Wireless electrocochleography in awake chinchillas: A model to study crossmodal modulations at the peripheral level.

The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research.

Magnetic/Acoustic Dual-Controlled Microrobot Overcoming Oto-Biological Barrier for On-Demand Multidrug Delivery against Hearing Loss.

Multidrug combination therapy in the inner ear faces diverse challenges due to the distinct physicochemical properties of drugs and the difficulties of overcoming the oto-biologic barrier. Although nanomedicine platforms offer potential solutions to multidrug delivery, the access of drugs to the inner ear remains limited. Micro/nanomachines, capable of delivering cargo actively, are promising tools for overcoming bio-barriers. Herein, a novel microrobot-based strategy to penetrate the round window membrane (RWM) is presented and multidrug in on-demand manner is delivered. The tube-type microrobot (TTMR) is constructed using the template-assisted layer-by-layer (LbL) assembly of chitosan/ferroferric oxide/silicon dioxide (CS/Fe3O4/SiO2) and loaded with anti-ototoxic drugs (curcumin, CUR and tanshinone IIA, TSA) and perfluorohexane (PFH). Fe3O4 provides magnetic actuation, while PFH ensures acoustic propulsion. Upon ultrasound stimulation, the vaporization of PFH enables a microshotgun-like behavior, propelling the drugs through barriers and driving them into the inner ear. Notably, the proportion of drugs entering the inner ear can be precisely controlled by varying the feeding ratios. Furthermore, in vivo studies demonstrate that the drug-loaded microrobot exhibits superior protective effects and excellent biosafety toward cisplatin (CDDP)-induced hearing loss. Overall, the microrobot-based strategy provides a promising direction for on-demand multidrug delivery for ear diseases.

Practicality of multilayer round window reinforcement in the surgical management of superior semicircular canal dehiscence syndrome: a case report of long-term follow-up.

Several surgical techniques have been documented for approaching and repairing superior semicircular canal dehiscence syndrome (SCDS). These techniques encompass the trans-middle cranial fossa, transmastoid, endoscopic approaches, and round window reinforcement (RWR). RWR entails the placement of connective tissue with or without cartilage and around the round window niche, restricting the round window's movement to minimize the 3rd window effect and restore the bony labyrinth closer to its normal state. We employed the multilayer RWR technique, resulting in significant postoperative improvement and long-lasting effects for 3.7 years in 2 cases. Here, we present the clinical findings, surgical procedures, and the effectiveness of multilayer RWR. This technique can be the initial choice for surgical treatments of SCDS due to its high effectiveness, longer-lasting effect, and minimal risk of surgical complications.

Dependability of Electrode to Modiolus Distance in Patients Specific Electrode Selection: A Cadaveric Model Study.

OBJECTIVE: This study aims to discern the disparities in the electrode-to-modiolus distance (EMD) between cochleostomy and round window approaches when performed sequentially in the same temporal bone. Additionally, the study seeks to identify the cochlear metrics that contribute to these differences. METHODOLOGY: A cross-sectional study was conducted, involving the sequential insertion of a 12-electrode array through both round window and cochleostomy approaches in cadaveric temporal bones. Postimplantation high-resolution CT scans were employed to calculate various parameters. RESULTS: A total of 12 temporal bones were included in the imaging analysis, revealing a mean cochlear duct length of 32.892 mm. The EMD demonstrated a gradual increase from electrode 1 (C1) in the apex (1.9 ± 0.07 mm; n = 24) to electrode 12 (C12) in the basal turn (4.6 ± 0.24 mm; n = 12; p < 0.01). Significantly higher EMD values were observed in the cochleostomy group. Correlation analysis indicated a strong positive correlation between EMD and cochlear perimeter (CP) (rs = 0.64; n = 12; p = 0.03) and a strong negative correlation with the depth of insertion (DOI) in both the middle and basal turns (rs = - 0.78; n = 20; p < 0.01). Additionally, EMD showed a strong negative correlation with the DOI-CP ratio (rs = -0.81; n = 12; p < 0.01). CONCLUSION: The cochleostomy group exhibited a significantly higher EMD compared with the round window group. The strong negative correlation between EMD and DOI-CP ratio suggests that in larger cochleae with shallower insertions, EMD is greater than in smaller cochleae with deeper insertions. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

An easy method to determine crucial AMEI performance parameters from clinical routine data in individuals - Part 2: dynamic range.

