IOP and OPP Fluctuation as Risk Factors for Glaucoma

 描述（由申请人提供）：在所有主要前瞻性临床试验中观察到，眼内压（IOP）和年龄是青光眼发生和进展的最一致的独立风险因素，尽管在大多数人群中IOP并未随年龄增加而增加。青光眼在非洲血统的人中也更为普遍。降低IOP是唯一的临床治疗，已被证明可以延缓青光眼的发作和进展，但一旦受损，视神经乳头（ONH）被认为更容易进一步发展为青光眼，即使在临床干预已将平均IOP降低到“正常”水平后。我们以前解释这些发现意味着随着年龄的增长，非洲血统和先前的损害，ONH变得越来越容易受到昏迷性损伤。然而，还有一种似是而非的解释。眼外膜起到减震器的作用，对于给定的扰动，具有较硬眼外膜的眼睛具有较大的IOP波动。眼被膜随年龄增长而脱落，非洲人眼被膜随年龄增长更快 祖先和暴露于慢性升高的IOP后的视网膜病变。从这些数据中，我们可以得出结论，老年人、非洲血统的人和 在眼球被膜变硬的昏迷性眼睛中。因此，我们假设存在未知的年龄和疾病相关的IOP成分（如更大的IOP波动），这些成分独立地导致青光眼的发作和进展。 “波动”假说预测，老年人和有IOP升高史的眼睛中，即使平均IOP不变，IOP和IOP波动也更大，这是由于随年龄增长和对慢性IOP升高的反应而观察到的眼表重塑，这些影响独立地导致了青光眼发作和进展的风险。 对“波动”假说的支持将导致对IOP和IOP波动在增加的年龄和疾病相关的青光眼易感性中的重要性的全新理解，并为全新的临床诊断和治疗方式提供强有力的理论基础，这些临床诊断和治疗方式通过改变眼被膜硬度或眼内抑制IOP波动来降低IOP和IOP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的适当IOP测量频率并告知患者护理。

 DESCRIPTION (provided by applicant): Intraocular pressure (IOP) and age are the most consistent independent risk factors for development and progression of glaucoma seen 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 becomes increasingly vulnerable to glaucomatous injury with age, African ancestry, and prior damage. There is a plausible alternative explanation, however. The ocular coats act as a shock absorber, and eyes with stiffer ocular coats have larger IOP fluctuations for a given perturbation. The ocular coats stiffen with age, stiffen with age more quickly in people of African ancestry, and stiffen after exposure to chronically elevated IOP. From these data, we might conclude that IOP fluctuations will be larger in both the elderly, persons of African ancestry, and in glaucomatous eyes in which the ocular coats have stiffened. We therefore hypothesize there are unknown age- and disease-related components of IOP (such as greater IOP fluctuation) that independently contribute to the onset and progression of glaucoma. The "fluctuation" hypothesis predicts that IOP and OPP fluctuations are greater in the elderly and in eyes with a history of exposure to elevated IOP even if mean IOP is unchanged, due to remodelling of the ocular coats seen with aging and in response to chronic elevated IOP, and that these effects independently contribute to the risk for glaucomatous onset and progression. 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.