UNASSIGNED: There exists an unfulfilled requirement for effective cochlear pharmacotherapy. Controlled local drug delivery could lead to effective bioavailability. The round window niche (RWN), a cavity in the middle ear, is connected to the cochlea via a membrane through which drug can diffuse. We are developing individualized drug-eluting RWN implants (RNIs). To test their effectiveness in guinea pigs, a commonly used model in cochlear pharmacology studies, it is first necessary to develop guinea pig RNIs (GP-RNI).
UNASSIGNED: Since guinea pigs do not have a RWN such as it is present in humans and to reduce the variables in in vivo studies, a one-size-fits-all GP-RNI model was designed using 12 data sets of Dunkin-Hartley guinea pigs. The model was 3D-printed using silicone. The accuracy and precision of printing, distribution of the sample ingredient dexamethasone (DEX), biocompatibility, bio-efficacy, implantability and drug release were tested in vitro. The GP-RNI efficacy was validated in cochlear implant-traumatized guinea pigs in vivo.
UNASSIGNED: The 3D-printed GP-RNI was precise, accurate and fitted in all tested guinea pig RWNs. DEX was homogeneously included in the silicone. The GP-RNI containing 1% DEX was biocompatible, bio-effective and showed a two-phase and sustained DEX release in vitro, while it reduced fibrous tissue growth around the cochlear implant in vivo.
UNASSIGNED: We developed a GP-RNI that can be used for precise inner ear drug delivery in guinea pigs, providing a reliable platform for testing the RNI\'s safety and efficacy, with potential implications for future clinical translation.

OBJECTIVE: Little is known about the hearing characteristics in patients with congenital round window atresia (CRWA). This study aimed to investigate hearing characteristics in patients with CRWA by comparing them with two relatively common congenital middle ear anomalies: congenital stapedial fixation (CSF) and congenital ossicular discontinuity (COD).
METHODS: Literature searches yielded five patients with surgically confirmed CRWA (seven ears), who were included in the CRWA group, along with one of our patients. Air and bone conduction thresholds; air-bone gap (ABG); and presence and depth of the Carhart notch were analyzed. These audiometric variables in the CRWA group were compared with those in the CSF (n = 15) and COD (n = 22) groups, comprising patients identified from our institution\'s medical database.
RESULTS: Average bone and air conduction thresholds in the CRWA group were 16.4 (standard deviation [SD]: 2.9; 95 % confidence interval [CI]: 14.6-18.3) and 44.6 (SD: 3.5; 95 % CI: 42.6-47.3) dB hearing level (HL). Bone conduction thresholds at high frequencies (≥2 kHz) were higher than those at low frequencies (<2 kHz), while air conduction thresholds at high frequencies were lower than those at low frequencies: ABGs at high frequencies were significantly smaller than those at low frequencies (2 kHz vs. 0.5 kHz, p = 0.027; 2 kHz vs. 1 kHz, p = 0.041; 4 kHz vs. 0.5 kHz, p = 0.042; 4 kHz vs. 1 kHz, p = 0.027). There were no between-group differences in incidence and depth of the Carhart notch.
CONCLUSIONS: CRWA could manifest as a distinct audiometric pattern with poorer bone conduction and better air conduction at ≥2 kHz, resulting in significantly smaller ABGs at higher frequencies than that at lower frequencies. Our findings indicated that this pattern differed from that of CSF and COD. The unique beer bottle-shaped audiogram associated with CRWA might facilitate its early diagnosis in patients with congenital conductive hearing loss.

Sound transmission to the human inner ear by bone conduction pathway with an implant attached to the otic capsule is a specific case where the cochlear response depends on the direction of the stimulating force. A finite element model of the temporal bone with the inner ear, no middle and outer ear structures, and an immobilized stapes footplate was used to assess the directional sensitivity of the cochlea. A concentrated mass represented the bone conduction implant. The harmonic analysis included seventeen frequencies within the hearing range and a full range of excitation directions. Two assessment criteria included: (1) bone vibrations of the round window edge in the direction perpendicular to its surface and (2) the fluid volume displacement of the round window membrane. The direction of maximum bone vibration at the round window edge was perpendicular to the round window. The maximum fluid volume displacement direction was nearly perpendicular to the modiolus axis, almost tangent to the stapes footplate, and inclined slightly to the round window. The direction perpendicular to the stapes footplate resulted in small cochlear responses for both criteria. A key factor responsible for directional sensitivity was the small distance of the excitation point from the cochlea.