OBJECTIVE: The dynamic range (DR) available to the patient is a central parameter to determine speech intelligibility in quiet. DESIGN: In this retrospective study, the DR for the Vibrant Soundbridge implanted in individual patients was calculated using in situ thresholds of the patients and technical data of the implant system. The average DR across frequencies (0.5, 1, 2, 4 kHz) was correlated with the patients' assigned word recognition score (WRS) in quiet. STUDY SAMPLE: A data set of 66 cases (4 bilateral and 2 revised cases) from 60 implanted patients between 14.3-81.8 years were analysed. RESULTS: The relationship between DR and WRS was described by a sigmoidal growth function with R2=0.6371 and a maximum WRS (upper asymptote) of 93.5%. Word recognition scores in quiet improved with increasing DR. A significant shift in performance was detected from DR bin 2 (10-20 dB, median WRS 55%) to bin 3 (20-30 dB, median WRS 80%) and from DR bin 4 (30-40 dB, median WRS 82.5%) to bin 5 (40-50 dB, median WRS 90%). CONCLUSION: A minimum DR of 20 dB can yield sufficient speech intelligibility in quiet in implanted patients, however, an optimum DR is suggested to be 40 dB.

The impact of round window reinforcement on middle and inner ear mechanics with air and bone conduction stimulation.

The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of congenital anomalies or after cochlear implantation and is applied as a surgical treatment for hyperacusis. Multiple lumped and finite element models predict a low-frequency hearing loss with air conduction of up to 20 dB after RW reinforcement and limited to no effect on hearing with bone conduction stimulation. Experimental verification of these results, however, remains limited. Here, we present an experimental study measuring the impact of RW reinforcement on the middle and inner ear mechanics with air and bone conduction stimulation. In a within-specimen repeated measures design with human cadaveric specimens (n = 6), we compared the intracochlear pressures in scala vestibuli (PSV) and scala tympani (PST) before and after RW reinforcement with soft tissue, cartilage, and bone cement. The differential pressure (PDIFF) across the basilar membrane - known to be closely related to the hearing sensation - was calculated as the complex difference between PSV and PST. With air conduction stimulation, both PSV and PSTincreased on average up to 22 dB at frequencies below 1500 Hz with larger effect sizes for PST compared to PSV. The PDIFF, in contrast, decreased up to 11 dB at frequencies between 700 and 800 Hz after reinforcement with bone cement. With bone conduction, the average within-specimen effects were less than 5 dB for either PSV, PST, or PDIFF. The inter-specimen variability with bone conduction, however, was considerably larger than with air conduction. This experimental study shows that RW reinforcement impacts air conduction stimulation at low frequencies. Bone conduction stimulation seems to be largely unaffected. From a clinical point of view, these results support the hypothesis that delayed loss of air conduction hearing after cochlear implantation could be partially explained by the impact of RW reinforcement.

Importance of preoperative HRCT temporal bone in the orientation of the cochlea and its relation to intra-operative difficulties in cochlear implantation - predicting the grades of difficulty.

OBJECTIVE: This study emphasizes the role of preoperative high-resolution computed tomography (HRCT) temporal bone in evaluating the variation in cochlear orientation and proposes a grading system to determine the level of intraoperative difficulties encountered. METHODS: Preoperative correlation of middle ear and inner ear structures along with the basal turn angle (BTA) was done to assess the orientation. Patients were divided into three groups depending on BTA and radiology findings. RESULTS: Group A (BTA = 55°-60°) had statistically significant (p < 0.05) correlation between middle ear to inner ear structures on HRCT, whereas group B (BTA >60°) and C (BTA <55°) had variations in the alignment of middle ear structures to their corresponding inner ear structures. CONCLUSION: The association of BTA to the correlation between middle ear and inner ear structures can determine the orientation of the cochlea. This evaluation makes the surgeon aware of intraoperative challenges and helps in surgical planning.

