Intratympanic steroid treatment can reduce ROS and immune response in human perilymph investigated by in-depth proteome analysis.

Intratympanic (IT) steroid treatment is one of the most widely used and effective treatments for inner ear disorders such as sudden sensorineural hearing loss (SNHL). However, a clear mechanism of IT steroids in inner ear recovery has not yet been revealed. Therefore, we investigated proteome changes in extracted human perilymph after steroid treatment. In this study, we applied a tandem mass spectrometry (MS/MS)-based proteomics approach to discover global proteome changes by comparing human perilymph after steroid treatment with non-treated perilymph group. Using liquid chromatography-MS/MS analysis, we selected 156 differentially expressed proteins (DEPs) that were statistically significant according to Student's t-test. Functional annotation analysis showed that upregulated proteins after steroid treatment are related to apoptosis signaling, as well as reactive oxygen species (ROS) and immune responses. The protein-protein interaction (PPI) clusters the proteins associated with these processes and attempts to observe signaling circuitry, which mediates cellular response after IT steroid treatments. Moreover, we also considered the interactome analysis of DEPs and observed that those with high interaction scores were categorized as having equivalent molecular functions (MFs). Collectively, we suggest that DEPs and interacting proteins in human perilymph after steroid treatment would inhibit the apoptotic and adaptive immune processes that may lead to anti-inflammatory effects.

Space-Occupying Lesions of the Inner Ear Are Easily Misdiagnosed as Endolymphatic Hydrops in a Perilymph-Enhanced Sequence Without the Assistance of a Heavily T2-Weighted Sequence.

OBJECTIVE: The aim of the study was to explore the value of T2-sampling perfection with application-optimized contrasts by using different flip angle evolutions (T2-SPACE) in identifying space-occupying lesions of the inner ear. METHODS: We collected the T2-SPACE and 3-dimensional inversion-recovery sequence with real reconstruction (3D-real IR) images of 220 patients with inner ear symptoms, including 15 patients with inner ear space-occupying lesions. With T2-SPACE images hidden, a senior and junior radiologist made a diagnosis for all patients using only the 3D-real IR images. After 4 weeks the images were shuffled, and T2-SPACE images were made available to the 2 radiologists in addition to 3D-real IR to reconsider the diagnosis for all patients. RESULTS: With the SPACE images hidden, the correct diagnosis rate of the space-occupying lesions was 8/15 (53.3%) for the senior radiologist, whereas it was only 2/15 (13.3%) for the junior radiologist. Without the SPACE images hidden, the correct diagnosis rate of the space-occupying lesions was 15/15 (100.0%) for the senior radiologist, whereas it was 13/15 (86.7%) for the junior radiologist. Of the 15 patients, 7 had only vestibular space-occupying lesions, 2 had only cochlear space-occupying lesions, and 6 had both. No semicircular canal space-occupying lesion was observed. CONCLUSIONS: T2-SPACE can help identify space-occupying lesions of the inner ear that tend to be misdiagnosed as endolymphatic hydrops on 3D-real IR. The senior radiologist had a higher rate for the identification of space-occupying lesions than the junior radiologist when using only 3D-real IR, although the senior radiologist detection rate was still only 53.3%. With the addition of T2-SPACE, both the junior and senior radiologist achieved a high detection rate, which increased to 86.7% and 100%, respectively.

Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins.

As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.

In-depth proteome of perilymph in guinea pig model.

The vast majority of sensorineural hearing loss is caused by impairment of the inner ear cells. Proteomic analysis of perilymph may therefore improve our understanding of inner ear diseases and hearing loss. However, the investigation of the human perilymph proteome was limited due to technical difficulties in perilymph sampling. The guinea pig (Cavia porcellus) is frequently used as an experimental model in preclinical hearing research. In this study, we analyzed samples of perilymph collected from 12 guinea pigs to overcome limited experimental information regarding its proteome. We identified a total of 1413 proteins, establishing a greatly expanded proteome of the previously inferred guinea pig perilymph. This provides a comprehensive proteomic resource for the research community, which will facilitate future molecular-phenotypic studies using the guinea pig as an experimental model of relevance to human inner ear biology.

Impact of Systemic versus Intratympanic Dexamethasone Administration on the Perilymph Proteome.

