Otology and Neurotology Research

UNILATERAL HEARING LOSS IN CHILDREN

Clinical studies have shown that unilateral hearing loss in children is a greater disability than previously appreciated. A subset of children with unilateral hearing loss is at risk for grade retention and lower scholastic performance than children with binaural hearing. With the unique population of congenital aural atresia patients seen at UVA, we are trying to uncover the disabilities associated with unilateral hearing loss in children, identify which children are at risk for underperforming, and put in place habilitative measures that will contribute to their academic and social success.

The two primary disabilities associated with unilateral hearing loss are poor hearing in background noise and difficulty locating sound in space. We are enrolling patients with unilateral aural atresia and unilateral sensorineural hearing loss in a study where we perform hearing in noise testing (HINT) and sound localization testing before and after surgery to correct their unilateral conductive hearing loss. We hope to demonstrate an improvement in children’s HINT and sound localization ability after surgery for unilateral aural atresia. We eventually hope to follow these children longitudinally to document performance in school.

We are also exploring the role of sleep and fatigue in children with unilateral hearing loss.

Collaborators: Bradley Kesser, M.D.; Lincoln Gray, Ph.D. , James Madison University

Kesser BW, Kopinski, E, and Gray LC. Emergence of binaural summation after surgical correction of unilateral congenital aural atresia. Otol Neurotol. 2016;37(5):499-503.

Dougherty W and Kesser BW. Management of conductive hearing loss in children. In: Otolaryngol,Clin N Am. Kesser and Kenna (eds.).48(6). Philadelphia: Elsevier, 2015:955-974.

Kesser BW, Krook K, Gray LC. Impact of unilateral conductive hearing loss secondary to aural atresia on academic performance in children. Laryngoscope. 2013;123(9):2270-5

SURGICAL REPAIR OF CONGENITAL AURAL ATRESIA

Surgery for congenital aural atresia is a challenging operation with somewhat variable long-term hearing outcomes. We are analyzing long-term hearing outcomes and are looking at anatomic and audiologic factors that portend better hearing outcomes and better surgical candidacy for these children.

Collaborators: Bradley Kesser, MD; Lincoln Gray, Ph.D., James Madison University

 Reed R, Hubbard M, Kesser BW. Is there a right ear advantage in congenital aural atresia? Otol Neurotol. 2016;37(10):1577-82

 Casale GA, Nicholas BD, and Kesser BW. Acquired ear canal cholesteatoma in congenital aural atresia/stenosis. Otol Neurotol. 2014;35(8):1474-9

Nicholas BD and Kesser BW. Unilateral aural atresia: Current management issues and results. In Implantable Devices in Otorhinolaryngology, Buchman CA, ed. Curr Otorhinolaryngol Rep 2013;1:92-98

Nicholas B, Krook K, Gray LC, and Kesser BW. Does preoperative hearing predict postoperative hearing in surgery for congenital aural atresia? Otol Neurotol. 2012;33(6):1002-6

Oliver ER, Hughley BB, Shonka DC, Kesser BW. Revision Aural Atresia Surgery: Indications and Outcomes. Otol Neurotol. 2011;32(2):252-8.

Kesser BW. Surgery for Congenital Aural Atresia. Operative Techniques in Otolaryngology-Head and Neck Surgery: Techniques for the Ear (Part II). Brian J. McKinnon, MD, MBA, ed. 2010;21(4):278-86

Shonka DC, Jahrsdoerfer RA, Kesser BW. The Jahrsdoerfer Grading Scale in Surgery for Congenital Aural Atresia. Arch Otolaryngol Head Neck Surg 2008;134(8):873-7

Dobratz E, Rastogi A, Jahrsdoerfer RA, and Kesser BW. To POP or not: Ossiculoplasty in congenital aural atresia surgery. Laryngoscope 2008;118(8):1452-7

SIMULATION IN TEACHING SURGERY

In collaboration with a faculty member from the Department of Biomedical Engineering (Shayn Peirce-Cottler, Ph.D.), we have designed an anatomical model of the human ear canal, eardrum, and middle ear space to teach medical students, medical residents, and family medicine residents diagnostic and pneumatic otoscopy. The tool can also be used to teach otolaryngology residents myringotomy with tympanostomy tube insertion, as the model comes with anatomically correct ear canal dimensions, tympanic membrane and middle ear space that can be filled with various fluids to simulate otitis media with effusion. We have embarked on studies to evaluate the construct and predictive validity of the simulator as well as best practices to teach a surgical procedure.

Collaborators: Bradley Kesser, M.D.; Shayn Peirce-Cottler, Ph.D., Department of Biomedical Engineering

Hallman M, Murphy, L, Tillar M, Peirce S, Keeley M, and Kesser BW. Interval vs. massed training: How best do we teach surgery? Otolaryngol Head Neck. 2014;150:61-7.

