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

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.