Glucocorticoids are the first-line treatment for sensorineural hearing loss, but little is known about the mechanism of their protective effect or the impact of route of administration. The recent development of hollow microneedles enables safe and reliable sampling of perilymph for proteomic analysis. Using these microneedles, we investigate the effect of intratympanic (IT) versus intraperitoneal (IP) dexamethasone administration on guinea pig perilymph proteome. Guinea pigs were treated with IT dexamethasone (n = 6), IP dexamethasone (n = 8), or untreated for control (n = 8) 6 h prior to aspiration. The round window membrane (RWM) was accessed via a postauricular approach, and hollow microneedles were used to perforate the RWM and aspirate 1 µL of perilymph. Perilymph samples were analyzed by liquid chromatography-mass spectrometry-based label-free quantitative proteomics. Mass spectrometry raw data files have been deposited in an international public repository (MassIVE proteomics repository at https://massive.ucsd.edu/) under data set # MSV000086887. In the 22 samples of perilymph analyzed, 632 proteins were detected, including the inner ear protein cochlin, a perilymph marker. Of these, 14 proteins were modulated by IP, and three proteins were modulated by IT dexamethasone. In both IP and IT dexamethasone groups, VGF nerve growth factor inducible was significantly upregulated compared to control. The remaining adjusted proteins modulate neurons, inflammation, or protein synthesis. Proteome analysis facilitated by the use of hollow microneedles shows that route of dexamethasone administration impacts changes seen in perilymph proteome. Compared to IT administration, the IP route was associated with greater changes in protein expression, including proteins involved in neuroprotection, inflammatory pathway, and protein synthesis. Our findings show that microneedles can mediate safe and effective intracochlear sampling and hold promise for inner ear diagnostics.

Signal and morphological changes in the endolymph of patients with vestibular schwannoma on non-contrast 3D FLAIR at 3 Tesla.

BACKGROUND: Non-contrast FLAIR revealed increased signal within the inner ear in patients with vestibular schwannoma, which is generally assumed to occur in the perilymph; however, the majority of previous studies did not differentiate between the endolymph and perilymph. Therefore, endolymph signal changes have not yet been investigated in detail. The purpose of the present study was three-fold: (1) to assess perilymph signal changes in patients with vestibular schwannoma on heavily T2-weighted (T2W) 3D FLAIR, also termed positive perilymphatic images (PPI), (2) to evaluate signal and morphological changes in the endolymph on PPI, and (3) to establish whether vertigo correlates with the signal intensity ratios (SIR) of the vestibular perilymph or vestibular endolymphatic hydrops. METHODS: Forty-two patients with unilateral vestibular schwannoma were retrospectively recruited. We semi-quantitatively and qualitatively evaluated the perilymph signal intensity on the affected and unaffected sides. We also quantitatively examined the signal intensity of the vestibular perilymph and assessed the relationship between vertigo and the SIR of the vestibular perilymph on the affected side. We semi-quantitatively or qualitatively evaluated the endolymph, and investigated whether vestibular hydrops correlated with vertigo. RESULTS: The perilymph on the affected side showed abnormal signal more frequently (signal intensity grade: overall mean 1.45 vs. 0.02; comparison of signal intensity: overall mean 36 vs. 0 cases) and in more parts (the entire inner ear vs. the basal turn of the cochlea and vestibule) than that on the unaffected side. No significant difference was observed in the SIR of the vestibular perilymph with and without vertigo (5.54 vs. 5.51, p = 0.18). The endolymph of the vestibule and semicircular canals showed the following characteristic features: no visualization (n = 4), signal change (n = 1), or vestibular hydrops (n = 10). A correlation was not observed between vestibular hydrops and vertigo (p = 1.000). CONCLUSIONS: PPI may provide useful information on signal and morphological changes in the endolymph of patients with vestibular schwannoma. Further research is warranted to clarify the relationship between vertigo and the MR features of the inner ear.

A case of perilymphatic fistula caused by surgical drilling with preserved normal hearing.

We introduce our horrible experience of lateral semicircular canal exposure due to unintended drilling during left facial nerve decompression. Nearly half of the canal was drilled-out, however, the membranous labyrinth was preserved and the defect was covered with temporal fascia. Immediately after surgery, the patient complained of vertigo with right beating nystagmus. However, the patient could hear an audible tuning fork sound and the Weber-test showed left-sided deviation. The vertigo gradually subsided and the facial palsy was completely recovered 3 months after the surgery. One and half years later, the patient spent a normal life with normal hearing nevertheless after this terrifying episode.

Junctional Modulation of Round Window Membrane Enhances Dexamethasone Uptake into the Inner Ear and Recovery after NIHL.

