WO2015161175A1 - Procédés de cochléostomie chimique - Google Patents

Procédés de cochléostomie chimique Download PDF

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Publication number
WO2015161175A1
WO2015161175A1 PCT/US2015/026335 US2015026335W WO2015161175A1 WO 2015161175 A1 WO2015161175 A1 WO 2015161175A1 US 2015026335 W US2015026335 W US 2015026335W WO 2015161175 A1 WO2015161175 A1 WO 2015161175A1
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Prior art keywords
cochleostomy
pag
cochlea
agent
hearing
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PCT/US2015/026335
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English (en)
Inventor
Anthony J. Ricci
Markus E. HUTH
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The Board Of Trustees Of The Leland Stanford Junior University
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Publication of WO2015161175A1 publication Critical patent/WO2015161175A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0066—Medicaments; Biocides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F11/00—Methods or devices for treatment of the ears or hearing sense; Non-electric hearing aids; Methods or devices for enabling ear patients to achieve auditory perception through physiological senses other than hearing sense; Protective devices for the ears, carried on the body or in the hand
    • A61F11/20—Ear surgery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/21—Acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/14—Materials or treatment for tissue regeneration for ear reconstruction or ear implants, e.g. implantable hearing aids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526—Head electrodes
    • A61N1/0541—Cochlear electrodes

Definitions

  • the cochlea remains of the few sites in the body that is non-accessible to surgery.
  • compositions and methods are provided for performing a chemical cochleostomy.
  • an effective dose of a decalcifying agent is applied to an exposed basal turn of the cochlea, for a time sufficient to resorb or substantially thin the bony capsule.
  • the appropriate thinness can be observed as the point at which the remaining bone is sufficiently translucent that the underlying blood vessels can be observed. At this point, gentle palpitations of the region result in bowing of the remaining bone.
  • a final step may be performed manually to remove the thinned bone.
  • the resulting cochleostomy allows access to the inner ear for treatment, including without limitation implantation of a device, while preserving hearing.
  • Devices include, without limitation, multichannel cochlear implants, electric-acoustic stimulation devices, etc. Delivery of therapeutic and diagnostic formulations and devices can be performed.
  • the access to the inner ear can be utilized in methods of stapedectomy, stapedotomy, etc. Bony resorption can be utilized as part of otosclerosis surgery, and for safe resoprtion of bone within the middle ear for non-cochleostomy applications.
  • the access to the inner ear can also be utilized in methods of skull base surgery when the inner ear is opened to provide more extensive surgical approaches to the cranial vault.
  • the decalcifying agent is an acid.
  • the decalcifying agent is a chelating agent.
  • Agents suitable for this purpose include, without limitation, phosphoric acid, EDTA, maleic acid, citric acid, lactic acid, formic acid, trichloroacetic acid, etc.
  • the agent is phosphoric acid.
  • the effective dose of a decalcifying agent is provided in a semi-solid formulation, e.g. a lotion, gel, paste, etc.
  • the effective dose of a decalcifying agent is provided in a patch, preferably in a size, geometry and formulation suitable for the purposes of the invention. Patches may also include components such as an adhesive layer, impermeable backing membrane, release liner, and the like.
  • the invention comprises a method of (i) surgically exposing the basal turn of the cochlea; (ii) contacting the exposed basal turn with an effective dose of a decalcifying agent, e.g. provided in a gel, patch, etc. for a period of time sufficient to resorb or substantially thin the bone; and (iii) neutralizing or removing the decalcifying agent.
  • the method may further comprise (iv) manual removal of the thinned bone to expose the inner ear.
  • the method further comprises surgically accessing the inner ear, e.g. implanting a hearing device, therapeutic agents; etc.
  • Another aspect of the invention relates to the use of a decalcifying agent in the manufacture of a medicament for cochleostomy, wherein the medicament is administered to a the basal turn of the cochlea of an individual for a period of time and dose sufficient to effect a resorption or substantial thinning of the bone.
  • Still another aspect of the present invention provides a kit for chemical cochleostomy.
