Browsing by Author "Chiang, Harry"

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    3D-Printed Microneedles Create Precise Perforations in Human Round Window Membrane in Situ.
    (Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2020-02) Chiang, Harry; Yu, Michelle; Aksit, Aykut; Wang, Wenbin; Stern-Shavit, Sagit; Kysar, Jeffrey W; Lalwani, Anil K

    Hypothesis

    Three-dimensional (3D)-printed microneedles can create precise holes on the scale of micrometers in the human round window membrane (HRWM).

    Background

    An intact round window membrane is a barrier to delivery of therapeutic and diagnostic agents into the inner ear. Microperforation of the guinea pig round window membrane has been shown to overcome this barrier by enhancing diffusion 35-fold. In humans, the challenge is to design a microneedle that can precisely perforate the thicker HRWM without damage.

    Methods

    Based on the thickness and mechanical properties of the HRWM, two microneedle designs were 3D-printed to perforate the HRWM from fresh frozen temporal bones in situ (n = 18 total perforations), simultaneously measuring force and displacement. Perforations were analyzed using confocal microscopy; microneedles were examined for deformity using scanning electron microscopy.

    Results

    HRWM thickness was determined to be 60.1 ± 14.6 (SD) μm. Microneedles separated the collagen fibers and created slit-shaped perforations with the major axis equal to the microneedle shaft diameter. Microneedles needed to be displaced only minimally after making initial contact with the RWM to create a complete perforation, thus avoiding damage to intracochlear structures. The microneedles were durable and intact after use.

    Conclusion

    3D-printed microneedles can create precise perforations in the HRWM without damaging intracochlear structures. As such, they have many potential applications ranging from aspiration of cochlear fluids using a lumenized needle for diagnosis and creating portals for therapeutic delivery into the inner ear.
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    Anatomical and Functional Consequences of Microneedle Perforation of Round Window Membrane.
    (Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2020-02) Yu, Michelle; Arteaga, Daniel N; Aksit, Aykut; Chiang, Harry; Olson, Elizabeth S; Kysar, Jeffrey W; Lalwani, Anil K

    Hypothesis

    Microneedles can create microperforations in the round window membrane (RWM) without causing anatomic or physiologic damage.

    Background

    Reliable delivery of agents into the inner ear for therapeutic and diagnostic purposes remains a challenge. Our novel approach employs microneedles to facilitate intracochlear access via the RWM. This study investigates the anatomical and functional consequences of microneedle perforations in guinea pig RWMs in vivo.

    Methods

    Single three-dimensional-printed, 100 μm diameter microneedles were used to perforate the guinea pig RWM via the postauricular sulcus. Hearing was assessed both before and after microneedle perforation using compound action potential and distortion product otoacoustic emissions. Confocal microscopy was used ex vivo to examine harvested RWMs, measuring the size, shape, and location of perforations and documenting healing at 0 hours (n = 7), 24 hours (n = 6), 48 hours (n = 6), and 1 week (n = 6).

    Results

    Microneedles create precise and accurate perforations measuring 93.1 ± 29.0 μm by 34.5 ± 16.8 μm and produce a high-frequency threshold shift that disappears after 24 hours. Examination of perforations over time demonstrates healing progression over 24 to 48 hours and complete perforation closure by 1 week.