Delivery of substances into the inner ear via local routes is increasingly being used in clinical treatment. Studies have focused on methods to increase permeability through the round window membrane (RWM) and enhance drug diffusion into the inner ear. However, the clinical applications of those methods have been unclear and few studies have investigated the efficacy of methods in an inner ear injury model. Here, we employed the medium chain fatty acid caprate, a biologically safe, clinically applicable substance, to modulate tight junctions of the RWM. Intratympanic treatment of sodium caprate (SC) induced transient, but wider, gaps in intercellular spaces of the RWM epithelial layer and enhanced the perilymph and cochlear concentrations/uptake of dexamethasone. Importantly, dexamethasone co-administered with SC led to significantly more rapid recovery from noise-induced hearing loss at 4 and 8 kHz, compared with the dexamethasone-only group. Taken together, our data indicate that junctional modulation of the RWM by SC enhances dexamethasone uptake into the inner ear, thereby hastening the recovery of hearing sensitivity after noise trauma.

[Peculiarities of differential diagnostics of perilymphatic fistulas of the labyrinth windows of non-inflammatory genesis]. / Osobennosti differentsial'noi diagnostiki perilimfaticheskikh fistul okon labirinta nevospalitel'nogo geneza.

THE PURPOSE OF THE STUDY: To determine the value of the results of various audiological and vestibulometric studies for the differential diagnosis of non-inflammatory perilymphatic fistulas of the labyrinth windows (PFOLW). MATERIAL AND METHODS: The retrospective and prospective analysis of the informative value of the results of audiological and vestibulometric studies was carried out in 124 people with different combinations of cochleovestibular complaints, who had different pathology of the inner and middle ear, with different terms of the disease - from several days to 30 years. To assess the informativeness of the applied testing, the following operational characteristics were determined: general sensitivity (Se), specificity (Sp) and the prognostic value of a positive result (PPV=positive predictive value). A pair-by-pair comparison of the prognostic value of a positive result of vestibulometric and audiometric tests was performed using the Pearson criterion χ2 and the exact Fisher criterion. RESULTS: It is shown that none of the tests used has 100% reliability, but the consistent application of some of them can successfully improve the diagnosis of idiopathic PFOL. When comparing the results of a number of tests, such as the Fukuda walking test and / or the Babinsky-Weil walking test, audiometric tests with head clone and hyperventilation, the test of fluid injection into the external auditory canal and the test of J. Frasser & L. Flood, it was found that the average prognostic value of a positive result was 87.3%, which is statistically significantly higher than the average result (47.9%) for other samples. CONCLUSIONS: Correlations of the results of simple vestibulometric and audiometric tests allow us to recommend them to improve the diagnosis of idiopathic perilymphatic fistulas of the labyrinth windows. The possibilities of modern electrophysiological audiological research methods are subject to further study.

Use of topical fluorescein in the diagnosis and localization of perilymphatic fistula.

OBJECTIVE: The purpose of this video presentation is to demonstrate the effect of intraoperative dilute topical fluorescein in perilympatic fistula diagnosis and localization. MATERIALS AND METHODS: Explorative tympanotomy was performed for the diagnosis, localization and repair of the fistula in the patient who had a pre-diagnosis of perilymphatic fistula. Topical fluorescein was applied intraoperatively to localize the defect. RESULT: A clear change of color was distinguished from yellow to green leading to diagnosis of the perilymphatic fistula and also showed the origin of the fistula. CONCLUSION: Topical application of dilute fluorescein is a convenient and effective tool in the diagnosis and localization of perilymphatic fistula.

CT and MRI for the diagnosis of perilymphatic fistula: a study of 17 surgically confirmed patients.

BACKGROUND: We evaluated the usefulness of CT and MRI for the diagnosis of perilymphatic fistula (PLF) of the round (RW) and/or oval (OW) windows, with surgery as gold standard. METHODS: We retrospectively enrolled 17 patients who presented a surgically confirmed PLF of the round (RW) or oval (OW) windows. All patients were imaged by CT + MRI (T2W SSFP without contrast) prior to surgery (= gold standard). Two radiologists, analyzed the RW and OW on the side of the clinical symptoms and sensitivity (Se) + Specificity (Sp) were calculated. RESULTS: Round window fistula was the most frequent (71%). The best sign of PLF on imaging was a fluid filling of the window niches, which had good Se (83-100% for RW, 66-83% for OW) and Sp (60% for RW, 91-100% for OW). Disorientation of the footplate and pneumolabyrinth were also only observed in 50% of OW PLF. CONCLUSION: The combination of CT and MRI is a reliable tool for a fast and accurate diagnosis of round and oval window perilymphatic fistula, with good sensitivity (> 80%). The most common sign of PLF on imaging is the presence of a fluid-filling in the RW (especially if > 2/3 of the RW niche) or in the OW niches on both CT and MRI. A disorientation of the footplate or the presence of a pneumolabyrinth are clearly in favor of an oval window perilymphatic fistula.

