Anatomy of the Round Window Region With Relation to Selection of Entry Site Into the Scala Tympani.

OBJECTIVES/HYPOTHESIS: The aim of cochlear implantation is to safely insert an electrode array into the scala tympani (ST) while avoiding damage to surrounding structures. There is disagreement on the optimal way of entering the ST-the round window (RW) approach versus cochleostomy. Regardless of the chosen approach, it is vital to understand the regional anatomy, which is complex, difficult to conceptualize, and rarely dissected in temporal bone courses. The goal of this study was to examine the anatomy of the RW to gain more in-depth knowledge on the local relationships of the anatomical structures and propose an approach for entering the ST in cochlear implant surgery tailored to the encountered anatomy. STUDY DESIGN: Cadaveric prevalence study and expert opinion with literature review. METHODS: Cadaveric temporal bone dissection (n = 13) by the first author assessing the RW anatomy. RESULTS: The round window membrane (RWM) and the osseous spiral lamina (OSL) are curved structures, each with a horizontal and a vertical part. The two horizontal portions are very closely apposed. The relationship between the OSL and the RWM determines the best site for a cochleostomy, which if required is best placed anteroinferiorly to the RWM. The distance between the oval window inferior margin and the RW membrane is less than 2 to 3 mm. The ST initially extends inferiorly and medially to the RW. CONCLUSIONS: The findings of our dissection have implications for cochlear implant surgery in aiming to avoid trauma to the OSL and basilar membrane and aid decision making in choosing the safest surgical approach. LEVEL OF EVIDENCE: 5. Laryngoscope, 131:E598-E604, 2021.

Distribution of PLGA nanoparticles in chinchilla cochleae.

OBJECTIVES: To study the distribution of polylactic/glycolic acid-encapsulated iron oxide nanoparticles (PLGA-NPs) in chinchilla cochleae after application on the round window membrane (RWM). STUDY DESIGN AND SETTING: Six chinchillas (12 ears) were equally divided into controls (no treatments) and experimentals (PLGA-NP with or without magnetic exposure). After 40 minutes of PLGA-NP placement on the RWM, perilymph was withdrawn from the scala tympani. The RWM and cochleae were fixed with 2.5% glutaraldehyde and processed for transmission electron microscopy. RESULTS: Nanoparticles were found in cochleae with or without exposure to magnet forces appearing in the RWM, perilymph, endolymph, and multiple locations in the organ of Corti. Electron energy loss spectroscopy confirmed iron elements in nanoparticles. CONCLUSION: The nanoparticles were distributed throughout the inner ear after application on the chinchilla RWM, with and without magnetic forces. SIGNIFICANCE: PLGA-NP applied to the RWM may have potential for sustained therapy to the inner ear.

Round window membrane. Structure function and permeability: a review.

The ultrastructure of the round window membrane of humans, monkeys, felines, and rodents discloses three basic layers: an outer epithelium, a middle core of connective tissue, and an inner epithelium. Interspecies variations are mainly in terms of thickness, being thinnest in rodents and thicker in humans. Morphologic evidence suggests that the layers of the round window participate in absorption and secretion of substances to and from the inner ear, and that the entire membrane could play a role in the defense system of the ear. Different substances, including antibiotics, local anesthetics, and tracers such as cationic ferritin, horseradish peroxidase, and 1 mu latex microspheres, are placed in the middle ear side traverse the membrane. Cationic ferritin and 1 micron microspheres placed in perilymph become incorporated by the inner epithelial cells of the membrane. Permeability is selective; factors include size, concentration, liposolubility, electrical charge, and thickness of the membrane. Passage of substances through the round window membrane is by different pathways, the nature of which is seemingly decided at the outer epithelium of the round window membrane.

Influence of pH on the ototoxicity of cisplatin: a round window application study.

