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Intratympanic drug delivery is now widely used in the clinical setting. A variety of medications and substances have been shown to pass from the middle to the inner ear via the round window membrane (RWM) (1).
The surface area of the round window is approximately 2.5 mm2. The RWM is thicker around the edges and thinner in the center, with an average thickness of approximately 70 microns. There are three basic layers to the ultrastructure of the RWM: an outer epithelium, a middle core of connective tissue, and an inner epithelium. Morphologic evidence suggests that the layers of the round window participate in absorption and secretion of substances to and from the inner ear. Mucosal membrane veils that cover the round window membrane, forming "false" membranes have also been described (1). The fact that these membranes are three-layered, with epithelial cells of the same type bounding both sides, suggests that these membranes consist of juxtaposed epithelium overlying the promontory as shown in this case (Figs. 1 and and22).
A number of factors can limit free passage of substances from the middle ear to the inner ear. These include the morphological barrier of the RWM itself, the molecular weight of the substance, its concentration, liposolubility, and electrical charge in the middle ear (2, 3). Substances with less than a 1.000 molecular weight are transmitted actively within a short time, while substances with molecular weight of greater than 1.000 are transported by pinocytosis. High-osmolarity solution increases RWM permeability by a factor of 2 to 3, benzyl alcohol increases permeability by a factor of 3 to 5, and suctioning near the RWM increases permeability by a factor of 10 to 15 (2).
Therefore, the morphological integrity of the RWM plays an important role in controlling the passage of substances into the inner ear (4). Obliteration of the round window niche has been described in congenital anomalies, otosclerosis, chronic otitis media, after middle ear surgery, and as an end result in suppurative labyrinthitis. Obstruction and obliteration of the round window has been also observed in patients who have no history of pathology or manipulation in this area (3).
Intratympanic drug delivery has become widely used in the treatment of common otologic diseases, including Ménière’s disease, sudden sensorineural hearing loss, and autoimmune inner ear disease. However, little is currently known about how clinically used drug preparations affect round window membrane permeability or how much drug is actually delivered to the cochlea.
Variations in available drug formulations can potentially alter RWM permeability properties and affect the amount of drug delivered to the inner ear (2), but the morphological integrity of the RWM also plays an important role in controlling the passage of substances into the inner ear (4). In a previous study from our institution of 202 temporal bones from 117 patients, 11% of the ears were found to have a fibrous tissue or fat plug, and 21.3% had an extraneous (false) round window membrane. These anatomic variations of the round window niche may explain the wide variations found in dosage of medication required to produce a clinical result (1).
The potential implications of round window obstruction by “fibrous tissue plugs” or “false membranes” among patients cannot be ignored when these patients need to undergo treatment with intratympanic injections.
Ivan Domènech Juan, Hospital de Bellvitge; USP Institut Universitari Dexeus, Barcelona, Spain.
Fred H. Linthicum, Jr, House Ear Institute, Los Angeles, California, USA.