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“金标准”眼压计的力学缺陷和固液膜解耦原理与实现
Alternative TitleThe defects of Goldmann applanation tonometer in mechanics and approach to decoupling the effects of corneal resistance and surface tension of tears from intraocular pressure measurement
卢怡煊
Thesis Advisor白以龙 ; 杨荣
2023-05-24
Degree Grantor中国科学院大学
Place of Conferral北京
Subtype博士
Degree Discipline固体力学
Keyword压平眼压计 眼压 液膜 角膜 解耦
Abstract

眼压是青光眼诊断的重要指标,是反映眼内状态的基本参量。控制青光眼发展的有效途径是控制眼压。目前的研究表明,眼压每升高1 mmHg会将青光眼的患病风险提高10%。由于眼压无法直接测得,现有眼压计均通过外部响应进行反演获得眼压。眼压测量要求在体原位,测量的眼压值在10 mmHg量级,这要求仪器有较高测量精度(约1‰大气压)。现有眼压计以Goldmann眼压计为“金标准”,然而它的测量原理,采取了笼统地将角膜反力和泪膜张力(方向相反)完全抵消的处理方案。两力抵消与否,实际上与难以确定的角膜(弹性模量)和泪膜的性质密切相关。这种处理方案会导致眼压测量值低估,达到造成视神经损伤的量级,严重影响青光眼的诊断和治疗。本文针对“金标准”眼压计的上述力学缺陷,使用与角膜性质相近的水凝胶/硅水凝胶材料(用于制造隐形眼镜),制备与真实角膜形状接近的人工角膜模拟Goldmann压平眼压计的角膜压平过程,同时制备与人工角膜含水率相当的单轴拉伸试样确定水凝胶材料的弹性模量。采用微力材料试验机测试压头合力与压头下降位移、液膜扩展半径的关系,确定角膜和液膜对压头作用关系。建立分离角膜和液膜对眼压作用的方法,确定解耦影响对应的深度/载荷/接触面积。同时对猪眼球进行整体压平试验,确认测试规律的可靠性。
本文的主要研究内容可分为:深入分析固膜(角膜)与液膜(泪膜)的力学响应和解耦固、液膜对眼压作用的原理两个方面。
(1)从模拟和实验角度,确定了压平实验过程中,压头合力,角膜反力,液膜张力,眼压产生的力随压头下降位移,液膜扩展半径的影响,并得到如下结果:(a)压头合力W随着液膜扩展半径a的增加而增加。相同的液膜扩展半径a,厚度较大,曲率半径较小或弹性模量较高的角膜对应的压头合力W越大,对应得到的眼压测量值IOPG越大;(b)压平实验过程中存在的力学量,压头合力W,液膜张力Ft,角膜反力Fc和眼压IOP产生的力FIOP之间的关系可以表达为:W + Ft = FIOP + Fc = IOP×𝜋×(𝑎−𝑎0)2+Fc;(c)液膜张力Ft在眼压测量过程中可以视为一个定值,并且量级基本在1 mN;(d)角膜反力Fc在压平半径位于角膜厚度区间内与压平半径ac呈现良好的线性关系,即Fc~K1×ac,系数K1的大小与角膜厚度t,角膜曲率半径R,和角膜弹性模量E有关,K1=2Et2/R。
(2)深入分析角膜反力和液膜张力与压平深度、液膜扩展面积等直接可测量之间的关系及差异,建立反解控制方程。得到如下结果:(a)根据压平实验过程中存在的力学量的表达式,通过设定三个特定的液膜扩展半径a1,a2,a3为参考,可以得到三元一次方程组,通过方程组的求解,可以得到眼压IOP,以及弹性模量E;(b)根据猪眼球整体压平实验的实验结果,得到了猪角膜的弹性模量E的范围为7-40 kPa。