  • the kit includes a formulation that provides for an effective dose of a decalcifying agent, e.g. in the form of a gel, lotion, patch, and the like.
  • the kit may also comprise instructions for use.
  • compositions and methods of use disclosed herein can be used to aid in cochlear implantation with hearing preservation, by preventing damage to the inner ear during cochlear implantation.
  • the method of the invention provide for reproducible local bone removal, and cochlear access in the absence of mechanical drilling.
  • FIGS 1A-F A. Opened bulla (dashes), tympanic membrane (TM), basal turn (BT), round window (RW), vestibular system (VS). B. PAG on cochlea. C. Cochlea thinned using PAG. D. PAG Cochleostomy. E. Micro— pick cochleostomy. F. Combined PAG/micro— pick cochleostomy.
  • FIGS 2A and 2B Representative hematoxylin and eosin sections of cochlea thinned by PAG (A) and a control cochlea (B). Arrows delineate otic capsule thinning and arrowhead demonstrates where the otic capsule is broached, leaving underlying endosteal membrane intact.
  • Figures 3A and 3B ABR thresholds following bulla opening (A) and thinning of the cochlea with two separate five— minute applications of phosphoric acid gel (B). No significant threshold shifts were observed.
  • Figures 5A and 5B ABR thresholds following combined PAG/micro-pick cochleostomy, with initial chemical thinning and subsequent manual removal of the last osseous layer. No significant shifts were seen following cochleostomy (A), or on postoperative day 2 or 9 (B).
  • an effective dose of a decalcifying agent is applied to an exposed basal turn of the cochlea, for a time sufficient to resorb or substantially thin the bony capsule.
  • a final step may be performed manually to remove the thinned bone.
  • the resulting cochleostomy allows access to the inner ear for treatment, including without limitation implantation of a device, while preserving hearing.
  • Cochlea The two human cochleae are mirror-shaped, fluid-filled, coiled, fairly symmetrical bony tubes (3.2-4.2 cm long) situated in the petrous pyramids of the temporal bones. Perilymph; the fluid inside the scalae vestibuli and tympani communicates with the CSF via the cochlear aqueduct. It is surrounded by a compact bony structure; the otic capsule. It is the hardest bone in the body with a trilamellar arrangement with islands of modified cartilage and high-mineral content, which increases the stiffness of the bony labyrinth. Vibrations of fluid in the cochlea are reflected and not absorbed by the temporal bone. However, the mechanosensitivity of tissues within the inner ear make it difficult to drill this bone without loss of hearing.
  • the basal end of the cochlea is of great interest. It curves in three dimensions, resembling a "fish hook.”
  • a cochleostomy is made, and it is the site of the round window.
  • the hook anatomy varies between individuals, which makes it difficult for the surgeon to optimally place the cochleostomy and reach scala tympani (ST) without destroying any inner ear structures.
  • ST scala tympani
  • the large variations in cochlear lengths, angles between turns, and position in the skull base can influence the straightforwardness for the insertion of a device, particularly passing the first turn.
  • Decalcifying agent refers to an agent that, when applied to a bone, will remove calcium from bone, causing the bone to resorb and thin.
  • Many agents are known for this purpose in the art, and one or a combination of agents can be formulated for use in the methods of the invention.
  • Preferred agents act on the bone within a period of time suitable for surgery, for example such that the end point is reached within about 30 minutes, within about 25 minutes, within about 20 minutes, within about 15 minutes, within about 10 minutes, within about 5 minutes.
  • Decalcifying agents of particular interest include acids. Acids used for this purpose include, without limitation, phosphoric acid, maleic acid, citric acid, lactic acid, trichloroactetic acid, formic acid, etc. Phosphoric acid is of particular interest, for example in a 30-40% gel formulation. [0026] Decalcifying acids are usually used at a pH of not more than about 2, not more than about 1.75, not more than about 1.5, not more than about 1 .25, not more than about 1 ; and may be in a pH range of from about 0.1 to about 2, from about 0.1 to 1.5, from about 0.1 to about 1.
