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A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery

INTRODUCTION: Tumor necrosis factor-α (TNF-α) is a multifunctional, proinflammatory cytokine that mediates pleiotropic biological functions, especially inflammation and immunoregulation. We hypothesized that blocking TNF-α with a monoclonal antibody would decrease inflammation and subconjunctival sc...

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Autores principales: Nikita, Eleni, Moulin, Alexandre, Vergados, Ioannis, Brouzas, Dimitrios, Theodossiadis, Panagiotis G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693834/
https://www.ncbi.nlm.nih.gov/pubmed/28669026
http://dx.doi.org/10.1007/s40123-017-0096-4
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author Nikita, Eleni
Moulin, Alexandre
Vergados, Ioannis
Brouzas, Dimitrios
Theodossiadis, Panagiotis G.
author_facet Nikita, Eleni
Moulin, Alexandre
Vergados, Ioannis
Brouzas, Dimitrios
Theodossiadis, Panagiotis G.
author_sort Nikita, Eleni
collection PubMed
description INTRODUCTION: Tumor necrosis factor-α (TNF-α) is a multifunctional, proinflammatory cytokine that mediates pleiotropic biological functions, especially inflammation and immunoregulation. We hypothesized that blocking TNF-α with a monoclonal antibody would decrease inflammation and subconjunctival scarring in an animal model of experimental filtration surgery. METHODS: In a randomized, prospective, masked-observer study, 30 New Zealand albino rabbits underwent glaucoma filtration surgery. The animals were allocated to receive either intraoperative application of infliximab (group A) or mitomycin C (MMC) at a concentration of 0.2 mg/ml (group B) or balanced salt solution (BSS, control) (group C). Different infliximab doses, namely 1.0, 2.0, 3.0, 4.0, 5.0 mg in 0.1 ml, were applied. Bleb survival and characteristics were evaluated over a 30-day period. The animals were killed on postoperative day 15 or 30. Histology of the operated eyes was performed to evaluate and grade the amount of scarring in each group. Cellular density was evaluated in each case. RESULTS: Infliximab did not appear to improve outcomes in this model of glaucoma filtration surgery. Bleb survival was significantly higher in the MMC group compared to the other groups (p < 0.001 for both comparisons). Vascularity was also significantly lower in the MMC group compared to the other groups (p = 0.018 for both comparisons). There was a significant decrease in cellular density in the MMC group compared to the control (p = 0.0352) and the infliximab group (p < 001). CONCLUSION: Our results have shown that trabeculectomies in the infliximab group failed faster and displayed more scarring, compared to the control and MMC groups. This outcome suggests that the infliximab doses used in this pilot study resulted in a subconjunctival TNF-α concentration, which acted as a stimulator to fibroblasts.
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spelling pubmed-56938342017-11-29 A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery Nikita, Eleni Moulin, Alexandre Vergados, Ioannis Brouzas, Dimitrios Theodossiadis, Panagiotis G. Ophthalmol Ther Original Research INTRODUCTION: Tumor necrosis factor-α (TNF-α) is a multifunctional, proinflammatory cytokine that mediates pleiotropic biological functions, especially inflammation and immunoregulation. We hypothesized that blocking TNF-α with a monoclonal antibody would decrease inflammation and subconjunctival scarring in an animal model of experimental filtration surgery. METHODS: In a randomized, prospective, masked-observer study, 30 New Zealand albino rabbits underwent glaucoma filtration surgery. The animals were allocated to receive either intraoperative application of infliximab (group A) or mitomycin C (MMC) at a concentration of 0.2 mg/ml (group B) or balanced salt solution (BSS, control) (group C). Different infliximab doses, namely 1.0, 2.0, 3.0, 4.0, 5.0 mg in 0.1 ml, were applied. Bleb survival and characteristics were evaluated over a 30-day period. The animals were killed on postoperative day 15 or 30. Histology of the operated eyes was performed to evaluate and grade the amount of scarring in each group. Cellular density was evaluated in each case. RESULTS: Infliximab did not appear to improve outcomes in this model of glaucoma filtration surgery. Bleb survival was significantly higher in the MMC group compared to the other groups (p < 0.001 for both comparisons). Vascularity was also significantly lower in the MMC group compared to the other groups (p = 0.018 for both comparisons). There was a significant decrease in cellular density in the MMC group compared to the control (p = 0.0352) and the infliximab group (p < 001). CONCLUSION: Our results have shown that trabeculectomies in the infliximab group failed faster and displayed more scarring, compared to the control and MMC groups. This outcome suggests that the infliximab doses used in this pilot study resulted in a subconjunctival TNF-α concentration, which acted as a stimulator to fibroblasts. Springer Healthcare 2017-07-01 2017-12 /pmc/articles/PMC5693834/ /pubmed/28669026 http://dx.doi.org/10.1007/s40123-017-0096-4 Text en © The Author(s) 2017 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
Nikita, Eleni
Moulin, Alexandre
Vergados, Ioannis
Brouzas, Dimitrios
Theodossiadis, Panagiotis G.
A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery
title A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery
title_full A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery
title_fullStr A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery
title_full_unstemmed A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery
title_short A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery
title_sort pilot study on ocular safety and efficacy of infliximab as an antifibrotic agent after experimental glaucoma filtration surgery
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693834/
https://www.ncbi.nlm.nih.gov/pubmed/28669026
http://dx.doi.org/10.1007/s40123-017-0096-4
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