Cisplatin is an antineoplastic agent that produces a number of dose-limiting side effects, including ototoxicity. We investigated the effect of pH on cisplatin ototoxicity. Auditory brainstem responses (ABR) were recorded in chinchillas. Then the auditory bullae were opened and acidic (pH=6.5), neutral (pH=7.4) or alkaline (pH=10.2) phosphate-buffered saline (PBS) was applied to the round window membrane. After 30 min, any remaining solution was removed and cisplatin solution was applied to the round window membrane. After 3 days, follow-up ABRs were performed and the cochleae were processed for morphological analysis. Neutral PBS+cisplatin administration resulted in profound threshold changes at all frequencies. Acidic PBS+cisplatin administration showed had a trend of increased threshold changes, but the change did not reach statistical significance. However, the degree of hair cell loss was significantly higher than that of the neutral PBS-cisplatin group. Alkaline PBS significantly reduced cisplatin-induced threshold changes (P<0.05) compared to the neutral PBS group. Because the pH of cisplatin solution was 6.0, pH 6.0 PBS was applied to round window membrane. This acidic PBS solution did not cause any hearing impairment. These results demonstrate that pH can modulate the ototoxic effects of cisplatin.

Ototoxicity of sodium nitroprusside.

Nitric oxide (NO) not only has normal physiological roles like vasodilation and neurotransmission in the living organism, it could also have possible neurodestructive effects under certain pathological conditions. The present study aimed to determine whether direct exposure of guinea pig cochlea to a NO donor like sodium nitroprusside (SNP), or a nitric oxide synthase (NOS) inhibitor like N(G)-nitro-L-arginine methyl ester (L-NAME), would cause damage to the auditory hair cells. A piece of gelfoam was placed on the round window of the right ear of adult albino guinea pigs. It was then soaked with 0.1 ml of SNP (3.4 microM), 0.1 ml of L-NAME (9.3 microM or 18.5 microM) or 0.1 ml of injection water, the vehicle used to dissolve the above chemicals. Twelve animals receiving SNP were perfused 1 day, 2, 3 and 7 days later, with three animals being used for each survival period. Six animals receiving L-NAME were allowed to survive up to 7 days before perfusion. Eight animals receiving injection water or 0.45% saline were used as controls. With the scanning electron microscope, the inner and outer hair cells were counted over a 1 mm length of the basilar membrane in each turn of every cochlea. The results showed that, in animals treated with L-NAME at both concentrations stated, no significant loss of either inner or outer hair cells was noted in any part of the cochlea studied. However, as early as 1 day after SNP treatment, a striking loss of inner and outer hair cells was observed in the three lower turns of the cochlea. Damage to the outer hair cells was extended to the apical turn with increasing survival period, but no significant loss of inner hair cells was evident in the apical turn at any of the survival periods studied. To rule out the possibility that the effects were due to the presence of cyanide, a metabolite of SNP, hydroxycobalamin was introduced into the scala tympani of three animals through a cannula-osmotic pump device during SNP treatment. There was no significant difference in the results between the groups with and without hydroxycobalamin infusion 7 days after SNP treatment. The present study suggests that an excessive production of NO in the inner ear could lead to extensive loss of hair cells.

Hair cell regeneration after local application of gentamicin at the round window of the cochlea in the pigeon.

Hair cells in the basilar papilla of birds have the capacity to regenerate after injury. Methods commonly used to induce cochlear damage are systemic application of ototoxic substances such as aminoglycoside antibiotics or loud sound. Both methods have disadvantages. The systemic application of antibiotics results in damage restricted to the basal 50% of the papilla and has severe side effects on the kidneys. Loud sound damages only small parts of the papilla and is restricted to the short hair cells. The present study was undertaken to determine the effect of local aminoglycoside application on the physiology and morphology of the avian basilar papilla. Collagen sponges loaded with gentamicin were placed at the round window of the cochlea in adult pigeons. The time course of hearing thresholds was determined from auditory brain stem responses elicited with pure tone bursts within a frequency range of 0.35-5.565 kHz. The condition of the basilar papilla was determined from scanning electron micrographs. Five days after application of the collagen sponges loaded with gentamicin severe hearing loss, except for the lowest frequency tested, was observed. Only at the apical 20% of the basilar papilla hair cells were left intact, all other hair cells were missing or damaged. At all frequencies there was little functional recovery until day 13 after implantation. At frequencies above 1 kHz functional recovery occurred at a rate of up to 4 dB/day until day 21, beyond that day recovery continued at a rate below 1 dB/day until day 48 at the 5.6 kHz. Below 1 kHz recovery occurred up to day 22, the recovery rate was below 2 dB/day. A residual hearing loss of about 15-25 dB remained at all frequencies, except for the lowest frequency tested. At day 20 new hair cells were seen on the basilar papilla. At day 48 the hair cells appeared to have recovered fully, except for the orientation of the hair cell bundles. The advantage of the local application of the aminoglycoside drug over systemic application is that it damages almost all hair cells in the basilar papilla and it has no toxic side effects. The damage is more extensive than with systemic application.