  • the formulation of a decalcifying agent desirably contains the acid in the region of bone for contact, e.g. in a lotion, gel, paste, patch, etc.
  • Neutralizing agent It may be desirable to remove or neutralize the decalcifying agent.
  • neutralization can be accomplished by contacting the treated surface with an appropriate buffer to raise the pH to appropriately neutral levels, e.g. to at least about pH 5, at least about pH 6, and may be up to or above pH 7.
  • an appropriate buffer to raise the pH to appropriately neutral levels, e.g. to at least about pH 5, at least about pH 6, and may be up to or above pH 7.
  • the decalcifying agent may be suctioned off to remove excess; or where a film or patch it used, the film or patch is physically removed.
  • Neutralizing agents which may be combined with physical barriers, may also find use in surrounding the decalcifying agent at the time of application in order to protect the surrounding tissue.
  • a slow release neutralizing agent is added to the decalcifying agent, such the acid is neutralized by the desired endpoint of the decalcification.
  • the term "effective dose” or “therapeutically effective dose” refers to the amount of an agent that is sufficient to effect the desired results.
  • the dose of decalcifying agent is typically the amount, which may be administered one, two, three, four or more times on the site, that is sufficient to cover the surface of the bony surface.
  • the volume may be from about 10 ⁇ , from about 25 ⁇ , from about 50 ⁇ , from about 75 ⁇ , from about 100 ⁇ , from about 125 ⁇ , and up to about 1 ml, up to about 750 ⁇ , up to about 500 ⁇ , up to about 250 ⁇ , up to about 100 ⁇ .
  • the surface area can range from about 1 mm 2 to about 100 mm 2 , for example around about 5 mm 2 , 10 mm 2 , 25 mm 2 , 35 mm 2 , 50 mm 2 , 75 mm 2 , etc.
  • the specific dose will vary depending on the particular agent chosen, the dosing regimen to be followed, whether it is administered in combination with other compounds, timing of administration, and the physical delivery system in which it is carried.
  • Suitable conditions shall have a meaning dependent on the context in which this term is used. That is, when used in connection with an antibody, the term shall mean conditions that permit an antibody to bind to its corresponding antigen. When used in connection with contacting an agent to a cell, this term shall mean conditions that permit an agent capable of doing so to enter a cell and perform its intended function. In one embodiment, the term “suitable conditions” as used herein means physiological conditions.
  • the decalcifying agent is formulated in a gel, paste or lotion composition.
  • the compositions of the invention include a pharmaceutically acceptable vehicle to act as a dilutant, dispersant or carrier, so as to facilitate its distribution and uptake when the composition is applied to the bone. Vehicles other than or in addition to water can include liquid or solid emollients, solvents, humectants, thickeners and powders.
  • the therapeutically acceptable vehicle will usually be from about 5%, from about 10%, from about 20%, from about 30%, from about 40%, from about 50%, from about 60%, from about 70% up to about 99.9%, up to about 95%, up to about 90%, up to about 80%, up to about 70%, up to about 60%, up to about 50% of the composition, and can, in the absence of other adjuncts, form the balance of the composition.
  • compositions may be in the form of aqueous, aqueous/alcoholic or oily solutions; dispersions of the lotion or serum type; anhydrous or lipophilic gels; emulsions of liquid or semi-liquid consistency, which are obtained by dispersion of a fatty phase in an aqueous phase (O/W) or conversely (W/O); or suspensions or emulsions of smooth, semi-solid or solid consistency of the cream or gel type.
  • These compositions are formulated according to the usual techniques as are well known to this art.
  • Emulsifiers which may be used include glyceryl stearate, polysorbate 60, PEG-6/PEG- 32/glycol stearate mixture, etc.
  • Solvents which may be used include the lower alcohols, in particular ethanol and isopropanol, and propylene glycol.
  • Hydrophilic gelling agents include silica gel, carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides, such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, representative are the modified clays such as bentones, fatty acid metal salts such as aluminum stearates and hydrophobic silica, or ethylcellulose and polyethylene.
