Skip to main content
Top
Published in: BMC Ophthalmology 1/2017

Open Access 01-12-2017 | Research article

Visual prognosis better in eyes with less severe reduction of visual acuity one year after onset of Leber hereditary optic neuropathy caused by the 11,778 mutation

Authors: Yukihiko Mashima, Kazuteru Kigasawa, Kei Shinoda, Masato Wakakura, Yoshihisa Oguchi

Published in: BMC Ophthalmology | Issue 1/2017

Login to get access

Abstract

Background

Patients with Leber hereditary optic neuropathy (LHON) have a progressive decrease of their visual acuity which can deteriorate to <0.1. Some patients can have a partial recovery of their vision in one or both eyes. One prognostic factor associated with a recovery of vision is an early-age onset. The purpose of this study was to determine other clinical factors that are predictive of a good visual recovery.

Methods

Sixty-one Japanese LHON patients, with the 11,778 mutation and a mean age of 23.1 ± 12.1 years at the onset, were studied. All patients were initially examined at an acute stage of LHON and were followed for 3 to 10 years. At 1 year after the onset, the lowest visual acuity was <0.1 in all eyes. We studied the following parameters of patients with/without a final visual acuity of ≥ 0.2: sex; heavy consumption of cigarettes and alcohol; taking idebenone; mean age at onset; mean lowest visual acuity; and distribution of the lowest and the final visual acuity.

Results

Fifteen (24.6%) of the 61 patients or 25 (20.5%) of the 122 eyes had a recovery of their visual acuity to ≥ 0.2. The mean age at onset of these 15 patients with visual recovery to ≥ 0.2 was 17.5 ± 7.7 years, and that of the 46 patients without visual recovery to ≥ 0.2 was 25.0 ± 12.8 years (P = 0.02, Mann-Whitney U test). The mean lowest visual acuity of the 25 eyes with visual recovery ≥ 0.2 was 0.04, and that of the 97 eyes without visual recovery to ≥ 0.2 was 0.015 (P < 0.001, Mann-Whitney U test). Fifty percent (15/30) of the eyes whose lowest visual acuity was ≥ 0.04 during 1 year after the onset had a visual recovery to ≥ 0.2, while 11% (10/92) of the eyes whose the lowest visual acuity was ≤ 0.03 had a visual recovery to ≥ 0.2 (P < 0.001, χ 2 test). There were no significant differences in the other clinical factors.

