Documenta Ophthalmologica

, Volume 130, Issue 3, pp 179–187 | Cite as

Clinical and electrophysiology findings in Slovene patients with Leber hereditary optic neuropathy

  • Martina Jarc-VidmarEmail author
  • Mojca Tajnik
  • Jelka Brecelj
  • Ana Fakin
  • Maja Sustar
  • Mateja Naji
  • Branka Stirn-Kranjc
  • Damjan Glavač
  • Marko Hawlina
Original Research Article



To report clinical and electrophysiology findings in Slovene patients with Leber hereditary optic neuropathy (LHON).


Eight patients with LHON (11–26 years; one female and seven males) were examined in acute stages and at follow-up visits by means of Snellen visual acuity, Ishihara color vision, Goldmann or Octopus G2TOP perimetry, fluorescein angiography (FAG), pattern electroretinogram (PERG), visual evoked potentials (VEP) and genetic testing.


Patients presented with typical LHON phenotype with bilateral visual acuity loss, abnormal color vision, central scotoma and hyperemic discs with no leakage on FAG. In the acute stage, electrophysiology was performed in 7/8 patients. The PERG P50 component was normal in 14/14 eyes, while the N95 component was reduced in 7/14 eyes. VEP wave P100 was reduced and delayed in 14/14 eyes. In this stage, temporal pallor of the optic disc was visible in 4/7 eyes with reduced PERG N95. At follow-up (1–11 months after), a reduced PERG N95 component was seen in 13/14 eyes and severely affected VEP in all eyes. In the only eye with a normal PERG N95, hyperemic optic disc was seen 5 months after visual acuity loss, while it was atrophic in all the others. Known mutations (14484T>C, 3460G>A) were found in 2/8 patients, while in others high-throughput sequencing identified new potentially pathogenic mutations.


In Leber hereditary optic neuropathy, a reduced N95 component of PERG and severely reduced VEP P100 may be present already in the acute stage of disease, before optic disc pallor appears, suggesting primary dysfunction of retinal ganglion cells.


LHON Leber hereditary optic neuropathy Electrophysiology PERG VEP 



All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. This study was partially supported by Slovenian Research Agency (ARRS P3-0333). The authors are grateful to Mrs. Marija Jesenšek, Mrs. Ana Jeršin and Mrs. Helena Lindič, who were involved in the clinical ERG and VEP recording.