  • a quantity of the composition for example from 1 to 100 ml, is applied to a site of interest from a suitable container or applicator and, if necessary, it is then spread over and/or rubbed into the site using the hand or fingers or a suitable device.
  • the product may be specifically formulated for use as a treatment for a specific area.
  • the lotion or gel composition of the invention can be formulated in any form suitable for application to the site of interest.
  • the composition can be packaged in any suitable container to suit its viscosity and intended use.
  • the invention accordingly also provides a closed container containing a therapeutically acceptable composition as herein defined, for example a pre-loaded syringe containing a unit dose of the decalcifying agent.
  • Medical dressings or patches suitable for use in the methods of the present invention for contacting a bone with a decalcifying agent can be any material that is biologically acceptable and stable to the acid.
  • the patch can be a semi-solid film or gel, and may further comprise a support of a woven or non-woven fabric of synthetic or non-synthetic fibers, or any combination thereof.
  • a film or gel can be provided in a unit dose suitable for the resorption of the otic capsule.
  • subject means a vertebrate, preferably a mammal, more preferably a human.
  • Mammalian species that provide samples for analysis include canines; felines; equines; bovines; ovines; etc. and primates, particularly humans.
  • Animal models, particularly small mammals, e.g. murine, lagomorpha, etc. can be used for experimental investigations.
  • therapeutic agent refers to a molecule or compound that confers some beneficial effect upon administration to a subject.
  • the beneficial effect includes enablement of diagnostic determinations; amelioration of a disease, symptom, disorder, or pathological condition; reducing or preventing the onset of a disease, symptom, disorder or condition; and generally counteracting a disease, symptom, disorder or pathological condition.
  • treatment or “treating,” or “palliating” or “ameliorating” are used interchangeably. These terms refer to an approach for obtaining beneficial or desired results including but not limited to a therapeutic benefit and/or a prophylactic benefit.
  • therapeutic benefit is meant any therapeutically relevant improvement in or effect on one or more diseases, conditions, or symptoms under treatment.
  • the compositions may be administered to a subject at risk of developing a particular disease, condition, or symptom, or to a subject reporting one or more of the physiological symptoms of a disease, even though the disease, condition, or symptom may not have yet been manifested.
  • contact, administer, deliver are synonymous and mean the transfer of the composition being referred to from one reservoir or repository to a tissue, cell, or part of an organ, tissue, fluid or space.
  • Implantable device The methods of the invention find use in combination with a variety of implantable devices and drug delivery vehicles for the inner ear. Many such devices are known and used in the art, and need not be described in detail herein.
  • conductive hearing loss and many types of sensorineural hearing loss are treated surgically, and utilize cochleostomy methods.
  • hearing loss can arise from the absence or the destruction of the hair cells in the cochlea which then no longer transduce acoustic signals into auditory nerve impulses.
  • cochlear implant systems, or cochlear prostheses have been developed that can bypass the hair cells located in the cochlea by presenting electrical stimulation directly to the auditory nerve fibers. This leads to the perception of sound in the brain and provides at least partial restoration of hearing function.
  • a cochlear prosthesis operates by directly stimulating the auditory nerve cells, bypassing the defective cochlear hair cells that normally transduce acoustic energy into electrical activity to the connected auditory nerve cells.
  • a cochlear implant system typically comprises both an external unit that receives and processes ambient sound waves and an implanted processor/cochlear lead that receives data from the external unit and uses that data to directly stimulate the auditory nerve.
  • the cochlear lead includes an electrode array that is implanted within one of the cochlear ducts, such as the scala tympani. To minimize damage to sensitive tissues within the patient's cochlea, it can be desirable for the electrode array to be accurately placed within the cochlea using a minimum amount of insertion force.
  • the cochlear implant should be designed so that the insertion forces do not kink or otherwise damage the delicate wires and electrodes contained within the implant.
  • Revision surgery can be used to explant a cochlear electrode array from the cochlea and replace it with a new electrode array.
