Marcos V. Goycoolea

Clinical Aspects of Round Window Membrane Permeability Under Normal and Pathological Conditions

Current research and an overall review of 25 years of round window membrane studies are presented. The approach, rationale and concepts that have evolved from these studies are described. Ultrastructural studies of the round window membrane of humans, monkeys, felines and rodents have disclosed 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 thickest in humans. Morphologic evidence suggests that the layers of the round window participate in resorption and secretion of substances to and from the inner ear, and that the membrane could play a role in the defense system of the ear. Different substances, including antibiotics and tracers, when placed in the middle ear side traverse the membrane. Tracers placed in perilymph become incorporated into the membrane by the inner epithelial cells. Permeability is selective and factors affecting permeability include size, concentration, electrical charge, thickness of the membrane and facilitating agents. Passage of substances through the membrane is by different pathways, the nature of which is seemingly decided at the outer epithelium of the membrane. Round window membrane studies have provided increased knowledge of the anatomy and function of this structure, as well as new insights into pathology and pathogenesis. The concepts that have evolved from these studies are potentially useful for understanding middle and inner ear interactions, and for eventual drug delivery (based on permeability) to the inner ear.

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‐μm 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‐μm 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 authors viewpoint are discussed.

Pathogenesis of Otitis Media

Pathogenesis of otitis media was studied in humans and various animal models primarily from a pathological and chemical point of view. Findings were correlated and interpreted for various forms of otitis media in longitudinal and parallel studies, including acute purulent otitis media (POM), serous otitis media (SOM), mucoid or secretory otitis media (MOM), and chronic suppurative otitis media (COM), especially as regards the continuum or interrelated changes of various groups. Purulent otitis media was produced in chinchillas by direct inoculation of less than 100 pneumococci into the middle ear space. Serous otitis media was produced in chinchillas and cats following Eustachian tube obstruction with silicone. Mucoid otitis media followed the development of SOM in cats after two to four weeks of tubal occlusion. Samples of middle ear effusion (MEE) and serum, obtained from children with SOM and MOM after myringotomy for ventilation tube placement, were evaluated. The three components studied were MEE, epithelium and the subepithelial space (SES). Inflammatory changes in the SES were significant for all forms of otitis media, but especially for POM and SOM. Epithelial metaplasia to secretory cells was most prominent in MOM. Chemical factors involved in pathogenesis and defense were studied. Lactic dehydrogenase and lysozyme, chemical indicators of inflammatory activity, were greater in POM and MOM than in SOM. Immunoglobulins (A, G, & M) were greater in MOM than in SOM. The similarity of findings between the groups suggests a strong relationship between them. The ability of certain types of otitis media to evolve into another substantiates the concept of the continuum for some patients. Pathogenesis is dependent upon various extrinsic factors of etiopathogenesis, while the form that otitis media takes seems to rely mostly on relative activity of the SES and the epithelium.

Silent otitis media

There is a traditional view that chronic otitis media and chronic mastoiditis must exist in the presence of a tympanic membrane perforation. Based on a human histopathological study of 123 temporal bones with chronic otitis media out of 333 temporal bones with all forms of otitis media pathology, only 24 patients (36 ears) had symptoms of otological disease recorded on their charts and only 19.5% of these had an associated tympanic membrane perforation. Unsuspected findings of chronic otitis media (active or inactive) are occasionally confirmed at exploratory tympanotomy. Such quiet chronic pathological findings in the middle ear have occurred in association with endolymphatic hydrops and cochlear end organ lesions suggesting the possibility that silent chronic otitis media may help explain sensorineural hearing loss, vertigo, and tinnitus for certain patients.

Prevalence of facial canal dehiscence and of persistent stapedial artery in the human middle ear: a report of 1000 temporal bones.

A total of 1000 temporal bones were used to study the prevalence of facial canal dehiscence and of persistent stapedial artery in detail. Of the temporal bones studied, 560 (56%) contained at least one facial canal dehiscence. There was a 76.3% prevalence of bilaterality of this canal wall gap. The most common site of dehiscence was the oval window area. The concept of microdehiscence of the facial canal is introduced. One third of the temporal bones observed had a microdehiscence of the facial canal, usually located at the oval window area (74.9%) and found bilaterally 40% of the time. The authors found a 0.48% prevalence (5 out of 1045) of persistent stapedial artery. This is the first histological study of temporal bones to report a prevalence of this vascular anomaly.