An easy method to determine crucial AMEI performance parameters from clinical routine data in individuals - Part 1: maximum output.

OBJECTIVE: The frequency specific maximum output (MO) of active middle ear implants is the most crucial parameter for speech intelligibility. We determined individual MO from clinical routine data in round window (RW) coupling of the Vibrant Soundbridge (VSB). DESIGN: Monocentric, retrospective analysis. STUDY SAMPLE: 68 ears implanted with the VSB at the RW were analysed. Using bone conduction and direct threshold, MO was determined for combinations of implants (VORP502, VORP503) and processors (Samba, Amadé). Coupling modes were: (A) without coupler (N = 28), (B) spherical coupler (N = 19), (C) soft coupler (N = 10) or (D) custom-made "Hannover coupler" (N = 11). RESULTS: The MO frequency dependence was similar for coupling types (A-D) with a maximum at 1.5 kHz. No differences between groups were observed, although the average MO of the soft coupler was 10 dB lower. The average MO (0.5, 1.0, 2.0, 4.0 kHz) was (A) 77.6 ± 15.0 dB HL, (B) 81.0 ± 11.1 dB HL, (C) 67.6 ± 17.9 dB HL (C), and (D) 79.6 ± 11.7 dB HL (D). CONCLUSION: The individual MO can be determined from patients' clinical data. It permits in-depth analyses of patient outcomes and definition of evidence-based indication and decision criteria.

Erratum: Surgical procedure of intratympanic injection and inner ear pharmacokinetics simulation in domestic pigs.

[This corrects the article DOI: 10.3389/fphar.2024.1348172.].

Oval and round window reinforcement surgery leads to improvements in sound tolerance and quality of life for hyperacusis patients.

PURPOSE: Hyperacusis is an audiological disorder in which patients become persistently sensitive and intolerant to everyday environmental sounds. For those patients that fail conservative options, a minimally invasive surgical procedure has been developed. MATERIALS & METHODS: Retrospective case series of 73 adult patients with hyperacusis who underwent oval and round window reinforcement surgery between 1/2017-6/2023. Small pieces of temporalis fascia were used to reinforce the round and oval windows. Patients were separated into two groups based on their preoperative speech Loudness Discomfort Level (LDL). Patients with a preoperative speech LDL ≤ 70 dB were placed in the "low LDL group" whereas patients with a preoperative speech LDL >70 dB were placed in the "high LDL group." Preoperative and one-week postoperative audiogram and speech LDLs were compared. Quality of life was assessed using the Glasgow Benefit Inventory (GBI) survey. RESULTS: 73 patients met inclusion criteria - 21 patients in the low LDL group and 52 in the high LDL group. Patients in the high LDL group significantly improved their LDLs by an average of 3.5 dB (P < 0.0001). 42 patients (80.8 %) in the high LDL group had improvement and would recommend the surgery for hyperacusis. Patients in the low LDL group significantly improved their LDL by an average of 12.9 dB (P = 0.032). Ten patients (47.6 %) from the low LDL group experienced improvement and would recommend hyperacusis surgery. CONCLUSION: Many patients with hyperacusis who undergo oval and round window reinforcement can receive significant improvement in sound tolerance and quality of life. Patients with a pre-op speech LDL > 70 dB have the greatest potential for improvement with surgery (80.8 %), probably because their hyperacusis was less severe. In the high LDL group(>70dB) the improvement in 1-10 scale went from 8.6 pre-op to 2.4 post op. In the low LDL group(<70dB) went from 9.2 pre-op to 6.8 post-op. These findings were consistent with the GBI results.

