Development and Evaluation of a Computable Phenotype for Normal Tension Glaucoma

Purpose: To develop a computable phenotype for normal tension glaucoma (NTG) to enhance disease identification from electronic health records (EHRs). Design: Retrospective cohort study. Subjects: Deidentified EHR data from an academic medical center identified 1851 patients aged ≥40 years, with glau...

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Main Authors: Fountane Chan, MD, Wei-Chun Lin, MD, PhD, Alan Tang, Benjamin Y. Xu, MD, PhD, Sophia Y. Wang, MD, MS, Michael V. Boland, MD, PhD, Catherine Q. Sun, MD, Sally Baxter, MD, MSc, Brian Stagg, MD, MS, Michelle Hribar, PhD, Aiyin Chen, MD
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Language:English
Published: Elsevier 2025-11-01
Series:Ophthalmology Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666914525001563
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author Fountane Chan, MD
Wei-Chun Lin, MD, PhD
Alan Tang
Benjamin Y. Xu, MD, PhD
Sophia Y. Wang, MD, MS
Michael V. Boland, MD, PhD
Catherine Q. Sun, MD
Sally Baxter, MD, MSc
Brian Stagg, MD, MS
Michelle Hribar, PhD
Aiyin Chen, MD
author_facet Fountane Chan, MD
Wei-Chun Lin, MD, PhD
Alan Tang
Benjamin Y. Xu, MD, PhD
Sophia Y. Wang, MD, MS
Michael V. Boland, MD, PhD
Catherine Q. Sun, MD
Sally Baxter, MD, MSc
Brian Stagg, MD, MS
Michelle Hribar, PhD
Aiyin Chen, MD
author_sort Fountane Chan, MD
collection DOAJ
description Purpose: To develop a computable phenotype for normal tension glaucoma (NTG) to enhance disease identification from electronic health records (EHRs). Design: Retrospective cohort study. Subjects: Deidentified EHR data from an academic medical center identified 1851 patients aged ≥40 years, with glaucoma and available clinical notes. Methods: Of these 1851 patients, 200 were randomly selected for a chart review to receive gold standard diagnoses. Four rule-based NTG computable phenotypes were developed and tested. Phenotype 1 relied on NTG International Classification of Diseases (ICD)-9 and ICD-10 codes. Phenotype 2 incorporated structured intraocular pressure (IOP) data and medication lists. Phenotype 3 used only structured IOP data. Phenotype 4 combined structured IOP and medication data natural language processing (NLP) to extract IOP values and NTG mentions from chart notes. Internal and external validation were performed. Main Outcome Measures: F1 score, sensitivities, specificities, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Results: Chart review identified NTG in 30% of patients, and only 7% had NTG ICD codes. Phenotype 1 had an F1 of 36.8%, sensitivity 24.1%, specificity 97%, PPV 77.8%, NPV 74.9%, and accuracy 75.1%. Compared with ICD codes, phenotypes 2 and 3 had F1 of 66.7% and 69.8%, sensitivity 77.6% and 89.7%, specificity 76.3% and 71.1%, PPV 58.4% and 57.1%, NPV 88.8% and 94.1%, and accuracy of 76.7% and 76.7%, respectively. Incorporating NLP, phenotype 4 had the best performance with an F1 of 77.4%, sensitivity 82.8%, specificity 86.7%, PPV 72.7%, NPV 92.1%, and accuracy 85.5%. Phenotypes 2 to 4 increase NTG case detection fourfold compared with phenotype 1. Conclusions: Normal tension glaucoma phenotypes using NLP achieved the best overall performance, and those incorporating structured data perform better than ICD codes alone. The NTG ICD code-based phenotype is highly specific but lacks sensitivity. Insights from this study may inform the development of computable phenotypes for other disease subtypes within broader disease categories. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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spelling doaj-art-cdaace00bb0b4238a23828502d4fc5e32025-08-20T03:25:49ZengElsevierOphthalmology Science2666-91452025-11-015610085810.1016/j.xops.2025.100858Development and Evaluation of a Computable Phenotype for Normal Tension GlaucomaFountane Chan, MD0Wei-Chun Lin, MD, PhD1Alan Tang2Benjamin Y. Xu, MD, PhD3Sophia Y. Wang, MD, MS4Michael V. Boland, MD, PhD5Catherine Q. Sun, MD6Sally Baxter, MD, MSc7Brian Stagg, MD, MS8Michelle Hribar, PhD9Aiyin Chen, MD10Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, OregonCasey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, OregonRoski Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CaliforniaRoski Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CaliforniaByers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, CaliforniaDepartment