  • revision surgery it is sometimes difficult to insert a compliant pre-curved or lateral electrode array due to the presence of scar tissue/ossification that has formed around the previous electrode array.
  • a stiffer electrode can be used to ensure insertion to the full depth of the electrode.
  • a number of drug delivery devices for the inner ear are known in the art, e.g. see any one of U.S. Patent nos. 8,507,525; 8,486,052; 8,404,654; 8,333,726; 8,303,990; 8,268,866; 8,197,461 ; 8,192,488; 8,126,572; 7,840,260; 7,815,615; 7,589,1 10; 7,498,360; 7,387,614; 7,220,431 ; 7,206,639; etc.
  • the methods of the invention find use for providing access to the inner ear and can be used in combination with such implants and devices.
  • the methods of the invention provide a means for atraumatic cochleostomy, that reliably can be performed without loss of hearing. Such methods find use in a wide variety of situations where access to the inner ear is desired for application of therapeutic agents, implantation of devices, access to the cranial vault, and the like, where maintenance of residual hearing is desired. [0051] The methods initially involve surgical access to the optic capsule, by opening and exposing the skin, and the soft tissue overlying the auditory bulla. The bony auditory bulla is removed to the point that exposes the basal turn of the cochlea.
  • the exposed basal turn is contacted with an effective dose of a decalcifying agent in a formulation as described herein.
  • a decalcifying agent in a formulation as described herein.
  • multiple applications are required, e.g. two, three, four or more.
  • the decalcification process is allowed to continue until the otic capsule is substantially thinned, e.g. where the remaining bone is less than about 0.25 mm thick.
  • the appropriate thinness can be observed as the point at which the remaining bone is sufficiently translucent that the underlying blood vessels can be observed. At this point, gentle palpitations of the region result in bowing of the remaining bone.
  • the active agent is removed or otherwise neutralized with a neutralizing agent, rinsed with buffer, etc.
  • the remaining thinned bone is readily removed surgically by any convenient method, e.g. a right angle pick or forceps.
  • the inner ear is made accessible, and the surgery may further comprise implantation of a device, drug delivery, surgical access, and the like.
  • Embodiments of the invention include the provision of agents for use in the methods of the invention, preferably in surgical packs, e.g. sterilized and in a unit dose.
  • the unit dose of the decalcifying agent may be the dose required to reach the desired endpoint, or may be a single dose where multiple doses are required to reach the desired endpoint.
  • Such a unit dose may be provided as a pre-loaded syringe; as a film or gel; in a container suitable for storage of an acid and accompanied by a delivery device; and the like.
  • the kit may further comprise a neutralizing agent, e.g. a buffer appropriate for the acid that is used.
  • a neutralizing agent e.g. a buffer appropriate for the acid that is used.
  • the neutralizing agent can be packaged with the decalcifying agent, e.g. as provided on the border of a patch or film, co-formulated as a slow release for mixing with the acid; etc., or can be separately packaged, e.g. a unit dose in a syringe, container, gel, film, etc.
  • Kits may further comprise additional dressings, surgical tools, instructions for use and the like.
  • Atraumatic, hearing preservation cochleostomy is performed in the guinea pig, which serves as a relevant animal model for treatment of humans.
  • the methods of the invention are used to safely resorb and thin the bony otic capsule of the cochlea, without damage to the underlying membranous labyrinth and Organ of Corti.
  • the cochleostomy is performed by anesthetizing 250-800 gm Hartley guinea pigs using intraperitoneal injection of ketamine and xylazine. Hair is removed postauricularly along the planned incision site using electric razor and Nair. A local anesthetic of 1 % lidocaine with 1 :100,000 epinephrine is infiltrated into the planned incision site. The skin is incised using a scalpel, and the soft tissue overlying the auditory bulla is incised using a hand held heat cautery.
  • the bony auditory bulla is exposed, entered, and the bone removed as far medially as the vestibular system, anterolateral ⁇ as the tympanic membrane, and posteriorly as the neck. This exposes the basal turn of the cochlea.