Other Abstract

Intraocular pressure (IOP) is an important indicator for diagnosing glaucoma, and it is an essential parameter to show the intraocular status. Researches show that when intraocular pressure increases 1 mmHg, the risk of getting glaucoma increases by 10%. It is not directly measureable due to its inner attribute; hence, the tonometers exist now all utilize the outer response of the cornea to obtain IOP. The measurement of IOP is done in vivo, and its magnitude is 10 mmHg, which require the tonometer to have a resolution of 1‰ atm. Goldmann applanation tonometer (GAT) is considered as a “gold standard” in IOP measurement, however, it bases on the assumption of the cancelation of corneal reaction force and surface tension of tears. The assumption highly depends on the properties of cornea (elastic modulus) and tears, which are difficult to be determined. This assumption would cause the IOP measured to be lower than the actual situation, with a magnitude that could reach the critical pressure to cause the damage of optic nerve, which will greatly jeopardize the diagnose and treatment of glaucoma. In view of the above mechanical defects of "gold standard" tonometer, hydrogel/silicon hydrogel materials (used for contact lenses) with similar properties to cornea were used to prepare artificial cornea with similar shape to real cornea to simulate the corneal flattening process of Goldmann tonometer. At the same time, the elastic modulus of the hydrogel material was determined by uniaxial tensile sample with the same water content as the artificial cornea. The relationship between the resultant force of the indenter and the descending displacement of the indenter and the liquid film spreading radius was tested by micro-force material testing machine, and the interaction between the cornea and the liquid film on the indenter was determined. Establish a method to separate the effect of cornea and liquid film on IOP and determine the depth/load/contact area corresponding to the decoupling effect. At the same time, the whole pig eyeball was flattened to confirm the reliability of the test law.
The main research content of this paper can be divided into two aspects: to investigate the mechanical response of solid (cornea) and liquid (tears) film and the principle of decoupling the effect of cornea and liquid film on IOP.
(1) With the results of simulation and experiment, the influences of the resultant force of the indenter, the corneal reaction force, the surface tension of liquid film, and the force generated by the intraocular pressure with the descending displacement of the indenter and the liquid film spreading radius during the flattening experiment were determined. The result is as follows: (a) The resultant force of the indenter, W, increases with the increase of liquid film spreading radius, a. With the same liquid film spreading radius, a, the cornea with larger thickness, smaller curvature radius or higher elastic modulus has larger resultant force, W, and the corresponding measured value of intraocular pressure IOPG is larger; (b) The relationship between resultant force of the indenter, W, surface tension of liquid film, Ft, corneal reaction force, Fc, and force generated by intraocular pressure, FIOP, during the flattening experiment can be expressed as follows: W + Ft = FIOP + Fc = IOP×𝜋×(𝑎−𝑎0)2+Fc; (c) The surface tension of liquid film, Ft, can be regarded as a constant value in the process of intraocular pressure measurement, and the magnitude is 1 mN; (d) The corneal reaction force, Fc, showed a good linear relationship with the flattening radius, ac, within the thickness range of cornea, that is, Fc~K1× ac. The coefficient, K1, was related to corneal thickness, t, corneal radius of curvature, R, and corneal elastic modulus, E, K1=2Et2/R.
(2) The relationship and difference between corneal reaction force, surface tension of liquid film, depth and liquid film spreading area were analyzed, and the inverse solution governing equation was established. The results are as follows: (a) According to the expression of the mechanical quantity existing in the process of the flattening experiment, by setting three specific liquid film spreading radius a1, a2 and a3 as the reference, the ternary first-order equations can be obtained. By solving the equations, the intraocular pressure IOP and the elastic modulus E can be obtained. (b) According to the results of the pig eyeball flattening experiment, the range of elastic modulus E of the pig cornea was 7 to 40 kPa.

Language中文
Document Type学位论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/92346
Collection非线性力学国家重点实验室
Recommended Citation
GB/T 7714
卢怡煊. “金标准”眼压计的力学缺陷和固液膜解耦原理与实现[D]. 北京. 中国科学院大学,2023.
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