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

描述(申请人提供)：青光眼治疗的目标是实现长期平均眼压(IOP)的降低。眼压是一个动态变量，表现出显著的不可预测的波动。这种波动使青光眼治疗效果的评估变得复杂：在开始治疗后，观察到的眼压变化可能归因于治疗方法的改变、自发的改变或两者的组合。理想的方法是获得大量的治疗前眼压测量和大量的治疗后眼压测量，以确定可归因于治疗的平均眼压下降。不幸的是，眼压不能很容易地自我测量；通常，唯一可用的测量方法是在医生的办公室里获得的，通常是每隔三到四个月进行一次探视。因此，表征短期和长期的眼压行为，以及开始降眼压治疗后的眼压变化，使用如此低的采样率是困难的，如果不是不可能的话。单眼治疗药物试验的开发是为了向临床医生提供一种使用有限的短期数据来预测长期治疗性眼压下降的手段。单眼试验取决于几个假设的有效性，包括对侧眼之间眼压变异性的对称性，对治疗反应在对侧眼之间的对称性，以及单眼治疗缺乏对侧交叉效应。这些假设中的每一个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，它对另一只眼睛对治疗的反应预测不佳。需要一种有效的替代单眼试验的方法，以允许短期确定长期治疗效果。我们已经开发了几种候选方法来短期确定降压治疗的长期疗效。我们的假设是，其中一个或多个指标将比单眼更好地预测长期眼压下降。 药物试验。我们的具体目标是(1)证明目前的临床标准单眼试验不能充分预测长期眼压下降；以及(2)确定是否有任何候选的短期评估模型足以预测长期眼压下降。为了实现这些目标，我们将招募患有青光眼或高眼压的受试者参加临床试验，在该试验中，每个受试者对局部药物降低治疗的反应将使用每种模型进行评估。通过确定每个模型的组内相关系数，将每个模型的性能与黄金标准：平均眼压降低(三次治疗前和三次治疗中眼压测量的平均值之差)进行比较。这项研究的结果可能有助于眼部护理提供者在开始青光眼治疗时对长期药物疗效做出准确的短期估计。这将帮助青光眼患者更快地实现足够的眼压降低，并避免长期使用无效药物，所有这些都只需较少的办公室就诊。

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.