  • Approximately 15 ⁇ of 34% phosphoric acid gel (PAG) is applied to the basal turn of the cochlea, just distal to the round window, using a blunt 25 gauge needle. After 5 minutes, the PAG is suctioned off. It is reapplied twice more for 5 minutes each. After about three five minute applications, the bony capsule is resorbed, resulting in cochleostomy. The soft tissues closed over the bulla can be sutured to perform postoperative audiograms. Following the last application of PAG, the cochlear surface is then rinsed with a buffered solution.
  • PAG phosphoric acid gel
  • This method leaves a very thin layer of bone is left covering the membranous labyrinth.
  • the thin layer of bone is then manually removed using a right angle pick, completing the cochleostomy.
  • Hearing preservation cochleostomy can be performed in an animal model using a novel technique of thinning cochlear bone with PAG and manually completing cochleostomy.
  • Minimally traumatic, hearing preservation cochleostomy will be integral to the future of inner ear surgery. Although most cochleostomies performed today are in patients who have severe or profound sensorineural hearing loss for the purposes of cochlear implantation, with the advent of electric acoustic stimulation devices, preservation of residual hearing has become increasingly important. Minimally traumatic cochleostomy is also important for furthering in vivo hearing research. The ability to access the inner ear without perturbation is critical to ensuring that studies of the cochlea are reliable and accurate.
  • the dorsolateral surface of the auditory bulla was opened using a pick and cupped forceps as far anteriorly as the tympanic membrane, as far posteriorly as the neck, and as far medially as the vestibular system (see Figure 1 ).
  • Anatomic landmarks were identified, including the incudostapedial joint, round window, and basal turn of the cochlea (see Figure 1A). All cochleostomies were performed along the basal turn of the cochlea, overlying the scala tympani. For those animals undergoing mechanical cochleostomy, this was achieved using a right— angle pick.
  • Audiometry Audiometric measurements were performed in a sound-proofed booth.
  • Auditory evoked brainstem responses were obtained at 2, 6, 10 and 16 kHz using custom hardware and MATLAB software described previously. Briefly, needle electrodes were placed subcutaneously at the vertex and behind the ipsilateral ear for measurement, and on a hind limb as a ground electrode. For those animals undergoing cochleostomies, the cochleostomy site was left open during audiometric measurements. The sound intensity level was raised in 10 dB steps from 10 to 80 dB SPL, and 500 responses at each sound level were recorded and averaged. The peak value of the ABR was measured and the threshold at each frequency was calculated to be when this value was five standard deviations above the noise floor.
  • Topical steroids application of hyaluronic acid, and variation in cochleostomy site have also been investigated.
  • Lasers of various wavelengths carbon dioxide, erbium:yttrium-aluminum- garnet, and potassium-titanyl-phosphate, for example
  • piezoelectric devices have been used as alternatives to diamond burrs.
  • Modifications for humans may include an increase the time that needed to resorb the thicker human otic capsule, or to increase the strength of the PAG by compounding it with a stronger acid.
  • Another tactic might be to start the cochleostomy using a drill, follow with PAG, then finish manually with a micro-pick.
  • a neutralizing agent or buffer could be prophylactically applied as a physical barrier surrounding the intended cochleostomy site to prevent spread to unintended sites.

Abstract

L'invention concerne des procédés pour une cochléostomie de préservation de l'audition traumatique par l'administration locale d'un agent décalcifiant appliqué à la capsule otique exposée de la cochlée, pendant une durée suffisante pour résorber ou sensiblement affiner la capsule osseuse. Quand la capsule est amincie, une étape finale peut être effectuée manuellement pour retirer l'os aminci.
PCT/US2015/026335 2014-04-17 2015-04-17 Procédés de cochléostomie chimique WO2015161175A1 (fr)

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Cited By (1)

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WO2017151105A1 (fr) * 2016-02-29 2017-09-08 Advanced Bionics Ag Systèmes et procédés d'utilisation d'une réponse évoquée pour déterminer une valeur d'audiogramme comportemental

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