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.

OBJECTIVE: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière\'s disease.
METHODS: Prospective, unblinded, cohort study.
METHODS: Tertiary care neurotology clinic.
METHODS: Adults 18 to 85 years with a diagnosis of unilateral definite Menière\'s disease per Barany society criteria.
METHODS: A single injection of a long-acting gel formulation under direct visualization into the round window niche.
METHODS: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer.
RESULTS: Ten subjects with unilateral Menière\'s disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment.
CONCLUSIONS: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy.

BACKGROUND: Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach.
METHODS: Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas\' Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures.
RESULTS: Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens (p = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture.
CONCLUSIONS: Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans.

The feasibility of low frequency pure tone generation in the inner ear by laser-induced nonlinear optoacoustic effect at the round window was demonstrated in three human cadaveric temporal bones (TB) using an integral pulse density modulation (IPDM). Nanosecond laser pulses with a wavelength in the near-infrared (NIR) region were delivered to the round window niche by an optical fiber with two spherical lenses glued to the end and a viscous gel at the site of the laser focus. Using IPDM, acoustic tones with frequencies between 20 Hz and 1 kHz were generated in the inner ear. The sound pressures in scala tympani and vestibuli were recorded and the intracochlear pressure difference (ICPD) was used to calculate the equivalent sound pressure level (eq. dB SPL) as an equivalent for perceived loudness. The results demonstrate that the optoacoustic effect produced sound pressure levels ranging from 140 eq. dB SPL at low frequencies ≤ 200 Hz to 90 eq. dB SPL at 1 kHz. Therefore, the produced sound pressure level is potentially sufficient for patients requiring acoustic low frequency stimulation. Hence, the presented method offers a potentially viable solution in the future to provide the acoustic stimulus component in combined electro-acoustic stimulation with a cochlear implant.

OBJECTIVE: 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.
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.
CONCLUSIONS: 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.

Efficient and minimally invasive drug delivery to the inner ear is a significant challenge. The round window membrane (RWM), being one of the few entry points to the inner ear, has become a vital focus of investigation. However, due to the complexities of isolating the RWM, our understanding of its pharmacokinetics remains limited. The RWM comprises three distinct layers: the outer epithelium, the middle connective tissue layer, and the inner epithelial layer, each potentially possessing unique delivery properties. Current models for investigating transport across the RWM utilize in vivo animal models or ex vivo RWM models which rely on cell cultures or membrane fragments. Guinea pigs serve as a validated preclinical model for the investigation of drug pharmacokinetics within the inner ear and are an important animal model for the translational development of delivery vehicles to the cochlea. In this study, we describe an approach for explantation of a guinea pig RWM with surrounding cochlear bone for benchtop drug delivery experiments. This method allows for preservation of native RWM architecture and may provide a more realistic representation of barriers to transport than current benchtop models.

BACKGROUND: This study proposed a classification of the vertical portion of the facial nerve (VPFN) location, incorporating the previous classifications regarding the posterior-to-anterior and medial-to-lateral dimensions. We also evaluated the implication of this proposed classification on the round window visibility during pediatric cochlear implantation (CI).
METHODS: It was a retrospective multicenter observational cohort study. This study included 334 cases that underwent CI between 2015 and 2022 at multiple referral institutes. Two physicians evaluated the preoperative computed tomography images of 334 patients and determined the radiological type of the VPFN. These types were matched with intraoperative round window accessibility.
RESULTS: The Spearman\'s correlation coefficient showed a strong correlation between the proposed VPFN type and the intraoperative round window visibility, as the P-value was <.001.
CONCLUSIONS: This classification could provide the surgeon preoperatively with the precise location of the VPFN in the lateral-to-medial and posterior-to-anterior dimensions. Furthermore, this location classification of the VPFN was significantly correlated with intraoperative round window accessibility, with an accuracy of 90.42%. Therefore, types C and D were expected to have difficult accessibility into the round window, and more surgical interventions were needed to modify the posterior tympanotomy or use other approaches.