Human audiometric thresholds do not predict specific cellular damage in the inner ear

Abstract

Introduction As otology enters the field of gene therapy and human studies commence, the question arises whether audiograms – the current gold standard for the evaluation of hearing function – can consistently predict cellular damage within the human inner ear and thus should be used to define inclusion criteria for trials. Current assumptions rely on the analysis of small groups of human temporal bones post mortem or from psychophysical identification of cochlear “dead regions” in vivo, but a comprehensive study assessing the correlation between audiometric thresholds and cellular damage within the cochlea is lacking. Methods A total of 131 human temporal bones from 85 adult individuals (ages 19-92 years, median 69 years) with sensorineural hearing loss due to various etiologies were analyzed. Cytocochleograms – which quantify loss of hair cells, neurons, and strial atrophy along the length of the cochlea – were compared with subjects’ latest available audiometric tests prior to death (time range 5 hours to 22 years, median 24 months). The Greenwood function and the equivalent rectangular bandwidth were used to infer, from cytocochleograms, cochlear locations corresponding to frequencies tested in clinical audiograms. Correlation between audiometric thresholds at clinically tested frequencies and cell type-specific damage in those frequency regions was examined by calculating Spearman’s correlation coefficients. Results Similar audiometric profiles reflected widely different cellular damage in the cochlea. In our diverse group of patients, audiometric thresholds tended to be more influenced by hair cell loss than by neuronal loss or strial atrophy. Spearman’s correlation coefficient across frequencies was at most 0.7 and often below 0.5, with 1.0 indicating perfect correlation. Conclusions Audiometric thresholds do not predict specific cellular damage in the human inner ear. Our study highlights the need for better non- or minimally-invasive tools, such as cochlear endoscopy, to establish cellular-level diagnosis and thereby guide therapy and monitor response to treatment.

Drug delivery into the cochlear apex: Improved control to sequentially affect finely spaced regions along the entire length of the cochlear spiral

“…But, it is not clear that auditory thresholds can precisely identify the damaged, diseased, and normal cochlear cell types that influence the generation of objective measurements (e.g., Probst et al 1987; Canlon et al 1993, Subramaniam et al 1995; Bian & Chertoff 2001, Harding et al 2002; Lichtenhan et al 2005; Moleti et a. 2014; Landegger et al 2016). One likely reason for this conundrum is that probe levels have to be increased to quantify auditory threshold in ears with sensorineural hearing loss, thus stimulating un-intended cochlear regions away from the cochlear frequency place that is tuned best to the probe frequency.…”

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