Ototoxicity (cochleotoxicity) classifications: A review

Objective: Drug-mediated ototoxicity, specifically cochleotoxicity, is a concern for patients receiving medications for the treatment of serious illness. A number of classification schemes exist, most of which are based on pure-tone audiometry, in order to assist non-audiological/non-otological specialists in the identification and monitoring of iatrogenic hearing loss. This review identifies the primary classification systems used in cochleototoxicity monitoring. By bringing together classifications published in discipline-specific literature, the paper aims to increase awareness of their relative strengths and limitations in the assessment and monitoring of ototoxic hearing loss and to indicate how future classification systems may improve upon the status-quo. Design: Literature review. Study sample: PubMed identified 4878 articles containing the search term ototox*. Results: A systematic search identified 13 key classification systems. Cochleotoxicity classification systems can be divided into those which focus on hearing change from a baseline audiogram and those that focus on the functional impact of the hearing loss. Conclusions: Common weaknesses of these grading scales included a lack of sensitivity to small adverse changes in hearing thresholds, a lack of high-frequency audiometry (>8 kHz), and lack of indication of which changes are likely to be clinically significant for communication and quality of life.     

Ultrastructural localization of gentamicin in the cochlea

The ultrastructural distribution of gentamicin in the cochlea was investigated immunocytochemically. Specific labeling was restricted to the organ of Corti, in particular to the outer and inner hair cells, the Deiters' cells, Hensen's cells and the tympanic layer cells of the basilar membrane. Other cochlear tissues did not demonstrate any labeling. At the subcellular level, gentamicin was found in lysosomes, multivesicular bodies and small tubules and vesicles.

A model is proposed in which it is hypothesized that gentamicin is internalized by endocytotic vesicles and is transferred to the lysosomal compartment as well as to the endoplasmic reticulum and Golgi complex.