Conclusion

A final visual acuity of ≥ 0.2 was associated with a less severe reduction of the visual acuity at 1 year after the onset. Our findings can be used to predict the visual prognosis in LHON patients.
Literature
1.
go back to reference Yu-Wai-Man P, Griffiths PG, Brown DT, Howell N, Turnbull DM, Chinnery PF. The epidemiology of Leber hereditary optic neuropathy in the north east of England. Am J Hum Genet. 2003;72:333–9.CrossRef Yu-Wai-Man P, Griffiths PG, Brown DT, Howell N, Turnbull DM, Chinnery PF. The epidemiology of Leber hereditary optic neuropathy in the north east of England. Am J Hum Genet. 2003;72:333–9.CrossRef
2.
go back to reference Puomila A, Hämäläinen P, Kivioja S, Savontaus ML, Koivumäki S, Huoponen K, et al. Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland. Eur J Hum Genet. 2007;15:1079–89.CrossRefPubMed Puomila A, Hämäläinen P, Kivioja S, Savontaus ML, Koivumäki S, Huoponen K, et al. Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland. Eur J Hum Genet. 2007;15:1079–89.CrossRefPubMed
3.
go back to reference Newman NJ. The hereditary optic neuropathies. In: Miller NR, Newman NJ, editors. Walsh and Hoyt's clinical neuro-ophthalmology, vol. 1. 5th ed. Baltimore: Williams and Wilkins; 1998. p. 741–73. Newman NJ. The hereditary optic neuropathies. In: Miller NR, Newman NJ, editors. Walsh and Hoyt's clinical neuro-ophthalmology, vol. 1. 5th ed. Baltimore: Williams and Wilkins; 1998. p. 741–73.
4.
go back to reference Mackey DA, Oostra RJ, Rosenberg T, Nikoskelainen E, Bronte-Stewart J, Poulton J, et al. Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. Am J Hum Genet. 1996;59:481–5.PubMedPubMedCentral Mackey DA, Oostra RJ, Rosenberg T, Nikoskelainen E, Bronte-Stewart J, Poulton J, et al. Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy. Am J Hum Genet. 1996;59:481–5.PubMedPubMedCentral
5.
go back to reference Mashima Y, Yamada K, Wakakura M, Kigasawa K, Kudoh J, Shimizu N, et al. Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy. Curr Eye Res. 1998;17:403–8.CrossRefPubMed Mashima Y, Yamada K, Wakakura M, Kigasawa K, Kudoh J, Shimizu N, et al. Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy. Curr Eye Res. 1998;17:403–8.CrossRefPubMed
6.
go back to reference Yu-Wai-Man P, Griffiths PG, Chinnery PF. Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies. Prog Retin Eye Res. 2011;30:81–114.CrossRefPubMedPubMedCentral Yu-Wai-Man P, Griffiths PG, Chinnery PF. Mitochondrial optic neuropathies - disease mechanisms and therapeutic strategies. Prog Retin Eye Res. 2011;30:81–114.CrossRefPubMedPubMedCentral
7.
go back to reference Newman NJ, Lott MT, Wallace DC. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am J Ophthalmol. 1991;111:750–62.CrossRefPubMed Newman NJ, Lott MT, Wallace DC. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. Am J Ophthalmol. 1991;111:750–62.CrossRefPubMed
8.
go back to reference Oostra RJ, Bolhuis PA, Wijburg FA, Zorn-Ende G, Bleeker-Wagemakers EM. Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome. J Med Genet. 1994;31:280–6.CrossRefPubMedPubMedCentral Oostra RJ, Bolhuis PA, Wijburg FA, Zorn-Ende G, Bleeker-Wagemakers EM. Leber's hereditary optic neuropathy: correlations between mitochondrial genotype and visual outcome. J Med Genet. 1994;31:280–6.CrossRefPubMedPubMedCentral
9.
go back to reference Riordan-Eva P, Sanders MD, Govan GG, Sweeney MG, Da Costa J, Harding AE. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain. 1995;118:319–37.CrossRefPubMed Riordan-Eva P, Sanders MD, Govan GG, Sweeney MG, Da Costa J, Harding AE. The clinical features of Leber's hereditary optic neuropathy defined by the presence of a pathogenic mitochondrial DNA mutation. Brain. 1995;118:319–37.CrossRefPubMed
10.
