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Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model

INTRODUCTION: To establish the preclinical safety and equivalency of ophthalmic viscosurgical devices (OVDs) comprised of bacterially sourced sodium hyaluronate (HA) to animal sourced HA using pyrogenicity and aqueous exchange models in rabbits and a novel mini-pig model to evaluate corneal endothel...

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Autores principales: Leang, Ronika S., Kloft, Lisa J., Gray, Brad, Gwon, Arlene E., Huang, Ling C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393256/
https://www.ncbi.nlm.nih.gov/pubmed/30778776
http://dx.doi.org/10.1007/s40123-019-0167-9
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author Leang, Ronika S.
Kloft, Lisa J.
Gray, Brad
Gwon, Arlene E.
Huang, Ling C.
author_facet Leang, Ronika S.
Kloft, Lisa J.
Gray, Brad
Gwon, Arlene E.
Huang, Ling C.
author_sort Leang, Ronika S.
collection PubMed
description INTRODUCTION: To establish the preclinical safety and equivalency of ophthalmic viscosurgical devices (OVDs) comprised of bacterially sourced sodium hyaluronate (HA) to animal sourced HA using pyrogenicity and aqueous exchange models in rabbits and a novel mini-pig model to evaluate corneal endothelial cell protection in vivo. METHODS: HEALON OVD and HEALON5 OVD containing animal-derived HA and HEALON PRO OVD and HEALON5 PRO OVD containing bacterial-derived HA were used. Two rabbit aqueous exchange studies were conducted where aqueous humor was exchanged with OVDs in six animals each to observe potential ocular inflammation, intraocular pressure (IOP) response, corneal health and pachymetry until 7 days post procedure, as well as overall assessment of the OVDs. Endothelial cell protection was evaluated in a Yucatan mini-pig cataract surgery model where HEALON PRO and HEALON5 PRO OVDs were compared to HEALON and HEALON5 OVDs, respectively. Following cataract surgery with use of OVDs in six animals per study, animals were evaluated for ocular and general health, IOP, corneal thickness, ocular inflammation, and endothelial cell protection on days 1, 3, 7 and 14 post-surgery. RESULTS: All rabbit studies demonstrated equivalence between bacterial-derived and animal-derived OVDs. Mild, post-surgical irritation, IOP increase, and corneal thickness measurements were not significantly different in HEALON PRO OVD and HEALON5 PRO OVD compared to HEALON and HEALON5 OVDs, respectively. The mini-pig model developed to investigate endothelial cell protection was successful in demonstrating equivalence between the OVDs studied. Changes in IOP mirrored actual surgical procedures, while corneal pachymetry and endothelial cell density remained constant for all OVDs used. Slit lamp observations showed expected inflammation following surgical procedures, likely due to challenges encountered during surgical procedures. CONCLUSION: Rabbit pyrogenicity and aqueous exchanged paired with a novel simulated cataract surgery mini-pig model demonstrate equivalence of OVDs regardless of HA source. Albeit with challenges, the mini-pig model was shown to be a promising tool for endothelial cell evaluation during the development of new OVDs for ophthalmic use. FUNDING: Johnson & Johnson Surgical Vision, Inc.
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spelling pubmed-63932562019-03-15 Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model Leang, Ronika S. Kloft, Lisa J. Gray, Brad Gwon, Arlene E. Huang, Ling C. Ophthalmol Ther Original Research INTRODUCTION: To establish the preclinical safety and equivalency of ophthalmic viscosurgical devices (OVDs) comprised of bacterially sourced sodium hyaluronate (HA) to animal sourced HA using pyrogenicity and aqueous exchange models in rabbits and a novel mini-pig model to evaluate corneal endothelial cell protection in vivo. METHODS: HEALON OVD and HEALON5 OVD containing animal-derived HA and HEALON PRO OVD and HEALON5 PRO OVD containing bacterial-derived HA were used. Two rabbit aqueous exchange studies were conducted where aqueous humor was exchanged with OVDs in six animals each to observe potential ocular inflammation, intraocular pressure (IOP) response, corneal health and pachymetry until 7 days post procedure, as well as overall assessment of the OVDs. Endothelial cell protection was evaluated in a Yucatan mini-pig cataract surgery model where HEALON PRO and HEALON5 PRO OVDs were compared to HEALON and HEALON5 OVDs, respectively. Following cataract surgery with use of OVDs in six animals per study, animals were evaluated for ocular and general health, IOP, corneal thickness, ocular inflammation, and endothelial cell protection on days 1, 3, 7 and 14 post-surgery. RESULTS: All rabbit studies demonstrated equivalence between bacterial-derived and animal-derived OVDs. Mild, post-surgical irritation, IOP increase, and corneal thickness measurements were not significantly different in HEALON PRO OVD and HEALON5 PRO OVD compared to HEALON and HEALON5 OVDs, respectively. The mini-pig model developed to investigate endothelial cell protection was successful in demonstrating equivalence between the OVDs studied. Changes in IOP mirrored actual surgical procedures, while corneal pachymetry and endothelial cell density remained constant for all OVDs used. Slit lamp observations showed expected inflammation following surgical procedures, likely due to challenges encountered during surgical procedures. CONCLUSION: Rabbit pyrogenicity and aqueous exchanged paired with a novel simulated cataract surgery mini-pig model demonstrate equivalence of OVDs regardless of HA source. Albeit with challenges, the mini-pig model was shown to be a promising tool for endothelial cell evaluation during the development of new OVDs for ophthalmic use. FUNDING: Johnson & Johnson Surgical Vision, Inc. Springer Healthcare 2019-02-18 2019-03 /pmc/articles/PMC6393256/ /pubmed/30778776 http://dx.doi.org/10.1007/s40123-019-0167-9 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Leang, Ronika S.
Kloft, Lisa J.
Gray, Brad
Gwon, Arlene E.
Huang, Ling C.
Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model
title Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model
title_full Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model
title_fullStr Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model
title_full_unstemmed Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model
title_short Preclinical Safety Evaluation of Ophthalmic Viscosurgical Devices in Rabbits and a Novel Mini-Pig Model
title_sort preclinical safety evaluation of ophthalmic viscosurgical devices in rabbits and a novel mini-pig model
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393256/
https://www.ncbi.nlm.nih.gov/pubmed/30778776
http://dx.doi.org/10.1007/s40123-019-0167-9
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