常规检验标志物联合机器学习的青光眼风险预测模型的构建与评估
Development and Evaluation of a Glaucoma Risk Prediction Model Using Routine Laboratory Biomarkers and Machine Learning
DOI: 10.12677/acm.2025.15113305, PDF,    科研立项经费支持
作者: 肖 利, 阴 益, 李 健, 王自林:自贡市第一人民医院检验科,四川 自贡
关键词: 青光眼机器学习检验组学Glaucoma Machine Learning Laboratory Omics (Clinlabomics)
摘要: 目的:基于常规检验标志物联合机器学习,构建并在独立验证集中评价一个可解释、可部署的青光眼个体化风险预测模型,综合考察其判别力、校准度与决策净获益,旨在为基层医疗提供低成本、易推广的早筛分诊工具。方法:纳入自贡市第一人民医院2022年3月~2025年3月就诊人群共1200例,按7:3分为训练集(n = 840)与验证集(n = 360),两集青光眼/对照比例近1:1。以单因素分析与LASSO正则化联合筛选特征,确定6个关键变量;构建多种模型并以Logistic作为主模型。主要评价指标包括AUC/ROC、Brier分数与校准曲线、决策曲线分析;同时报告阈值相关指标(准确率、敏感度、特异度、F1、Kappa、Youden指数、PPV、NPV)。结果:验证集中,主模型(Logistic)取得较优的综合性能(AUC约0.78~0.86;Brier约0.17),校准曲线贴近理想线;在DCA的0.1~0.6阈值区间获得稳定且高于Treat-all/none的净获益。SVM与XGBoost的区分度接近,但校准与净获益整体略逊。结论:仅依托常规检验数据即可获得具有良好区分度、可靠概率刻度与实用净获益的青光眼风险模型。该方案可及、低成本、标准化,适合在基层与体检场景作为“先分层、后影像/专科”的补充路径,值得在多中心前瞻性研究中进一步验证与再校准。
Abstract: Objective: To develop an interpretable and deployable individualized glaucoma risk prediction model based on routine laboratory biomarkers combined with machine learning, and to evaluate its discrimination, calibration, and clinical net benefit in an independent validation cohort, aiming to provide a low-cost and scalable early triage tool for primary care. Methods: A total of 1200 individuals presenting to Zigong First People’s Hospital from March 2022 to March 2025 were included and randomly split 7:3 into a training set (n = 840) and a validation set (n = 360), with an approximately 1:1 glaucoma/control ratio in both sets. Features were selected by combining univariable analysis with LASSO regularization to determine six key variables. Multiple algorithms were trained and evaluated, with logistic regression prespecified as the primary model. Primary endpoints were AUC/ROC, Brier score with calibration curves, and decision curve analysis (DCA); threshold-based metrics (accuracy, sensitivity, specificity, F1 score, Cohen’s κ, Youden’s index, PPV, NPV) were also reported. Results: In the validation set, the primary model (logistic regression) showed favorable overall performance (AUC ~0.78~0.86; Brier ~0.17) with calibration close to the ideal line; across the 0.1~0.6 threshold range, DCA indicated consistent net benefit exceeding treat-all and treat-none strategies. SVM and XGBoost achieved comparable discrimination but exhibited slightly inferior calibration and net benefit. Conclusions: A glaucoma risk model can be derived solely from routine laboratory data, achieving good discrimination, reliable probability scaling, and practical clinical net benefit. This standardized, low-cost approach is well suited for primary-care and health-check settings as a “pre-stratification before imaging/specialist referral” pathway and merits further multicenter prospective validation and recalibration.
文章引用:肖利, 阴益, 李健, 王自林. 常规检验标志物联合机器学习的青光眼风险预测模型的构建与评估[J]. 临床医学进展, 2025, 15(11): 1957-1966. https://doi.org/10.12677/acm.2025.15113305

参考文献

[1] Tham, Y., Li, X., Wong, T.Y., Quigley, H.A., Aung, T. and Cheng, C. (2014) Global Prevalence of Glaucoma and Projections of Glaucoma Burden through 2040. Ophthalmology, 121, 2081-2090. [Google Scholar] [CrossRef] [PubMed]
[2] Steinmetz, J.D., Bourne, R.R.A., Briant, P.S., et al. (2021) Causes of Blindness and Vision Impairment in 2020 and Trends over 30 Years. The Lancet Global Health, 9, e144-e160.
