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: 9004215
• 负责人: J CRAWFORD DOWNS
• 金额: $ 49.53万
• 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: 2015-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9004215
• 关键词: Affect; African; Age; Aging; Animals; Axon; Baltimore; Bilateral; Blood Pressure; Blood flow; Chronic; Clinical; Clinical Research; Clinical Treatment; Clinical Trials; Contralateral; Cornea; Data; Development; Disease; Elderly; Exposure to; Eye; Frequencies; Glaucoma; Hour; Image; Individual; Injury; Intervention; Knowledge; Lasers; Latino; Lead; Los Angeles; Measurement; Measures; Modality; Modeling; Modification; Optic Disk; Patient Care; Patients; Perfusion; Persons; Physiologic Intraocular Pressure; Population; Predisposition; Race; Recording of previous events; Retinal; Retinal Ganglion Cells; Risk; Risk Factors; Shock; Surveys; System; Telemetry; Testing; Thick; clinical Diagnosis; in vivo; nonhuman primate; pressure; prospective; public health relevance; response; retinal nerve fiber layer

 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.

 描述（由适用提供）：在所有主要的前瞻性临床试验中，目前尚未证明IOP在大多数人群中显示出随着年龄的增长而增加，但发现眼内压（IOP）和年龄是青光眼发展和发展的最一致的独立风险因素。青光眼在非洲血统的人中也更加普遍。降低IOP是唯一已显示出延迟青光眼的发作和进展的临床治疗方法，但是一旦受损，视神经头（ONH）即使在临床干预后也更容易受到进一步的青光眼进展的影响，即使临床干预已降低了平均IOP至正常”水平。我们以前已经将这些发现解释为意味着ONH越来越容易受到青光眼伤害的影响，随着年龄的增长，非洲血统和先前的损害。但是，有一个合理的替代解释。我们的遥测IOP数据表明，在醒来的时间内，眼睛每小时大约需要7,000个IOP尖峰。此外，基线高于基线的IOP尖峰> 1 mmHg造成多达15％的IOP侮辱的15％。这是一个非同寻常的发现，因为IOP尖峰代表了IOP总损伤中以前未知且潜在的高度伤害组成部分，在先前的动物或临床研究中尚待表征或考虑。我们假设较大的IOP和眼部灌注压力（OPP）波动独立地有助于青光眼的发作和进展，除了平均IOP。我们将通过阐明与视网膜神经节细胞（RGC）轴突损失并升高IOP诱导的眼外涂层僵硬时，通过阐明IOP，OPP及其波动的年龄和疾病相关的变化来检验这种组织假设。 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 diagnostics and treatment modalities that employee IOP and OPP fluctuation reduction through modification of ocular coats stiffness or intraocular damping of IOP fluctuation.如果我们的结果不支持“波动”假设，那么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中适当的IOP测量频率并为患者护理提供信息。