Non-dimensional analysis of retinal microaneurysms: critical threshold for treatment

Abstract

Fluid dynamics play a fundamental role in the development of diabetic retinopathy, one of the leading causes of blindness in the Western world, affecting over 4 million people in the US alone. The disease is defined by microaneurysms, local expansions of capillaries that disturb the hemodynamic forces experienced by the endothelium leading to dysfunction, leakage and edema. Here we present a method to identify microaneurysms with a high risk of leakage based on a critical ratio of microaneurysm to vessel diameter. We derive this non-dimensional parameter from an analytical solution and generalize it using experimentally validated numerical methods. We show that this non-dimensional parameter defines the shear force experienced by endothelial cells, below which endothelial dysfunction is evident in vivo. Our results demonstrate the involvement of vWF in diabetic retinopathy, and explain a perceived disconnect between microaneurysm size and leakage. This method will allow experts to treat microaneurysms poising a high-risk of leakage, prior to edema, minimizing damage and saving vision.

Estimation of Diabetic Retinal Microaneurysm Perfusion Parameters Based on Computational Fluid Dynamics Modeling of Adaptive Optics Scanning Laser Ophthalmoscopy

“…Several studies have evaluated the pathogenesis and natural history of MAs using ex vivo (e.g., transmission electron microscopy and scanning electron microscopy) and in vivo (scanning laser ophthalmoscopy and optical coherence tomography) imaging approaches to characterize pericyte loss, basement membrane thickening, and endothelial proliferation and disruption (Wise, 1957 ; Cogan et al, 1961 ; de Oliveira, 1966 ; Ashton, 1974 ; Moore et al, 1999 ). One study (Ezra et al, 2013 ) proposed using MA-to-vessel radius ratio as a potential marker for assessing risk of leakage, and suggested that shear stress at the MA wall may lead to endothelial dysfunction.…”

Rapid development of entity-based data models for bioinformatics with persistence object-oriented design and structured interfaces

“…Aneurysms’ data was integrated with our previously published criteria of aneurysm risk of rapture [ 7 ]. A schematic of the database with its different associations is shown in Fig.…”

“…A more substantial ‘data to knowledge’ utility of this database can be developed. For example, our predictive model of aneurysms’ risk of rapture uses a non-dimensional analysis of fluid dynamics to set a critical geometrical threshold of treatment [ 7 ]. Piccinelli and colleagues could derive geometrical measures of patients’ aneurysms’ geometries, which can be used with the prediction model to determine risk of rapture [ 29 ].…”

“…Today, biological data is not limited to sequential information, which is typically stored in primary databases such as NCBI’s Nucleotide and Protein data sets. Biological data also encompass graphs [ 4 ], statistical models [ 5 ], geometric information [ 6 ], vector fields [ 7 ], patterns [ 8 ], images [ 9 ], computational models [ 10 ] and others. A recent important advance regarding data heterogeneity was developed by Allan and colleagues, who have developed OMERO, an open source software platform which uses a server-based middleware application to provide a unified interface for images, matrices and tables [ 9 ].…”

Multimodal Imaging of Microvascular Abnormalities in Retinal Vein Occlusion

“…In contrast, Ezra et al [ 130 ] suggested that the microaneurysm radius/associated vessel diameter ratio might be a useful metric for predicting leakage risk.…”