Capturing the Pattern of Transition From Carrier to Affected in Leber Hereditary Optic Neuropathy

Am J Ophthalmol. 2022 Sep:241:71-79. doi: 10.1016/j.ajo.2022.04.016. Epub 2022 May 2.


Purpose: To capture the key features patterning the transition from unaffected mutation carriers to clinically affected Leber hereditary optic neuropathy (LHON), as investigated by optical coherence tomography.

Design: Observational case series.

Methods: Four unaffected eyes of 4 patients with LHON with the first eye affected were followed across conversion to affected, from 60 days before to 170 days after conversion. The primary outcome measures were multiple timepoints measurements of peripapillary retinal nerve fiber layer (RNFL) thickness for temporal emi-side of the optic nerve (6 sectors from 6-11, clockwise for the right eye and counterclockwise for the left eye) in all patients and nasal emi-macular RNFL and ganglion cell layer (GCL) thickness in 2 patients.

Results: While the presymptomatic stage was characterized by a dynamic thickening of sector 8, the beginning of the conversion coincided with an increase in the thickness of the sectors bordering the papillo-acular bundle (6 and 7 for the inferior sectors, 10 and 11 for the superior sectors) synchronous with the thinning of sectors 8 and then 9. Conversely, the GCL did not undergo significant changes until the onset of visual loss when a significant reduction of thickness became evident.

Conclusion: In this study we demonstrated that the thinning of sector 8 can be considered the structural hallmark of the conversion from the presymptomatic to the affected state in LHON. It is preceded by its own progressive thickening extending from the optic nerve head toward the macula and occurs regardless of the amount of swelling of the rest of the peripapillary fibers.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Nerve Fibers
  • Optic Atrophy, Hereditary, Leber* / diagnosis
  • Optic Atrophy, Hereditary, Leber* / genetics
  • Optic Disk*
  • Retinal Ganglion Cells
  • Tomography, Optical Coherence / methods