Protecting against electrode insertion trauma using dexamethasone

Chambers, Scott; Newbold, Carrie; Stathopoulos, Dimitra; Needham, Karina; Miller, Chris D.; Risi, Frank; Enke, Ya Lang; Timbol, Godofredo; Cowan, Robert

doi:10.1080/14670100.2018.1509531

Cited by 15 publications

(15 citation statements)

References 30 publications

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“…Many experimental studies in animals have demonstrated that the use of corticosteroids is able to preserve hearing thresholds, increase the survival of hair cells and spiral ganglia, and decrease the formation of new fibrotic tissue within implanted cochlea (20)(21)(22)(23)(24)(25)(26)(27). Clinical studies demonstrate lower impedances and improved preservation of low-frequency residual hearing in patients when corticosteroids are used in CI surgery (28)(29)(30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

“…Data from two published animal studies favor the local application of glucocorticoids over systemic application in order to minimize the consequences of insertion trauma (26,27). On the contrary, results of another study showed better hair cell protection after local application but a more robust prevention of fibrosis for systemic administration (37).…”

Section: Introductionmentioning

confidence: 99%

“…Results of clinical pilot studies considering pure tone audiometry or electrode impedance measurement showed a slight tendency in favor for local application but only included few patients (32,33). Additionally, a prolonged application after insertion seems to be more effective in suppressing adverse effects than single-shot glucocorticoid application prior to insertion of the cochlear implant electrode (22)(23)(24)(25)(26)(27). In a guinea pig model of insertion trauma, the measurements of inflammatory cytokines in perilymph revealed that suppression of inflammation is most successful when glucocorticoids are applied intracochlearly (26).…”

Section: Introductionmentioning

confidence: 99%

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Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

et al. 2020

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“…Work by Chambers et al demonstrated greater hearing threshold shifts in implantation models eliciting more mechanical trauma regardless of DEX [32]. This study examined the benefit of DEX in two implant models: a low trauma model where an electrode array was carefully introduced into the cochlea, and a high trauma model where a steel wire was inserted and withdrawn twice prior to insertion of the electrode array.…”

Section: Drug-eluting Electrodementioning

confidence: 99%

Inner Ear Pharmacotherapy for Residual Hearing Preservation in Cochlear Implant Surgery: A Systematic Review

et al. 2022

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Cochlear implantation initiates an inflammatory cascade in which both acute insertion trauma and chronic foreign body reaction lead to intracochlear fibrosis and loss of residual hearing. Several strategies have been proposed to attenuate the local reactive process after implantation, including intracochlear drug delivery. The present study gives an overview of what is being investigated in the field of inner ear therapeutics and cochlear implant surgery. The aim is to evaluate its potential benefit in clinical practice. A systematic search was conducted in PubMed, Embase, and Cochrane Library databases identifying comparative prospective studies examining the effect of direct inner ear drug application on mechanical cochlear trauma. Both animal and human studies were considered and all studies were assessed for quality according to the validated risk of bias tools. Intracochlear administration of drugs is a feasible method to reduce the local inflammatory reaction following cochlear implantation. In animal studies, corticosteroid use had a significant effect on outcome measures including auditory brainstem response, impedance, and histological changes. This effect was, however, only durable with prolonged drug delivery. Significant differences in outcome were predominantly seen in studies where the cochlear damage was extensive. Six additional reports assessing non-steroidal agents were found. Overall, evidence of anti-inflammatory effects in humans is still scarce.

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“…Sustained concentrations of about 60 and 100 ng/mL were observed in the perilymph for the 1 and 10% loaded rods respectively, demonstrating the potential for therapeutic dosing by loading of DEX into the silicone of a CI electrode array. Commercial arrays with silicone loaded with 40% (w/w) DEX demonstrated inhibition of osteoneogenesis and reduced SGN loss four weeks postimplant in a guinea pig model of high insertion trauma [33]. Briggs and colleagues demonstrated a first-time-in-human study of a DEX-eluting investigational electrode array [34**].…”

Section: Steroid Elution Coatingsmentioning

confidence: 99%

Microtechnologies for inner ear drug delivery

Forouzandeh

Borkholder²

2020

Current Opinion in Otolaryngology &Amp; Head &Amp; Neck Surgery

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Purpose of review-Treatment of auditory dysfunction is dependent on inner ear drug delivery, with microtechnologies playing an increasingly important role in cochlear access and pharmacokinetic profile control. This review examines recent developments in the field relevant to both clinical and animal research environments.Recent findings-Micropump technologies are being developed that provide dynamic control of flow rates with refillable reservoirs to enable timed delivery of a series of multiple agents for protection or regeneration therapies. These micropumps can be combined with cochlear implants with integral catheters or used independently with cochleostomy or RWM delivery modalities for therapy development in animal models. Sustained release of steroids with coated cochlear implants remains an active area of research with first-time-in-human demonstration of reduced electrode impedances. Advanced coatings containing neurotrophin producing cells have enhanced spiral ganglion neuron survival in animal models, and have proven safe in a human study. Microneedles have emerged as a novel method for controlled microperforation of the round window membrane with significant enhancement in permeability, which can be combined with emerging matrix formulations that optimize biological interaction and drug release kinetics.Summary-Microsystem technologies and associated fabrication techniques are providing enhanced and more controlled access to the inner ear for advanced drug delivery approaches, alone and in conjunction with cochlear implants.

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Protecting against electrode insertion trauma using dexamethasone

Abstract: Dexamethasone-eluting intra-cochlear arrays may inhibit osteoneogenesis, and reduce spiral ganglion neuron loss following traumatic cochlear implantation.

Cited by 15 publications

References 30 publications

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

Inner Ear Pharmacotherapy for Residual Hearing Preservation in Cochlear Implant Surgery: A Systematic Review

Microtechnologies for inner ear drug delivery

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