Membranous Labyrinth Position in the Lateral Semicircular Canal: Considerations for Gene Therapy Delivery

Fenestration of the lateral semicircular canal has been proposed to improve intracochlear gene therapy delivery, but the relationship between the membranous and bony labyrinths at the canal apex has not been systematically defined.

We examined 62 human temporal bones, including 31 unaffected specimens and 31 with chronic otitis media, using histologic review to assess the membranous-to-bony relationship at the apex.

In all specimens, the membranous labyrinth directly contacted the outer circumferential bony wall.

This consistent finding, independent of disease state, indicates that fenestration at the lateral canal apex carries a high risk of membranous injury. Potential consequences include hearing loss, vestibular dysfunction, and reduced therapeutic effect. Inadvertent entry into the endolymphatic compartment might not adequately support perilymphatic flow and compromise therapeutic delivery. Because fenestration of the outer circumference of the lateral semicircular canal is histologically unfavorable, histologic assessment of proposed fenestration sites is necessary.