Uncertainty propagation and sensitivity analysis: results from the Ocular Mathematical Virtual Simulator

Prud'Homme, Christophe; Sala, Lorenzo; Szopos, Marcela

doi:10.3934/mbe.2021105

Cited by 6 publications

(6 citation statements)

References 40 publications

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“…Compartmental models have been used to investigate the relationships between intravascular and extravascular pressures and haemodynamics in the retina and choroid [64,93,120,205,226,233,254,256]. In these models, similar vessels are sorted into compartments, e.g.…”

Section: Effects Of Extravascular Pressure On Haemodynamicsmentioning

confidence: 99%

“…Because blood flow measurements may not be able to capture shifts in blood volumes during experiments (head tilting or microgravity conditions), IOP or systemic blood pressure shifts have been used as metrics for validation and analysis. The interplay between systemic blood pressure, IOP and compression of the CRA by the lamina cribrosa were also investigated by Prud'homme et al [233]. In the context of a sensitivity analysis, they created three virtual populations (normotensive, hypertensive and hypotensive) which differ by their blood pressure waveform.…”

Section: Effects Of Extravascular Pressure On Haemodynamicsmentioning

confidence: 99%

“…Furthermore, the use of digital evidence to inform clinical trials is also gaining traction. The recent increase in the number of literature reviews on mathematical models of the eye and the retina and the development of platforms for simulating the eye accessible to non-modellers demonstrate increased interest in ophthalmology [19,22,37,129,233,245,252].…”

Section: Introductionmentioning

confidence: 99%

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Advancing treatment of retinal disease through in silico trials

2023

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Treating retinal diseases to prevent sight loss is an increasingly important challenge. Thanks to the configuration of the eye, the retina can be examined relatively easily in situ. Owing to recent technological development in scanning devices, much progress has been made in understanding the structure of the retina and characterising retinal biomarkers. However, treatment options remain limited and are often of low efficiency and efficacy.In recent years, the concept of in silico clinical trials has been adopted by many pharmaceutical companies to optimise and accelerate the development of therapeutics. In silico clinical trials rely on the use of mathematical models based on the physical and biochemical mechanisms underpinning a biological system. With appropriate simplifications and assumptions, one can generate computer simulations of various treatment regimens, new therapeutic molecules, delivery strategies and so forth, rapidly and at a fraction of the cost required for the equivalent experiments. Such simulations have the potential not only to hasten the development of therapies and strategies but also tooptimise the use of existing therapeutics.In this paper, we review the state-of-the-art in in silico models of the retina for mathematicians, biomedical scientists and clinicians, highlighting the challenges to developing in silico clinical trials. Throughout this paper, we highlight key findings from in silico models about the physiology of the retina in health and disease. We describe the main building blocks of in silico clinical trials and identify challenges to developing in silico clinical trials of retinal diseases.

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Section: Effects Of Extravascular Pressure On Haemodynamicsmentioning

confidence: 99%

Section: Effects Of Extravascular Pressure On Haemodynamicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advancing treatment of retinal disease through in silico trials

2023

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“…On the other hand, they usually suffer from high variability due to (i) operator‐dependent and instrument‐dependent measurements, which can be different across clinical centers and (ii) inherent differences among individuals. To take into account these sources of uncertainty and variability, we refer to the preliminary sensitivity analysis we carried out in Reference 18 for the 0D components of the OMVS.…”

Section: Omvs Input Datamentioning

confidence: 99%

“…A preliminary version of the OMVS has been presented in Reference 16 and subsequently used in Reference 17 to target specific clinical applications related to glaucoma. A detailed uncertainty quantification and global sensitivity analysis study was conducted for a reduced version of the OMVS framework in Reference 18. However, until now, the full OMVS framework and the specific question of its validation have not been tackled directly yet.…”

Section: Introductionmentioning

confidence: 99%

The ocular mathematical virtual simulator: A validated multiscale model for hemodynamics and biomechanics in the human eye

Sala,

Prud'homme,

Guidoboni

et al. 2023

Numer Methods Biomed Eng

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We present our continuous efforts from a modeling and numerical viewpoint to develop a powerful and flexible mathematical and computational framework called Ocular Mathematical Virtual Simulator (OMVS). The OMVS aims to solve problems arising in biomechanics and hemodynamics within the human eye. We discuss our contribution towards improving the reliability and reproducibility of computational studies by performing a thorough validation of the numerical predictions against experimental data. The OMVS proved capable of simulating complex multiphysics and multiscale scenarios motivated by the study of glaucoma. Furthermore, its modular design allows the continuous integration of new models and methods as the research moves forward, and supports the utilization of the OMVS as a promising non‐invasive clinical investigation tool for personalized research in ophthalmology.

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Model order reduction and sensitivity analysis for complex heat transfer simulations inside the human eyeball

Saigre,

Prud'homme,

Szopos

2024

Numer Methods Biomed Eng

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Heat transfer in the human eyeball, a complex organ, is significantly influenced by various pathophysiological and external parameters. Particularly, heat transfer critically affects fluid behavior within the eye and ocular drug delivery processes. Overcoming the challenges of experimental analysis, this study introduces a comprehensive three‐dimensional mathematical and computational model to simulate the heat transfer in a realistic geometry. Our work includes an extensive sensitivity analysis to address uncertainties and delineate the impact of different variables on heat distribution in ocular tissues. To manage the model's complexity, we employed a very fast model reduction technique with certified sharp error bounds, ensuring computational efficiency without compromising accuracy. Our results demonstrate remarkable consistency with experimental observations and align closely with existing numerical findings in the literature. Crucially, our findings underscore the significant role of blood flow and environmental conditions, particularly in the eye's internal tissues. Clinically, this model offers a promising tool for examining the temperature‐related effects of various therapeutic interventions on the eye. Such insights are invaluable for optimizing treatment strategies in ophthalmology.

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Uncertainty propagation and sensitivity analysis: results from the Ocular Mathematical Virtual Simulator

Cited by 6 publications

References 40 publications

Advancing treatment of retinal disease through in silico trials

Advancing treatment of retinal disease through in silico trials

The ocular mathematical virtual simulator: A validated multiscale model for hemodynamics and biomechanics in the human eye

Model order reduction and sensitivity analysis for complex heat transfer simulations inside the human eyeball

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