IOP and OPP Fluctuation as Risk Factors for Glaucoma

 描述(申请人提供)：在所有主要的前瞻性临床试验中，眼压(IOP)和年龄被发现是青光眼发生和进展的最一致的独立危险因素，尽管在大多数人群中眼压并没有显示出随着年龄的增加而增加。青光眼在非洲血统的人中也更为普遍。降低眼压是唯一被证明可以延缓青光眼发生和发展的临床治疗方法，但一旦受损，视神经头(ONH)被认为更容易进一步发展，即使在临床干预将平均眼压降低到“正常”水平后也是如此。我们先前将这些发现解释为，随着年龄的增长、非洲血统和既往损害，ONH越来越容易受到青光眼损伤的影响。然而，还有一种看似合理的替代解释。我们的遥测眼压数据显示，在醒着的时候，眼睛每小时会受到大约7000次眼压峰值&5毫米汞柱的影响。此外，平均而言，眼压高于基线1毫米汞柱的眼压峰值占眼睛在清醒时必须吸收的总眼压的15%。这是一个非同寻常的发现，因为眼压峰值代表了眼压总体侮辱中一种以前未知的、潜在的高度伤害的成分，这一成分尚未在之前的动物或临床研究中得到表征或考虑。我们假设，除平均眼压外，较高的眼压和眼灌注压(OPP)波动对青光眼的发生和发展也有独立影响。我们将通过阐明年龄和疾病相关的眼压和OPP的变化及其波动来验证这一组织假说，因为它们与视网膜神经节细胞(RGC)轴突丢失和高眼压诱导的眼表僵硬有关。支持“波动”假说将使人们对眼压和眼压波动在年龄和疾病相关青光眼易感性增加中的重要性有一个全新的认识，并为采用全新的临床诊断和治疗方法提供强有力的理论基础，这些方法通过改变眼衣硬度或眼内抑制眼压波动来降低眼压和OPP波动。如果我们的结果不支持“波动”假设，我们获得的关于这些变量的自然波动的知识将重新定义患者适当的眼压测量频率，并为患者护理提供信息。

 DESCRIPTION (provided by applicant): Intraocular pressure (IOP) and age were found to be the most consistent independent risk factors for development and progression of glaucoma in all of the major prospective clinical trials, even though IOP has not been shown to increase with age in most populations. Glaucoma is also much more prevalent in persons of African ancestry. Lowering IOP is the only clinical treatment that has been shown to retard the onset and progression of glaucoma, but once damaged, the optic nerve head (ONH) is thought to be more susceptible to further glaucomatous progression even after clinical intervention has lowered mean IOP to `normal' levels. We have previously interpreted these findings to mean that the ONH is increasingly vulnerable to glaucomatous injury with advancing age, African ancestry, and prior damage. There is a plausible alternative explanation, however. Our telemetric IOP data show that the eye is subjected to about 7,000 IOP spikes >5 mmHg per hour during waking hours. Also, IOP spikes >1 mmHg above baseline are responsible for up to 15% of the total IOP insult the eye must absorb during waking hours on average. This is an extraordinary finding, in that IOP spikes represent a previously unknown and potentially highly injurious component of the IOP total insult that has yet to be characterized or considered in previous animal or clinical studies. We hypothesize that greater IOP and ocular perfusion pressure (OPP) fluctuation independently contribute to the onset and progression of glaucoma in addition to mean IOP. We will test this organizing hypothesis by elucidating the age- and disease-related changes in IOP, OPP, and their fluctuations as they relate to retinal ganglion cell (RGC) axon loss and elevated IOP-induced ocular coat stiffening. Support for the "fluctuation" hypothesis would lead to an entirely new understanding of the importance of IOP and OPP fluctuation in the increased age- and disease-related susceptibility to glaucoma and provide strong rationale for totally new clinical diagnosis and treatment modalities that employ IOP and OPP fluctuation reduction through modification of ocular coats stiffness or intraocular damping of IOP fluctuations. If our results do not support the "fluctuation" hypothesis, the knowledge we gain about the natural fluctuations of these variables will redefine the appropriate IOP measurement frequency in patients and inform patient care.