Review of Round Window Membrane Permeability

The round window membrane (RWM) is permeable to certain biological substances. Those substances that can pass through the RWM have the potential to cause inner ear damage, leading to functional disturbances. The RWM is permeable to water, and the existence of osmotically active substances in the middle ear cavity can induce an alteration of inner ear fluid osmolality, leading to membrane displacement. However, several limiting factors exist that prevent free passage of substances from the middle ear to the inner ear. These include the morphological barrier of the three-layered RWM, the molecular weight of the substances, and the nature and concentration of substances in the middle ear cavity. The degree and duration of the inflammation in the middle ear cavity, as well as the morphological integrity of the RWM, also play an important role in controlling the passage of noxious substances into the inner ear. Further characterization of the factors involved in RWM permeability, and clarification of the mechanisms of the inner ear damages caused by substances passing into the inner ear through the RWM, are necessary for an understanding of the inner ear dysfunction caused by middle ear inflammation.

Endolymphatic hydrops and otitis media.

Clinical observation of patients with fluctuant sensorineural hearing loss following or occurring with chronic otitis media led to the hypothesis that endolymphatic hydrops can result from chronic otitis media. Illustrative case reports are described. This hypothesis resulted in a temporal bone study of 560 cases in which 109 temporal bones demonstrated the presence of hydrops and 194 evidenced otitis media. Seventy‐five cases demonstrated both otitis media and hydrops, of which 20 cases were selected for more detailed histo‐pathological study. An interesting finding was the presence of apical hydrops in every case of the latter group. Statistical interpretation of this data helped rule out a coincidental or chance occurrence. A discussion of this clinical relationship included the significance of subclinical (silent) otitis media as a possible cause of endolymphatic hydrops.

Otosclerosis: the University of Minnesota temporal bone collection.

A study of 1452 human temporal bones revealed a previously unpublished material of 144 bones with otosclerosis. After exclusion of infants and individuals of races other than white, the incidence of otosclerosis was 12.75%. Of the bones with otosclerosis, 56.1% belonged to men and 43.9% to women. The incidence of clinical and histologic otosclerosis was practically the same for men (44.7% to 55.3%) as for women (47% to 53%). However, the incidence of bilateral otosclerosis was higher in women (88.9%) than in men (65.2%). Bilateral otosclerosis was present in 75.6%, whereas it was unilateral in 24.4%. Sixty-six (66) ears (45.8%) had clinical otosclerosis, whereas 78 (54.2%) had histologic otosclerosis—frequently unifocal lesions. The most common site was anterior to the oval window (117 ears, 81.25%), followed by round window niche (52 ears, 36.11%), apical and medial cochlear wall (31 ears, 21.52%), and anterior wall of the internal auditory canal (27 ears, 18.75%). The activity of lesions was directly related to their size. Smaller lesions were predominantly inactive, whereas medium and larger lesions were predominantly active. There was a positive correlation when the size of the lesions, activity, and degree of cochlear endosteal involvement were compared with bone conduction thresholds (37 cases). Correlations between size and activity, and between activity and associated sensorineural hearing loss did not necessarily follow the sequence of an initial active stage (spongiotic) to a final inactive one (sclerotic). Comparison of cases of otosclerosis with equivalent age groups of the normal population yielded worse bone conduction thresholds for the otosclerosis cases only in the age group 60 to 69 years and older. Comparison of average bone conduction thresholds between bones with one site of endosteal involvement (28.26 dB HL) revealed no significant differences. Bones with two or more sites of endosteal involvement had significant differences. Bones with two or more sites of endosteal involvement had significantly worse bone conduction thresholds (62 dB HL). The overall results are not suggestive of an association of sensorineural hearing loss with otosclerosis without stapedial fixation.

Oval and round window changes in otitis media. Potential pathways between middle and inner ear

A longitudinal sequential study of oval and round window changes in otitis media in an experimental animal (cat) using Eustachian tube obstruction was done. Thirty‐two animals were used.

A longitudinal study of cellular changes in experimental otitis media.

A longitudinal sequential study of otitis media in an experimental animal (cat) using eustachian tube obstruction was done. Fifty animals were used. The continuum of mucoperiosteal changes from one day to six months after obstruction revealed gradual changes that were similar for each animal. Stages were defined, and by using different staining techniques, including immunocytochemistry, an overall middle ear defense system was postulated and documented. Nonspecific as well as specific defense systems, including localized immunity, were described. Effusions were studied in a continuum, and their pathogenesis was discussed.