Endoscope-Assisted Cochlear Implantation in Atretic Round Window.

Different techniques have been proposed for cochlear implant (CI) from its conventional transmastoid posterior tympanotomy approach. Endoscopy role in the otologic field is still relatively new, but it provides a better surgical view with improved image clarity, especially in the challenging anatomical visualization of the critical structures in CI surgery. A 3-year-old girl with bilateral progressive profound hearing loss was scheduled for left cochlear implant surgery. The pre-operative high-resolution computed tomography (HRCT) of the temporal bone and magnetic resonance (MR) of internal acoustic meatus reported no significant abnormality of the middle and inner ears structures bilaterally. The standard left postauricular cortical mastoidectomy and posterior tympanotomy were performed. However, the microscopic view could not visualize the round window (RW) niche despite a widened extended posterior tympanotomy and surgical field manipulation. Transfacial recess endoscopic examination was done and was able to identify the possibly atretic RW. With endoscopic guidance, CI electrodes were inserted via cochleostomy, and intraoperative impedance measurement and neural response telemetry were obtained both during surgery and the postoperative phase. No intra- and postoperative complications were observed in this case. Following activation, the CI was functioning well. In conclusion, atretic RW is a rare anomaly found intraoperatively during CI surgery. Endoscope-assisted electrode insertion offers excellent visualization of targeted middle ear structures, especially in limited or abnormal anatomy of RW, which could minimize the risk of surgical complications.

Influence of inner ear impedance on middle ear sound transfer functions.

Introduction: For experimental studies on sound transfer in the middle ear, it may be advantageous to perform the measurements without the inner ear. In this case, it is important to know the influence of inner ear impedance on the middle ear transfer function (METF). Previous studies provide contradictory results in this regard. With the current study, we investigate the influence of inner ear impedance in more detail and find possible reasons for deviations in the previous studies. Methods: 11 fresh frozen temporal bones were prepared in our study. The factors related to inner ear impedance, including round window membrane stiffness, cochleostomy, cochlea fluid and cochlea destruction were involved in the experimental design. After measuring in the intact specimen as a reference (step 1), the round window membrane was punctured (step 2), then completely removed (step 3). The cochleostomy was performed (step 4) before the cochlear fluid was carefully suctioned through scala tympani (step 5) and scala vestibuli (step 6). Finally, cochlea was destroyed by drilling (step 7). Translational and rotational movement of the stapes footplate were measured and calculated at each step. The results of the steps were compared to quantify the effect of inner ear impedance changing related to the process of cochlear drainage. Results: As the inner ear impedance decreases from step 1 to 7, the amplitudes of the METF curves at each frequency gradually increase in general. From step 6 on, the measured METF are significantly different with respect to the intact group at high frequencies above 3 kHz. The differences are frequency dependent. However, the significant decrement of rotational motion appears at the frequencies above 4.5 kHz from the step 5. Conclusion: This study confirms the influence of inner ear impedance on METF only at higher frequencies (≥3 kHz). The rotational motions are more sensitive to the drainage of fluid at the higher frequency. Study results that found no influence of cochlea impedance may be due to incomplete drainage of the cochlea.

Radiological Parameters Predicting the Round Window Niche Visibility through Facial Recess Approach in Cochlear Implantation.

Aim: The aim was to study the radiological parameters using High Resolution Computed Tomography (HRCT) temporal bone to predict the Round Window Niche (RWN) visibility through the facial recess approach and to study radiological types of the round window niche. Materials and Methods: Prospective study was done in the patients underwent CI surgery from 2019 to 2021. HRCT radiological parameters of the patients and their intraoperative visualisation from video recordings were compared to predict the most feasible parameters to predict good visualisation of RWN. Results: Among 51 patients (34 males, 17 females) in 48 children round window membrane insertion was done and in three children cochleostomy was done and in two children partial canal wall drilling was done due to poor visualisation of RWN area. Multiple parameters to assess the visibility of the RWN were used. Facial recess width (4.2 mm), location of the mastoid segment of facial nerve (2 mm), external auditory canal to basal turn of cochlea angle (< 13.50) and the radiological types (tunnel shape and semi-circular shape) of the RWN by HRCT were found to be significant parameters in predicting a good visualisation of the RWN. Conclusion: HRCT parameters prepare the surgeon to face the possibility of a difficult surgery and plan to deal with difficult situations. This would eventually lead to better preparedness of surgeons for management of complications.