    Conclusion

    Microneedles can create a temporary microperforation in the RWM without causing significant anatomic or physiologic dysfunction. Microneedles have the potential to mediate safe and effective intracochlear access for diagnosis and treatment of inner ear disease.
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    Challenges in the Management of Symptomatic Fallopian Canal Meningoceles: A Multicenter Case Series and Literature Review
    (Otology & Neurotology, 2024-04) Filip, Peter; Chiang, Harry; Goldberg, Allison; Khorsandi, Azita S; Moonis, Gul; Moody Antonio, Stephanie A; Wanna, George; Cosetti, Maura
    Objective To describe the presentations, the diagnosis, our treatment approaches, and the outcomes for 11 patients with fallopian canal meningocele (FCM). Study Design: Multicenter Retrospective case series. Setting Tertiary referral centers. Patients Patients (N = 11) with radiographically or intraoperatively identified, symptomatic FCM. Interventions Surgical repair of cerebrospinal fluid (CSF) leak and meningocele versus observation. Main Outcome Measures Presentation (including symptoms, radiographic imaging, and comorbidities), management (including surgical approach, technique for packing, use of lumbar drain), clinical outcomes (control of CSF leak, meningitis, facial nerve function), and revision surgery. Results Patients presented with spontaneous CSF leak (n = 7), conductive (N = 11) and sensorineural hearing loss (n = 3), nonpositional intermittent vertigo (n = 3), headaches (n = 4), and recurrent meningitis (n = 1). Risk factors in our series included obesity (n = 4), Chiari 1 malformation (n = 1), and head trauma (n = 2). Noncontrast computed tomography of the temporal bone and magnetic resonance imaging were positive for FCM in 10 patients. Eight patients were managed surgically via a transmastoid approach (n = 4), combined transmastoid and middle fossa (N = 3), or middle fossa alone (n = 1); three were managed conservatively with observation. Postoperative complications included worsened facial nerve palsy (n = 1), recurrent meningitis (n = 1), and persistent CSF leak that necessitated revision (n = 1). Conclusions Facial nerve meningoceles are rare with variable presentation, often including CSF otorrhea. Management can be challenging and guided by symptomatology and comorbidities. Risk factors for FCM include obesity and head trauma, and Chiari 1 malformation may present with nonspecific otologic symptoms, in some cases, meningitis and facial palsy. Layered surgical repair leads to high rates of success; however, this may be complicated by worsening facial palsy.
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    Characterizing Olfactory Dysfunction in Patients with Unilateral Cleft Lip Nasal Deformities.
    (Facial plastic surgery & aesthetic medicine, 2023-05) Russel, Sarah M; Chiang, Harry; Finlay, John B; Shah, Reanna; Marcus, Jeffrey R; Jang, David W; Abi Hachem, Ralph; Goldstein, Bradley J; Frank-Ito, Dennis Onyeka
    Background: Unilateral cleft lip nasal deformity (uCLND) is associated with olfactory dysfunction, but the underlying etiology remains poorly understood. Objective: To investigate the etiology of uCLND-associated olfactory dysfunction using clinical, computational, and histologic assessments. Methods: Inclusion criteria: uCLND patients >16 years undergoing septorhinoplasty. Exclusion criteria: prior septoplasty or rhinoplasty, pregnancy, sinusitis. Measured outcomes: patient-reported scores, rhinomanometry, smell identification and threshold tests, computational fluid dynamics (CFD) airflow simulations, and histologic analysis of olfactory epithelium. Results: Five uCLND subjects were included: 18-23 years, three male and two female, four left-sided cleft and one right-sided cleft. All subjects reported moderate to severe nasal obstruction. Smell identification and threshold tests showed varying degrees of hyposmia. Nasal resistance was higher on the cleft side versus noncleft side measured by rhinomanometry (median 3.85 Pa-s/mL, interquartile range [IQR] = 21.96, versus 0.90 Pa-s/mL, IQR = 5.17) and CFD (median 1.04 Pa-s/mL, IQR = 0.94 vs. 0.11 Pa-s/mL, IQR = 0.12). Unilateral olfaction varied widely and was dependent on unilateral percentage olfactory airflow. Biopsies revealed intact olfactory neuroepithelium. Conclusions: uCLND-associated olfactory dysfunction appears to be primarily conductive in etiology and highly susceptible to variations in nasal anatomy. Clinical Trial Registration number: NCT04150783.
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    Comparing Patient-Reported Outcomes with Computational Fluid Dynamics-Derived Nasal Airflow After Nasal Airway Surgery: Prioritizing the Patient's Perception of Nasal Obstruction.
    (Facial plastic surgery & aesthetic medicine, 2024-08) Chiang, Harry; Frank-Ito, Dennis O
    Background: Some patients report persistent nasal obstruction after surgical treatment despite objective improvement. Objective: To compare patients' perceptions of nasal obstruction after surgery with objective nasal airflow as determined by computational fluid dynamics (CFD) modeling: (1) Is perception driven by a more symptomatic side? (2) Can symptom improvement be predicted with CFD modeling? Methods: Pre/postoperative Nasal Obstruction Symptom Evaluation (NOSE) and visual analog scale (VAS) score were collected for patients undergoing nasal obstruction surgery. Pre/postoperative computed tomography was used to generate patient-specific airway models for CFD simulation at 15 L/min resting inspiration. Results: Ten patients (22-53 years, seven men and three women) underwent septoplasty, turbinate reduction, and/or rhinoplasty. Postoperative NOSE was most correlated with postoperative VAS score from the "affected" side (R2 = 0.59, p < 0.01), and postoperative NOSE was strongly predicted by a two-parameter model using parameters only from the "affected" side (R2 = 0.84, adjusted R2 = 0.80, p < 0.01). Conclusion: The postoperative state of the initially "affected" side drives outcomes after nasal obstruction surgery. Surgeries should prioritize improving the "affected" side. A two-parameter model using the VAS and nasal airflow from only the "affected" side strongly predicts NOSE and is promising for the future using virtual planning to individualize procedures to optimize outcome.
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    Inner ear delivery: Challenges and opportunities.
    (Laryngoscope investigative otolaryngology, 2020-02) Szeto, Betsy; Chiang, Harry; Valentini, Chris; Yu, Michelle; Kysar, Jeffrey W; Lalwani, Anil K

