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      Anterior and posterior ratio of corneal surface areas: A novel index for detecting early stage keratoconus

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          Abstract

          Purpose

          To evaluate the diagnostic ability of the ratio of anterior and posterior corneal surface areas (As/Ps) comparing with other keratoconus screening indices in distinguishing forme fruste keratoconus (FFKC) from normal eyes.

          Methods

          In this comparative study, 13 eyes of 13 patients with FFKC, 29 eyes of 29 patients with keratoconus (KC) and 88 eyes of 88 patients with normal subjects were involved.

          The As/Ps measured by the anterior segment optical coherence tomography (AS-OCT) and other indices measured by AS-OCT and rotating Scheimpflug–based corneal tomography were evaluated. The area under receiver-operating-characteristics (AU-ROC) was calculated to assess the diagnostic ability in discriminating FFKC from normal eyes.

          Results

          The As/Ps, the Belin/Ambrosio display enhanced ectasia total derivation value (BAD-D) and posterior and anterior elevation values showed the AU-ROC 0.9 or more in differentiating FFKC from normal eyes (0.980, 0.951, 0.924 and 0.903, respectively). The sensitivity and specificity were 0.92 and 0.96 for the As/Ps, 1.00 and 0.90 for BAD-D, 0.85 and 0.86 for posterior elevation value, and 0.85 and 0.96 for anterior elevation value, respectively.

          Conclusions

          Among the several indices for keratoconus screening which we evaluated, the As/Ps obtained by AS-OCT had the large AU-ROC with high sensitivity and specificity in detecting FFKC, which was comparable with BAD-D obtained by rotating Scheimpflug–based corneal tomography. The As/Ps may provide information for improving the diagnostic accuracy of KC, even in the initial stage of the disease.

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          Most cited references19

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          Global consensus on keratoconus and ectatic diseases.

          Despite extensive knowledge regarding the diagnosis and management of keratoconus and ectatic corneal diseases, many controversies still exist. For that reason, there is a need for current guidelines for the diagnosis and management of these conditions. This project aimed to reach consensus of ophthalmology experts from around the world regarding keratoconus and ectatic diseases, focusing on their definition, concepts, clinical management, and surgical treatments. The Delphi method was followed with 3 questionnaire rounds and was complemented with a face-to-face meeting. Thirty-six panelists were involved and allocated to 1 of 3 panels: definition/diagnosis, nonsurgical management, or surgical treatment. The level of agreement considered for consensus was two thirds. Numerous agreements were generated in definitions, methods of diagnosing, and management of keratoconus and other ectatic diseases. Nonsurgical and surgical treatments for these conditions, including the use of corneal cross-linking and corneal transplantations, were presented in a stepwise approach. A flowchart describing a logical management sequence for keratoconus was created. This project resulted in definitions, statements, and recommendations for the diagnosis and management of keratoconus and other ectatic diseases. It also provides an insight into the current worldwide treatment of these conditions.
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            On determining the most appropriate test cut-off value: the case of tests with continuous results

            There are several criteria for determination of the most appropriate cut-off value in a diagnostic test with continuous results. Mostly based on receiver operating characteristic (ROC) analysis, there are various methods to determine the test cut-off value. The most common criteria are the point on ROC curve where the sensitivity and specificity of the test are equal; the point on the curve with minimum distance from the left-upper corner of the unit square; and the point where the Youden’s index is maximum. There are also methods mainly based on Bayesian decision analysis. Herein, we show that a proposed method that maximizes the weighted number needed to misdiagnose, an index of diagnostic test effectiveness we previously proposed, is the most appropriate technique compared to the aforementioned ones. For determination of the cut-off value, we need to know the pretest probability of the disease of interest as well as the costs incurred by misdiagnosis. This means that even for a certain diagnostic test, the cut-off value is not universal and should be determined for each region and for each disease condition.
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              Use of a support vector machine for keratoconus and subclinical keratoconus detection by topographic and tomographic data.

              To define a new classification method for the diagnosis of keratoconus based on corneal measurements provided by a Scheimpflug camera combined with Placido corneal topography (Sirius, CSO, Florence, Italy).
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: Resources
                Role: Resources
                Role: Resources
                Role: ResourcesRole: Supervision
                Role: ResourcesRole: Supervision
                Role: MethodologyRole: ResourcesRole: Supervision
                Role: Resources
                Role: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 April 2020
                2020
                : 15
                : 4
                : e0231074
                Affiliations
                [1 ] Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
                [2 ] Department of Ophthalmology, Baptist Eye Institute, Kyoto, Japan
                [3 ] Department of Biostatistics, Kyoto Prefectural University of Medicine, Kyoto, Japan
                [4 ] Department of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
                Singapore Eye Research Institute, SINGAPORE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-2203-5776
                Article
                PONE-D-19-34557
                10.1371/journal.pone.0231074
                7117727
                32240243
                ff28ed1d-23fe-4ade-86e0-16bcca7207ea
                © 2020 Itoi et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 December 2019
                : 15 March 2020
                Page count
                Figures: 3, Tables: 2, Pages: 12
                Funding
                Funded by: Grant-in-Aid for Young Scientists B
                Award ID: 18K16930
                Award Recipient :
                Koji Kitazawa received Grant-in-Aid for Young Scientists B for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Biology and Life Sciences
                Anatomy
                Head
                Eyes
                Medicine and Health Sciences
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                Ophthalmology
                Eye Diseases
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                Anatomy
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                Medicine and Health Sciences
                Anatomy
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                Diagnostic Medicine
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