Biomechanical Mechanism Of Angle Closure In Primary Angle Closure Glaucoma

Primary angle closure glaucoma (PACG) is associated with the most common cause of blindness in China. The angle closure of primary angle closure suspect (PACS) can either progress slowly or appear acutely in some conditions, resulting in the irreversible loss of visual function. To know the mechanism and to select which PACS has high risk are important for the preventive treatment of primaryangle closure disease.Recent studies suggest that static anatomical factors and dynamic trigger factors interplay in the pathogenesis of PACG. Ocular static anatomical factors include shallow anterior chamber, small chamber angle, large iris and lens with great curvature, and short axial length. They may be easier to narrow the angle in some dynamic conditions. However, restricted by technical challenges, few studies discuss whether those anatomical factors themself may change the aqueous flow, and then affect the iris behavior and the probability of PACGIn addition, those static differences can’t adequately explain the different prevalence of PACS with the same anatomic features. More and more studies that look at the dynamic changes in the eye provide important new information about angle closure. Pupil block, for instance, is widely accepted as an increased resistance of aqueous flow from the posterior chamber to the anterior chamber at the space between the lens and the iris, tending to push the iris and then close the angle. The maximum force may occur particularly when the pupil is in the mild dilated position. Normal eyes also have a certain size of physiological force. Therefore, another annoying clinical problem is how to estimate the pupil-blocking force quantitatively and to determine a real value for the threshold of PACG.Pupil block does not play the only role in the occurrence of angle closure. PACS who had a patent peripheral iridotomy will also occur angle narrowing, though it elimated the pupil block. Some therefore have suggested that the mechanism of PACG is complicated and multiplex. Considering the iris as the key structure of angle closure, there is no doubt that iris deformation and its mechanics are playing a more and more important role in the dynamic triggered mechanism.Biomechanics has been developed as a science concerned with the biofluid mechanics, solid biomechanics and sports biomechanics. It focuses on the measurements of anatomical features and mechanical properties by means of the methods of mechanics experimental techniques. Computer simulations and experiments are also applied in the study based on the physical principle such as Newton’s laws of conservation. Howerer, recent breakthroughs in the multi-disciplines have resulted from efforts to provide a wide application of biomechanical principle and method in the medical research. They can provide new research direction for exploring biological phenomena of disease emergence and development.Thus, by using biomechanical theory and research methods, this study found a new perspective to explore the mechanisms of angle closure. As described below, it explained from a static view into a dynamic view, from in vitro simulation into in vivo measurements:Firstly, taking the fluid dynamic theory as a starting point, this study used the computer simulation to describe the aqueous humor flow of PACS with its static anatomy, and to explore the effect of fluid to the biomechanics behavior of anterior chanmber tissue such as iris.Secondly, basing on the Mopstone’vector formula, this study combined with a customized image-processing software to estimate pupil blocking force quantitatively, and to determine the pathological threshold of angle closure in the PACS.Finally, focusing on the iris dynamic changes, this study analyzed the relationship between the iris configuration and the angle closure, and investigated the protective role of iris compression during the provocative test of pharmacologic mydriasis. Part13D reconstruction of anterior chamber and numerical simulation of fluid dynamics in primary angle closure suspectsPurpose:To reconstruct a3D model of human anterior chamber based on the OCT imaging, and to explore the effect ofanatomical difference between the normal and the PACS on the fluid dynamics.Methods:According to the OCT imaging of33PACS and33age-and gender-matched normal subjects,3D anterior chamber models were reconstructed respectively by the method of UG parametric design. And numerical simulations of fluid dynamics in the whole anterior chamber were analyzed by the finite volume methods using the CFX software. The streamline, velocity, temperature, shear stress and heat flux in the anterior chamber were obtained from the results of numerical simulations.Results:3D finite volume models of PACS and normal controls were built. Different anatomy of anterior chamberin the PACS appeared to have no apparent influence on the streamline and temperature distribution. The aqueous vortex was induced mainly by the buoyancy, which went like ellipse along the anterior chamber in the standing position, but spread from the pupillary axis as a circular in the prone and supine positons. The temperature distribution was linear which was similar to the heat conduction in solids. Narrow anterior chamber of PACS, limiting the space of convection, led to a decrease of velocity andshear stress, a weakening of heating upper chamber, but an increase of heat flux in each position. The average aqueous velocity of the PACS and the normal