IOP and OPP Fluctuation as Risk Factors for Glaucoma

IOP 和 OPP 波动是青光眼的危险因素

• 批准号: 9251283
• 负责人: J CRAWFORD DOWNS
• 金额: --
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251283
• 关键词: Affect; African; Age; Aging; Axon; Baltimore; Barbados; Bilateral; Blood Pressure; Blood flow; Body Temperature; Chronic; Clinical; Clinical Treatment; Clinical Trials; Contralateral; Cornea; Data; Development; Disease; Elderly; Electrooculogram; Exposure to; Eye; Eye diseases; Frequencies; Glaucoma; Image; Injury; Intervention; Knowledge; Lasers; Latino; Lead; Los Angeles; Measurement; Measures; Modality; Modeling; Modification; Monitor; Optic Disk; Patient Care; Patients; Perfusion; Persons; Physiologic Intraocular Pressure; Population; Predisposition; Race; Recording of previous events; Rest; Retinal; Retinal Ganglion Cells; Risk; Risk Factors; Shock; Surveys; System; Telemetry; Testing; Thick; Time; Wireless Technology; clinical Diagnosis; in vivo; pressure; prospective; public health relevance; response; retinal nerve fiber layer

 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.

 描述（由申请人提供）：在所有主要的前瞻性临床试验中，眼压 (IOP) 和年龄是青光眼发生和进展最一致的独立危险因素，尽管在大多数研究中，眼压 (IOP) 并未被证明会随着年龄的增长而增加。青光眼在非洲血统的人群中也更为普遍，降低眼压是唯一已被证明可以延缓青光眼发病和进展的治疗方法，但一旦视神经受损。即使在临床干预已将平均眼压降低至“正常”水平后，人们仍认为眼部（ONH）更容易受到青光眼进展的影响。我们之前将这些发现解释为随着年龄的增长、非洲血统，ONH 变得越来越容易受到进一步的青光眼损伤。然而，还有一种可能的替代解释是，眼外皮起到减震器的作用，并且眼外皮较硬的眼睛对于给定的扰动具有更大的眼压波动。皮毛随着年龄的增长而变硬，非洲人的皮毛随着年龄的增长变硬得更快 从这些数据中，我们可以得出结论，老年人、非洲血统的人和黑人的眼压波动都会更大。 因此，在眼表层变硬的青光眼眼中，存在与年龄和疾病相关的未知眼压成分（例如更大的眼压波动），这些成分独立地导致青光眼的发生和进展。即使平均 IOP 没有变化，老年人和有高 IOP 接触史的眼睛的 IOP 和 OPP 波动也更大，这是由于随着年龄的增长以及对慢性高眼压的反应，眼表层会发生重塑。 IOP，并且这些影响独立地导致青光眼发病和进展的风险，对“波动”假说的支持将导致对 IOP 和 OPP 波动在年龄和疾病相关易感性增加中的重要性的全新认识。青光眼，并为全新的临床诊断和治疗方式提供了强有力的理由，该方式通过改变眼表层硬度或眼内眼压波动的阻尼来降低眼压和眼压波动。根据“波动”假设，我们获得的有关这些变量自然波动的知识将重新定义患者适当的 IOP 测量频率并为患者护理提供信息。