Dexamethasone is widely used in preclinical studies and clinical trials to treat inner ear disorders. The results of those studies vary widely, maybe due to the different dexamethasone formulations used. Laboratory (lab) and medical grade (med) dexamethasone (DEX, C22H29FO5) and dexamethasone dihydrogen phosphate-disodium (DPS, C22H28FNa2O8P) were investigated for biocompatibility and bio-efficacy in vitro. The biocompatibility of each dexamethasone formulation in concentrations from 0.03 to 10,000 µM was evaluated using an MTT assay. The concentrations resulting in the highest cell viability were selected to perform a bio-efficiency test using a TNFα-reduction assay. All dexamethasone formulations up to 900 µM are biocompatible in vitro. DPS-lab becomes toxic at 1000 µM and DPS-med at 2000 µM, while DEX-lab and DEX-med become toxic at 4000 µM. Bio-efficacy was evaluated for DEX-lab and DPS-med at 300 µM, for DEX-med at 60 µM, and DPS-lab at 150 µM, resulting in significantly reduced expression of TNFα, with DPS-lab having the highest effect. Different dexamethasone formulations need to be applied in different concentration ranges to be biocompatible. The concentration to be applied in future studies should carefully be chosen based on the respective dexamethasone form, application route and duration to ensure biocompatibility and bio-efficacy.

Modern therapy of inner ear disorders is increasingly shifting to local drug delivery using a growing number of pharmaceuticals. Access to the inner ear is usually made via the round window membrane (RWM), located in the bony round window niche (RWN). We hypothesize that the individual shape and size of the RWN have to be taken into account for safe reliable and controlled drug delivery. Therefore, we investigated the anatomy and its variations. Cone beam computed tomography (CBCT) images of 50 patients were analyzed. Based on the reconstructed 3D volumes, individual anatomies of the RWN, RWM, and bony overhang were determined by segmentation using 3D SlicerTM with a custom build plug-in. A large individual anatomical variability of the RWN with a mean volume of 4.54 mm3 (min 2.28 mm3, max 6.64 mm3) was measured. The area of the RWM ranged from 1.30 to 4.39 mm2 (mean: 2.93 mm2). The bony overhang had a mean length of 0.56 mm (min 0.04 mm, max 1.24 mm) and the shape was individually very different. Our data suggest that there is a potential for individually designed and additively manufactured RWN implants due to large differences in the volume and shape of the RWN.

Background After introducing the first Cochlear Implants also in children theses are grown with electrical intracochlear stimulation and subsequent auditory cortical development. Over the meantime the positioning of the electrode was changed orientated on the development of electrode design, ability to insert atraumatic and on the widening of the indications towards highfrequency deafness. Methods In this pilot study we analysed five prelingually deafened patients implanted as child in the late 90’s and had a reimplantation 2016 or later. We compared CT and DVT (cone beam CT) scans of the temporal bone and measured the insertion angle, the cochlear coverage, the total length of the electrode in the cochlea and the distance of the first active electrode to the round window. Moreover, we compared their speech understanding before and after reimplantation. Results The results show a lowering in the insertion angle, the cochlear coverage, the total length of the electrode in the cochlea, in the distance of the first active electrode to the round window and in the speech understanding after reimplantation. Conclusion These results show a difference in the depth of insertion while the speech understanding is not significantly improving in this group—although the technology is advanced. The influence of auditory maturation with CI in these patients will be discussed.

This retrospective study aimed to investigate the range of hearing levels in a cochlear implant (CI) elderly population receiving electric-acoustic-stimulation (EAS) or electric-stimulation (ES) alone. The investigation evaluates the degree of hearing preservation (HP) and the speech comprehension resulting from EAS or ES-only to identify audiometric factors that predict adequate EAS and ES use. We analyzed the pure tone audiometry and speech perception in quiet and noise preoperatively and 12-months after activation of 89 elderly adults (age of 65 years old or older), yielding in total 97 CIs. Thirty-two (33.1%) patients were potential EAS candidates preoperatively, of which 18 patients used EAS at the time of first fitting and the other 14 patients continued to use their residual hearing for EAS at 12-months. Post-treatment, patients with EAS system and ES-only users’ with longer electrodes showed better results in monosyllable word scores in quiet than ES-only users with shorter electrodes. A similar trend was revealed for the speech recognition in noise. Patients with an EAS system benefit from maintaining their natural residual hearing. Nevertheless, strict preoperative patient selection is warranted particularly in elderly patients, in whom the hearing thresholds for EAS indication differ slightly from that in younger adults.

