Modelling subretinal injections to improve delivery of treatment for age-related eye diseases

黄斑变性是导致60岁以上成年人严重视力丧失的主要原因之一。AMD是一种视网膜疾病，其导致视网膜中心区域（黄斑）的功能改变和降低，在最严重的情况下，其导致中心视力丧失。由于解剖学和生理学的限制，将治疗药物递送到视网膜的该区域是具有挑战性的。视网膜下注射是一种用于治疗视网膜疾病的各种创新眼部疗法的递送技术，例如基因疗法。视网膜下注射技术包括在RPE细胞和光感受器之间的空间中递送治疗。滤过泡的位置似乎受到几个因素的调节，包括相对于中心凹的位置、视网膜的厚度、视网膜血管的位置以及视网膜与RPE之间的粘附。在此过程中，针对中央凹和不可预测的扩大的滤过泡相对于注射点的方向是持续存在的问题。计算模型可以是一个有用的工具，有一个更好的理解的物理和解剖因素，发挥了至关重要的作用，在水泡的产生和传播。使用经验证的有限元建模可以是一种快速方法，可以帮助改进视网膜下注射技术，从而提高患者的治疗效果并扩大眼科治疗的范围。这里的目标是开发一个3D计算模型的眼睛，包括解剖特征，如血管，以准确地再现视网膜下注射过程。为了建立精确描述的计算机模型，对视网膜条进行拉伸测试，以确定视网膜的生物力学特性。从90只猪眼上共切下130个条，每组10个样品，以比较视网膜不同区域的生物力学特性。总共测试了13个不同的组，以评估血管的影响、视网膜的各向异性特性以及象限之间的差异。结果表明，血管显著影响视网膜的强度和硬度。此外，在相同象限中提取但具有不同取向的条带显示出不同的拉伸强度，这表明视网膜在其表面上是各向异性的。使用Abaqus CAE，创建二维有限元模型以模拟视网膜和视网膜色素上皮（RPE）之间的粘附，结合视网膜的生物力学特性。进行参数研究以评估注射参数对滤过泡形状的影响，获得的结果表明IOP和注射速率显著影响滤过泡形状，其中IOP升高和注射速率加快导致滤过泡高度增大。为了更好地模拟视网膜下滤过泡的产生，已经开发了结合猪眼的几何形状和生物力学特性的3D有限元模型。关于3D模型的工作仍在进行中，重点是改进内聚层属性的定义，以生成与实际应用中观察到的高度和宽度相同的视网膜下水泡。以这种方式，可以使用视网膜下泡的图像来验证模型，并执行参数研究以评估注射参数对泡形状的影响。

Age-related macular degeneration is one of the main causes of severe vision loss in adults over 60. AMD is a retinal disease that causes an alteration and a reduction in the functionality of the central area of the retina (macula), which in the most severe cases causes the loss of central vision. Delivery of therapeutic drugs to this area of the retina is challenging due to anatomical and physiological limitations. Subretinal injection is a delivery technique for a variety of innovative ocular therapies used to treat retinal diseases, such as gene therapy. Subretinal injection technique consists in the delivery of treatment in the space between the RPE cells and the photoreceptors. The location of the bleb seems to be regulated by several factors including the location relative to the fovea, the thickness of the retina, the location of retinal blood vessels and the adhesion between retina and RPE. Targeting the fovea and the unpredictable direction of the enlarging bleb with respect to the injection point are persistent problems during this procedure. Computational model can be a useful tool to have a better understanding of the physical and anatomical factors that play a crucial role in bleb generation and propagation. Use of validated finite element modelling can be a fast method that can help to refine the technique of subretinal injections, thereby enhancing patient outcomes and expanding the horizons of ophthalmic therapies. Here the aim was to develop a 3D computational model of the eye that includes anatomical features, such as blood vessels, to accurately reproduce the subretinal injection procedure. In order to build accurately described computer models, the biomechanical properties of the retina were determined performing tensile test on retinal strips. A total of 130 strips, ten samples for each group, were dissected from 90 porcine eyes to compare the biomechanical properties in the different areas of the retina. A total of thirteen different groups have been tested, to evaluate the effects of the blood vessels, the anisotropic properties of the retina and the difference between the quadrants. The results obtained showed that blood vessels significantly impact the strength and stiffness of the retina. Additionally, strips extracted in the same quadrants, but with different orientations, showed different tensile strength suggesting that the retina is anisotropic across its surface. Using Abaqus CAE, a two-dimensional finite element model was created to mimic the adhesion between the retina and the retinal pigment epithelium (RPE), incorporating the biomechanical properties of the retina. A parametric study was performed to assess the impact of the injection parameters on bleb shape and the results obtained showed that IOP and the injection rate significantly influence bleb shape, where increased IOP and faster injection rate result in larger bleb heights. To better mimic the subretinal bleb generation, a 3D finite element model incorporating the geometry and biomechanical properties of a porcine eye has been developed. Work on the 3D model is still ongoing, focusing on improving the definition of the cohesive layer properties to generate a subretinal bleb with the same height and width as those observed in actual applications. In this way, it would be possible to validate the model using images of subretinal blebs and perform a parametric study to evaluate the effects of the injection parameters on the bleb shape.