Ya Liu1, Claude Jolly2, Susanne Braun3, Thomas Janssen4, Elias Scherer4, Jochen Steinhoff4, Harald Ebenhoch4, Andrea Lohner4, Thomas Stark4, Jan Kiefer5. 1. Department of Otolaryngology-Head and Neck Surgery, Beijing Naval General Hospital, Beijing 100048, PR China. 2. Electrode Research Section, MED-EL Medical Electronics, Innsbruck, Austria. 3. MED-EL Deutschland GmbH, Starnberg, Germany. 4. Clinic for Otorhinolaryngology, Head- and Neck Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 5. HNO-Zentrum Neupfarrplatz, 12/II, 93047 Regensburg, Germany. Electronic address: Jn.Kiefer@googlemail.com.
Abstract
AIM: This study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation. METHODS: Guinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann-Whitney U test (1-tailed) was used for statistical analyses. RESULTS: ABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4-24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively. CONCLUSION: Cochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.
AIM: This study evaluated the impact of a dexamethasone-releasing silicone implant on hearing function preservation, cochlear morphology and perilymph pharmacokinetics after cochlear implantation. METHODS:Guinea pigs were implanted unilaterally with silicone rods containing either 2% dexamethasone (DEXA group, n = 18) or no dexamethasone (control group, n = 17). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were measured preoperatively and over 6 months postoperatively. Cochlear histology using standard hematoxylin and eosin (H&E) staining and tumor necrosis factor (TNF)-alpha staining was performed 1 month postoperatively. Twenty-two guinea pigs were involved in the pharmacokinetic study, and real-time drug concentrations in perilymph were investigated using high-performance liquid chromatography (HPLC). The Mann-Whitney U test (1-tailed) was used for statistical analyses. RESULTS: ABR and DPOAE testing demonstrated decreased hearing function immediately postoperatively followed by a progressive hearing loss within the first day postoperatively. There was almost no observable hearing improvement in the control group from 1 week to 6 months postoperatively, but hearing levels in the DEXA group improved gradually from 1 week to 12 weeks. Hearing loss in the DEXA and control group was 5.0 ± 3.4 dB and 21.7 ± 5.3 dB, respectively at a 16-kHz stimulus frequency 6 months postoperatively. The difference in threshold shifts was present throughout all measured frequencies, and it was significant at 4-24 kHz. The morphological study revealed new fibrosis formation in the scala tympani, which encapsulated the implanted electrode. TNF-alpha positive staining in the cochleae of the DEXA group was less evident than the control group. The pharmacokinetic study revealed a peak perilymph concentration 30 min postoperatively and sustained dexamethasone release at least 1 week postoperatively. CONCLUSION: Cochlear implants that incorporate dexamethasone can release drug chronically in the inner ear and induce significant long-term recovery and preservation of auditory function after implantation.
Authors: Ya Liu; Claude Jolly; Susanne Braun; Thomas Stark; Elias Scherer; Stefan K Plontke; Jan Kiefer Journal: Eur Arch Otorhinolaryngol Date: 2015-08-29 Impact factor: 2.503
Authors: Verena Scheper; Roland Hessler; Mareike Hütten; Maciej Wilk; Claude Jolly; Thomas Lenarz; Gerrit Paasche Journal: PLoS One Date: 2017-08-31 Impact factor: 3.240