Purpose

To assess the diagnostic performance and generalizability of logistic regression in classifying primary vitreoretinal lymphoma (PVRL) versus uveitis from intraocular cytokine levels in a single-center retrospective cohort, comparing a logistic regression model and previously published Interleukin Score for Intraocular Lymphoma Diagnosis (ISOLD) scores against the interleukin 10 (IL-10)-to-interleukin 6 (IL-6) ratio.

Design

Retrospective cohort study.

Participants

Patient histories, pathology reports, and intraocular cytokine levels from 2339 patient entries in the National Eye Institute Histopathology Core database.

Methods

Patient diagnoses of PVRL versus uveitis and associated aqueous or vitreous IL-6 and IL-10 levels were collected retrospectively. From these data, cytokine levels were compared between diagnoses with the Mann–Whitney U test. A logistic regression model was trained to classify PVRL versus uveitis from aqueous and vitreous IL-6 and IL-10 samples and compared with ISOLD scores and IL-10-to-IL-6 ratios.

Main Outcome Measures

Area under the receiver operating characteristic curve (AUC) for each classifier and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at the optimal cutoff (maximal Youden index) for each classifier.

Results

Seventy-seven lymphoma patients (10 aqueous samples, 67 vitreous samples) and 84 uveitis patients (19 aqueous samples, 65 vitreous samples) treated between October 5, 1999, and September 16, 2015, were included. Interleukin 6 levels were higher and IL-10 levels were lower in uveitis patients compared with lymphoma patients (P < 0.01). For vitreous samples, the logistic regression model, ISOLD score, and IL-10-to-IL-6 ratio achieved AUCs of 98.3%, 97.7%, and 96.3%, respectively. Sensitivity, specificity, PPV, and NPV at the optimal cutoffs for each classifier were 94.2%, 96.9%, 97%, and 94% for the logistic regression model; 92.7%, 100%, 100%, and 92.9% for the ISOLD score; and 94.2%, 95.3%, 95.6%, and 93.9% for the IL-10-to-IL-6 ratio. All models achieved complete separation between uveitis and lymphoma in the aqueous data set.

Conclusions

The accuracy of the logistic regression model and generalizability of the ISOLD score to an independent patient cohort suggest that intraocular cytokine analysis by logistic regression may be a promising adjunct to cytopathologic analysis, the gold standard, for the early diagnosis of primary vitreoretinal lymphoma. Further validation studies are merited.

中文翻译：

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通过白细胞介素6和白细胞介素10水平对原发性玻璃体视网膜淋巴瘤与葡萄膜炎进行Logistic回归分类。

目的

为了评估单中心回顾性队列中从眼内细胞因子水平对原发性玻璃体视网膜淋巴瘤（PVRL）与葡萄膜炎进行分类的logistic回归的诊断性能和一般性，比较了logistic回归模型和先前发布的白内障眼内淋巴瘤诊断（ISOLD）得分相对于白介素10（IL-10）与白介素6（IL-6）的比例。

设计

回顾性队列研究。

参加者

美国国立眼科研究所组织病理学核心数据库中来自2339位患者的患者病史，病理报告和眼内细胞因子水平。

方法

回顾性收集患者对PVRL与葡萄膜炎的诊断，以及相关的房水或玻璃体IL-6和IL-10水平。从这些数据中，比较了使用Mann-Whitney U检验进行诊断的细胞因子水平。训练了逻辑回归模型以对房水和玻璃体IL-6和IL-10样本中PVRL与葡萄膜炎进行分类，并与ISOLD评分和IL-10-IL-6比值进行比较。

主要观察指标

每个分类器的接收器工作特性曲线（AUC）下的面积以及每个分类器的最佳截止值（最大Youden指数）处的灵敏度，特异性，正预测值（PPV）和负预测值（NPV）。

结果

纳入1999年10月5日至2015年9月16日期间接受治疗的77例淋巴瘤患者（10例水样，67例玻璃体样本）和84例葡萄膜炎患者（19例水样，65例玻璃体样本）。与淋巴瘤患者相比，葡萄膜炎患者的白细胞介素6水平较高，IL-10水平较低（P<0.01）。对于玻璃体样品，逻辑回归模型，ISOLD评分和IL-10-IL-6比值分别达到98.3％，97.7％和96.3％的AUC。对于每个分类器，最佳分类的敏感性，特异性，PPV和NPV分别为94.2％，96.9％，97％和94％。ISOLD分数分别为92.7％，100％，100％和92.9％；IL-10-与IL-6的比例分别为94.2％，95.3％，95.6％和93.9％。所有模型均在水性数据集中实现了葡萄膜炎和淋巴瘤之间的完全分离。

结论

Logistic回归模型的准确性和ISOLD评分对独立患者队列的可推广性表明，通过Logistic回归进行眼内细胞因子分析可能是细胞病理学分析（金标准）用于早期诊断原发性玻璃体视网膜淋巴瘤的有希望的辅助手段。值得进一步的验证研究。