar 

  34. Cupini LM, Massa R, Floris R, et al. Migraine-like disorder segregating with mtDNA 14484 Leber hereditary optic neuropathy mutation. Neurology. 2003;60(4):717–9. https://doi.org/10.1212/01.wnl.0000048662.77572.fb.

    CAS  CrossRef  PubMed  Google Scholar 

  35. La Morgia C, Achilli A, Iommarini L, et al. Rare mtDNA variants in Leber hereditary optic neuropathy families with recurrence of myoclonus. Neurology. 2008;70(10):762–70. https://doi.org/10.1212/01.wnl.0000295505.74234.d0.

    CAS  CrossRef  PubMed  Google Scholar 

  36. Meire FM, Van Coster R, Cochaux P, Obermaier-Kusser B, Candaele C, Martin JJ. Neurological disorders in members of families with Leber's hereditary optic neuropathy (LHON) caused by different mitochondrial mutations. Ophthalmic Genet. 1995;16(3):119–26. https://doi.org/10.3109/13816819509059971.

    CAS  CrossRef  PubMed  Google Scholar 

  37. Nikoskelainen EK, Marttila RJ, Huoponen K, et al. Leber's "plus": neurological abnormalities in patients with Leber's hereditary optic neuropathy. J Neurol Neurosurg Psychiatry. 1995;59(2):160–4. https://doi.org/10.1136/jnnp.59.2.160.

    CAS  CrossRef  PubMed  PubMed Central  Google Scholar 

  38. Yu-Wai-Man P, Griffiths PG, Burke A, et al. The prevalence and natural history of dominant optic atrophy due to OPA1 mutations. Ophthalmology. 2010;117(8):1538–1546.e1. https://doi.org/10.1016/j.ophtha.2009.12.038.

    CrossRef  PubMed  Google Scholar 

  39. Yen MY, Wang AG, Lin YC, Fann MJ, Hsiao KJ. Novel mutations of the OPA1 gene in Chinese dominant optic atrophy. Ophthalmology. 2010;117(2):392–6.e1. https://doi.org/10.1016/j.ophtha.2009.07.019.

    CrossRef  PubMed  Google Scholar 

  40. Chen J, Xu K, Zhang X, et al. Mutation screening of mitochondrial DNA as well as OPA1 and OPA3 in a Chinese cohort with suspected hereditary optic atrophy. Invest Ophthalmol Vis Sci. 2014;55(10):6987–95. Published 2014 Sep 9. https://doi.org/10.1167/iovs.14-14953.

    CAS  CrossRef  PubMed  Google Scholar 

  41. Amati-Bonneau P, Valentino ML, Reynier P, et al. OPA1 mutations induce mitochondrial DNA instability and optic atrophy 'plus' phenotypes. Brain. 2008;131(Pt 2):338–51. https://doi.org/10.1093/brain/awm298.

    CrossRef  PubMed  Google Scholar 

  42. Hudson G, Amati-Bonneau P, Blakely EL, et al. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain. 2008;131(Pt 2):329–37. https://doi.org/10.1093/brain/awm272.

    CrossRef  PubMed  Google Scholar 

  43. Yu-Wai-Man P, Shankar SP, Biousse V, et al. Genetic screening for OPA1 and OPA3 mutations in patients with suspected inherited optic neuropathies. Ophthalmology. 2011;118(3):558–63. https://doi.org/10.1016/j.ophtha.2010.07.029.

    CrossRef  PubMed  Google Scholar 

  44. Nasca A, Rizza T, Doimo M, et al. Not only dominant, not only optic atrophy: expanding the clinical spectrum associated with OPA1 mutations. Orphanet J Rare Dis. 2017;12(1):89. Published 2017 May 12. https://doi.org/10.1186/s13023-017-0641-1.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  45. Grenier J, Meunier I, Daien V, et al. WFS1 in optic neuropathies: mutation findings in nonsyndromic optic atrophy and assessment of clinical severity. Ophthalmology. 2016;123(9):1989–98. https://doi.org/10.1016/j.ophtha.2016.05.036.

    CrossRef  PubMed  Google Scholar 

  46. Bansal V, Boehm BO, Darvasi A. Identification of a missense variant in the WFS1 gene that causes a mild form of Wolfram syndrome and is associated with risk for type 2 diabetes in Ashkenazi Jewish individuals. Diabetologia. 2018;61(10):2180–8. https://doi.org/10.1007/s00125-018-4690-3.

    CAS  CrossRef  PubMed  Google Scholar 

  47. Rigoli L, Aloi C, Salina A, et al. Wolfram syndrome 1 in the Italian population: genotype-phenotype correlations. Pediatr Res. 2020;87(3):456–62. https://doi.org/10.1038/s41390-019-0487-4.

    CAS  CrossRef  PubMed  Google Scholar 

  48. Karzon R, Narayanan A, Chen L, Lieu JEC, Hershey T. Longitudinal hearing loss in Wolfram syndrome. Orphanet J Rare Dis. 2018;13(1):102. Published 2018 Jun 27. https://doi.org/10.1186/s13023-018-0852-0.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  49. Klopstock T, Yu-Wai-Man P, Dimitriadis K, et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain. 2011;134(Pt 9):2677–86. https://doi.org/10.1093/brain/awr170.

    CrossRef  PubMed  PubMed Central  Google Scholar 

  50. Bueno GE, Ruiz-Castañeda D, Martínez JR, Muñoz MR, Alascio PC. Natural history and clinical characteristics of 50 patients with Wolfram syndrome. Endocrine. 2018;61(3):440–6. https://doi.org/10.1007/s12020-018-1608-2. Epub 2018 May 4. PMID: 29728875.

  51. Pemp B, Kircher K, Reitner A. Visual function in chronic Leber's hereditary optic neuropathy during idebenone treatment initiated 5 to 50 years after onset. Graefes Arch Clin Exp Ophthalmol. 2019;257(12):2751–7. https://doi.org/10.1007/s00417-019-04444-6.

    CAS  CrossRef  PubMed  Google Scholar 

  52. Carelli V, Carbonelli M, de Coo IF, et al. International consensus statement on the clinical and therapeutic management of Leber hereditary optic neuropathy. J Neuroophthalmol. 2017;37(4):371–81. https://doi.org/10.1097/WNO.0000000000000570.

  53. Zuccarelli M, Vella-Szijj J, Serracino-Inglott A, Borg J-J. Treatment of Leber’s hereditary optic neuropathy: an overview of recent developments. Eur J Ophthalmol. 2020; https://doi.org/10.1177/1120672120936592.

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Carey, A.R. (2021). Hereditary Optic Neuropathy. In: Henderson, A.D., Carey, A.R. (eds) Controversies in Neuro-Ophthalmic Management. Springer, Cham. https://doi.org/10.1007/978-3-030-74103-7_9

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