[3] Zhang, N., Wang, J., Li, Y. and Jiang, B. (2021) Prevalence of Primary Open Angle Glaucoma in the Last 20 Years: A Meta-Analysis and Systematic Review. Scientific Reports, 11, Article No. 13762. [Google Scholar] [CrossRef] [PubMed]
[4] 中华医学会眼科学分会. 中国青光眼指南(2020年) [J]. 中华眼科杂志, 2020, 56(8): 573-586.
[5] Brusini, P., Salvetat, M.L. and Zeppieri, M. (2021) How to Measure Intraocular Pressure: An Updated Review of Various Tonometers. Journal of Clinical Medicine, 10, Article 3860. [Google Scholar] [CrossRef] [PubMed]
[6] Da Silva, F. and Lira, M. (2022) Intraocular Pressure Measurement: A Review. Surv Ophthalmol, 67, 1319-1331.
[7] Bengtsson, B. and Heijl, A. (2000) False-Negative Responses in Glaucoma Perimetry. Investigative Ophthalmology & Visual Science, 41, 702-709.
[8] Gardiner, S.K., Crabb, D.P., et al. (2016) Visual Field Reliability: Evidence-Based Criteria. Ophthalmology, 123, 1365-1373.
[9] De Moraes, C.G., Liebmann, J.M., Ritch, R., Krupin, T., Low-Pressure Glaucoma Treatment Study Group, et al. (2015) Reliability Indices and Rates of Visual Field Change in Glaucoma. Investigative Ophthalmology & Visual Science, 56, 3444-3450.
[10] Vizzeri, G., Weinreb, R.N., Gonzalez-Garcia, A.O., Bowd, C., Medeiros, F.A., Sample, P.A., et al. (2009) Agreement between Spectral-Domain and Time-Domain OCT for Measuring RNFL Thickness. British Journal of Ophthalmology, 93, 775-781. [Google Scholar] [CrossRef] [PubMed]
[11] Leung, C.K.S., Lam, S., Weinreb, R.N., Liu, S., Ye, C., Liu, L., et al. (2010) Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography. Ophthalmology, 117, 1684-1691. [Google Scholar] [CrossRef] [PubMed]
[12] Abera, A. and Gessesse, G.W. (2023) Diagnostic Performance of Optical Coherence Tomography Macular Ganglion Cell Inner Plexiform Layer and Retinal Nerve Fiber Layer Thickness in Glaucoma Suspect and Early Glaucoma Patients at St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia. PLOS ONE, 18, e0263959.
[13] Ting, D.S.W., Pasquale, L.R., Peng, L., Campbell, J.P., Lee, A.Y., Raman, R., et al. (2018) Artificial Intelligence and Deep Learning in Ophthalmology. British Journal of Ophthalmology, 103, 167-175. [Google Scholar] [CrossRef] [PubMed]
[14] De Fauw, J., Ledsam, J.R., Romera-Paredes, B., Nikolov, S., Tomasev, N., Blackwell, S., et al. (2018) Clinically Applicable Deep Learning for Diagnosis and Referral in Retinal Disease. Nature Medicine, 24, 1342-1350. [Google Scholar] [CrossRef] [PubMed]
[15] Vickers, A.J. and Elkin, E.B. (2006) Decision Curve Analysis: A Novel Method for Evaluating Prediction Models. Medical Decision Making, 26, 565-574. [Google Scholar] [CrossRef] [PubMed]
[16] Van Calster, B., McLernon, D.J., van Smeden, M., Wynants, L. and Steyerberg, E.W. (2019) Calibration: The Achilles Heel of Predictive Analytics. BMC Medicine, 17, Article No. 230. [Google Scholar] [CrossRef] [PubMed]
[17] Ozgonul, C., Sertoglu, E., Mumcuoglu, T. and Kucukevcilioglu, M. (2016) Neutrophil-To-Lymphocyte Ratio and Platelet-To-Lymphocyte Ratio as Novel Biomarkers of Primary Open-Angle Glaucoma. Journal of Glaucoma, 25, e815-e820. [Google Scholar] [CrossRef] [PubMed]
[18] Kopsidas, I., Parissis, N., et al. (2020) Differences of NLR/PLR among POAG, PACG and Controls. Bratislava Medical Journal, 121, 563-568.
