Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e. g., for delivery of glucocorticosteroids, antiapoptotic substances, or neurotrophins to the inner ear. The performance of cochlear implants may thus be improved by protecting neuronal structures from insertion trauma, reducing fibrosis in the inner ear, and by stimulating growth of neuronal structures in the direction of the electrodes. Controlled drug release after extracochlear or intracochlear application in conjunction with a CI can also be achieved by use of a biocompatible, resorbable controlled-release drug-delivery system. Two case reports for intracochlear controlled release drug delivery in combination with cochlear implants are presented. In order to treat progressive reduction in speech discrimination and increased impedance, two cochlear implant patients successfully underwent intracochlear placement of a biocompatible, resorbable drug-delivery system for controlled release of dexamethasone. The drug levels reached in inner ear fluids after different types of local drug application strategies can be calculated using a computer model. The intracochlear drug concentrations calculated in this way were compared for different dexamethasone application strategies.

Objective Controlled and uncontrolled studies with primary intratympanic (IT) or combined intratympanic and systemic application of glucocorticosteroids for idiopathic sudden hearing loss (ISSHL) were analyzed by means of a meta-analysis in an attempt to establish optimal local drug delivery protocols. Study Design A total of 25 studies with 28 treatment groups between January 2000 and June 2014 were selected that adequately described drug delivery protocols. Cochlear drug levels were calculated by a validated computer model of drug dispersion in the inner ear fluids based on the concentration and volume of glucocorticoids applied, the time the drug remained in the middle ear, and on the specific timing of injections. Various factors were compared with hearing outcome, including baseline data, individual parameters of the application protocols, calculated peak concentration (Cmax), and total dose (Area under the curve, AUC). Results There was no dependence of hearing outcome on individual parameters of the application protocol, Cmax or AUC. Final hearing threshold was notably independent of delay of treatment. Conclusion During primary IT or combined steroid therapy of ISSHL, the tendency towards early treatment having a positive effect on hearing improvement is thought to be a “sham effect”, likely related to spontaneous recovery. Change in pure tone average (PTA) may not be an adequate outcome parameter to assess effectiveness of the intervention, as it depends on the degree of initial hearing loss. Final PTA provides a better alternative.

Objective: To assess the efficacy of cochlear implantation (CI) after surgical removal of sporadic intracochlear or intravestibulocochlear schwannomas. Study Design: Nonconcurrent cohort study. Setting: Monocentric study at a tertiary referral center. Patients: Patients with tumor resection and CI between 2011 and 2018 and a historic control group of CI patients matched by age, CI electrode type, and follow-up. Interventions: Partial or subtotal cochleoectomy for tumor removal and single-stage CI. Outcome Measures: Main outcome measure: word recognition score for monosyllables in quiet at 65 dB SPL. Results: Sixteen patients with tumor removal and CI (6 female, 10 male; mean age 55 ± 14 years) and 16 control patients (6 female, 10 male; mean age 55 ± 15 years) were identified. In the tumor group, surprisingly good word recognition scores were reached even after substantial structural defects in the cochlear capsule. While 12 months after cochlear implantation mean word recognition score for monosyllables in quiet was 58% (SD: 26) and 41% (SD: 26) in the control groups, it was 75% (SD: 19%) in the tumor group. Conclusions: In patients with intracochlear schwannomas, despite substantial structural damage to the cochlear capsule by partial or subtotal cochleoectomy, a tendency toward better performance with respect to word recognition with CI was observed as compared with other CI patients. The surprisingly good functional results despite substantial cochlear trauma may change clinical thinking with respect to cochlear implantation also beyond this special indication.

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