Chronic rhinosinusitis (CRS) is a common disease in the general population that is increasing in incidence and prevalence, severely affecting patients’ quality of life. Medical treatment for CRS includes self-management techniques, topical and oral medical treatments, and functional endoscopic sinus surgery (FESS). FESS is a standard procedure to restore sinus ventilation and drainage by physically enlarging the inflamed sinus passageways. Nasal drug-releasing stents are implanted to keep the surgically expanded aperture to the sinus frontalis open. The outcome of such an intervention is highly variable. We defined the anatomical structures which should be removed, along with ‘no-go areas’ which need to be preserved during FESS. Based on these definitions, we used cone beam computed tomography (CBCT) images to measure the dimensions of the frontal neo-ostium in 22 patients. We demonstrate anatomical variability in the volume and diameter of the frontal sinus recess after surgery. This variability could be the cause of therapy failure of drug-eluting implants after FESS in some patients. Implants individually made to fit a given patient’s postsurgical anatomy may improve the therapeutic outcome.

3D-printing paves the way for personalized drug therapy via implants individualized for the patient specific anatomy in chronic paranasal sinus diseases. This study brings together the workflow of modeling, manufacturing, and sterilization of 3D-printed individualized frontal neo-ostium implants (FOI) for optimization of Endoscopic Sinus Surgery (ESS) and validates the implantability of the printed devices. The study sample consisted of six adult human cadavers. Digital volume tomography (DVT) images were taken before and after ESS. The FOI models were based on the post-ESS anatomy. The area to be implanted was analysed in the preand post-ESS DVT images for volume and surface area. A specialized surgeon in rhinology judged the implantability of the 3D-printed FOI. The mean values of volume and surface area tended to be larger in the post-operation situs than in preoperation DVT images and we are therefore not yet convinced that pre-operation images will reflect the correct anatomy for the personalization of the FOI. The workflow of manufacturing and implantation of individualized 3D-printed sterile FOI is established but future studies are needed for further improvement.

A new approach that offers the potential for local drug delivery to the inner ear is a 3D printed, patient individualized, drug-loaded implant that precisely fits into the round window niche (RWN). Anatomically correct digital light processing (DLP) 3D printed implant prototypes are beneficial for preoperative planning and rehearsal of implantation techniques due to tactile feedback. The aim is to define desired mechanical material properties for future RWN implants. For this purpose, RWN implant prototypes (RWN-IPs) were DLP 3D printed using commercially available E-Shell 500 and E-Shell 600 materials (Envisiontec GmbH, Gladbeck, Germany) and a selfestablished PEGDA700 composition. These photopolymers are suitable for 3D printing RWN-IPs that feature different mechanical characteristics. The (1) mechanical properties (tensile test) were investigated, (2) the implantation feasibility and (3) fitting accuracy in human cadaver RWN were evaluated. As a result, E-Shell 500 has relatively high stretchability (ɛm ~ 60%) while E-Shell 600 and PEGDA700 are brittle and PEGDA700 has low strength. The E-Shell 500 material performs by far the best at handling and insertion. EShell 600 has adequate strength but is hard to handle because of rigid material behavior. PEGDA700 enables high 3D printing accuracy but lacks adequate mechanical behavior for adequate insertion of implant prototypes in RWN.

Purpose: To evaluate if a specific type of cochlear implant (CI) electrode array (EA) reveals higher rates/prevalence of vestibular symptoms and to characterize their respective relationship to intracochlear position and objective vestibular function. Methods: This retrospective study included 71 cochlear implantations in patients older than 18 years. The electrode position within the cochlea, electrode insertion angle, and cochlear coverage were determined from postoperative multiplanar reconstructed cone-beam computed tomography scans. All device manufacturers were represented. Data related to preoperative and postoperative PTA as well as vestibular symptoms in the preoperative and postoperative stages were collected from the patient’s records. Results: Twelve of the 71 (16.9%) CI patients experienced vertigo symptoms in the early postoperative period. In 5 (7.0%) patients, the vertigo complaints lasted until the time of the first activation (5-6 weeks postoperative). Postoperative onset of vestibular symptoms was more often seen in patients receiving lateral wall (LW)/straight EAs (19%) compared to perimodiolar/precurved EAs (7%), but this was only a trend and no statistical significance was observed. Moreover, preoperative pathologic caloric responses (CRs) better predicted the postoperative onset of vestibular symptoms. Conclusion: The preoperative consideration of a complicated CI-induced vertigo is important in the counseling particularly of elderly patients. We identified some risk factors for post-CI vertigo that should be considered in the patient’s counseling: preoperative pathologic CRs, the extent of surgical trauma, and possibly the use of an LW EA, regardless of the length.