    Objectives

    The treatment of inner ear disorders remains challenging due to anatomic barriers intrinsic to the bony labyrinth. The purpose of this review is to highlight recent advances and strategies for overcoming these barriers and to discuss promising future avenues for investigation.

    Data sources

    The databases used were PubMed, EMBASE, and Web of Science.

    Results

    Although some studies aimed to improve systemic delivery using nanoparticle systems, the majority enhanced local delivery using hydrogels, nanoparticles, and microneedles. Developments in direct intracochlear delivery include intracochlear injection and intracochlear implants.

    Conclusions

    In the absence of a systemic drug that targets only the inner ear, the best alternative is local delivery that harnesses a combination of new strategies to overcome anatomic barriers. The combination of microneedle technology with hydrogel and nanoparticle delivery is a promising area for future investigation.

    Level of evidence

    NA.
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    Nasal airway obstruction in patients with cleft lip nasal deformity: a systematic review
    (Journal of Plastic, Reconstructive & Aesthetic Surgery, 2024-02) Chiang, Harry; Shah, Reanna; Washabaugh, Claire; Frank-Ito, Dennis O
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    Olfactory Drug Delivery with Intranasal Sprays after Nasal Midvault Reconstruction.
    (International journal of pharmaceutics, 2023-08) Chiang, Harry; Martin, Hannah L; Sicard, Ryan M; Frank-Ito, Dennis O
    Conductive olfaction and nose to brain drug delivery are important processes that remain limited by inadequate odorant or drug delivery to the olfactory airspace. Primary challenges include anatomic barriers and poor targeting to the olfactory region. This study uses computational fluid dynamics to investigate the effects of nasal midvault surgery on olfactory drug delivery with intranasal sprays. Soft tissue elevation, spreader flaps, and spreader grafts were performed on two fresh cadaveric specimens, using computed tomography for airway reconstruction. Nasal airflow and drug particle transport simulations were performed under these conditions: inhalation rate (15, 30L/min), spray velocity (1, 5, 10m/s), spray location (top, bottom, center, medial, lateral), head position (upright, supine, forward, backward), and particle size (1-100 µm). Simulation results were used to calculate drug particle deposition to the olfactory airspaces and bulbs. Total olfactory deposition was <5% but attained a maximum of 36.33% when sorted by particle size. There was no association between nasal midvault surgery and olfactory deposition. No single parameter or technique demonstrated superior olfactory deposition, but smaller particle size, slower spray velocity, and higher inhalation rate tended to optimize olfactory deposition, providing important implications for future intranasal spray and drug design to target the olfactory airspace.
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    Systematic Review of Otologic and Neurotologic Surgery Using the 3-dimensional Exoscope
    (Otology & Neurotology Open) Chiang, Harry; Ledbetter, Leila; Kaylie, David M
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    The evolution of facial reanimation techniques.
    (American journal of otolaryngology, 2023-05) Pan, Debbie R; Clark, Nicholas W; Chiang, Harry; Kahmke, Russel R; Phillips, Brett T; Barrett, Dane M
    This review article provides an updated discussion on evidence-based practices related to the evaluation and management of facial paralysis. Ultimately, the goals of facial reanimation include obtaining facial symmetry at rest, providing corneal protection, restoring smile symmetry and facial movement for functional and aesthetic purposes. The treatment of facial nerve injury is highly individualized, especially given the wide heterogeneity regarding the degree of initial neuronal insult and eventual functional outcome. Recent advancements in facial reanimation techniques have better equipped clinicians to approach challenging patient scenarios with reliable, effective strategies. We discuss how technology such as machine learning software has revolutionized pre- and post-intervention assessments and provide an overview of current controversies including timing of intervention, choice of donor nerve, and management of nonflaccid facial palsy with synkinesis. We highlight novel considerations to mainstay conservative management strategies and examine innovations in modern surgical techniques with a focus on gracilis free muscle transfer. Innervation sources, procedural staging, coaptation patterns, and multi-vector and multi-muscle paddle design are modifications that have significantly evolved over the past decade.