were0.875×10-4m·s-1and1.22×10-4m·s-1respectively in the standing position. The average shear stress of cornea were3.24×10-4Pa and4.52×10-4Pa respectively, the average shear stress of iris were3.01×10-4Pa and4.73×10-4Pa respectively. The average heat flux of cornea were-1765.05W·m-2and-992.474W·m-2respectively, the average heat flux of iris were2574.5W-m"2and1646.94W·m-2respectively, and the average heat flux of lens were709.514W·m-2and633.012W·m-2respectively.Conclusions:It is comparatively true that those models simulate the real aqueous flow characteristic of anterior chamber parametes in PACS. The results of numerical simulations are useful for studying the aqueous dynamics and the pathogenesis of diseases related to the angle closure glaucoma. Part2Optical coherence tomography quantitative analysis of pupil-blocking force in primary angle closure suspectsPurpose:To compare pupil-blocking force (PBF) quantitatively between PACS and normal subjects, and to explore its diagnostic value and association with the anterior chamber parameters.Methods:54eyes of54patients with PACS,34eyes of34age-and gender-matched subjects with open angles underwent a history-taking process and an ophthalmological test, including vision, intraocular pressure, gonioscopy, axial length measurement, retinal nerve fibre layer and visual field analysis. All the enrolled eyes were imaged using OCT and pentacam scheimpflug system (Pentacam) under a standardized dark condition. PBF and anterior chamber parameters especially iris and angle values were estimated quantitatively using a computer image processing. ROC curves were used to analyze the diagnostic value of PBF. The regression analysis was showed to determine the variables associated most strongly with the PBF.Results:Compared with the open-angle eyes, PACS had narrower anterior segment (central anterior chamber depth CACD, peripheral anterior chamber depth PACD, anterior chamber volume ACV, angle opening distance at500um AOD500, anterior chamber angle ACA)(P<0.001) and thinner iris at2000um (IT2000, P<0.05) with greater curvature (Ⅰ-curv, P<0.001). The difference of pupillary diameter (PD), iris thickness at750um (IT750), iris cross-sectional area (IS), iris volume (IV) and central corneal thickness (CCT), corneal volume (CV) had no statistical significance (P>0.05). The PBF of PACS was twice as much as that of open-angle eyes (0.0792±0.0522λ, vs.0.0300±0.0226λ,λ meant the young’s modulus of iris stroma, P<0.001). The area under ROC curve of PBF in the diagnosis of PACS was0.840, and the best cut-off point was0.0321λ, with the sensitivity and specificity were0.926and0.588respectively. While the area under ROC curve of PBF in the diagnosis of PBF at high risk was0.741, and the best cut-off point was0.0768λ, with the sensitivity and specificity were0.615and0.855respectively. Based on the multivariate analysis, significant predictors of PBF included female (P=0.024), an acute episode of the fellow eye (P<0.001), IT750(P<0.001) and I-curv (P<0.001).Conclusions:The pupil block of PACS forces dramatically more than does that of open-angle eyes. OCT quantitative analysis of PBF may be helpful for understanding the mechanics of pupil block and making decision considering prophylactic peripheral iridotomy. Part3Anterior segment changes after pharmacologic mydriasis in primary angle closure suspects.Purpose: To compare the changes of anterior segment especially iris parameters induced by pharmacologic mydriasis between PACS and normal controls, and to explore the role and mechanism of dynamic iris involved in the development of PACG.Methods:The study comprised19eyes of19PACS and19eyes of19age-and sex-matched normal controls. All the eyes underwent a history-taking and a thorough ophthalmological examination, including visual acuity, intra-ocular pressure, gonioscopy, axial length measurement, retinal nerve fibre layer and visual field analysis by an independent ophthalmologist. Pentacam and OCT measurements before and30min after instillation of compound tropicamid were performed and compared in a standardized dark room. Biometric evaluations of irisand chamber angle were estimated by a special image-processing software. Statistical analysis was submitted to calculate the inner-and inter-group differences, and then to evaluate the relationships between the change of AOD500and other variables.Results:Baseline corneal parameters (corneal curvature Km, astigmatism Astig, CV, CCT) and iris variables (IT750, IS, IV) did not differ significantly between PACS and normal controls. PACS had smaller PD (P<0.05), more I-curv (P<0.001), narrower anterior chamber (CACD, PACD, ACV, AOD500)(P<0.001) and smaller axial length (AL, P<0.05) in comparison with normal controls. Pharmacologic mydriasis led to a significant increment in IT750, CACD, PACD, and ACV (P<0.001), whereas a significant decrement in I-curv, IS and IV (P<0.001) in both groups. AOD500was increased significantly in normal controls (-0.074±0.111mm, P<0.05), but not in PACS (-0.020±0.087mm, P>0.05). Iris volume change per millimeter of pupil dilation (△IV/△PD) decreased significantly less in PACS than normal controls (-2.47±1.33mm2vs.-3.63±1.58mm2, P<0.05). Linear regression analysis showed that the change of AOD500was associated mostly with the change of CACD and△IV/APD (P=0.002), followed by gender (P<0.05).Conclusions:Smaller△IV/△PD is related significantly with the less anterior angle opening in PACS after pharmacologic mydriasis. Dynamic iris compressibility may be as a prospective indicator of angle closure development.