Round Window Visibility in Cochlear Implantation : Pre-operative Prediction Using Various Radiological Parameters.

Purpose: The round window approach has become the most preferred route for electrode insertion in cochlear implant surgery; however, it is not possible at times due to difficult round window membrane (RWM) visibility. Our study aims to investigate the relationship between preoperative radiological parameters and the surgical visibility of the RWM in Cochlear implant patients. Methodology: A prospective cross-sectional study of 31 patients, age < 6 years, with bilateral severe to profound sensorineural hearing loss was conducted at a tertiary care hospital. The preoperative HRCT temporal bone scan was studied, and the parameters evaluated were facial nerve location, facial recess width, and RWM visibility prediction. All patients were operated on via the posterior tympanotomy. The surgical RWM visibility was done after optimal drilling of the posterior tympanotomy recess. The relationship between the radiological parameters and surgical visibility of RWM was evaluated. Results: The difference in the facial nerve location as per the type of RWM was found to be significant (p value < 0.05). However, the facial recess width was not significantly associated with RWM visibility. The radiological prediction of RWM visibility by tracing the prediction line over RWM was significantly associated with intraoperative RWM visibility. Conclusion: The goal to look for preoperative scans is to predict the ease or difficulty of RWM visibility during surgery. The difficult visualization of the RWM, can result in dire intraoperative consequences. A comprehensive understanding of preoperative radiological parameters, coupled with meticulous surgical planning, is crucial to address these challenges effectively by focusing on enhancing RWM visualization.

A Benchtop Round Window Model for Studying Magnetic Nanoparticle Transport to the Inner Ear.

INTRODUCTION: The round window membrane (RWM) presents a significant barrier to the local application of therapeutics to the inner ear. We demonstrate a benchtop preclinical RWM model and evaluate superparamagnetic iron oxide nanoparticles (SPIONs) as vehicles for magnetically assisted drug delivery. METHODS: Guinea pig RWM explants were inset into a 3D-printed dual chamber benchtop device. Custom-synthesized 7-nm iron core nanoparticles were modified with different polyethylene glycol chains to yield two sizes of SPIONs (NP-PEG600 and NP-PEG3000) and applied to the benchtop model with and without a magnetic field. Histologic analysis of the RWM was performed using transmission electron microscopy (TEM) and confocal microscopy. RESULTS: Over a 4-h period, 19.5 ± 1.9% of NP-PEG3000 and 14.6 ± 1.9% of NP-PEG600 were transported across the guinea pig RWM. The overall transport increased by 1.45× to 28.4 ± 5.8% and 21.0 ± 2.0%, respectively, when a magnetic field was applied. Paraformaldehyde fixation of the RWM decreased transport significantly (NP-PEG3000: 7.6 ± 1.5%; NP-PEG600: 7.0 ± 1.6%). Confocal and electron microscopy analysis demonstrated nanoparticle localization throughout all cellular layers and layer-specific transport characteristics within RWM. CONCLUSION: The guinea pig RWM explant benchtop model allows for targeted and practical investigations of transmembrane transport in the development of nanoparticle drug delivery vehicles. The presence of a magnetic field increases SPION delivery by 45%-50% in a nanoparticle size- and cellular layer-dependent manner. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3355-3362, 2024.

Surgical procedure of intratympanic injection and inner ear pharmacokinetics simulation in domestic pigs.