  1. 1.
    Yen MY, Wang AG, Wei YH (2006) Leber’s hereditary optic neuropathy: a multifactorial disease. Prog Retin Eye Res 25(4):381–396CrossRefPubMedGoogle Scholar
  2. 2.
    Kirches E (2011) LHON: mitochondrial mutations and more. Curr Genomics 12(1):44–54CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Fraser JA, Biousse V, Newman NJ (2010) The neuro-ophthalmology of mitochondrial disease. Surv Ophthalmol 55(4):299–334CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Nikoskelainen EK, Huoponen K, Juvonen V et al (1996) Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology 103(3):504–514CrossRefPubMedGoogle Scholar
  5. 5.
    Yu-Wai-Man P, Griffiths PG, Chinnery PF (2011) Mitochondrial optic neuropathies—disease mechanisms and therapeutic strategies. Prog Retin Eye Res 30(2):81–114CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Holder GE (1997) The pattern electroretinogram in anterior visual pathway dysfunction and its relationship to the pattern visual evoked potential: a personal clinical review of 743 eyes. Eye 11:924–934CrossRefPubMedGoogle Scholar
  7. 7.
    Klopstock T, Yu-Wai-Man P, Dimitriadis K et al (2011) A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy. Brain 134:2677–2686CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF (2009) Inherited mitochondrial optic neuropathies. J Med Genet 46(3):145–158CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Huoponen K, Vilkki J, Aula P et al (1991) A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy. Am J Hum Genet 48(6):1147–1153PubMedCentralPubMedGoogle Scholar
  10. 10.
    Howell N, Bindoff LA, McCullough DA et al (1991) Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees. Am J Hum Genet 49(5):939–950PubMedCentralPubMedGoogle Scholar
  11. 11.
    Wallace DC, Singh G, Lott MT et al (1988) Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science 242(4884):1427–1430CrossRefPubMedGoogle Scholar
  12. 12.
    Johns DR, Neufeld MJ, Park RD (1992) An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy. Biochem Biophys Res Commun 187(3):1551–1557CrossRefPubMedGoogle Scholar
  13. 13.
    Kumar M, Kaur P, Saxena R et al (2012) Clinical characterization and mitochondrial DNA sequence variations in Leber hereditary optic neuropathy. Mol Vis 18:2687–2699PubMedCentralPubMedGoogle Scholar
  14. 14.
    Korkiamaki P, Kervinen M, Karjalainen K et al (2013) Prevalence of the primary LHON mutations in Northern Finland associated with bilateral optic atrophy and tobacco–alcohol amblyopia. Acta Ophthalmol 91(7):630–634CrossRefPubMedGoogle Scholar
  15. 15.
    Taylor RW, Jobling MS, Turnbull DM, Chinnery PF (2003) Frequency of rare mitochondrial DNA mutations in patients with suspected Leber’s hereditary optic neuropathy. J Med Genet 40(7):e85CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Odom JV, Bach M, Brigell M et al (2010) ISCEV standard for clinical visual evoked potentials (2009 update). Doc Ophthalmol 120(1):111–119CrossRefPubMedGoogle Scholar
  17. 17.
    Bach M, Brigell MG, Hawlina M et al (2013) ISCEV standard for clinical pattern electroretinography (PERG): 2012 update. Doc Ophthalmol 126(1):1–7CrossRefPubMedGoogle Scholar
  18. 18.
    Hawlina M, Konec B (1992) New noncorneal HK-loop electrode for clinical electroretinography. Doc Ophthalmol 81(2):253–259CrossRefPubMedGoogle Scholar
  19. 19.
    Shibata K, Shibagaki Y, Nagai C, Iwata M (1999) Visual evoked potentials and electroretinograms in an early stage of Leber’s hereditary optic neuropathy. J Neurol 246(9):847–849CrossRefPubMedGoogle Scholar
  20. 20.
    Riordan-Eva P, Harding AE (1995) Leber’s hereditary optic neuropathy: the clinical relevance of different mitochondrial DNA mutations. J Med Genet 32(2):81–87CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Dorfman LJ, Nikoskelainen E, Rosenthal AR, Sogg RL (1977) Visual evoked potentials in Leber’s hereditary optic neuropathy. Ann Neurol 1(6):565–568CrossRefPubMedGoogle Scholar
  22. 22.
    Mondelli M, Rossi A, Scarpini C et al (1990) BAEP changes in Leber’s hereditary optic atrophy: further confirmation of multisystem involvement. Acta Neurol Scand 81(4):349–353CrossRefPubMedGoogle Scholar
  23. 23.
    Ziccardi L, Sadun F, De Negri AM et al (2013) Retinal function and neural conduction along the visual pathways in affected and unaffected carriers with Leber’s hereditary optic neuropathy. Invest Ophthalmol Vis Sci 54:6893–6901CrossRefPubMedGoogle Scholar
  24. 24.
    Kwittken J, Barest HD (1958) The neuropathology of hereditary optic atrophy (Leber’s disease); the first complete anatomic study. Am J Pathol 34(1):185–207PubMedCentralPubMedGoogle Scholar
  25. 25.
    Cortopassi G, Danielson S, Alemi M et al (2006) Mitochondrial disease activates transcripts of the unfolded protein response and cell cycle and inhibits vesicular secretion and oligodendrocyte-specific transcripts. Mitochondrion 6(4):161–175CrossRefPubMedGoogle Scholar
  26. 26.
    Carelli V, Ross-Cisneros FN, Sadun AA (2004) Mitochondrial dysfunction as a cause of optic neuropathies. Prog Retin Eye Res 23(1):53–89CrossRefPubMedGoogle Scholar
  27. 27.
    Lenassi E, Robson AG, Hawlina M, Holder GE (2012) The value of two-field pattern electroretinogram in routine clinical electrophysiologic practice. Retina 32(3):588–599CrossRefPubMedGoogle Scholar
  28. 28.
    Acaroglu G, Kansu T, Dogulu CF (2001) Visual recovery patterns in children with Leber’s hereditary optic neuropathy. Int Ophthalmol 24(6):349–355CrossRefPubMedGoogle Scholar
  29. 29.
    Barboni P, Savini G, Valentino ML et al (2006) Leber’s hereditary optic neuropathy with childhood onset. Invest Ophthalmol Vis Sci 47(12):5303–5309CrossRefPubMedGoogle Scholar
  30. 30.
    Hrynchak PK, Spafford MM (1994) Visual recovery in a patient with Leber hereditary optic neuropathy and the 14484 mutation. Optom Vis Sci 71(10):604–612CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Martina Jarc-Vidmar
    • 1
    Email author
  • Mojca Tajnik
    • 2
  • Jelka Brecelj
    • 1
  • Ana Fakin
    • 1
  • Maja Sustar
    • 1
  • Mateja Naji
    • 3
  • Branka Stirn-Kranjc
    • 1
  • Damjan Glavač
    • 2
  • Marko Hawlina
    • 1
  1. 1.Eye HospitalUniversity Medical CentreLjubljanaSlovenia
  2. 2.Department of Molecular Genetics, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia
  3. 3.University Medical Center MariborMariborSlovenia

Personalised recommendations