Kozak Igor, Sample Pamela A, Hao Jiucang, Freeman William R, Weinreb Robert N, Lee Te-Won, Goldbaum Michael H
Department of Ophthalmology, University of California at San Diego, USA.
Trans Am Ophthalmol Soc. 2007;105:111-8; discussion 119-20.
To test the following hypotheses: (1) eyes from patients with human immunodeficiency virus (HIV) have retinal damage that causes subtle field defects, (2) sensitive machine learning classifiers (MLCs) can use these field defects to distinguish fields in HIV patients and normal subjects, and (3) the subtle field defects form meaningful patterns. We have applied supervised MLCs--support vector machine (SVM) and relevance vector machine (RVM)--to determine if visual fields in patients with HIV differ from normal visual fields in HIV-negative controls.
HIV-positive patients without visible retinopathy were divided into 2 groups: (1) 38 high-CD4 (H), 48.5 +/- 8.5 years, whose CD4 counts were never below 100; and (2) 35 low-CD4 (L), 46.1 +/- 8.5 years, whose CD4 counts were below 100 at least 6 months. The normal group (N) had 52 age-matched HIV-negative individuals, 46.3 +/- 7.8 years. Standard automated perimetry (SAP) with the 24-2 program was recorded from one eye per individual per group. SVM and RVM were trained and tested with cross-validation to distinguish H from N and L from N. Area under the receiver operating characteristic (AUROC) curve permitted comparison of performance of MLCs. Improvement in performance and identification of subsets of the most important features were sought with feature selection by backward elimination.
SVM and RVM distinguished L from N (L: AUROC = 0.804, N: 0.500, P = .0002 with SVM and L: .800, P = .0002 with RVM) and H from N (H: 0.683, P = .022 with SVM and H: 0.670, P = .038 with RVM). With best-performing subsets derived by backward elimination, SVM and RVM each distinguished L from N (L: 0.843, P < .00005 with SVM and L: 0.870, P < .00005 with RVM) and H from N (H: 0.695, P = .015 with SVM and H: 0.726, P = .007 with RVM). The most important field locations in low-CD4 individuals were mostly superior near the blind spot. The location of important field locations was uncertain in high-CD4 eyes.
This study has confirmed that low-CD4 eyes have visual field defects and retinal damage. Ranking located important field locations superiorly near the blind spot, implying damage to the retina inferiorly near the optic disc. Though most fields appear normal in high-CD4 eyes, SVM and RVM were sufficiently sensitive to distinguish these eyes from normal eyes with SAP. The location of these defects is not yet defined. These results also validate the use of sensitive MLC techniques to uncover test differences not discernible by human experts.
验证以下假设:(1)人类免疫缺陷病毒(HIV)感染者的眼睛存在视网膜损伤,导致细微的视野缺损;(2)灵敏的机器学习分类器(MLC)可利用这些视野缺损区分HIV感染者与正常受试者的视野;(3)细微的视野缺损构成有意义的模式。我们应用了有监督的MLC——支持向量机(SVM)和相关向量机(RVM)——来确定HIV感染者的视野是否不同于HIV阴性对照的正常视野。
无可见视网膜病变的HIV阳性患者分为两组:(1)38例高CD4(H)组,年龄48.5±8.5岁,其CD4细胞计数从未低于100;(2)35例低CD4(L)组,年龄46.1±8.5岁,其CD4细胞计数至少6个月低于100。正常组(N)有52例年龄匹配的HIV阴性个体,年龄46.3±7.8岁。每组中每人的一只眼睛采用24-2程序进行标准自动视野计检查(SAP)。通过交叉验证对SVM和RVM进行训练和测试,以区分H组与N组以及L组与N组。受试者操作特征(AUROC)曲线下面积可比较MLC的性能。通过反向消除法进行特征选择,以寻求性能的提升和最重要特征子集的识别。
SVM和RVM能够区分L组与N组(L组:SVM的AUROC = 0.804,N组:0.500,P = 0.0002;RVM的L组:0.800,P = 0.0002)以及H组与N组(H组:SVM的AUROC = 0.683,P = 0.022;RVM的H组:0.670,P = 0.038)。利用反向消除法得到的最佳性能子集,SVM和RVM均能区分L组与N组(L组:SVM的AUROC = 0.843,P < 0.00005;RVM的L组:0.870,P < 0.00005)以及H组与N组(H组:SVM的AUROC = 0.695,P = 0.015;RVM的H组:0.726,P = 0.007)。低CD4个体中最重要的视野位置大多在靠近盲点的上方。高CD4眼睛中重要视野位置的定位尚不确定。
本研究证实低CD4的眼睛存在视野缺损和视网膜损伤。分级显示重要视野位置在靠近盲点的上方,这意味着视神经盘下方的视网膜受到损伤。尽管大多数高CD4眼睛的视野看起来正常,但SVM和RVM对利用SAP区分这些眼睛与正常眼睛足够敏感。这些缺损的位置尚未明确。这些结果还验证了使用灵敏的MLC技术来发现人类专家难以察觉的测试差异的有效性。