Leber Hereditary Optic Neuropathy – An Overview

Satya Maripi

Introduction

Leber hereditary optic neuropathy (LHON) is one of the most common ophthalmological mitochondrial disorders, characterised by optic neuropathies resulting in bilateral central vision loss (1) (2). A point mutation in mitochondrial DNA, most common being G3460, G11778A and T14484C, results in disruption of the retinal ganglionic cells due to dysregulation of the respiratory chain. The worldwide prevalence since it was first described in 1858 is approximately 1 in 50,000. As it is a mitochondrial disorder, it mainly effects young males in their second or third decade of life with males being 5 times more likely to be afflicted (3).

Symptoms and Signs

The initial typical course of presentation of LHON is asymptomatic and painless with a gradual unilateral loss of central vision, there is in most cases (75%) an interval of approximately 6-8 weeks before bilateral involvement (3). Other important symptoms are deterioration of visual acuity and colour perception – note there is no involvement of pupillary reflexes.

It is important to note that LHON in a vast majority of patient will lead to irreversible permanent vision loss bilaterally.

Investigations

Ophthalmological investigations should include (3):

  • Slit lamp and/or indirect ophthalmoscopy – used to identify any gross abnormalities, especially within the fundus
  • Optical coherence tomography (OCT) – characterisation and quantification of fundal changes
  • Electroretinograms (ERG) – non-specific, however will be abnormal in LHON due to involvement of the optic nerve fibres and retinal ganglion cells
  • Genetic testing – used for final confirmation and more useful for prognostic evaluation

Treatment

As is characteristic of mitochondrial disorders, management and treatment is limited, and is largely only supportive in nature. These supportive measures include counselling patients about exacerbating factors in mitochondrial disorders such as smoking, alcohol and toxins. In addition, visual rehabilitation has been shown to be helpful with patients who have retained peripheral vision (4).

Conclusion

LHON is a common mitochondrial disorder characterised by irreversible bilateral blindness in the young male population demographic. Investigations focus around ruling out other pathologies of similar presentations, and therapy is restricted to supportive.

References

  1. McClelland C, Meyerson C, Van Stavern G. Leber hereditary optic neuropathy: Current perspectives. Clinical Ophthalmology. 2015;1165. doi:10.2147/opth.s62021
  • Man PYW, Turnbull DM, Chinnery PF. Leber hereditary optic neuropathy [Internet]. BMJ Publishing Group Ltd; 2002 [cited 2023 Jul 12]. Available from: https://jmg.bmj.com/content/39/3/162
  •  Esmaeil A, Ali A, Behbehani R. Leber’s hereditary optic neuropathy: Update on current diagnosis and treatment. Frontiers in Ophthalmology. 2023;2. doi:10.3389/fopht.2022.1077395
  • Hage R, Vignal-Clermont C. Leber hereditary optic neuropathy: Review of treatment and management. Frontiers in Neurology. 2021;12. doi:10.3389/fneur.2021.651639

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