Comparison of electrode impedance measures between a dexamethasone-eluting and standard Cochlear™ Contour Advance® electrode in adult cochlear implant recipients

Highlights

• The dexamethasone eluting electrode array provided sustained lower electrode impedance measures compared to the control group.

• The pattern of change in both standard MP1+2 and 4-point impedance measures varied by cochlear region and by device groups.

• Impedance increases on basal electrodes after 3 months was mediated by the early delivery of dexamethasone.

Abstract

Objective

To compare the difference in electrode impedance across discrete time points to 24 months post-activation for two groups of adult cochlear implant recipients, one using an investigational perimodiolar (Contour Advance®) array augmented with 40% concentration weight per weight (w/w) dexamethasone (the Drug Eluting Electrode, ‘DEE’ Group), and the other the commercially available Contour Advance (’Control’ Group).

Design

Ten adult subjects were implanted with the DEE and fourteen with the Control. Electrode impedances were measured intra-operatively, one-week post-surgery, at initial activation (approximately two-weeks post-surgery), and at approximately one, three, six, 12 and 24 months post-activation. Two different impedance measurements were obtained: 1) in MP1+2 mode using Custom Sound programming software; and 2) 4-point impedance measures utilising BP+2 stimulation mode with recording on non-stimulating electrodes. Data were analysed with respect to both impedance averaged across all electrodes, and impedance for electrodes grouped into basal, middle and apical sections.

Results

Group mean MP1+2 impedance for the DEE was significantly lower than for the Control at all post-operative time points examined, and for each of the basal, middle and apical cochlear regions. Group mean 4-point impedance was significantly lower for the DEE than the Control in the basal region at six, 12 and 24 months post-activation and in the middle region at 12- and 24-months post-activation. The pattern of change in MP1+2 impedance differed significantly in the early post-operative period prior to device activation. A significant 4.8 kOhm reduction in impedance between surgery and one-week was observed for the DEE group but not for the Control. A 2.0 kOhm increase between the one and two week post-operative time points was observed for the Control but not for the DEE group.

Conclusion

While rates of adoption of different surgical approaches differed between the groups and this may have had a confounding effect, the results suggest that passive elution of dexamethasone from the investigational device was associated with a change in the intracochlear environment following surgical implantation of the electrode array, as evidenced by the lower electrode impedance measures.

Introduction

Electrode impedances are measured as part of routine clinical practice during the programming procedure for cochlear implant devices, primarily to confirm normal electrode function. There is increasing evidence that lower electrode impedance post-surgery is indicative of a reduction in the post-surgical cascade of inflammation, fibrosis and osteoneogenesis. Such evidence primarily stems from research with steroid-eluting electrode arrays, which report reduction in infiltration of inflammatory cells to the cochlear following implantation (Farhadi et al., 2013), reduction in fibrotic tissue (Bas et al., 2016; Wilk et al., 2016; Wrzeszcz et al., 2015), a reduction in electrode impedance (Bas et al., 2016; Wilk et al., 2016), and reduction in osteoneogenesis (Chambers et al., 2019). Additionally, use of steroid-eluting electrode arrays has been shown to protect against spiral ganglion neuron loss (Bas et al., 2016; Chambers et al., 2019; Scheper et al., 2017).

A number of pre-clinical studies have investigated the impact of steroid elution on electrode impedance measures. Bas et al. (2016) reported a gradual increase in impedance (from approximately 8 to 23 kOhm) over the course of three months for a standard non-eluting cochlear implant electrode array, which was reduced or blocked in the presence of 0.1%, 1% and 10% of dexamethasone base. In that study, the arrays were only briefly stimulated at one, three, seven, 14, 30, 60 and 90 days, rather than daily as would be expected in a clinical scenario. Wilk et al. (2016) also examined impedance change over the course of 3 months, comparing a non-eluting array with a 1% and 10% dexamethasone-eluting array, with electrodes stimulated for 1 h once weekly. As for the Bas et al. (2016) study, electrode impedance was significantly lower for the dexamethasone-eluting arrays compared to the non-eluting array at three months post-implantation. In addition, this study demonstrated a moderate correlation between fibrosis and electrode impedance, with the reduction of both in the presence of dexamethasone, similar to the previously reported association between intracochlear fibrotic tissue response post-implantation and electrode impedance measures (Tykocinski et al., 2005, 2001).

In addition to the pre-clinical investigations, the impact of local steroid administration on electrode impedance in cochlear implant recipients has been examined clinically. Early investigations indicated that local steroid delivery at the time of implantation could reduce electrode impedance in adult (Enticott et al., 2011; Paasche et al., 2009) and pediatric populations (De Ceulaer et al., 2003). De Ceulaer et al. (2003) found impedances in the steroid groups were significantly lower than in the non-steroid groups two months post-surgery (approximately 1 kOhm), however whether this was maintained to 12 months depended on the electrode type used (Straight or Contour®). Paasche et al. (2009) observed a significant difference in impedance between control and steroid groups at three months (of approximately 2 kOhm), although this effect did not reach statistical significance at three years post-surgery. It was noted that the steroid effect was greater on the basal and middle electrodes. It is of interest to note that electrode impedances reduced over time in both the steroid and the control groups. More recently a double-blind randomized placebo-controlled trial showed a small but statistically significant reduction in electrode impedances, by 1–2 kOhm on the middle array electrode contacts, between one and 12 months after surgery when topical methylprednisolone was applied to the round window during surgery (Enticott et al., 2011). However there are challenges with local steroid application as the time taken for diffusion into the perilymph is too slow for its clinical application during surgery (Chang et al., 2009), and recent pharmacokinetic modelling suggests that dexamethasone will be eliminated before it reaches the apex of the cochlea (Salt and Plontke, 2018).

Elution of corticosteroids from the implanted electrode array provides a clinically viable alternative to previously tested topical or systemic routes of administration and has the additional benefit of enabling a prolonged delivery of the drug directly into the cochlea. The viability and safety of steroid elution from cochlear implant electrodes has previously been reported in a number of pre-clinical studies (Astolfi et al., 2016; Bas et al., 2016; Douchement et al., 2015; Eshraghi et al., 2011; Farhadi et al., 2013; Liu et al., 2015; Nguyen et al., 2015; Niedermeier et al., 2012; Stathopoulos et al., 2015, 2014; Wilk et al., 2016).

This is a first-time-in-human study of a dexamethasone-eluting investigational electrode array. The effect of dexamethasone elution on electrode impedances, from the time of cochlear implant surgery to two years post-implantation, was examined. A comparison of the pattern of electrode impedance for the drug-eluting electrode array to the pattern for a standard electrode array of the same design was conducted.