Introduction: One major obstacle in validating drugs for the treatment or prevention of hearing loss is the limited data available on the distribution and concentration of drugs in the human inner ear. Although small animal models offer some insights into inner ear pharmacokinetics, their smaller organ size and different barrier (round window membrane) permeabilities compared to humans can complicate study interpretation. Therefore, developing a reliable large animal model for inner ear drug delivery is crucial. The inner and middle ear anatomy of domestic pigs closely resembles that of humans, making them promising candidates for studying inner ear pharmacokinetics. However, unlike humans, the anatomical orientation and tortuosity of the porcine external ear canal frustrates local drug delivery to the inner ear. Methods: In this study, we developed a surgical technique to access the tympanic membrane of pigs. To assess hearing pre- and post-surgery, auditory brainstem responses to click and pure tones were measured. Additionally, we performed 3D segmentation of the porcine inner ear images and used this data to simulate the diffusion of dexamethasone within the inner ear through fluid simulation software (FluidSim). Results: We have successfully delivered dexamethasone and dexamethasone sodium phosphate to the porcine inner ear via the intratympanic injection. The recorded auditory brainstem measurements revealed no adverse effects on hearing thresholds attributable to the surgery. We have also simulated the diffusion rates for dexamethasone and dexamethasone sodium phosphate into the porcine inner ear and confirmed the accuracy of the simulations using in-vivo data. Discussion: We have developed and characterized a method for conducting pharmacokinetic studies of the inner ear using pigs. This animal model closely mirrors the size of the human cochlea and the thickness of its barriers. The diffusion time and drug concentrations we reported align closely with the limited data available from human studies. Therefore, we have demonstrated the potential of using pigs as a large animal model for studying inner ear pharmacokinetics.

The Value of Endoscopic Exposure of Round Window in Cochlear Implant via Facial Recess.

Introduction Cochlear implantation has been considered as the best treatment in patients with severe to profound hearing loss unaidable with hearing aids. The main value of endoscope-assisted cochlear implantation is improved visibility of the RW Objective to assess the value of endoscopic assisted CI surgery via facial recess approach without elevating tympanic anulus. Methods This Prospective case series study non-randomized sample was performed on 50 patients with severe to profound hearing loss unaidable with hearing aids undergoing unilateral endoscopic assisted cochlear implant surgery with round window electrode insertion Results There were 23 male and 27 female patients. Most of the cases were children (41 cases). Of those 50 patients, 39 were prelingually hearing impaired. Four cases had various inner ear abnormalities. The standard mastoidectomy and Posterior Tympanotomy approach were used for all cases. Endoscopic identification of the RW through the PT enabled us to perform regular surgery in all cases. The current study concludes the difference between microscopic exposure and endoscopic exposure represented by Saint Tomas classification found that endoscopic exposure of round window classification is better represented by downgrading in the classification of round window exposure as type I 29(58%), type IIa 18(36%) type IIb 3 (6%) Non were type III by endoscopic exposure compared to microscopic exposure of round window is a type I 7(14%), type II 14(28%), type IIb 22(44%) and type III 7 (14%). Conclusion Endoscopy proved a great value in exposure and identification of RW in CI surgery through posterior tympanotomy approach.

Comparison of depth of electrode insertion between cochleostomy and round window approach: a cadaveric study.