go back to reference Nikoskelainen EK, Huoponen K, Juvonen V, Lamminen T, Nummelin K, Savontaus ML. Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology. 1996;103:504–14.CrossRefPubMed Nikoskelainen EK, Huoponen K, Juvonen V, Lamminen T, Nummelin K, Savontaus ML. Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology. 1996;103:504–14.CrossRefPubMed
11.
go back to reference Spruijt L, Kolbach DN, de Coo RF, Plomp AS, Bauer NJ, Smeets HJ, et al. Influence of mutation type on clinical expression of Leber hereditary optic neuropathy. Am J Ophthalmol. 2006;141:676–82.CrossRefPubMed Spruijt L, Kolbach DN, de Coo RF, Plomp AS, Bauer NJ, Smeets HJ, et al. Influence of mutation type on clinical expression of Leber hereditary optic neuropathy. Am J Ophthalmol. 2006;141:676–82.CrossRefPubMed
12.
go back to reference Johns DR, Heher KL, Miller NR, Smith KH. Leber's hereditary optic neuropathy. Clinical manifestations of the 14484 mutation. Arch Ophthalmol. 1993;111:495–8.CrossRefPubMed Johns DR, Heher KL, Miller NR, Smith KH. Leber's hereditary optic neuropathy. Clinical manifestations of the 14484 mutation. Arch Ophthalmol. 1993;111:495–8.CrossRefPubMed
13.
go back to reference Johns DR, Smith KH, Miller NR. Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation. Arch Ophthalmol. 1992;110:1577–81.CrossRefPubMed Johns DR, Smith KH, Miller NR. Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation. Arch Ophthalmol. 1992;110:1577–81.CrossRefPubMed
14.
go back to reference Hotta Y, Fujiki K, Hayakawa M, Nakajima A, Kanai A, Mashima Y, et al. Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA. Jpn J Ophthalmol. 1995;39:96–108.PubMed Hotta Y, Fujiki K, Hayakawa M, Nakajima A, Kanai A, Mashima Y, et al. Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA. Jpn J Ophthalmol. 1995;39:96–108.PubMed
15.
go back to reference Jacobson DM, Stone EM. Difficulty differentiating Leber's from dominant optic neuropathy in a patient with remote visual loss. J Clin Neuro-ophthalmol. 1991;11:152–7. Jacobson DM, Stone EM. Difficulty differentiating Leber's from dominant optic neuropathy in a patient with remote visual loss. J Clin Neuro-ophthalmol. 1991;11:152–7.
16.
go back to reference Stone EM, Newman NJ, Miller NR, Johns DR, Lott MT, Wallace DC. Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation. J Clin Neuro-ophthalmol. 1992;12:10–4. Stone EM, Newman NJ, Miller NR, Johns DR, Lott MT, Wallace DC. Visual recovery in patients with Leber's hereditary optic neuropathy and the 11778 mutation. J Clin Neuro-ophthalmol. 1992;12:10–4.
17.
go back to reference Zhu D, Economou EP, Antonarakis SE, Maumenee IH. Mitochondrial NA mutation and heteroplasmy in type I Leber hereditary optic neuropathy. Am J Med Genet. 1992;42:173–9.CrossRefPubMed Zhu D, Economou EP, Antonarakis SE, Maumenee IH. Mitochondrial NA mutation and heteroplasmy in type I Leber hereditary optic neuropathy. Am J Med Genet. 1992;42:173–9.CrossRefPubMed
18.
go back to reference Salmaggi A, Carrara F, Zeviani M. Remarkable recovery of visual function in a patient with Leber's optic neuropathy and multiple mutations of mitochondrial DNA. Intern J Neuroscience. 1994;77:261–6.CrossRef Salmaggi A, Carrara F, Zeviani M. Remarkable recovery of visual function in a patient with Leber's optic neuropathy and multiple mutations of mitochondrial DNA. Intern J Neuroscience. 1994;77:261–6.CrossRef
19.
go back to reference Oostra RJ, Tijmes NT, Cobben JM, Bolhuis PA, van Nesselrooij BP, Houtman WA, et al. On the many faces of Leber hereditary optic neuropathy. Clin Genet. 1997;51:388–93.CrossRefPubMed Oostra RJ, Tijmes NT, Cobben JM, Bolhuis PA, van Nesselrooij BP, Houtman WA, et al. On the many faces of Leber hereditary optic neuropathy. Clin Genet. 1997;51:388–93.CrossRefPubMed
20.
