Questions:
49. What are the 4 most common neuro-ophthalmic manifestations of mitochondrial disorders?
50. Name 8 mitochondrial disorders with neuro-ophthalmic manifestations?
51. What are the ophthalmic and systemic manifestations of CPEO (chronic progressive external ophthalmoplegia)?
52. What are the ophthalmic and systemic manifestations of LHON (Leber hereditary optic neuropathy)?

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Questions with answers:
49. What are the 4 most common neuro-ophthalmic manifestations of mitochondrial disorders?
1. Bilateral optic neuropathy (Leber hereditary optic neuropathy or dominant optic atrophy)
2. Ophthalmoplegia with ptosis (chronic progressive external ophthalmoplegia)
3. Pigmentary retinopathy
4. Retrochiasmal visual loss (MELAS)

50. Name 8 mitochondrial disorders with neuro-ophthalmic manifestations?
1. LHON (Leber hereditary optic neuropathy)
2. DOA (dominant optic atrophy)
3. CPEO (chronic progressive external ophthalmoplegia) & KSS (Kearns-Sayre syndrome)
4. MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes)
5. NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa)/Leigh syndrome
6. MERRF (myoclonic epilepsy and ragged red fibers)
7. MIDD (maternally inherited diabetes mellitus and deafness)
8. MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) 

51. What are the ophthalmic and systemic manifestations of CPEO (chronic progressive external ophthalmoplegia)?
Ophthalmic – ophthalmoplegia, ptosis, and pigmentary retinopathy.

Systemic – myopathy ragged red fibers, peripheral neuropathy, deafness, vestibular dysfunction, basal ganglia lesions, cardiac conduction abnormalities, short stature, gastrointestinal dysmotility, delayed sexual maturation/hypogonadism, hypomagnesemia, hypoparathyroidism, and hypothyroidism.

52. What are the ophthalmic and systemic manifestations of LHON (Leber hereditary optic neuropathy)?
LHON is classically associated with mitochondrial base pair mutations G11778A (guanine to adenine at position 11778), T14484C (tyrosine to cytosine), and G3460A. These mutations primarily affect respiratory chain complex I genes, mitochondrial genes ND1, ND4 and ND6 among others.³

Ophthalmic manifestations: early disc microangiopathy, pseudo disc edema, vascular tortuosity, optic atrophy

Systemic manifestations: LHON plus
Some pedigrees of LHON have systemic findings: cardiac arrhythmias, peripheral neuropathies, dystonia, myoclonus, ataxia, juvenile-onset encephalopathy, spastic dystonia, and psychiatric disturbances, a demyelinating syndrome that is radiologically and clinically identical to multiple sclerosis.² 

In the majority of patients with LHON, visual dysfunction is the only significant manifestation of the disease.

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The information below is from: Neuro-ophthalmology Illustrated-2nd Edition. Biousse V and Newman NJ. 2012. Thieme

20.10 Mitochondrial Disorders
The mitochondrial diseases are a heterogeneous group of disorders in which clinical presentation, inheritance, histopathology, or biochemical or genetic analysis suggests primary mitochondrial dysfunction. In many of these disorders, the central nervous system and the eye figure prominently. ▶Table 20.4 lists the neuro-ophthalmic and systemic manifestations of several mitochondrial disorders.

The most common neuro-ophthalmic abnormalities seen in mitochondrial disorders include the following:
● Bilateral optic neuropathy (Leber hereditary optic neuropathy or dominant optic atrophy)
● Ophthalmoplegia with ptosis (chronic progressive external ophthalmoplegia)
● Pigmentary retinopathy
● Retrochiasmal visual loss (MELAS)

References:
​1. Neuro-ophthalmology Illustrated-2nd Edition. Biousse V and Newman NJ. 2012. Thieme
2. Leber Optic Atrophy
StatPearls [Internet] https://www.ncbi.nlm.nih.gov/books/NBK482499/
Ari Shemesh; Gitanjli Sood; Edward Margolin.
Last Update: July 6, 2020.
3. Leber Hereditary Optic Neuropathy
EyeWiki AAO
Original article contributed by: Sonya Babar Shah, MD
All contributors: Jacob Winters, MD, Bayan Al Othman, MD, K. David Epley, M.D., Michael S. Vaphiades, DO, Moran R. Levin, MD and Sonya Babar Shah, MD
Assigned editor: Bayan Al Othman, MD, Bayan Al Othman, MD
Review: Assigned status Up to Date by Bayan Al Othman, MD on June 30, 2020.
https://eyewiki.aao.org/Leber_Hereditary_Optic_Neuropathy#:~:text=LHON%20is%20classically%20associated%20with,ND4%20and%20ND6%20among%20others.

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