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Case 32


Contributors: Bhadra U. Pandya MD (C) and Dr. Jonathan Micieli MD, CM, FRCSC

Patient Presentation: A 47-year-old woman presented to a tertiary neuro-ophthalmology clinic with a 3-month history of progressively worsening bilateral vision loss. Her past medical history was significant for non-small-cell lung cancer (NSCLC) which was diagnosed around the time her vision loss began. She was treated with whole brain radiation and Osimertinib, and her vision subsequently worsened 6 weeks later. Her medications included levetiracetam, tinzaparin, dexamethasone, hydromorphone, and pantoprazole. There was no family history of vision loss, and she did not smoke or drink alcohol.


On initial examination, her visual acuity was 20/320 OD and counting fingers OS. There was no RAPD. Dilated fundus examination was performed and is shown below:


Question 1: What is the most significant finding on fundus examination?

An OCT RNFL and Humphrey visual field testing (24-2) were performed and shown below:


Question 2: Based on the patient’s presentation, history, and fundus findings, what is the differential diagnosis?

Magnetic resonance imaging (MRI) of the brain and orbits with contrast was performed, and no compressive lesions or evidence of demyelinating disease was noted.  

To investigate nutritional deficiencies, RBC folate and B12 levels were checked and were normal.  Whole-blood trace metal analysis was performed and was unremarkable.

Question 3: What is the most likely diagnosis in this patient?

Mitochondrial genetic testing was subsequently performed to test for the three primary mutations associated with LHON, which was found to be negative.

Nuclear DNA sequencing was performed and a single point-mutation in a gene associated with mitochondrial disease was observed.

Question 4: Which nuclear genes have been associated with LHON phenotype?

Question 5: Which one of the following is not currently established as a risk factor for LHON?


  1. Shah SH, Schiapparelli LM, Ma Y, et al. Quantitative transportomics identifies Kif5a as a major regulator of neurodegeneration. Elife. 2022;11:e68148. Published 2022 Mar 8. doi:10.7554/eLife.68148

  2. Meyerson C, Van Stavern G, McClelland C. Leber hereditary optic neuropathy: current perspectives. Clin Ophthalmol. 2015;9:1165-1176. Published 2015 Jun 26. doi:10.2147/OPTH.S62021

Learning Objectives:

  1. To understand the history and exam findings of LHON

  2. To understand the association between pathogenic nuclear DNA mutations and LHON

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