[19] Chuang, S. and Chang, C. (2024) Platelet-to-Lymphocyte Ratio and Lymphocyte-To-Monocyte Ratio in Glaucoma: A Meta-Analysis. Biomarkers in Medicine, 18, 39-49. [Google Scholar] [CrossRef] [PubMed]
[20] Zhou, M., Wang, W., Huang, W. and Zhang, X. (2014) Diabetes Mellitus as a Risk Factor for Open-Angle Glaucoma: A Systematic Review and Meta-Analysis. PLOS ONE, 9, e102972. [Google Scholar] [CrossRef] [PubMed]
[21] Tielsch, J.M., Katz, J., Quigley, H.A., Javitt, J.C. and Sommer, A. (1995) Diabetes, Intraocular Pressure, and Primary Open-Angle Glaucoma in the Baltimore Eye Survey. Ophthalmology, 102, 48-53. [Google Scholar] [CrossRef] [PubMed]
[22] Lin, H., Stein, J.D., Nan, B., Childers, D., Newman-Casey, P.A., Thompson, D.A., et al. (2015) Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons with Diabetes Mellitus. JAMA Ophthalmology, 133, 915-923. [Google Scholar] [CrossRef] [PubMed]
[23] Kim, M., Woo, S.J., Park, K.H., et al. (2018) Lower Serum Uric Acid Levels in POAG. Acta Ophthalmologica, 96, e691-e699.
[24] Li, S., Shao, M., Cao, W. and Sun, X. (2019) Association between Pretreatment Serum Uric Acid Levels and Progression of Newly Diagnosed Primary Angle-Closure Glaucoma: A Prospective Cohort Study. Oxidative Medicine and Cellular Longevity, 2019, Article ID: 7919836. [Google Scholar] [CrossRef] [PubMed]
[25] Liu, Q., Liu, D., Yan, D., Huang, W., Ji, X., Hui, J., et al. (2020) Gender-Specific Association between Serum Uric Acid and Incident High Intraocular Pressure in Chinese Population: A Cross-Sectional Study. Investigative Ophthalmology & Visual Science, 61, 10.
[26] Klaver, J.H., Greve, E.L., Goslinga, H., Geijssen, H.C. and Heuvelmans, J.H. (1985) Blood and Plasma Viscosity Measurements in Patients with Glaucoma. British Journal of Ophthalmology, 69, 765-770. [Google Scholar] [CrossRef] [PubMed]
[27] Broadway, D.C. and Drance, S.M. (1997) Evidence of Coagulation Activation in Untreated POAG. Ophthalmology, 104, 80-85.
[28] Li, S., Gao, Y., Shao, M., Tang, B., Cao, W. and Sun, X. (2017) Association between Coagulation Function and Patients with Primary Angle Closure Glaucoma: A 5-Year Retrospective Case-Control Study. BMJ Open, 7, e016719. [Google Scholar] [CrossRef] [PubMed]
[29] Tham, Y., Tao, Y., Zhang, L., Rim, T.H.T., Thakur, S., Lim, Z.W., et al. (2020) Is Kidney Function Associated with Primary Open-Angle Glaucoma? Findings from the Asian Eye Epidemiology Consortium. British Journal of Ophthalmology, 104, 1298-1303. [Google Scholar] [CrossRef] [PubMed]
[30] Collins, G.S., Reitsma, J.B., Altman, D.G. and Moons, K.G.M. (2015) Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD): The TRIPOD Statement. Annals of Internal Medicine, 162, 55-63. [Google Scholar] [CrossRef] [PubMed]
[31] Vickers, A.J., Cronin, A.M., Elkin, E.B. and Gonen, M. (2008) Extensions to Decision Curve Analysis, a Novel Method for Evaluating Diagnostic Tests, Prediction Models and Molecular Markers. BMC Medical Informatics and Decision Making, 8, Article No. 53. [Google Scholar] [CrossRef] [PubMed]
[32] Zhao, L., Leng, Y., Hu, Y., Xiao, J., Li, Q., Liu, C., et al. (2024) Understanding Decision Curve Analysis in Clinical Prediction Model Research. Postgraduate Medical Journal, 100, 512-515. [Google Scholar] [CrossRef] [PubMed]