Clinical efficacy of hyperbaric oxygen therapy on idiopathic sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as unexplained hearing loss of at least 30 decibels (dB) occurring within 72 hours over at least three contiguous frequencies. ISSHL is common and has a significant effect on quality of life. Hyperbaric oxygen (HBO2) therapy is a medical treatment method that aims to increase the level of dissolved oxygen in the tissues. Correcting perilymph hypoxia is the goal of HBO2 therapy for ISSHL. In recent years, HBO2 therapy has been increasingly involved in the treatment of ISSHL. The medical records of 135 patients who had received HBO2 therapy for ISSHL were reviewed. Demographic properties of patients, severity of hearing loss, delay until HBO2 therapy, number of HBO2 therapy sessions and outcomes were evaluated. Findings of the present study are similar to most of previous studies that demonstrate that HBO2 therapy as adjunctive treatment results in an improvement of hearing. Early treatment is important for ISSHL, and HBO2 therapy is recommended in the early period, particularly within 14 days of onset.

Endogenous α1-antitrypsin levels in the perilymphatic fluid correlates with severity of hearing loss.

OBJECTIVES: To determine the levels of endogenous α1-antitrypsin in the perilymph of patients undergoing cochlear implant (CI), and its reverse association with the severity of hearing loss. STUDY DESIGN: Retrospective study. SETTING: Tertiary care university hospital. PARTICIPANTS: The study includes 38 patients undergoing CI surgery, 11 patients diagnosed with congenital deafness and 27 non-congenital deafness, eight patients diagnosed with moderate hearing loss (N = 8; PTA = 70 dB), severe hearing loss (N = 11; PTA 70-90 dB) and profound hearing loss (N = 19; PTA > 90 dB). MAIN OUTCOME AND MEASURE: 1 to 12 µL perilymphatic fluids were collected by micropipette. α1-antitrypsin levels were determined, and current and historic audiological parameters were obtained. RESULTS: The congenital and non-congenital group exhibited AAT concentrations of 2.5 ± 1.9 × 106 LFQ and 3.2 ± 1.2 × 106 LFQ, respectively (mean ± SD; P = .38). Mean levels of α1-antitrypsin in the perilymph fluid within the moderate group was 3.64 × 106  ± 2.1 × 106 LFQ vs 3.5 × 106  ± 1.2 × 106 in severe hearing loss (P = .81) and 2.4 × 106  ± 1.1 × 106 LFQ in the profound hearings loss group (P = .06). The difference in levels of AAT in samples from the severe hearings loss group vs the profound hearings loss group reached statistical significance (P = .04). CONCLUSION: Insufficiency in α1-antitrypsin levels in the perilymph fluid of the inner ear appears to display a relationship with the severity of hearing loss. The prospect of introducing clinical-grade plasma-purified α1-antitrypsin directly onto the site of cochlear injury deserves thorough investigation.

An LCMS-based untargeted metabolomics protocol for cochlear perilymph: highlighting metabolic effects of hydrogen gas on the inner ear of noise exposed Guinea pigs.

INTRODUCTION: Noise-induced hearing loss (NIHL) is an increasing problem in society and accounts for a third of all cases of acquired hearing loss. NIHL is caused by formation of reactive oxygen species (ROS) in the cochlea causing oxidative stress. Hydrogen gas (H2) can alleviate the damage caused by oxidative stress and can be easily administered through inhalation. OBJECTIVES: To present a protocol for untargeted metabolomics of guinea pig perilymph and investigate the effect of H2 administration on the perilymph metabolome of noise exposed guinea pigs. METHODS: The left ear of guinea pigs were exposed to hazardous impulse noise only (Noise, n = 10), noise and H2 (Noise + H2, n = 10), only H2 (H2, n = 4), or untreated (Control, n = 2). Scala tympani perilymph was sampled from the cochlea of both ears. The polar component of the perilymph metabolome was analyzed using a HILIC-UHPLC-Q-TOF-MS-based untargeted metabolomics protocol. Multivariate data analysis (MVDA) was performed separately for the exposed- and unexposed ear. RESULTS: MVDA allowed separation of groups Noise and Noise + H2 in both the exposed and unexposed ear and yielded 15 metabolites with differentiating relative abundances. Seven were found in both exposed and unexposed ear data and included two osmoprotectants. Eight metabolites were unique to the unexposed ear and included a number of short-chain acylcarnitines. CONCLUSIONS: A HILIC-UHPLC-Q-TOF-MS-based protocol for untargeted metabolomics of perilymph is presented and shown to be fit-for-purpose. We found a clear difference in the perilymph metabolome of noise exposed guinea pigs with and without H2 treatment.