INTRODUCTION: Round window approach and cochleostomy approach can have different depth of electrode insertion during cochlear implantation which itself can alter the audiological outcomes in cochlear implant. OBJECTIVE: The current study was conducted to determine the difference in the depth of electrode insertion via cochleostomy and round widow approach when done serially in same temporal bone. METHODOLOGY: This is a cross-sectional study conducted in the Department of Otorhinolaryngology in conjunction with Department of Anatomy and Department of Diagnostic and Interventional Radiology over a period of 1 year. 12-electrode array insertion was performed via either approach (cochleostomy or round window) in the cadaveric temporal bone. HRCT temporal bone scan of the implanted temporal bone was done and depth of insertion and various cochlear parameters were calculated. RESULT: A total of 12 temporal bones were included for imaging analysis. The mean cochlear duct length was 32.892 mm; the alpha and beta angles were 58.175° and 8.350°, respectively. The mean angular depth of electrode insertion via round window was found to be 325.2° (SD = 150.5842) and via cochleostomy 327.350 (SD = 112.79) degree and the mean linear depth of electrode insertion via round window was found to be 18.80 (SD = 4.4962) mm via cochleostomy 19.650 (SD = 3.8087) mm, which was calculated using OTOPLAN 1.5.0 software. There was a statically significant difference in linear depth of insertion between round window and cochleostomy. Although the angular depth of insertion was higher in CS group, there was no statistically significant difference with round window type of insertion. CONCLUSION: The depth of electrode insertion is one of the parameters that influences the hearing outcome. Linear depth of electrode insertion was found to be more in case of cochleostomy compared to round window approach (p = 0.075) and difference in case of angular depth of electrode insertion existed but not significant (p = 0.529).

Surgical Considerations in Inner Ear Gene Therapy from Human Temporal Bone Anatomy.

OBJECTIVE(S): Recently directed methods of inner ear drug delivery underscore the necessity for understanding critical anatomical dimensions. This study examines anatomical measurements of the human middle and inner ear relevant for inner ear drug delivery studied with three different imaging modalities. METHODS: Post-mortem human temporal bones were analyzed using human temporal bone histopathology (N = 24), micro computerized tomography (µCT; N = 4), and synchrotron radiation phase-contrast imaging (SR-PCI; N = 7). Nine measurements involving the oval and round windows were performed when relevant anatomical structures were visualized for subsequent age-controlled analysis, and comparisons were made between imaging methods. RESULTS: Combined human temporal bone histopathology showed the mean distance to the saccule from the center of the stapes footplate (FP) was 2.07 ± 0.357 mm and the minimum distance was 1.23 mm. The mean distance from the round window membrane (RWM) to the osseous spiral lamina (OSL) was 1.75 ± 0.199 mm and the minimum distance was 1.43 mm. Instruments inserted up to 1 mm past the center of the FP are unlikely to cause saccular damage, provided there are no endolymphatic hydrops. Similarly, instruments inserted up to 1 mm through the RWM in the trajectory toward the OSL are unlikely to cause OSL damage. CONCLUSION: The combined analyses of inner-ear dimensions of age-controlled groups and imaging modalities demonstrate critical dimensions of importance to consider when inserting delivery vehicles into the human cochlea. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:2879-2888, 2024.

Pharmacokinetics of monoclonal antibodies locally-applied into the middle ear of guinea pigs.

Countless therapeutic antibodies are currently available for the treatment of a broad range of diseases. Some target molecules of therapeutic antibodies are involved in the pathogenesis of sensorineural hearing loss (SNHL), suggesting that SNHL may be a novel target for monoclonal antibody (mAb) therapy. When considering mAb therapy for SNHL, understanding of the pharmacokinetics of mAbs after local application into the middle ear is crucial. To reveal the fundamental characteristics of mAb pharmacokinetics following local application into the middle ear of guinea pigs, we performed pharmacokinetic analyses of mouse monoclonal antibodies to FLAG-tag (FLAG-mAbs), which have no specific binding sites in the middle and inner ear. FLAG-mAbs were rapidly transferred from the middle ear to the cochlear fluid, indicating high permeability of the round window membrane to mAbs. FLAG-mAbs were eliminated from the cochlear fluid 3 h after application, similar to small molecules. Whole-body autoradiography and quantitative assessments of cerebrospinal fluid and serum demonstrated that the biodistribution of FLAG-mAbs was limited to the middle and inner ear. Altogether, the pharmacokinetics of mAbs are similar to those of small molecules when locally applied into the middle ear, suggesting the necessity of drug delivery systems for appropriate mAb delivery to the cochlear fluid after local application into the middle ear.