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Segmenting OCT for detecting drug efficacy in CRAO

PURPOSE: Thinning of the inner layers of the retina occurs in patients with central retinal artery occlusion (CRAO). The mechanism for such thinning may be partially due to proteolysis by a calcium-activated protease called calpain. Calpain inhibitor SNJ-1945 ameliorated the proteolysis in a past se...

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Autores principales: Shearer, Thomas R., Hwang, Thomas S., Steinkamp, Peter N., Azuma, Mitsuyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732080/
https://www.ncbi.nlm.nih.gov/pubmed/33306701
http://dx.doi.org/10.1371/journal.pone.0242920
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author Shearer, Thomas R.
Hwang, Thomas S.
Steinkamp, Peter N.
Azuma, Mitsuyoshi
author_facet Shearer, Thomas R.
Hwang, Thomas S.
Steinkamp, Peter N.
Azuma, Mitsuyoshi
author_sort Shearer, Thomas R.
collection PubMed
description PURPOSE: Thinning of the inner layers of the retina occurs in patients with central retinal artery occlusion (CRAO). The mechanism for such thinning may be partially due to proteolysis by a calcium-activated protease called calpain. Calpain inhibitor SNJ-1945 ameliorated the proteolysis in a past series of model experiments. The purposes of the present retrospective study were to: 1) use segmentation analysis of optical coherence tomography (OCT) images to mathematically model the loss of specific retinal layers in CRAO patients, and 2) predict the number of patients and days of observation needed for clinical trials of inhibitors against CRAO. METHODS: A retrospective case control study was conducted by computer-aided search for CRAO (ICD10 H43.1) with at least one OCT procedure (CPT: 92134) in the OHSU Epic patient data base. RESULTS: After initial swelling, thinning of the inner retinal layers, especially the ganglion cell (GCL) layer followed exponential decay curves. Using sample size statistics and GCL thickness as a marker in a 30-day clinical trial, 19 eyes/group could theoretically detect a 20% beneficial effect of an inhibitor against CRAO. Other markers, such as the whole retinal thickness and combined inner layers could also be used as less-specific markers. CONCLUSIONS: Using thickness changes in the GCL layer to monitor the efficacy of potential inhibitors against CRAO is practical in human trials requiring a reasonable number of patients and relatively short trial period. TRANSLATIONAL RELEVANCE: Measurement of GCL thickness would be a useful indicator of CRAO progression in a clinical trial of putative inhibitors.
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spelling pubmed-77320802020-12-17 Segmenting OCT for detecting drug efficacy in CRAO Shearer, Thomas R. Hwang, Thomas S. Steinkamp, Peter N. Azuma, Mitsuyoshi PLoS One Research Article PURPOSE: Thinning of the inner layers of the retina occurs in patients with central retinal artery occlusion (CRAO). The mechanism for such thinning may be partially due to proteolysis by a calcium-activated protease called calpain. Calpain inhibitor SNJ-1945 ameliorated the proteolysis in a past series of model experiments. The purposes of the present retrospective study were to: 1) use segmentation analysis of optical coherence tomography (OCT) images to mathematically model the loss of specific retinal layers in CRAO patients, and 2) predict the number of patients and days of observation needed for clinical trials of inhibitors against CRAO. METHODS: A retrospective case control study was conducted by computer-aided search for CRAO (ICD10 H43.1) with at least one OCT procedure (CPT: 92134) in the OHSU Epic patient data base. RESULTS: After initial swelling, thinning of the inner retinal layers, especially the ganglion cell (GCL) layer followed exponential decay curves. Using sample size statistics and GCL thickness as a marker in a 30-day clinical trial, 19 eyes/group could theoretically detect a 20% beneficial effect of an inhibitor against CRAO. Other markers, such as the whole retinal thickness and combined inner layers could also be used as less-specific markers. CONCLUSIONS: Using thickness changes in the GCL layer to monitor the efficacy of potential inhibitors against CRAO is practical in human trials requiring a reasonable number of patients and relatively short trial period. TRANSLATIONAL RELEVANCE: Measurement of GCL thickness would be a useful indicator of CRAO progression in a clinical trial of putative inhibitors. Public Library of Science 2020-12-11 /pmc/articles/PMC7732080/ /pubmed/33306701 http://dx.doi.org/10.1371/journal.pone.0242920 Text en © 2020 Shearer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shearer, Thomas R.
Hwang, Thomas S.
Steinkamp, Peter N.
Azuma, Mitsuyoshi
Segmenting OCT for detecting drug efficacy in CRAO
title Segmenting OCT for detecting drug efficacy in CRAO
title_full Segmenting OCT for detecting drug efficacy in CRAO
title_fullStr Segmenting OCT for detecting drug efficacy in CRAO
title_full_unstemmed Segmenting OCT for detecting drug efficacy in CRAO
title_short Segmenting OCT for detecting drug efficacy in CRAO
title_sort segmenting oct for detecting drug efficacy in crao
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732080/
https://www.ncbi.nlm.nih.gov/pubmed/33306701
http://dx.doi.org/10.1371/journal.pone.0242920
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