The value of four stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI.

PURPOSE: There is still a clinical-radiologic discrepancy in patients with Menière's disease (MD). Therefore, the purpose of this study was to investigate the reliability of current MRI endolymphatic hydrops (EH) criteria according to Baráth in a larger study population and the clinical utility of new imaging signs such as a supplementary fourth low-grade vestibular EH and the degree of perilymphatic enhancement (PE) in patients with Menière's disease (MD). METHODS: This retrospective study included 148 patients with probable or definite MD according to the 2015 American Academy of Otolaryngology, Head and Neck Surgery criteria who underwent a 4-h delayed intravenous Gd-enhanced 3D-FLAIR MRI between January 2015 and December 2016. Vestibular EH, vestibular PE, cochlear EH, and cochlear PE were reviewed twice by three experienced readers. Cohen's Kappa and multivariate logistic regression were used for analysis. RESULTS: The intra- and inter-reader reliability for the grading of vestibular-cochlear EH and PE was excellent (0.7 < kappa < 0.9). The two most distinctive characteristics to identify MD are cochlear PE and vestibular EH which combined gave a sensitivity and specificity of 79.5 and 93.6%. By addition of a lower grade vestibular EH, the sensitivity improved to 84.6% without losing specificity (92.3%). Cochlear EH nor vestibular PE showed added-value. CONCLUSIONS: MRI using vestibular-cochlear EH and PE grading system is a reliable technique. A four-stage vestibular EH grading system in combination with cochlear PE assessment gives the best diagnostic accuracy to detect MD.

Audiovestibular Phenotypes and Advanced Magnetic Resonance Imaging Features of Cochlin Gene Mutation Carriers.

OBJECTIVE: To describe clinical and imaging findings in a group of patients affected by nonsyndromic deafness A9 (DFNA9), using advanced magnetic resonance imaging (MRI) with 3-dimensional (3D) fluid-attenuated inversion recovery (FLAIR) sequence. METHOD: A retrospective case review was conducted in a tertiary referral center in Italy. Four sequential adult DFNA9-affected patients, who had undergone MRI at our Department between January 2017 and June 2018, were enrolled (male = 2, female = 2; median age: 65.6 years; 8 diseased ears analyzed). Three patients were relatives; the fourth was unrelated. The main outcome measures - age, sex, records of audiological and vestibular testing, genetic assessment, MRI findings - were analyzed. RESULTS: All subjects suffered from bilateral progressive sensorineural hearing loss, more severely at the high frequencies and with a typical clinical pattern of bilateral chronic degenerative cochleovestibular deficit. Aural fullness was reported at the onset of the disease. All patients revealed a pathogenic heterozygous mutation in the Limulus factor C, Coch-5b2 and Lgl1 domain of cochlin. None of the patients showed a significant vestibular and cochlear endolymphatic hydrops at MRI, while high bilateral contrast enhancement on 4-h delayed postcontrast 3D FLAIR sequence was observed in all ears. CONCLUSIONS: Increased perilymph enhancement on 4-h delayed postcontrast 3D FLAIR sequence is the common imaging feature of DFNA9 ears, suggesting that blood-labyrinthine barrier breakdown may play the main role in the pathophysiology of this disease. Significant hydrops has been excluded by MRI. This finding might be clinically useful in differentiating DFNA9 disease from other pathologies with similar clinical findings like Ménière's disease.

Gusher in stapes surgery: a systematic review.

