J Korean Ophthalmol Soc.  2019 Jan;60(1):96-101. 10.3341/jkos.2019.60.1.96.

A Case of Leber Hereditary Optic Neuropathy Showing Optic Disc Hyperfluorescence

• Park YJ
• Lim HT

• KMID: 2431847
• DOI: http://doi.org/10.3341/jkos.2019.60.1.96

Abstract

PURPOSE
We report an unusual case of Leber hereditary optic neuropathy presenting with optic disc hyperfluorescence.
CASE SUMMARY
A 17-year-old male with sequential painless visual loss 3 weeks apart affecting first the left and then the right eye presented to our neuro-ophthalmology clinic. His best-corrected visual acuity was counting fingers in the right eye and 0.32 in the left eye. Fundus examination showed mild optic disc edema and hyperemia in both eyes, which were worse in the right eye. Fluorescein angiography revealed dye leakage from the right optic disc in the late phase. The results of magnetic resonance imaging of the brain and spinal cord were normal, and lumbar puncture study was unremarkable. Mitochondrial DNA sequencing revealed a pathognomonic 11778 mutation for Leber hereditary optic neuropathy. His vision deteriorated to 0.03 in both eyes 6 months later, but slowly started to improve 11 months after onset. At 2 years, his corrected visual acuity was 0.2 in both eyes.
CONCLUSIONS
To our knowledge, this is the first report of optic disc hyperfluorescence in Leber hereditary optic neuropathy. This finding suggests that this mitochondrial optic neuropathy can masquerade as optic neuritis.

Keyword

Fluorescein angiography; Leber hereditary optic neuropathy; Optic atrophy

MeSH Terms

Adolescent
Brain
DNA, Mitochondrial
Edema
Fingers
Fluorescein Angiography
Humans
Hyperemia
Magnetic Resonance Imaging
Male
Optic Atrophy
Optic Atrophy, Hereditary, Leber*
Optic Nerve Diseases
Optic Neuritis
Spinal Cord
Spinal Puncture
Visual Acuity
DNA, Mitochondrial

Figure

• 

  Figure 1 Serial fundus photographs and fluorescein angiography of the patient. (A) Fundus photograph of the patient taken at the initial visit showing bilateral optic disc edema, hyperemia, and peripapillary telangiectasia, which was worse in the right eye. (B) Fluorescein angiogram taken at the initial visit revealed distinct leakage from the right optic disc in the late phase (9 minutes 44 seconds) (C) Fundus photograph taken at the two years follow-up showing diffuse optic disc pallor and peripapillary retinal nerve layer defects in both eyes.

• 

  Figure 2 Spectral-domain optical coherence tomograph of the patient at the initial visit. Note that the peripapillary RNFL thickness was increased in both eyes, which corresponded to the optic disc swelling shown in fundus photographs. RNFL = retinal nerve fiber layer; ONH = optic nerve head; OU = oculus uterque; OD = oculus dexter; OS = oculus sinister; C/D = cup/disc; TEMP = temporal; SUP = superior; NAS = nasal; INF = inferior; S = superior; N = nasal; I = inferior; T = temporal.

• 

  Figure 3 Mitochondrial DNA sequence chromatogram of the patient. A homoplasmy mutation, m.11778 G>A in MTND4 gene was found. The mutation was one of the common three primary mitochondrial DNA (mtDNA) point mutations causing Leber hereditary optic neuropathy. MTND4 = mitochondrial nicotinamide adenine dinucleotide - hydrogen dehydrogenase subunit 4.

Reference

1. Newman NJ. Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol. 2005; 140:517–523.

2. Yu-Wai-Man P, Griffiths PG, Brown DT, et al. The epidemiology of Leber hereditary optic neuropathy in the North East of England. Am J Hum Genet. 2003; 72:333–339.

3. Wallace DC, Singh G, Lott MT, et al. Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science. 1988; 242:1427.

4. 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; 111:750–762.

5. Smith J, Hoyt WF, Susac JO. Ocular fundus in acute leber optic neuropathy. Arch Ophthalmol. 1973; 90:349–354.

6. Riordan-Eva P, Harding AE. Leber's hereditary optic neuropathy: the clinical relevance of different mitochondrial DNA mutations. J Med Genet. 1995; 32:81–87.

7. Sadun AA, Salomao SR, Berezovsky A, et al. Subclinical carriers and conversions in Leber hereditary optic neuropathy: a prospective psychophysical study. Trans Am Ophthalmol Soc. 2006; 104:51–61.

8. Hsu TK, Wang AG, Yen MY, Liu JH. Leber's hereditary optic neuropathy masquerading as optic neuritis with spontaneous visual recovery. Clin Exp Optom. 2014; 97:84–86.

9. Schachat AP, Wilkinson CP, Hinton DR, et al. Ryan's Retina. 6th ed. 1. Toronto: Elsevier;2017. p. 19–44.

10. Sadun AA, Win PH, Ross-Cisneros FN, et al. Leber's hereditary optic neuropathy differentially affects smaller axons in the optic nerve. Trans Am Ophthalmol Soc. 2000; 98:223–232. discussion 232-5.

11. Nikoskelainen EK, Huoponen K, Juvonen V, et al. Ophthalmologic findings in Leber hereditary optic neuropathy, with special reference to mtDNA mutations. Ophthalmology. 1996; 103:504–514.

12. Piotrowska A, Korwin M, Bartnik E, Tońska K. Leber hereditary optic neuropathy-historical report in comparison with the current knowledge. Gene. 2015; 555:41–49.

13. Wan MJ, Adebona O, Benson LA, et al. Visual outcomes in pediatric optic neuritis. Am J Ophthalmol. 2014; 158:503–507.e2.

14. Golnik K. Nonglaucomatous optic atrophy. Neurol Clin. 2010; 28:631–640.