Short-Term Estimation of Long-Term Intraocular Pressure Reduction in Glaucoma

描述（由申请人提供）：青光眼治疗的目标是实现长期平均眼内压（IOP）降低。IOP是一个动态变量，表现出显著的不可预测的波动。这种波动使青光眼治疗有效性的评估复杂化：开始治疗后，观察到的IOP变化可能归因于治疗变化、自发变化或两者的组合。理想的方法是获得大量治疗前IOP测量值和大量治疗中IOP测量值，以确定可归因于治疗的平均IOP降低。不幸的是，IOP不能容易地自我测量;通常，唯一可用的测量值是在医生办公室访问期间获得的那些测量值，这些访问通常以三个月或四个月的间隔安排。因此，使用如此低的采样率来表征短期和长期IOP行为以及在开始IOP降低治疗之后IOP的变化是困难的（如果不是不可能的话）。开发单眼治疗药物试验是为了向临床医生提供一种使用有限的短期数据预测长期治疗性IOP降低的方法。单眼试验取决于几个假设的有效性，包括对侧眼之间IOP变异性的对称性，对侧眼之间IOP对治疗反应的对称性，以及单侧治疗缺乏对侧交叉效应。这些假设都受到了最近数据的挑战，最近对单眼药物试验的许多研究表明，它很难预测对侧眼对治疗的反应。需要一种有效的替代单眼试验，以允许短期确定长期治疗疗效。我们已经开发了几种候选方法，用于降低IOP治疗的长期疗效的短期测定。我们的假设是，其中一个或多个将更好地预测长期IOP降低比单眼 药物试验我们的具体目的是（1）证明单眼试验（当前的临床标准）不足以预测长期IOP降低;（2）确定任何候选短期评估模型是否足以预测长期IOP降低。为了实现这些目标，我们将在临床试验中招募患有青光眼或高眼压的受试者，其中将使用每种模型评估每名受试者对局部药物降低IOP治疗的反应。通过确定每个模型的组内相关系数，将每个模型的性能与金标准进行比较：平均IOP降低（三次治疗前和三次治疗中IOP测量值的平均值差异）。这项研究的结果可能有助于眼保健提供者在开始青光眼治疗时对长期药物疗效进行准确的短期估计。这将有助于青光眼患者更快地实现眼压的充分降低，并避免长期使用无效药物，所有这些都减少了办公室访问。

DESCRIPTION (provided by applicant): The goal of glaucoma therapy is to achieve long-term mean intraocular pressure (IOP) reduction. IOP is a dynamic variable and exhibits significant unpredictable fluctuation. This fluctuation complicates the assessment of glaucoma treatment efficacy: following the initiation of therapy, an observed change in IOP may be attributable to therapeutic change, spontaneous change, or a combination of both. The ideal approach would be to attain numerous pre-treatment IOP measurements and numerous on treatment IOP measurements, in order to establish the mean IOP reduction attributable to therapy. Unfortunately, IOP cannot be easily self-measured; generally, the only measurements available are those obtained in the physician's office during visits that are typically scheduled at intervals of three or four months. Therefore, characterizing short-and long-term IOP behavior, and the change in IOP after initiation of lOP-lowering therapy, using such a low sampling rate is difficult if not impossible. The monocular therapeutic drug trial was developed to provide clinicians with a means of predicting long-term therapeutic IOP reductions using limited short-term data. The monocular trial depends on the validity of several assumptions, including symmetry of IOP variability between fellow eyes, symmetry of IOP responses to therapy between fellow eyes, and the lack of a contralateral crossover effect from unilateral therapy. Each of these assumptions has been challenged by recent data, and numerous recent studies of the monocular drug trial demonstrated that it poorly predicted the fellow eye's response to therapy. An effective alternative to the monocular trial is needed to permit short-term determination of long-term treatment efficacy. We have developed several candidate methods for short-term determination of the long-term efficacy of lOP-lowering therapy. Our hypothesis is that one or more of these will better predict long-term IOP reduction than the monocular drug trial. Our specific aims are (1) to demonstrate that the monocular trial, the current clinical standard, inadequately predicts long-term IOP reduction; and (2) to determine if any of the candidate short-term assessment models adequately predict long-term IOP reduction. To accomplish these aims, we will enroll subjects with glaucoma or ocular hypertension in a clinical trial in which each subject's response to topical medical lOP-lowering therapy will be evaluated using each model. Each model's performance will be compared to the gold standard: mean IOP reduction (the difference in the mean of three pre-treatment and three on-treatment IOP measurements), by determining intraclass correlation coefficients for each model. The results of this study may help eyecare providers make accurate short-term estimates of long-term drug efficacy when starting glaucoma therapy. This will help glaucoma patients achieve adequate reduction of eye pressure more quickly, and avoid long-term use of ineffective medications, all with fewer office visits.