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压（IOP）降低。眼压是一个动态变量，具有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复杂化：在治疗开始后，观察到的IOP变化可能归因于治疗改变、自发变化或两者的结合。理想的方法是获得大量的治疗前IOP测量和治疗后IOP测量，以确定可归因于治疗的平均IOP降低。不幸的是，眼内压不容易自我测量；一般来说，唯一可用的测量是在医生办公室通常每隔三到四个月的访问期间获得的。因此，使用如此低的采样率来描述短期和长期IOP行为，以及开始降眼压治疗后IOP的变化，即使不是不可能，也是很困难的。开发单眼治疗药物试验的目的是为临床医生提供一种利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，包括眼间IOP变异性的对称性，眼间IOP治疗反应的对称性，以及单侧治疗对侧交叉效应的缺乏。这些假设都受到了最近数据的挑战，最近许多关于单眼药物试验的研究表明，它很难预测另一只眼睛对治疗的反应。需要一种有效的替代单眼试验的方法来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低lop治疗的长期疗效。我们的假设是，其中一项或多项指标比单眼更好地预测长期IOP降低

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.