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An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
Published on: January 25, 2019
Predictive modelling of thrombus formation in diabetic retinal microaneurysms
He Li1, Konstantina Sampani2,3, Xiaoning Zheng1
1Division of Applied Mathematics, Brown University, Providence, RI 02912, USA.
Abstract:
Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). Vision can be reduced at any stage of DR by MAs, which may enlarge, rupture and leak fluid into the neural retina. Recent advances in ophthalmic imaging techniques enable reconstruction of the geometries of MAs and quantification of the corresponding haemodynamic metrics, such as shear rate and wall shear stress, but there is lack of computational models that can predict thrombus formation in individual MAs. In this study, we couple a particle model to a continuum model to simulate the platelet aggregation in MAs with different shapes. Our simulation results show that under a physiologically relevant blood flow rate, thrombosis is more pronounced in saccular-shaped MAs than fusiform-shaped MAs, in agreement with recent clinical findings. Our model predictions of the size and shape of the thrombi in MAs are consistent with experimental observations, suggesting that our model is capable of predicting the formation of thrombus for newly detected MAs. This is the first quantitative study of thrombosis in MAs through simulating platelet aggregation, and our results suggest that computational models can be used to predict initiation and development of intraluminal thrombus in MAs as well as provide insights into their role in the pathophysiology of DR.
Insights
Computational models predict thrombosis in microaneurysms (MAs), early signs of diabetic retinopathy (DR). Saccular MAs show more thrombus formation than fusiform MAs, aiding DR understanding.
Area of Science:
- Biomedical Engineering
- Ophthalmology
- Computational Fluid Dynamics
Background:
- Microaneurysms (MAs) are early indicators of diabetic retinopathy (DR), potentially causing vision loss.
- Existing ophthalmic imaging quantifies MA geometry and hemodynamics, but lacks predictive models for thrombus formation.
- Thrombus formation within MAs is a key factor in DR pathophysiology.
Purpose of the Study:
- To develop and validate a computational model for simulating platelet aggregation and thrombus formation in MAs.
- To investigate the influence of MA shape on thrombosis.
- To provide a tool for predicting thrombus development in individual MAs.
Main Methods:
- Coupling of a particle model with a continuum model to simulate platelet aggregation.
- Modeling of blood flow within MAs of varying geometries (saccular and fusiform).
- Comparison of simulation results with experimental observations and clinical findings.
Main Results:
- Thrombosis was significantly more pronounced in saccular MAs compared to fusiform MAs under physiological blood flow.
- The model accurately predicted the size and shape of thrombi within MAs.
- Simulation results align with existing clinical observations.
Conclusions:
- The developed computational model is capable of predicting thrombus formation in MAs.
- MA shape is a critical factor influencing thrombosis.
- This study offers a novel quantitative approach to understanding MA thrombosis and its role in DR.