go back to reference Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S, Bailie M, et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain. 2011;134:2677–86.CrossRefPubMedPubMedCentral Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S, Bailie M, et al. A randomized placebo-controlled trial of idebenone in Leber's hereditary optic neuropathy. Brain. 2011;134:2677–86.CrossRefPubMedPubMedCentral
21.
go back to reference Klopstock T, Metz G, Yu-Wai-Man P, Büchner B, Gallenmüller C, Bailie M, et al. Persistence of the treatment effect of idebenone in Leber's hereditary optic neuropathy. Brain. 2013;136(Pt 2):e230.CrossRefPubMedPubMedCentral Klopstock T, Metz G, Yu-Wai-Man P, Büchner B, Gallenmüller C, Bailie M, et al. Persistence of the treatment effect of idebenone in Leber's hereditary optic neuropathy. Brain. 2013;136(Pt 2):e230.CrossRefPubMedPubMedCentral
22.
go back to reference Mashima Y, Kigasawa K, Wakakura M, Oguchi Y. Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy ? J Neuroophthalmol. 2000;20:166–70.CrossRefPubMed Mashima Y, Kigasawa K, Wakakura M, Oguchi Y. Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy ? J Neuroophthalmol. 2000;20:166–70.CrossRefPubMed
23.
go back to reference Sugiyama T, Azuma I. Effect of UF-021 on optic nerve head circulation in rabbits. Jpn J Ophthalmol. 1995;39:124–9.PubMed Sugiyama T, Azuma I. Effect of UF-021 on optic nerve head circulation in rabbits. Jpn J Ophthalmol. 1995;39:124–9.PubMed
24.
go back to reference Cuppoletti J, Malinowska DH, Tewari KP, Chakrabarti J, Ueno R. Cellular and molecular effects of unoprostone as a BK channel activator. Biochim Biophys Acta. 2007;1768:1083–92.CrossRefPubMed Cuppoletti J, Malinowska DH, Tewari KP, Chakrabarti J, Ueno R. Cellular and molecular effects of unoprostone as a BK channel activator. Biochim Biophys Acta. 2007;1768:1083–92.CrossRefPubMed
25.
go back to reference Barboni P, Savini G, Valentino ML, La Morgia C, Bellusci C, De Negri AM, et al. Leber's hereditary optic neuropathy with childhood onset. Invest Ophthalmol Vis Sci. 2006;47:5303–9.CrossRefPubMed Barboni P, Savini G, Valentino ML, La Morgia C, Bellusci C, De Negri AM, et al. Leber's hereditary optic neuropathy with childhood onset. Invest Ophthalmol Vis Sci. 2006;47:5303–9.CrossRefPubMed
26.
go back to reference Barboni P, Savini G, Valentino ML, Montagna P, Cortelli P, De Negri AM, et al. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. Ophthalmology. 2005;112:120–6.CrossRefPubMed Barboni P, Savini G, Valentino ML, Montagna P, Cortelli P, De Negri AM, et al. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber's hereditary optic neuropathy. Ophthalmology. 2005;112:120–6.CrossRefPubMed
27.
go back to reference Ramos Cdo V, Bellusci C, Savini G, Carbonelli M, Berezovsky A, Tamaki C, et al. Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy. Invest Ophthalmol Vis Sci. 2009;50:1666–74.CrossRefPubMed Ramos Cdo V, Bellusci C, Savini G, Carbonelli M, Berezovsky A, Tamaki C, et al. Association of optic disc size with development and prognosis of Leber's hereditary optic neuropathy. Invest Ophthalmol Vis Sci. 2009;50:1666–74.CrossRefPubMed
28.
go back to reference Torroni A, Petrozzi M, D'Urbano L, Sellitto D, Zeviani M, Carrara F, et al. Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. Am J Hum Genet. 1997;60:1107–21.PubMedPubMedCentral Torroni A, Petrozzi M, D'Urbano L, Sellitto D, Zeviani M, Carrara F, et al. Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. Am J Hum Genet. 1997;60:1107–21.PubMedPubMedCentral
29.
go back to reference Hudson G, Carelli V, Spruijt L, Gerards M, Mowbray C, Achilli A, et al. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background. Am J Hum Genet. 2007;81:228–33.CrossRefPubMedPubMedCentral Hudson G, Carelli V, Spruijt L, Gerards M, Mowbray C, Achilli A, et al. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background. Am J Hum Genet. 2007;81:228–33.CrossRefPubMedPubMedCentral