of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, MassachusettsDepartment of Ophthalmology, University of California San Francisco, San Francisco, California; F.I. Proctor Foundation, University of California San Francisco, San Francisco, CaliforniaFrom the Viterbi Family Department of Ophthalmology, Division of Ophthalmology Informatics and Data Science, Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, CaliforniaMoran Eye Center, University of Utah, Salt Lake, UtahCasey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, OregonCasey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon; Correspondence: Aiyin Chen, MD, 515 SW Campus Drive, Portland, OR 97239.Purpose: To develop a computable phenotype for normal tension glaucoma (NTG) to enhance disease identification from electronic health records (EHRs). Design: Retrospective cohort study. Subjects: Deidentified EHR data from an academic medical center identified 1851 patients aged ≥40 years, with glaucoma and available clinical notes. Methods: Of these 1851 patients, 200 were randomly selected for a chart review to receive gold standard diagnoses. Four rule-based NTG computable phenotypes were developed and tested. Phenotype 1 relied on NTG International Classification of Diseases (ICD)-9 and ICD-10 codes. Phenotype 2 incorporated structured intraocular pressure (IOP) data and medication lists. Phenotype 3 used only structured IOP data. Phenotype 4 combined structured IOP and medication data natural language processing (NLP) to extract IOP values and NTG mentions from chart notes. Internal and external validation were performed. Main Outcome Measures: F1 score, sensitivities, specificities, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Results: Chart review identified NTG in 30% of patients, and only 7% had NTG ICD codes. Phenotype 1 had an F1 of 36.8%, sensitivity 24.1%, specificity 97%, PPV 77.8%, NPV 74.9%, and accuracy 75.1%. Compared with ICD codes, phenotypes 2 and 3 had F1 of 66.7% and 69.8%, sensitivity 77.6% and 89.7%, specificity 76.3% and 71.1%, PPV 58.4% and 57.1%, NPV 88.8% and 94.1%, and accuracy of 76.7% and 76.7%, respectively. Incorporating NLP, phenotype 4 had the best performance with an F1 of 77.4%, sensitivity 82.8%, specificity 86.7%, PPV 72.7%, NPV 92.1%, and accuracy 85.5%. Phenotypes 2 to 4 increase NTG case detection fourfold compared with phenotype 1. Conclusions: Normal tension glaucoma phenotypes using NLP achieved the best overall performance, and those incorporating structured data perform better than ICD codes alone. The NTG ICD code-based phenotype is highly specific but lacks sensitivity. Insights from this study may inform the development of computable phenotypes for other disease subtypes within broader disease categories. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S2666914525001563Computable phenotypeEHRNatural language processingNormal tension glaucomaNTG
spellingShingle Fountane Chan, MD
Wei-Chun Lin, MD, PhD
Alan Tang
Benjamin Y. Xu, MD, PhD
Sophia Y. Wang, MD, MS
Michael V. Boland, MD, PhD
Catherine Q. Sun, MD
Sally Baxter, MD, MSc
Brian Stagg, MD, MS
Michelle Hribar, PhD
Aiyin Chen, MD
Development and Evaluation of a Computable Phenotype for Normal Tension Glaucoma
Ophthalmology Science
Computable phenotype
EHR
Natural language processing
Normal tension glaucoma
NTG
title Development and Evaluation of a Computable Phenotype for Normal Tension Glaucoma
title_full Development and Evaluation of a Computable Phenotype for Normal Tension Glaucoma
title_fullStr Development and Evaluation of a Computable Phenotype for Normal Tension Glaucoma
title_full_unstemmed Development and Evaluation of a Computable Phenotype for Normal Tension Glaucoma
title_short Development and Evaluation of a Computable Phenotype for Normal Tension Glaucoma
title_sort development and evaluation of a computable phenotype for normal tension glaucoma
topic Computable phenotype
EHR
Natural language processing
Normal tension glaucoma
NTG
url http://www.sciencedirect.com/science/article/pii/S2666914525001563
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