Gentamicin delivery to the inner ear: Does endolymphatic hydrops matter?

Abstract

IntroductionMiddle ear application of gentamicin is a common medical treatment for uncontrolled Ménière’s disease. The objective of the study was to evaluate the impact of endolymphatic hydrops on inner ear delivery.MethodsPerilymph gentamicin concentrations and correlation with endolymphatic hydrops in an animal model were assessed. A group of 24 guinea pigs was submitted to surgical obstruction of the endolymphatic sac and duct of the right ear. Gentamicin was applied either to the right ear’s round window niche or through a transtympanic injection. Perilymph specimens were collected at different times. Histologic morphometry was used to evaluate both turn-specific and overall hydrops degree.ResultsIn animals with endolymphatic hydrops, lower concentrations of gentamicin were observed after 20 or 120 minutes of exposure and in both types of administration, when compared to controls. This difference reached statistical significance in the round window niche application group (Mann-Whitney, p = 0,007). A negative correlation between perilymphatic gentamicin concentration and hydrops degree could be observed in both groups, after 120 minutes of exposure (Spearman correlation, round window niche p<0,001; TT p = 0,005).ConclusionsThe study indicates that the endolymphatic hydrops degree has a negative interference on the delivery of gentamicin into the inner ear following middle ear application.

Contralateral spreading of substances following intratympanic nanoparticle-conjugated gentamicin injection in a rat model

“…First, in addition to the Eustachian tube, investigations of other possible routes, such as the cochlear aqueduct or systemic vascular system, which may be associated with contralateral spreading, were not performed in this study. A previous study exhibited light immunostaining for gentamicin in the contralateral spiral ganglion cells with a lateral-to-medial gradient in the dorsal cochlear nucleus bordering the cochlear aqueduct 7 . Therefore, we cannot definitively conclude that the observed contralateral spreading was solely due to transmission via the Eustachian tube.…”

“…However, intratympanic gentamicin injection does not necessarily result in ototoxicity, as evident in reported intractable cases following gentamicin administration 4 . Individual differences in the permeability of the round window and the degree of endolymphatic hydrops are associated with the diffusion-to-clearance ratio of intratympanically injected substances 7 , 8 . Although gentamicin is mostly delivered to the basal turn of the cochlea via the round window, the Eustachian tube in the middle ear is a potential route for the clearance of gentamicin.…”

Low-Dose Intratympanic Gentamicin for Unilateral Ménière‘s Disease: Accuracy of Early Vestibulo-Ocular Reflex Gain Reduction in Predicting Long-Term Clinical Outcome

“…The possibility to in vivo observe endolymphatic hydrops is one of the major achievements in MD in recent years (30). Findings in the MRI are also being considered as an explanation for a reduced response to gentamicin as suggested by Marques et al (31), such that different degrees of hydrops could indicate corresponding modification of perilymphatic dynamics in the vestibule.…”