Experimental studies on round window structure: function and permeability.

Current research and an overall review of 12 years of round window membrane studies is presented. The approach, rationale, and concepts that have evolved from the studies are described. An ultrastructural study of the round window membrane of rhesus monkeys disclosed three basic layers: an outer epithelium, a middle core of connective tissue, and an inner epithelium. Morphologic evidence in monkeys, cats, and chinchillas suggests that these layers of the round window participate in absorption and secretion of substances to and from the inner ear, and that the entire membrane could play a role in the defense system of the ear. Cationic ferritin, horseradish peroxidase, 1-micron latex spheres, and neomycin-gold spheres placed in the middle ear of these experimental animals were observed to traverse the round window membrane through pinocytotic vesicles. Three-micron latex spheres and anionic ferritin were not incorporated by the membrane. Cationic ferritin and 1-micron latex spheres placed in perilymph were incorporated by the inner epithelial cells, suggesting absorptive capabilities of the round window membrane. Cationic ferritin was observed within the mesothelial cells underlying the scala tympani side of the basilar membrane, suggesting a role for these cells in the inner-ear defense system. A review of the subject and a general perspective from the author's viewpoint are discussed.

The round window membrane following application of staphylococcal exotoxin: an electron microscopic study.

The round window membrane has been considered as a pathway for the passage of toxic substances from the middle ear cavity to the vestibular labyrinth in cases of otitis media. To determine the role of the round window membrane in this passage, chinchillas were given intrabullar inoculations with staphylococcal exotoxin and the round window membranes were examined electron microscopically. We observed cytoplasmic vacuolization, intercellular edema, cellular and nuclear swelling of the surface epithelia and polymorphonuclear leukocyte (PMN) infiltration of the fibrous layer. Light microscopic observation of the labyrinth revealed PMN infiltration of the most basal portion of the scala tympani. These findings demonstrate a chemotactic effect of the toxin for PMNs and support the concept of the round window membrane as an important avenue of entry.

Structural changes in the round window membrane following exposure to Escherichia coli lipopolysaccharide and hydrocortisone.

The present study focused on structural changes of the round window membrane (RWM) from agents that evoke transient or permanent impairment of the auditory brainstem response when applied into the RW niche. Escherichia coli (E. coli) lipopolysaccharide (LPS) in sterile water (SW) and a 2% suspension of hydrocortisone (CORT), micronized in SW, were instilled into the round window (RW) niche of Sprague-Dawley rats. The morphology of the RWM was analyzed 3 to 21 days after instillation of either substance. Both substances caused minor structural alterations at the light microscopic level. The RWM showed a slight thickening and an invasion of inflammatory cells. At the ultrastructural level, the CORT-treated specimens showed an increased epithelial height and numerous microvilli, whereas the epithelium of the LPS-treated specimens was extended and contained few microvilli resembling those in the normal RWM. We postulate that the RWM may undergo dynamic structural changes when exposed to various agents. The structural alterations per se can influence the passage of substances from the middle ear to the inner ear.

Permeability of the human round-window membrane to cationic ferritin.

An ultrastructural study was done in three sequential steps to determine if the human round-window membrane was permeable to macromolecules. Cationic ferritin was first placed for one hour in the round-window niche of two live rhesus monkeys. The same tracer was then placed in the same manner in two rhesus monkeys that had been dead for one hour. In both groups, cationic ferritin was observed to traverse the round-window membrane through pinocytotic vesicles into the scala tympani. After establishing that the transport capabilities of the round-window membrane of the monkey remained present one hour after death, cationic ferritin was placed for one hour in the round-window niche of two humans who had been dead for 30 minutes and one hour. The tracer was observed to traverse the round-window membrane through pinocytotic vesicles into the scala tympani in both humans. This report may be the first to document morphologically the permeability of human round-window membranes to macromolecules.

Ultrastructural studies of the human round window membrane.

