title: Development of a safe dexamethasone-eluting electrode array for cochlear implantation.
abstract: OBJECTIVE
  Cochlear implantation can result in trauma leading to increased tissue response and loss of residual hearing. A single intratympanic application of the corticosteroid dexamethasone is sometimes used clinically during surgery to combat the potential effect of trauma on residual hearing. This project looked at the safety and efficacy of dexamethasone eluted from an intracochlear array in vivo.
  
  
  METHODS
  Three trials were conducted using normal hearing adult guinea pigs implanted with successive iterations of dexamethasone-eluting (DX1, DX2, and DX3) or non-eluting (control) intracochlear electrode arrays. The experimental period for each animal was 90 days during which hearing tests were performed at multiple time points.
  
  
  RESULTS
  There was no significant difference between matched control array and dexamethasone array groups in terms of spiral ganglion neuron density, organ of Corti condition, or fibrosis and ossification. A cochleostomy seal was present in all implanted cochleae. There were no differences in the degree of hearing threshold shifts between DX1 and DX3 and their respective control arrays. Cochleae implanted with DX2 arrays showed less hearing loss and marginally better spiral ganglion neuron survival than their control array counterparts. Post-explant inspection of the DX2 and DX3 arrays revealed a difference in pore density following dexamethasone elution.
  
  
  CONCLUSIONS
  The dexamethasone doses used were safe in the guinea pig cochlea. Dexamethasone did not inhibit formation of a cochleostomy seal. The level of hearing protection afforded by dexamethasone eluting from an intracochlear array may depend upon the degree of elution and level of trauma inflicted.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Stathopoulos
authors.forename: Scott
authors.initials: S
authors.lastname: Chambers
authors.forename: Ya Lang
authors.initials: YL
authors.lastname: Enke
authors.forename: Godofredo
authors.initials: G
authors.lastname: Timbol
authors.forename: Frank
authors.initials: F
authors.lastname: Risi
authors.forename: Christopher
authors.initials: C
authors.lastname: Miller
authors.forename: Robert
authors.initials: R
authors.lastname: Cowan
authors.forename: Carrie
authors.initials: C
authors.lastname: Newbold
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001309:Auditory Threshold; D019929:Cochlear Implantation / Q000009:adverse effects*; D003054:Cochlear Implants; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004867:Equipment Design; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D034381:Hearing Loss / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009925:Organ of Corti / Q000473:pathology; D013136:Spiral Ganglion / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D003907:Dexamethasone
keywords: Cochlear implantation; Corticosteroid; Dexamethasone; Drug delivery; Guinea pig; Hearing loss