Systems and methods for treating hearing loss
Systems and methods can be employed for trans-tympanic membrane access to the middle ear for delivery of a therapeutic agent, for example, to the round window niche adjacent to the cochlea under direct visualization. The systems and methods can also be used to improve accessibility and visualization for various otological surgical procedures, such as, but not limited to, cholesteatoma removal, tympanic membrane repair and ossicular chain repair.
1 . A method for delivering a therapeutic gel formulation to a round window niche of a cochlea under direct endoscopic visualization, the method comprising:
providing direct visualization of the round window niche of the cochlea using an endoscope in which a distal end of an endoscope shaft of the endoscope is inserted through a tympanic membrane and into a middle ear to visualize the round window niche of the cochlea, wherein the endoscope is configured to be coupled to an injector shaft of an otologic injector device using a two-channel alignment sleeve;
during direct visualization of the round window niche of the cochlea using the endoscope shaft inserted through the tympanic membrane, advancing the injector shaft of the otologic injector device such that a distal tip of the injector shaft moves toward the round window niche while the distal end of the endoscope is spaced proximally from the distal tip of the injector shaft to provide simultaneous direct visualization of the injector shaft and the round window niche, wherein the otologic injector device includes: a syringe containing the therapeutic gel formulation comprising an anti-inflammatory agent and a polymer composition including (i) a functional polymer comprising a first functional group that is about 5% to about 15% by weight of the polymer composition, (ii) a crosslinker comprising a second functional group that is about 0.2% to about 0.6% by weight of the polymer composition, and (iii) water, and wherein the injector shaft is configured to be connected to the syringe;
delivering the therapeutic gel formulation from the distal tip of the injector shaft to the round window niche while the endoscope provides said simultaneous direct visualization of the injector shaft and the round window niche of the cochlea, wherein the therapeutic gel formulation is at least partially cured to become a gel substance in situ after said delivering to the round window niche of the cochlea; and
after said delivering the therapeutic gel formulation to the round window niche of the cochlea, using the endoscope to visually verify retention of the therapeutic gel formulation at the round window niche of the cochlea.
2 . The method of claim 1 , wherein the distal tip of the injector shaft terminates at a beveled tip that defines a port through which the therapeutic gel formulation is ejected.
3 . The method of claim 1 , further comprising advancing a distal tip effector of a membrane modification instrument through the tympanic membrane and to the round window niche, and using the distal tip effector to tear a pseudomembrane at the round window niche while the distal end of the endoscope in the middle ear is spaced apart from the membrane modification instrument and provides visualization of the membrane modification instrument.
4 . The method of claim 1 , further comprising mixing first and second functional components to generate a crosslinking reaction for the therapeutic gel formulation.
5 . The method of claim 1 , wherein the anti-inflammatory agent is selected from the group consisting of: hydrocortisone, hydrocortisone acetate, dexamethasone, dexamethasone 21-phosphate, fluocinolone, medrysone, prednisolone, prednisolone 21-phosphate, prednisolone acetate, fluoromethalone, betamethasone, and triamcinolone.
6 . The method of claim 1 , wherein the anti-inflammatory agent of the therapeutic gel formulation is provided in an amount sufficient to move passively by diffusion across a membrane of the round window niche and into the cochlea.
7 . The method of claim 1 , wherein the endoscope shaft has an outer diameter larger than an outer diameter of the injector shaft and is sized to pass through a first incision through the tympanic membrane.
8 . The method of claim 7 , wherein the outer diameter of the injector shaft is sized to pass through a second incision through the tympanic membrane while positioned adjacent to the endoscope shaft.
9 . The method of claim 1 , wherein the injector shaft is configured to adjust between a non-curved shape and a curved shape during said advancing the injector shaft of the otologic injector device.
10 . The method of claim 1 , further comprising removably implanting at least one tympanic membrane port device in the tympanic membrane of a patient, the tympanic membrane port device including a central lumen having a diameter of 1 mm.
11 . The method of claim 1 , wherein the endoscope shaft is positionable through the tympanic membrane via an opening having a diameter of 1 mm.