An ultrastructural study of 14 round window membranes of seven human ears disclosed three basic layers: an outer epithelium lining the middle ear, a middle core of connective tissue, and an inner epithelium bordering the inner ear. Morphological evidence suggests that these layers participate in absorption and secretion of substances to and from the inner ear. A comparison of morphological features of round window membranes suggests that the average thickness of 70 microns does not change with advancing age. However, in the elderly, the connective tissue has a looser arrangement; there is an increase in ground substance; and elastic fibers thicken. Fibroblast nuclei become larger, rounder, and less uniform and have extensions. The ultrastructure of the "false round window membranes," with epithelial cells of the same type bounding both sides, suggests that these membranes consist of juxtaposed epithelial folds of the overlying promontory.

Ultrastructural studies of the round-window membrane of the cat.

An ultrastructural study of eight round-window membranes of four normal cats disclosed three basic layers: an outer epithelium (middle ear), a middle core of connective tissue, and an inner epithelium (inner ear). Morphologic evidence suggests that these layers participate in absorption and secretion of substances to and from the inner ear, such that the entire membrane could play a role in an inner ear "defense system." A comparison of morphologic features of round-window membranes from cats, rodents, and human beings suggests that the cat is a superior animal model for experimental studies. Cationic ferritin, placed for two hours in the round-window niche of four normal cats, was observed to traverse the round-window membrane through pinocytotic vesicles into the connective tissue layer. Evidence of exocytosis of tracer by the inner epithelial layer into the scala tympani is presented. When placed in perilymph, this same tracer was incorporated by inner epithelial cells, suggesting absorptive capabilities of the round-window membrane.

The permeability of the round window membrane during otitis media.

Studies of the permeability of the round window membrane (RWM) during otitis media are important because toxins and cellular components that occur in otitis media as well as pharmacologic agents used in treating the disease have the potential to cross the RWM and pass into the inner ear. Twenty-five cats were evaluated electron microscopically as to the passage of a tracer, horseradish peroxidase, through normal RWMs and RWMs three days, one week, and two weeks following eustachian tube obstruction. Passage at three days following obstruction was similar to passage through the normal RWM. Following one to two weeks of obstruction, the permeability of the membrane was drastically reduced. The reduction in permeability was probably due to the presence of residual effusion overlying the membrane, the presence of granulation tissue within the niche, and a thickening of the RWM.

Permeability of the round window membrane to middle-sized molecules in purulent otitis media.

The effect of pneumococcal otitis media on the permeability of the round window membrane was evaluated using tetraethylammonium ions as a tracer. Round window membrane permeability is reduced significantly at resolved stages of purulent otitis media. In contrast, measurements of round window membrane permeability indicate that acute purulent otitis media has a tendency to facilitate such permeability. Moreover, histologic observations of the round window membrane following bacterial inoculation further support the evidence of functional changes in round window membrane permeability. These findings indicate that the round window membrane in resolved stages of purulent otitis media plays a protective role in preventing the penetration of harmful substances into the inner ear.

Morphologic changes in the guinea pig cochlea following cochleostomy--a preliminary scanning electron microscope study.

Fistulization of the membranous labyrinth via a surgically created endolymphatic-perilymphatic shunt (cochleosacculotomy) is currently being advocated as a treatment for endolymphatic hydrops. As a preliminary study to the investigation of the effects of labyrinthine fistulization on the hydropic condition, we sought first to reproduce the cochleosacculotomy procedure in a series of normal animals. Fistulization of the cochlear duct was performed in 15 normal animals using a tungsten wire directed via the round window through the cochlear partition in the region of the organ of Corti. The animals were sacrificed at regular intervals and the cochleas examined for histopathologic changes with the scanning electron microscope. Observations suggest that discrete permanent fistulization of the cochlear duct in the normal guinea pig results in progressive sensory cell degeneration. The implication of these observations and the apparent difference between these results and the experience thus far reported in humans are discussed.

Permeability of the round window membrane to horseradish peroxidase in experimental otitis media.