Morris E, Kesser BW, Peirce-Cottler S, Keeley M. Development and validation of a novel ear simulator to teach pneumatic otoscopy. Simulation in Healthcare. 2012;7(1):22-6.

Volsky PG, Hughley BB, Peirce SM, and Kesser BW. Construct Validity of a Simulator for Myringotomy with Ventilation Tube Placement. Otolaryngol Head Neck Surg. 2009;141(5):603-8

PEDIATRIC COCHLEAR IMPLANTATION

Our nationally known Cochlear Implant Program provides an opportunity to restore hearing for those who have been unable to benefit from hearing aids. Our researchers are examining audiologic performance and quality of life issues in the children we serve. Future research can potentially identify predictive factors of postoperative performance in these children.

Collaborators: George T. Hashisaki, M.D.; Bradley Kesser, MD; Amber Kiser, Ph.D., Lori Grove, Ph.D.; Cynthia Clark, AuD.

SIGMOID SINUS DEHISCENCE, PULSATILE TINNITUS, AND CENTRAL VENOUS OUTFLOW ANATOMY

A subset of patients with pulsatile, pulse synchronous tinnitus (hears their own pulse in one ear) have abnormalities of the central venous outflow tract, the flow of blood from the brain out of the skull and into the jugular venous system. Using computer modeling and 3D printing, we are examining the venous outflow tracts of these patients looking for anatomic correlates that could cause turbulent blood flow and the pulse-synchronous tinnitus. These patients often show dehiscence of bone over the sigmoid sinus, and we are exploring the mechanism by which the bone that insulates the sinus from the ear/mastoid air cell system is lost over the sinus. Finally, the relationship of the anatomic findings, including transverse sinus stenosis, and idiopathic intracranial hypertension may elucidate the anatomic underpinnings of this clinical syndrome.

Collaborators: Bradley Kesser, MD; Haibo Dong, Ph.D., UVA Department of Mechanical and Aerospace Engineering

Schoeff S, Nicholas B, Mukherjee S, and Kesser BW. Imaging prevalence of sigmoid sinus dehiscence among patients with and without pulsatile tinnitus. Otolaryngol Head Neck. 2014;150(5):841-6

CPAP AND MIDDLE EAR AND SKULL BASE SURGERY

Continuous positive airway pressure (CPAP) masks help hundreds of patients with obstructive sleep apnea. What do we otologic surgeons recommend in patients who need CPAP who undergo ear surgery? We have surveyed otologists/neurotologists on current practices and recommendations for patients undergoing middle ear and skull base surgery with regard to use of CPAP after surgery. We have also embarked on a project looking at the utility of CPAP in patients with Eustachian tube dysfunction.

Collaborators: Bradley Kesser, MD; Douglas Ruhl, MD; George Hashisaki, MD

NEUROSCIENCE OF HEARING LOSS – Dr. Jung-Bum Shin

 Research focus I: Discovery of novel proteins involved in hearing and deafness

 Our lab uses a combination of proteomics, protein biochemistry, cell biology and mouse genetics tools to discover novel components involved in the molecular process of hearing. In short, we 1) sequence proteins in the sensory hair cell using mass spectrometry, 2) compare the proteomics data with genetic data to identify possible deafness genes, 3) characterize the function of these proteins, and 4) use the CRISPR/Cas9 system to generate transgenic mouse models to evaluate the role of these putative deafness genes in vivo. Presently, we are applying this workflow on 10 different potential deafness genes.

Research focus II: Neurodegeneration and protection of sensory hair cells

Aminoglycosides comprise a highly potent class of antibiotics, but their clinical use is limited due to nephrotoxicity and ototoxicity. Despite longstanding research efforts, our understanding of the mechanisms underlying aminoglycoside ototoxicity remains limited, and methods for clinical intervention have yet to emerge. We have recently found that the regulation of protein homeostasis in hair cells is severely affected by aminoglycosides. Protein homeostasis is at the center of general cellular homeostasis, and its dysregulation can activate various stress pathways leading to cellular degeneration and death. We are currently exploring the involvement of novel stress pathways in aminoglycoside-induced hair cell degeneration, with special emphasis on the discovery of novel drugs to prevent hair cell degeneration by blocking stress pathways.

Research focus III: CRISPR/Cas-mediated gene therapy of deafness mutations

Gene therapy to repair deafness mutations is a highly relevant goal in deafness research. In a remarkably short time period, the CRISPR/Cas9 system has emerged as arguably the most efficient genome engineering tool to date. The goal of this project is to engineer a novel, modified CRISPR system that allows packaging in an adeno-associated vector, which presently is the only system for in vivo delivery of genetic material into adult sensory hair cells. This tool will be used to repair deafness mutations in a mouse model.