12 . The method of claim 1 , further comprising applying light toward the round window niche to generate a crosslinking reaction for the therapeutic gel formulation.
13 . The method of claim 1 , wherein the endoscope shaft extends through a primary channel of the two-way alignment sleeve that remains external from the tympanic membrane, wherein the two-way alignment sleeve defines (i) the primary channel having a first diameter and extending to a distal end of the two-channel alignment sleeve, and (ii) an auxiliary working channel having a second diameter smaller than the first diameter and wherein a central longitudinal axis of the auxiliary working channel is in a non-parallel relationship with a central longitudinal axis of the primary channel, wherein advancing the injector shaft comprises sliding the injector shaft within the auxiliary working channel of the two-channel alignment sleeve and through the tympanic membrane, wherein the syringe is slidable through the auxiliary working channel of the two-channel alignment sleeve while the endoscope shaft is positioned within the primary channel of the two-channel alignment sleeve, wherein the non-parallel relationship of the auxiliary channel and the primary channel of the two-channel alignment sleeve is oriented to reduce a side-by-side size of the endoscope shaft and the injector shaft crossing through the tympanic membrane.
14 . The method of claim 13 , wherein the two-channel alignment sleeve is compressed against an exterior of the endoscope to affix the two-channel alignment sleeve to the endoscope while the endoscope shaft is positioned within the primary channel.
15 . The method of claim 14 , wherein said sliding the injector shaft of the otologic injector device comprises moving the distal tip of the injector shaft relative to both the two-channel alignment sleeve and the distal end of the endoscope.
16 . The method of claim 13 , wherein the non-parallel relationship is defined by an angle greater than 0° and less than 20°.
17 . The method of claim 13 , wherein the auxiliary working channel of the two-channel alignment sleeve is laterally separated from the primary channel by an intermediate wall portion of the two-channel alignment sleeve.
18 . The method of claim 13 , wherein during said sliding the injector shaft of the otologic injector device, the injector shaft extends from the distal end of the two-channel alignment sleeve in the non-parallel relationship with the central longitudinal axis of the primary channel at the distal end of the two-channel alignment sleeve.
19 . A method for delivering a therapeutic gel formulation to a round window niche of a cochlea under direct visualization, the method comprising:
providing direct visualization of the round window niche of the cochlea using a visualization shaft inserted through a tympanic membrane and into a middle ear to visualize the round window niche of the cochlea, wherein the visualization shaft is coupled to an injector shaft of an otologic injector device in a side-by-side configuration;
during direct visualization of the round window niche of the cochlea using the visualization shaft, advancing the injector shaft of the otologic injector device such that a distal tip of the injector shaft moves toward the round window niche of the cochlea while a distal end of the visualization shaft is spaced proximally from the distal tip of the injector shaft to provide simultaneous direct visualization of both the injector shaft and the round window niche using the visualization shaft, wherein the otologic injector device includes: the injector shaft connected with a syringe containing the therapeutic gel formulation including an anti-inflammatory agent and a polymer composition that comprises (i) a functional polymer comprising a first functional group that is about 5% to about 15% by weight of the polymer composition, (ii) a crosslinker comprising a second functional group that is about 0.2% to about 0.6% by weight of the polymer composition, and (iii) water;
delivering the therapeutic gel formulation from the distal tip of the injector shaft to the round window niche of the cochlea while the visualization shaft provides said simultaneous direct visualization of the injector shaft and the round window niche of the cochlea, wherein the first functional group of the functional polymer and the second functional group of the crosslinker are configured to form a gel at body temperature after said delivering the therapeutic gel formulation to the round window niche of the cochlea; and
after said delivering the therapeutic gel formulation to the round window niche of the cochlea, using the visualization shaft to verify retention of the therapeutic gel formulation at the round window niche of the cochlea using direct visualization.
20 . The method of claim 19 , wherein:
the anti-inflammatory agent comprises dexamethasone,
the functional polymer comprises at least one of pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate and succinimidyl ester, and
the second functional group comprises trilysine, or a salt thereof.