The permeability of the round window membrane (RWM) was studied by using horseradish peroxidase (HRP) in the different stages of otitis media developed in guinea pigs, and it was compared with normal RWM under transmission electron microscopic examination. The experimental model of otitis media was developed by inoculation of a Pseudomonas aeruginosa suspension. When HRP could penetrate into the inner layer of a normal RWM, the duration of HRP instillation into the round window niche was 10 minutes. The permeability of the RWM in otitis media was as follows: 3-day animals showed penetration of HRP into the middle layer. In 1-week animals, HRP had penetrated into the inner layer in all 10 ears. In 2-week animals, HRP had penetrated into the inner layer in 6 of 11 ears. In 4-week animals, however, HRP was not seen in 6 of 7 ears. HRP had penetrated through the damaged focus of the epithelial cells by inflammation. These results suggest that any derangement of the epithelial linings could increase the penetration of HRP and also ototoxic materials into the inner ear through the RWM.

Morphologic changes in round window membrane after topical hydrocortisone and dexamethasone treatment.

HYPOTHESIS: Are all glucocorticoids supposed to have the same effect on the round window membrane? BACKGROUND: Interest in glucocorticoids for topical treatment of inner ear diseases is increasing. The safety of such treatment should therefore be an important consideration before clinical use. METHODS: In this study the authors investigated the morphology of the round window membrane after topical instillation of dexamethasone or hydrocortisone into the middle ear. Twenty Sprague-Dawley rats were used. Five rats received 5 doses, and five rats 10 doses, of 1 microg (20 microl) dexamethasone in the right ear, and five others were given 5 doses, and five rats 10 doses, of 2% (20 microl) hydrocortisone solution, also in the right ear. Membrane morphology was studied in both light microscopy and transmission electron microscopy. The thickness of exposed membranes was measured and compared with that of control membranes. RESULTS: Thickening and microscopically signs of inflammation were observed in hydrocortisone-exposed membranes but not in dexamethasone-exposed membranes, which did not differ morphologically from those in control ears. CONCLUSION: Although hydrocortisone has anti-inflammatory properties, it seems to provoke inflammation in the round window membrane after topical instillation. Dexamethasone had no such effects, however.

Round window membrane in serous and purulent otitis media. Structural study in the rat.

The rat was used as an animal model to reveal structural alterations in the round window membrane (RWM) during serous otitis media (SOM) and purulent otitis media (POM) over a 6-week period. Comparison of POM animals and control animals showed that the RWM in the former became almost six times as thick as that in controls, whereas that of SOM animals was twice as thick. The structural changes in the RWM in POM animals were confined mainly to the epithelium facing the middle ear cavity and the subepithelial space, which was invaded by inflammatory cells and exhibited dilated vessels. The normal flat epithelium was transformed via cuboidal cells to a cylindric epithelium containing both ciliated and goblet cells. In SOM animals, light microscopy revealed only minor changes in the RWM structure. Ultrastructurally, however, the connective tissue layer exhibited dense aggregations of collagen, increased numbers of fibroblasts, and, in one case, elastic fibers. This last phenomenon was not observed in either POM ears or normal ears. The study showed that various inflammatory conditions of the middle ear, both noninfectious (SOM) and infectious (POM), can cause different structural alterations of the RWM. These structural changes may influence passage through the RWM differently.

The round window membrane: otological observations.

The membrane of the round window serves as a barrier between the middle and inner ear and has a well-established role in cochlear physiology. It is important in many otological conditions: otitis media, otosclerosis, trauma, sequelae to drugs reaching the middle ear, tumors, congenital dysplasia, sudden deafness. We here describe the first electron microscopic findings in round window membranes from adult humans, and various conditions in reference to these findings. Since surgical lesions are made in this membrane during cochlear implantation, and by some otologists in treating vertigo, preliminary findings of a lesioning experiment in animals are presented. Interestingly, early healing resulted from a mesothelial cellular reaction in the adjacent scala tympani, with formation of clots, while in the middle ear the epithelial cellular layer sealed the edges of the perforation, leading to formation of an indentation ("pocket"). Subsequently, the middle layer of the membrane contributed to healing.

Histological study of chronic electrode implantation through the round window of the guinea pig.

A platinum-iridium electrode with a Teflon cover tube was chronically implanted through the round window into the scala tympani of the guinea pig. Animals were sacrificed at 30 to 40 weeks after electrode implantation, and the cochleae were observed by scanning electron microscopy or with light microscopy. The results revealed that the electrode was firmly enclosed with fibrous tissue on the inside of the round window and with epithelial tissue on the outside. These tissues were considered to act as a barrier to the entry of infection while preventing leakage of the perilymph.