Yann Nguyen

Recent advances in local drug delivery to the inner ear

Inner ear diseases are not adequately treated by systemic drug administration mainly because of the blood-perilymph barrier that reduces exchanges between plasma and inner ear fluids. Local drug delivery methods including intratympanic and intracochlear administrations are currently developed to treat inner ear disorders more efficiently. Intratympanic administration is minimally invasive but relies on diffusion through middle ear barriers for drug entry into the cochlea, whereas intracochlear administration offers direct access to the colchlea but is rather invasive. A wide range of drug delivery systems or devices were evaluated in research and clinic over the last decade for inner ear applications. In this review, different strategies including medical devices, hydrogels and nanoparticulate systems for intratympanic administration, and cochlear implant coating or advanced medical devices for intracoclear administration were explored with special attention to in vivo studies. This review highlights the promising systems for future clinical applications as well as the current hurdles that remain to be overcome for efficient inner ear therapy.

Friction force measurement during cochlear implant insertion: application to a force-controlled insertion tool design

Hypothesis The aim of the study was to evaluate force profiles during array insertion in human cochlea specimens and to evaluate a mechatronic inserter using a 1-axis force sensor. Background Today, the surgical challenge in cochlear implantation is the preservation of the anatomic structures and the residual hearing. In routine practice, the electrode array is inserted manually with a limited sensitive feedback. Materials and Methods Hifocus 1J electrode arrays were studied. The bench test comprised a mechatronic inserter combined to a 1-axis force sensor between the inserter and the base of the array and a 6-axis force sensor beneath the cochlea model. Influence of insertion tube material, speed (0.15, 0.5, and 1.5 mm/s) and lubricant on frictions forces were studied (no-load). Different models were subsequently evaluated: epoxy scala tympani model and temporal bones. Results Frictions forces were lower in the plastic tube compared with those in the metal tube (0.09 ± 0.028 versus 0.14 ± 0.034 at 0.5 mm/s, p < 0.001) and with the use of hyaluronic acid gel. Speed did not influence frictions forces in our study. Insertion force profiles provided by the 1- and 6-axis force sensors were similar when friction forces inside the insertion tool (no-load measurements) were subtracted from the 1-axis sensor data in the epoxy and temporal bone models (mean error, 0.01 ± 0.001 N). Conclusion Using a sensor included in the inserter, we were able to measure array insertion forces. This tool can be potentially used to provide real-time information to the surgeon during the procedure.

Effect of liposomes on rheological and syringeability properties of hyaluronic acid hydrogels intended for local injection of drugs.

The aim of this work was to thoroughly study the effect of liposomes on the rheological and the syringeability properties of hyaluronic acid (HA) hydrogels intended for the local administration of drugs by injection. Whatever the characteristics of the liposomes added (neutral, positively or negatively charged, with a corona of polyethylene glycol chains, size), the viscosity and the elasticity of HA gels increased in a lipid concentration-dependent manner. Indeed, liposomes strengthened the network formed by HA chains due to their interactions with this polymer. The nature and the resulting effects of these interactions depended on liposome composition and concentration. The highest viscosity and elasticity were observed with liposomes covered by polyethylene glycol chains while neutral liposomes displayed the lowest effect. Despite their high viscosity at rest, all the formulations remained easily injectable through needles commonly used for local injections thanks to the shear-thinning behavior of HA gels. The present study demonstrates that rheological and syringeability tests are both necessary to elucidate the behavior of such systems during and post injection. In conclusion, HA liposomal gels appear to be a promising and versatile formulation platform for a wide range of applications in local drug delivery when an injection is required.

Cochlear implant insertion forces in microdissected human cochlea to evaluate a prototype array.

Cochlear implant array insertion forces are potentially related to cochlear trauma. We compared these forces between a standard (Digisonic SP; Neurelec, Vallauris, France) and an array prototype (Neurelec) with a smaller diameter. The arrays were inserted by a mechatronic tool in 23 dissected human cochlea specimens exposing the basilar membrane. The array progression under the basilar membrane was filmed together with dynamic force measurements. Insertion force profiles and depth of insertion were compared. The recordings showed lower insertion forces beyond 270° of insertion and deeper insertions with the thin prototype array. This will potentially allow larger cochlear coverage with less trauma.

Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear.

The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid. A prolonged residence time at the site of injection as well as in the round window were achieved without any negative effect on the hearing thresholds of the animals. The presence of liposomes in the formulation resulted in sustained release of the drug in the perilymph for 30days and promoted the conversion of the prodrug loaded within the liposomes (dexamethasone phosphate) into its active form (dexamethasone). In this way, therapeutic doses were attained in the perilymph. A small amount of intact liposomes was visualized in the perilymph, whereas the main proportion of liposomes seemed to be trapped in the round window resulting in a reservoir effect. Thus, the administration of hyaluronic acid liposomal gel to the middle ear is an efficient strategy for delivering corticoids to the inner ear in a sustained manner.

Diode laser in otosclerosis surgery: first clinical results.