OBJECTIVE: The aim of this study is to perform a systematic literature review on the occurrence of gusher during stapes surgery, to understand its surgical management and outcomes. METHODS: The PRISMA standard was applied to identify English, Italian or French-language studies, related to stapes surgery and mentioning gusher or perilymphatic leak. Full-texts lacking information on the management of gusher and/or the post-operative hearing outcome were excluded. RESULTS: Twenty-four articles were eventually included. Seventy-six patients were involved in the qualitative synthesis. The management of gusher mostly consisted in covering the oval window and/or filling the tympanic cavity, with absorbable and autologous graft materials. Packing of the external auditory canal was reported in 51 patients (67%). Gusher was related to complete/profound loss of hearing in 25% of the cases and to a worsening of hearing function in 31% of patients. In 19% of patients an improvement in hearing tests was reported; in 28% the hearing function was unchanged. Post-operative vestibular symptoms were reported in 7 patients, and were mainly mild and transient. The absence of vestibular symptoms was underlined in 9 cases, while in 79% of the patients the authors did not provide information. CONCLUSION: The unexpected occurrence of gusher during stapes surgery represents a relevant issue for the otologic surgeon. Its management most commonly consists in plugging the oval window and the tympanic cavity. In most of the cases, a stapes prosthesis could be positioned. The results on hearing and vestibular functions are widely variable.

Dexamethasone and Dexamethasone Phosphate Entry into Perilymph Compared for Middle Ear Applications in Guinea Pigs.

Dexamethasone phosphate is widely used for intratympanic therapy in humans. We assessed the pharmacokinetics of dexamethasone entry into perilymph when administered as a dexamethasone phosphate solution or as a micronized dexamethasone suspension, with and without inclusion of poloxamer gel in the medium. After a 1-h application to guinea pigs, 10 independent samples of perilymph were collected from the lateral semicircular canal of each animal, allowing entry at the round window and stapes to be independently assessed. Both forms of dexamethasone entered the perilymph predominantly at the round window (73%), with a lower proportion entering at the stapes (22%). When normalized by applied concentration, dexamethasone phosphate was found to enter perilymph far more slowly than dexamethasone, in accordance with its calculated lipid solubility and polar surface area properties. Dexamethasone phosphate therefore has a problematic combination of kinetic properties when used for local therapy of the ear. It is relatively impermeable and enters perilymph only slowly from the middle ear. It is then metabolized in the ear to dexamethasone, which is more permeable through tissue boundaries and is rapidly lost from perilymph. Understanding the influence of molecular properties on the distribution of drugs in perilymph provides a new level of understanding which may help optimize drug therapies of the ear.

The Effects of Gusher-Related Intracochlear Pressure Changes on Hearing Preservation in Cochlear Implantation: A Comparative Series.

AIM: To investigate and compare residual hearing preservation between patients based on the presence of intraoperative gusher. METHODOLOGY: We retrospectively compared 2 cohorts of cochlear implant recipients significantly distinguished by whether or not they experienced gusher intraoperatively. Patients underwent cochlear implantation using 24-mm lateral wall electrode arrays as well pharmacologic steroid protection. All patients were assessed by a hearing implant MDT. Hearing preservation rates and speech perception outcomes were assessed at 1, 6, 12, 24, 36, 48, and 60 months. RESULTS: The patients with no gusher demonstrated complete hearing preservation. The patients with gusher demonstrated significant postoperative reduction of hearing thresholds, which declined at a significantly higher pace during follow-up. All patients demonstrated significantly better speech performance after cochlear implantation. CONCLUSION: The present study suggests that intraoperative gusher is associated with a significant drop in residual hearing, both immediately and over time, which may be related to the large change in intracochlear pressure intraoperatively.

Proteome Analysis of Human Perilymph Using an Intraoperative Sampling Method.

The knowledge about the etiology and pathophysiology of sensorineural hearing loss (SNHL) is still very limited. This study aims at the improvement of understanding different types of SNHL by proteome analysis of human perilymph. Sampling of perilymph was established during inner ear surgeries (cochlear implantation, vestibular schwannoma surgeries), and safety of the sampling method was determined by checking hearing threshold with pure-tone audiometry postoperatively. An in-depth shot-gun proteomics approach was performed to identify cochlear proteins and the individual proteome in perilymph of patients. This method enables the identification and quantification of protein composition of perilymph. The proteome of 41 collected perilymph samples with volumes of 1-12 µL was analyzed by data-dependent acquisition, resulting in overall 878 detected protein groups. At least 203 protein groups were solely identified in perilymph, not in reference samples (serum, cerebrospinal fluid), displaying a specific protein pattern for perilymph. Samples were grouped by patient's age and surgery type, leading to the identification of some proteins specific to particular subgroups. Proteins with different abundances between different sample groups were subjected to classification by gene ontology annotations. The identified proteins might serve as biomarkers to develop tools for noninvasive inner ear diagnostics and to elucidate molecular profiles of SNHL.