{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:23:01Z","timestamp":1790360581696,"version":"4.1.0"},"reference-count":22,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T00:00:00Z","timestamp":1607644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Senju","award":["contract # GSODO0069A from Senju Pharmaceutical Co. to TRS"],"award-info":[{"award-number":["contract # GSODO0069A from Senju Pharmaceutical Co. to TRS"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Translational relevance<\/jats:title>\n                    <jats:p>Measurement of GCL thickness would be a useful indicator of CRAO progression in a clinical trial of putative inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0242920","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T13:51:19Z","timestamp":1607694679000},"page":"e0242920","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Segmenting OCT for detecting drug efficacy in CRAO"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-0878","authenticated-orcid":true,"given":"Thomas R.","family":"Shearer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter N.","family":"Steinkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyoshi","family":"Azuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,11]]},"reference":[{"key":"pone.0242920.ref001","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/eye.2013.25","article-title":"A review of central retinal artery occlusion: clinical presentation and Management","volume":"27","author":"DD Varma","year":"2013","journal-title":"Eye (Lond)"},{"key":"pone.0242920.ref002","unstructured":"Farris W, Waymack JR. Central Retinal Artery. Updated 2019. Occlusion. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470354\/"},{"key":"pone.0242920.ref003","unstructured":"Sim S and Daniel SW. Diagnosis and Management of Central Retinal Artery Occlusion. https:\/\/www.aao.org\/Assets\/d2945409-c547-4f1d\u2026\/august-2017-ophthalmic-pearls-pdfw"},{"issue":"Issue 1","key":"pone.0242920.ref004","article-title":"Interventions for acute non-arteritic central retinal artery occlusion","author":"SG Fraser","year":"2009","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"pone.0242920.ref005","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ajo.2005.03.038","article-title":"Central retinal artery occlusion: visual outcome","volume":"140","author":"SS Hayreh","year":"2005","journal-title":"Am J Ophthalmol"},{"key":"pone.0242920.ref006","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1167\/iovs.15-17360","article-title":"Hypoxia activates calpains in the nerve fiber layer of monkey retinal explants","volume":"56","author":"M Hirata","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0242920.ref007","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1152\/physrev.00029.2002","article-title":"Calpain system","volume":"83","author":"DE Goll","year":"2003","journal-title":"Physiol Rev"},{"key":"pone.0242920.ref008","unstructured":"www.HeidelbergEngineering.com"},{"key":"pone.0242920.ref009","unstructured":"Zar, JH Biostatistical Analysis. 5th ed., Prentice Hall:1974, pp147-9. Using: https:\/\/www.ai-therapy.com\/psychology-statistics\/sample-size-calculator."},{"key":"pone.0242920.ref010","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.oret.2017.12.012","article-title":"Normative data for retinal-layer thickness maps generated by spectral-domain OCT in a white population","volume":"2","author":"A Invernizzi","year":"2018","journal-title":"Ophthalmol Retina"},{"key":"pone.0242920.ref011","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1167\/tvst.7.1.20","article-title":"New normative database of inner macular layer thickness measured by Spectralis OCT used as reference standard for glaucoma detection","volume":"7","author":"M Nieves-Moreno","year":"2018","journal-title":"Trans Vis Sci Tech"},{"key":"pone.0242920.ref012","doi-asserted-by":"crossref","first-page":"9269","DOI":"10.1038\/srep09269","article-title":"Quantitative analysis of retinal layers' optical intensities on 3D optical coherence tomography for central retinal artery occlusion","volume":"5","author":"H Chen","year":"2015","journal-title":"Sci Rep"},{"key":"pone.0242920.ref013","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1167\/iovs.13-13769","article-title":"Change of retinal nerve fiber layer thickness in various retinal diseases treated with multiple intravitreal antivascular endothelial growth factor","volume":"55","author":"HJ Shin","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"pone.0242920.ref014","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10384-010-0841-x","article-title":"Inner neural retina loss in central retinal artery occlusion","volume":"54","author":"F Ikeda","year":"2010","journal-title":"Jpn J Ophthalmol"},{"key":"pone.0242920.ref015","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ajo.2015.01.001","article-title":"Retinal and choroidal changes and visual outcome in central retinal artery occlusion: an optical coherence tomography 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