Objective: To evaluate the functional results of otosclerosis surgery using diode laser. Study Design: Retrospective cohort analysis. Patients: One hundred seven patients operated on for otosclerosis with a diode laser (119 ears, all primary cases) and 141 patients operated on with a conventional technique (141 ears, all primary cases). Revision cases using the diode laser were also described. Methods: Preoperative tomographic computed scan findings and intraoperative observations were collected. Pure-tone and vocal audiometry was performed preoperatively and postoperatively (at 3 mo and 1 yr). Results: In the laser group, the air-bone gap was 29 ± 0.8 dB (n= 112) preoperatively and 9 ± 0.6 dB (n = 58) at 1 year. Air conduction was improved by 22 ± 1.7 dB at 1 year (n = 58). In the conventional group, the air-bone gap was 32 ± 0.9 dB (n=127) preoperatively and 10 ± 0.6 dB (n = 127) at 1 year. Air conduction was improved by 25 ± 1.1 dB (n = 127) at 1 year. No difference of hearing gain was observed between the 2 groups at 1 year. A decreased rate of footplate fracture was observed with the diode laser (3.6%) compared with the conventional technique (21.3%). Conclusion: Diode laser is a reliable and safe device for otosclerosis surgery. The functional results were similar to those reported in other series.

RobOtol: from design to evaluation of a robot for middle ear surgery

Middle ear surgery requires micro-surgical techniques and may benefit from robotic assistance. A prototype of tele-operated system is presented. Methods to determine design specifications, kinematic structure and optimization of the micro-manipulator are described. First evaluation of the robot by a stapedial removal through the external auditory meatus in human temporal bone specimens, simulating the surgery of otosclerosis, is presented. In this procedure, the robot yielded accessibility to the target area with a reduced visual impairment and, an enhanced tool stability compared to the surgeons hand.

Is Electrode-Modiolus Distance a Prognostic Factor for Hearing Performances after Cochlear Implant Surgery?

The aim of this study was to evaluate electrode array position in relation to cochlear anatomy and its influence on hearing performance in cochlear implantees. Twenty-two patients (25 ears) with Med-El cochlear implants were included in this retrospective study. A negative correlation was observed between electrode-modiolus distance (EMD) at the cochlear base and monosyllabic word discrimination 6 months after implantation. We found no correlation between EMD and hearing outcome at 12 months. The insertion depth/cochlear perimeter ratio appeared to negatively influence the EMD at the base. Indeed, deep insertions in small cochleae appeared to yield smaller EMD and better hearing performance. This observation supports the idea of preplanning the surgery by adapting the electrode array to the length of the available scala tympani.

Use of bone anchoring device in electromagnetic computer-assisted navigation in lateral skull base surgery

Abstract Conclusion: The use of the bone anchoring device associated with a fiducial marker, both fixed close to the operating field, improves the reproducibility and effectiveness of the computer-assisted navigation in lateral skull base surgery. Objectives: Computer-assisted navigation in lateral skull base surgery using the electromagnetic system Digipointeur® needs an external fiducial marker (titanium screw) close to the operating field to increase position accuracy (PA) to about 1 mm. Displacement of the emitter placed in the mouth (Buccostat®) induces a drift of the system, leading to at least 20% of unsuccessful procedures. The aim of this study was to evaluate the PA, stability, and reproducibility of computer-assisted navigation in lateral skull base surgery using a bone anchoring device to provide a fixed registration system near the operating field. Methods: Forty patients undergoing a lateral skull base procedure with the Digipointeur® system performed with both the titanium screw and bone anchoring device were included in this prospective study. They were divided in two groups. In the first one (n = 9), the PA was measured before and after screw registration for five intratemporal landmarks, during a translabyrinthine approach. In the second group (n = 31), all lateral skull base procedures were included and the PA was evaluated visually by the surgeon on different landmarks of the approaches as well as the stability of the system. Results: In the first group, the PA was 7.08 ± 0.59 mm and 0.77 ± 0.17 mm (mean ± SEM, p < 0.0001) before and after screw registration, respectively. In the second group, the PA was considered as accurate by the surgeon in all cases and no drift of the system was observed. Computer-assisted surgery was never abandoned due to increased stability of the bone-anchored emitter.

Middle ear and mastoid obliteration for cochlear implant in adults: indications and anatomical results.

Aim of the Study To review indications, anatomical results, and complications of cochlear implant (CI) surgery in adults for which middle ear and mastoid obliterations were performed. Patients and Methods Thirty cases (26 patients, 4 bilaterally implanted) of 837 CI surgeries (3.5%) performed between January 2009 and December 2013 have been included in this retrospective study. The mean follow-up was 21 ± 18 months (mean ± SD, range 3–58). There were 11 males and 15 females. The mean age was 59 ± 19 years (range 35–82). All surgeries were performed with a single-stage technique including a canal wall down mastoidectomy with external auditory canal closure and mastoid obliteration with fat. A postoperative CT scan was performed in all cases. Results Etiologies of hearing loss were mainly chronic otitis with or without cholesteatoma in 24 cases. Other etiologies were meningitis with cochlear ossification in one case, progressive hearing loss in two cases, enlarged vestibular aqueduct in one case, temporal bone fracture with CSF leak in one case, and congenital aural atresia in one case. Four of those 30 cases were revision CI surgery for electrode array misplacement (one case with cochlear ossification) or extrusion from an open cavity (one case) and recurrent cholesteatomas (two cases). All surgeries were uneventful and performed in a single stage. The electrode array was inserted in the basal turn (29 cases) or in the middle turn (one case) of the cochlea. No complications were observed. Two cases of postoperative abdominal hematoma were drained under local anesthesia. A major failure of the CI device occurred 5 months after surgery. Conclusion CI with mastoid and middle ear obliteration is a safe and effective technique for selected cases of cochlear implantation. Mastoid obliteration prevents from recurrent disease and lowering the facial ridge allows more space to manage extensive cochlear ossification or malformation.