Surgical Considerations in Inner Ear Gene Therapy from Human Temporal Bone Anatomy

Recently directed methods of inner ear drug delivery underscore the necessity for understanding critical anatomical dimensions. This study examines anatomical measurements of the human middle and inner ear relevant for inner ear drug delivery studied with three different imaging modalities.

Post-mortem human temporal bones were analyzed using human temporal bone histopathology (N = 24), micro computerized tomography (μCT; N = 4), and synchrotron radiation phase-contrast imaging (SR-PCI; N = 7). Nine measurements involving the oval and round windows were performed when relevant anatomical structures were visualized for subsequent age-controlled analysis, and comparisons were made between imaging methods.

Combined human temporal bone histopathology showed the mean distance to the saccule from the center of the stapes footplate (FP) was 2.07 ± 0.357 mm and the minimum distance was 1.23 mm. The mean distance from the round window membrane (RWM) to the osseous spiral lamina (OSL) was 1.75 ± 0.199 mm and the minimum distance was 1.43 mm. Instruments inserted up to 1 mm past the center of the FP are unlikely to cause saccular damage, provided there are no endolymphatic hydrops. Similarly, instruments inserted up to 1 mm through the RWM in the trajectory toward the OSL are unlikely to cause OSL damage.

The combined analyses of inner-ear dimensions of age-controlled groups and imaging modalities demonstrate critical dimensions of importance to consider when inserting delivery vehicles into the human cochlea.

N/A Laryngoscope, 134:2879-2888, 2024.