Round window

Houses have windows to let in the light and fresh air. The most common shape for a window is a rectangle, but you also see round windows and hexagonal windows and other creative shapes. A Norman window is made up of two geometric shapes a semicircle on top of a rectangle. One side of the rectangle is the same measure as the semicircle s diameter. Figure 19-10 shows two Norman windows. 

In the presence of an intact tympanic membrane, ototoxicity is less important, because the preparation has to be systemically absorbed for an ototoxic effect to occur. This issue is most relevant in cases of chronic suppurative otitis media with a perforated tympanic membrane for which the ototopical medication has the potential to reach the inner ear via the middle ear. Placed within the middle ear, ototopical medication may diffuse across the oval or round window, resulting in inner ear absorption. These windows consist of a thin membrane separating the middle ear space from the inner ear fluids. There is controversy regarding the clinical relevance of ototoxicity in cases of chronic suppurative otitis media. 

Alzamil, K.S. Linthicum, F.H., Jr. Extranious round window membranes and plugs possible effect on intratympanic therapy. Ann. Otol. Rhinol. Laryngol. 2000,109 (1), 30-32. 

In rats, ototoxicity caused by gentamicin or tobramycin was amehorated by melatonin, which did not interfere with the antibiotic action of the aminoglycosides (70). The free radical scavenging agent alpha-lipoic acid has previously been shown to protect against the cochlear adverse effects of systemically administered aminoglycoside antibiotics, and in a recent animal study it also prevented cochlear toxicity after the administration of neomycin 5% directly to the round window membrane over 7 days (71). 

We know very little about the pathology of the ear. And yet, hearing loss is a major component of cretinism. Old data summarized by Koenig (21) indicated that neurological endemic cretins present middle ear abnormalities characterized by hypertrophic bone changes of the promontorium, deformation of the ossicles, distorsion of the oval and round windows and thickening of the mucous membrane of the tympanic cavity. No data are available for the inner ear. 

The main element for hearing is the cochlea or inner ear. It is a fluid-filled coil that has two chambers over its length divided by thin tissue. Sound energy travels from the oval window or base of the cochlea to the distant end or apex of the coil. The waves travel through one chamber and reflect back through the second chamber to the round window, which deflects to adjust for the pressure from the waves. The round window and oval window both separate the inner ear from the middle ear. 

The retrotympanum represents more than one half of the posterior part of the tympanic cavity and includes the oval and round windows (Parlier-Cuau et al. 1998). VE allows displaying all the components of the retrotympanum (Fig. 10.2b) showing eminence and depressions, represented by pyramidal and styloid eminence, pyramidal ridge, ponticulus, subicu-lum, and eminence of the mastoid portion of the facial nerve (Pickett et al. 1995 Espinoza 1989). 

The promontory appears at VE as an eminence with a smooth surface that covers the round window. This opens from the tympanic cavity into the scala tympani of the cochlea. 

The middle ear is connected to the nasal pharynx by the Eustachian tube and to the inner ear via the oval and the round window. 

Goycoolea MV (2001) Clinical aspects of round window permeability under normal and pathological conditions. Acta Otolaryngol (Stockh) 121 437-447... 

Goycoolea MV, Muchow D, Schachem PA (1988) Experimental studies on round window membrane structure function and permeability. Laryngoscope 98(Suppl. 44) 1-20... 

The footplate of the stapes is joined to the round window. Since the eardrum and the membrane of the oval window can be stretched taut by means of muscles, a strong damping effect is achieved for frequencies exceeding 1000 Hz. Young people perceive frequencies of between 18,000 and 20,000 Hz. With advancing age, the audibility of the higher frequencies—namely above 12,000 Hz in people over 50—will decrease. This is called presbyakusia. 

Otosclerosis is an osteodystrophy of unknown aetiology in the enchondral labyrinthine capsule. Described demineralised areas (otospongiotic foci) occur that ossify later (otosclerotic foci). Most of them are very well detectable on CT. Commonly, they are localised near the oval window (Fig. 11.6), less commonly near the round window and around the cochlea and/or vestibular structures. According to the site of foci, fenestral, retrofenestral, and mixed forms are differentiated. 

Fig. 1 Anatomy of the external, middle, and iimer ear of a guinea pig. Major structures are as follows 1 external auditory canal, 2 tympanum, 3 malleus, 4 incus, 5 stapes, 6 round window, and 7 cochlea...

The first endpoint hsted in the guidance document is the determination of middle and inner ear exposure. As in all other prechnical safety assessment protocols, it is important that dose selection is based on the pharmacokinetics of the NCE and that otic exposure is primarily regulated by the drug s ability to penetrate the tympanic membrane and/or the round window (administration and distribution). Perilymph collections can be a useful tool to determine otic exposure. 

These variables can be minimized by design changes to the standard experimental protocol. It has been shown that utilization of smaller volumes, collected at least 4 mm from the round window, produces negligible CSF contamination. These small sample aliquots will yield more consistent drug concentrations regardless of differences in drug distribution (Salt et al. 2003). Additionally, although methods... 

Fig. 4 Photomicrographs of hematoxylin and eosin-stained sections of the middle ear from a guinea pig. 1 external auditory canal, 2 tympanic membrane, 3 junction of the tympanic membrane and malleus, 4 cochlea, 5 malleus, 6 incus, 7 stapes, 8 round window, 9 tensor tympani, 70 middle ear mucosa, 11 entrance to the eustachian tube...

Appropriate species selection for ototoxicity studies is essential for successful characterization of the ototoxicity of a compound. When selecting a model for ototoxicity studies, there are two important factors to cmisider. First and foremost is the bioavailabDity of the compound within the model selected. It is important to select a species in which there is adequate absorption though the round window and/or the tympanic membrane, if applicable. If perilymph concentrations of the NCE do not reach levels comparable to that of the human, the preclinical data serves no translational purpose. 

---