Hamilton Glaucoma Center, Department of Ophthalmology, University of California San Diego, LaJolla, California 92093, USA.
Invest Ophthalmol Vis Sci. 2012 Jun 14;53(7):3615-28. doi: 10.1167/iovs.11-8847.
To detect localized glaucomatous structural changes using proper orthogonal decomposition (POD) framework with false-positive control that minimizes confirmatory follow-ups, and to compare the results to topographic change analysis (TCA).
We included 167 participants (246 eyes) with ≥4 Heidelberg Retina Tomograph (HRT)-II exams from the Diagnostic Innovations in Glaucoma Study; 36 eyes progressed by stereo-photographs or visual fields. All other patient eyes (n = 210) were non-progressing. Specificities were evaluated using 21 normal eyes. Significance of change at each HRT superpixel between each follow-up and its nearest baseline (obtained using POD) was estimated using mixed-effects ANOVA. Locations with significant reduction in retinal height (red pixels) were determined using Bonferroni, Lehmann-Romano k-family-wise error rate (k-FWER), and Benjamini-Hochberg false discovery rate (FDR) type I error control procedures. Observed positive rate (OPR) in each follow-up was calculated as a ratio of number of red pixels within disk to disk size. Progression by POD was defined as one or more follow-ups with OPR greater than the anticipated false-positive rate. TCA was evaluated using the recently proposed liberal, moderate, and conservative progression criteria.
Sensitivity in progressors, specificity in normals, and specificity in non-progressors, respectively, were POD-Bonferroni = 100%, 0%, and 0%; POD k-FWER = 78%, 86%, and 43%; POD-FDR = 78%, 86%, and 43%; POD k-FWER with retinal height change ≥50 μm = 61%, 95%, and 60%; TCA-liberal = 86%, 62%, and 21%; TCA-moderate = 53%, 100%, and 70%; and TCA-conservative = 17%, 100%, and 84%.
With a stronger control of type I errors, k-FWER in POD framework minimized confirmatory follow-ups while providing diagnostic accuracy comparable to TCA. Thus, POD with k-FWER shows promise to reduce the number of confirmatory follow-ups required for clinical care and studies evaluating new glaucoma treatments. (ClinicalTrials.gov number, NCT00221897.).
使用虚假阳性控制的适当正交分解（POD）框架检测局部青光眼结构变化，以尽量减少确认性随访，并将结果与地形变化分析（TCA）进行比较。
我们纳入了来自诊断性青光眼创新研究的 167 名参与者（246 只眼），这些参与者进行了≥4 次海德堡视网膜断层扫描仪（HRT）-II 检查；36 只眼通过立体照片或视野进展。所有其他患者眼（n=210）无进展。使用 21 只正常眼评估特异性。使用混合效应方差分析估计每个 HRT 超像素在每次随访与其最近的基线（使用 POD 获得）之间的变化的显着性。使用 Bonferroni、Lehmann-Romano k 家族错误率（k-FWER）和 Benjamini-Hochberg 假发现率（FDR）I 型错误控制程序确定视网膜高度（红色像素）显著降低的位置。在每次随访中，观察阳性率（OPR）计算为盘内红色像素数与盘大小的比值。使用 POD 定义的进展是指一个或多个随访的 OPR 大于预期的假阳性率。使用最近提出的宽松、中度和保守进展标准评估 TCA。
进展者的敏感性、正常者的特异性和非进展者的特异性分别为 POD-Bonferroni=100%、0%和 0%；POD k-FWER=78%、86%和 43%；POD-FDR=78%、86%和 43%；POD k-FWER 与视网膜高度变化≥50 μm=61%、95%和 60%；TCA-宽松=86%、62%和 21%；TCA-中度=53%、100%和 70%；TCA-保守=17%、100%和 84%。
使用 POD 框架，k-FWER 可更好地控制 I 型错误，同时减少确认性随访，提供与 TCA 相当的诊断准确性。因此，POD 与 k-FWER 具有减少临床护理和评估新的青光眼治疗方法所需的确认性随访数量的潜力。（临床试验.gov 编号，NCT00221897。）
