Session: 07-07-03: Computational Modeling in Biomedical Applications III

Paper Number: 166050

Modeling Bleb Formation in Subretinal Injections Using Energy-Based Fracture Mechanics 

The study of subretinal injection and retinal drug delivery has gained significant attention with the rise of gene and cellular therapies for treating congenital retinal diseases and sub-macular hemorrhage. The injection involves the formation of a bleb, which can damage the retinal pigment epithelium (RPE) and surrounding structures, or even cause a macular hole if optimal delivery conditions are not considered. Previous research has shown that varying flow rates and pressures can cause different levels of retinal damage, but the optimal conditions for minimizing harm are still being explored.

Given the uncertainty of the biomechanical factors influencing bleb propagation, we aimed to assess the mechanism behind retinal detachment and damage using an energy-based fracture mechanic approach.

We designed a series of finite element analyses (FEA) of the posterior retinal structure to compute its stress-strain state under several injection pressures and bleb sizes. The energy release rate (ERR) along the bleb rim (the detachment interface between retina and choroid) was calculated via the J-integral across every bleb size and transmural pressure. The stress at the most critical bleb location was also collected to assess rupture on the retina’s surface.

We found that the exerted ERR and maximum stress nonlinearly increase with bleb size. Moreover, these mechanical metrics exhibit steeper gradients upon increased transmural pressures, passing from 0.25 J/mm³ and 0.998 MPa/mm at 4.70 mmHg, to 3.30 J/mm³ and 16.26 MPa/mm at 37.50 mmHg, respectively. The minimal pressure required for bleb propagation was determined for different bleb sizes, by identifying the pressure value at which the ERR met the detachment fracture toughness. Similarly, the pressure necessary for bleb rupture was captured by defining a permissible retinal stress. Curve fitting revealed that the pressure-to-bleb radius for detachment and rupture follows an inverse power law, with both the exponent and scaling factor dependent on the defined failure thresholds and material properties. The found numerical correlation provided a more representative depiction of the pressure changes than the traditional Young-Laplace equation, as it accounted for large deformations, bilaminar debonding, and non-spherical surface geometries. We also noted that detachment and rupture curves followed separate decay trends. Thus, depending on the retina's adhesive and strength characteristics, blebs may either form and propagate safely or fail at a specific size when the curves intersect—a scenario that becomes more pronounced with stronger retinal adhesive properties.

Observations in this study could enhance the understanding of the biomechanical effects of subretinal injection, guiding the precise selection of injection pressures to overcome retinal resistance while promoting safe and effective bleb propagation. Influencing biomechanical factors and trends also offer significant potential for advancing robot-assisted injections. Understanding the mechanical aspects of injection can enhance the precision and control offered by robotic systems, further improving the safety and efficacy of the procedure.

Presenting Author: Jose Colmenarez Florida Institute of Technology

Presenting Author Biography: PhD candidate in Biomedical Engineering at Florida Institute of Technology, conducting research in Dr. Gu's Biomechanics Lab. Focused on computational modeling of cardiovascular and ocular procedures, with an emphasis on integrating AI and biophysics to optimize clinical decision-making.

Authors:

Jose Colmenarez Florida Institute of Technology
Pengfei Dong Florida Institute of Technology
Linxia Gu Florida Institute of Technology