30.
go back to reference Sudoyo H, Suryadi H, Lertrit P, Pramoonjago P, Lyrawati D, Marzuki S. Asian-specific mtDNA backgrounds associated with the primary G11778A mutation of Leber's hereditary optic neuropathy. J Hum Genet. 2002;47:594–604.CrossRefPubMed Sudoyo H, Suryadi H, Lertrit P, Pramoonjago P, Lyrawati D, Marzuki S. Asian-specific mtDNA backgrounds associated with the primary G11778A mutation of Leber's hereditary optic neuropathy. J Hum Genet. 2002;47:594–604.CrossRefPubMed
31.
go back to reference Mashima Y, Sato EA, Ohde H, Oguchi Y. Macular nerve fibers temporal to fovea may have a greater potential to recover function in patients with Leber's hereditary optic neuropathy. Jpn J Ophthalmol. 2002;46:660–7.CrossRefPubMed Mashima Y, Sato EA, Ohde H, Oguchi Y. Macular nerve fibers temporal to fovea may have a greater potential to recover function in patients with Leber's hereditary optic neuropathy. Jpn J Ophthalmol. 2002;46:660–7.CrossRefPubMed
32.
go back to reference Altpeter EK, Blanke BR, Leo-Kottler B, Nguyen XN, Trauzettel-Klosinski S. Evaluation of fixation pattern and reading ability in patients with Leber hereditary optic neuropathy. J Neuroophthalmol. 2013;33:344–8.CrossRefPubMed Altpeter EK, Blanke BR, Leo-Kottler B, Nguyen XN, Trauzettel-Klosinski S. Evaluation of fixation pattern and reading ability in patients with Leber hereditary optic neuropathy. J Neuroophthalmol. 2013;33:344–8.CrossRefPubMed
33.
go back to reference Hadavi S, Markowitz SN, Reyes SV. Leber's neuropathy and preferred retinal loci. Can J Ophthalmol. 2013;48:e8–9.CrossRefPubMed Hadavi S, Markowitz SN, Reyes SV. Leber's neuropathy and preferred retinal loci. Can J Ophthalmol. 2013;48:e8–9.CrossRefPubMed
34.
go back to reference Hotta Y, Hayakawa M, Fujiki K, Shinohara K, Sado K, Kanai A, et al. An atypical Leber's hereditary optic neuropathy with the 11778 mutation. Br J Ophthalmol. 1993;77:748–50.CrossRefPubMedPubMedCentral Hotta Y, Hayakawa M, Fujiki K, Shinohara K, Sado K, Kanai A, et al. An atypical Leber's hereditary optic neuropathy with the 11778 mutation. Br J Ophthalmol. 1993;77:748–50.CrossRefPubMedPubMedCentral
35.
go back to reference Bynke H, Bynke G, Rosenberg T. Is Leber’s hereditary optic neuropathy a retinal disorder ? Neuro-Ophthalmology. 1996;16:115–23.CrossRef Bynke H, Bynke G, Rosenberg T. Is Leber’s hereditary optic neuropathy a retinal disorder ? Neuro-Ophthalmology. 1996;16:115–23.CrossRef
36.
go back to reference Mashima Y, Ohde H, Kamoshita I. A case of 37-year-old man with Leber’s hereditary optic neuropathy and visual recovery [article in Japanese]. Ganka Opthalmology. 2006;48:1171–7. Mashima Y, Ohde H, Kamoshita I. A case of 37-year-old man with Leber’s hereditary optic neuropathy and visual recovery [article in Japanese]. Ganka Opthalmology. 2006;48:1171–7.
37.
go back to reference Kobayashi Y, Endo Y, Ito N, Iijima Y, Mizuki N. A case of Leber's hereditary optic neuropathy in a female patient with the recrudescence of hyperthyroidism [article in Japanese]. Nippon Ganka Gakkai Zasshi. 2007;111:905–10.PubMed Kobayashi Y, Endo Y, Ito N, Iijima Y, Mizuki N. A case of Leber's hereditary optic neuropathy in a female patient with the recrudescence of hyperthyroidism [article in Japanese]. Nippon Ganka Gakkai Zasshi. 2007;111:905–10.PubMed
Metadata
Title
Visual prognosis better in eyes with less severe reduction of visual acuity one year after onset of Leber hereditary optic neuropathy caused by the 11,778 mutation
Authors
Yukihiko Mashima
Kazuteru Kigasawa
Kei Shinoda
Masato Wakakura
Yoshihisa Oguchi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2017
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-017-0583-3

Other articles of this Issue 1/2017

BMC Ophthalmology 1/2017 Go to the issue