OHTS and EGPS: Glaucoma detection using Confocal Scanning Laser Ophthalmology

描述（由申请人提供）：本研究的总体目标是汇集来自两项大型随机试验的共聚焦扫描激光检眼镜（CSLO）数据，即高眼压治疗研究（OHTS）和欧洲青光眼预防研究（EGPS），以提高我们预测高眼压患者原发性开角型青光眼（POAG）发展的能力，并增强我们对低血压治疗对视盘地形的影响的理解。此外，拟议的研究将使用EGPS数据集独立测试CSLO辅助研究中开发的预测模型，并提高检测可能预测POAG的椎间盘特征的统计能力。OHTS和EGPS在研究设计和测量方案上有相似之处，包括确定POAG，以及异常的病因特异性归因。为每个研究构建了通用格式的数据集并进行了合并。各协调中心的独立分析证实了OHTS对POAG发展的预测模型。这两项研究都采用了CSLO成像，对一部分参与者进行了类似的图像采集和处理方案。具体而言，OHTS的CSLO辅助研究有439名参与者的可分析的高质量CSLO数据，EGPS有470名参与者的可分析的CSLO数据。该建议将CSLO数据与现有合并的EGPS和OHTS数据集合并，并将包括909名高眼压患者的CSLO数据，中位随访时间超过4年，共有84个POAG终点。合并的样本，最大的纵向数据集的眼高血压受试者与CSLO成像将提供统计能力，以检验假设，可能不可能与一个单独的数据集。这种合作不会干扰每个研究分析自己数据集的能力。具体目标是：1)改进基线HRT指标的预测模型。建立统计模型，使用基线海德堡视网膜断层扫描（HRT）视盘地形参数来预测可重复性视野异常和/或视盘恶化检测到的POAG终点的发展。2)利用基线和随访HRT指标改进预测模型。确定基线HRT指标的预测准确性或这些指标在发展为POAG随访期间的变化。3)预测青光眼的早期症状。评估基线HRT单独或联合其他基线眼和人口统计学因素是否可预测POAG终点是否首先通过视野改变或视盘改变检测到。4)立体摄影与激光共聚焦扫描检出青光眼随时间变化的比较比较HRT自动变化检测算法对视盘变化的检测与立体照片的专家定性评估。公共卫生相关性：本研究的总体目标是汇总来自两项大型随机试验——高眼压治疗研究（OHTS）和欧洲青光眼预防研究（EGPS）的共聚焦扫描激光眼科检查（CSLO）数据，以提高我们预测高眼压患者原发性开角型青光眼（POAG）发展的能力，并增强我们对低眼压治疗对视盘地形的影响的理解。由于CSLO测量具有可重复性、客观、定量、无创性，并且对患者的配合要求最低，因此它们作为POAG早期诊断测试的潜力具有广泛的公共卫生意义。EGPS/OHTS联合样本有909多名随机参与者进行纵向CSLO测量，使其成为眼高血压个体中前瞻性获得CSLO测量的最大样本。

DESCRIPTION (provided by applicant): The overall goal of this study is to pool confocal scanning laser ophthalmoscopy (CSLO) data from two large randomized trials, the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS), to improve our ability to predict the development of primary open angle glaucoma (POAG) in ocular hypertensive patients and to enhance our understanding of the effect of ocular hypotensive treatment on optic disc topography. Moreover, the proposed study will use the EGPS dataset to independently test the prediction model developed in the CSLO Ancillary Study to the OHTS and to increase the statistical power for detection of disc features that may be predictive of POAG. OHTS and EGPS share similarities in study design and measurement protocols including ascertainment of POAG, and cause-specific attribution of abnormality. Datasets in a common format have been constructed for each study and merged. Independent analyses by each Coordinating Center have confirmed the OHTS prediction model for the development of POAG. Both studies included CSLO imaging on a subset of their participants with similar image acquisition and processing protocols. Specifically, the CSLO Ancillary Study to the OHTS has analyzable good quality CSLO data on 439 participants and the EGPS has analyzable CSLO data on 470 participants. This proposal will merge the CSLO data with the existing merged EGPS and OHTS dataset and will include CSLO data from 909 ocular hypertensive participants with a median follow-up of more than 4 years and a total of 84 POAG endpoints. The merged sample, the largest longitudinal dataset of ocular hypertensive subjects with CSLO imaging will provide statistical power to test hypotheses that might not be possible with one dataset alone. This collaboration will not interfere with each study's ability to analyze its own dataset. The Specific Aims are: 1) Improving Prediction Models using Baseline HRT indices. To develop statistical models that use baseline Heidelberg Retina Tomograph (HRT) topographic optic disc parameters to predict development of a POAG endpoint detected by reproducible visual field abnormalities and/or optic disc deterioration. 2) Improving Prediction Models Using Baseline and Follow-up HRT indices. To determine the predictive accuracy of baseline HRT indices or change in these indices during follow-up for developing POAG. 3) Predicting the first sign of glaucoma. To evaluate whether baseline HRT alone or in combination with other baseline ocular and demographic factors are predictive of whether a POAG endpoint is first detected by visual field changes or optic disc changes. 4) Comparison of stereophotography and confocal scanning laser ophthalmoscopy for detecting glaucomatous change over time. To compare the detection of optic disc changes using HRT automated change detection algorithms to expert qualitative assessment of stereophotographs. PUBLIC HEALTH RELEVANCE: The overall goal of this study is to pool confocal scanning laser ophthalmoscopy (CSLO) data from two large randomized trials, the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS), to improve our ability to predict the development of primary open angle glaucoma (POAG) in ocular hypertensive patients and to enhance our understanding of the effect of ocular hypotensive treatment on optic disc topography. Because CSLO measures are reproducible, objective, quantitative, non-invasive, and require minimal patient cooperation, their potential as an early diagnostic test for POAG has broad public health significance. The combined EGPS/OHTS sample has more than 909 randomized participants with longitudinal CSLO measurements making it the largest sample of prospectively obtained CSLO measurements in ocular hypertensive individuals.