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An intact blood-retinal barrier is critical to maintaining the function of the retina. Many diseases of the eye have been directly associated with impairment in vascular permeability, and methods to measure vascular permeability could offer a window into early detection of disease; however, there exist no direct measures of vascular permeability that have be translated to the clinic. This work details a complete clinical workflow to quantify vascular permeability and volumetric blood flow from fluorescein videoangiography data, with validation through realistic simulations. For optimizing the protocol, this study carried on frame rate of fluorescein videoangiography to generate a high-resolution image while minimizing the error.

Fluorescein videoangiography is often used to visualize diabetic retinopathy (DR), a degenerative disease characterized by degradation of retinal blood vessels. However, more sensitive and quantitative measures of increased vessel permeability in the asymptomatic phase of DR (non-proliferative DR) could help identify patients who would benefit from therapeutic intervention to avoid vision loss. Here, a modified “adiabatic approximation to the tissue-homogeneity model” was shown in simulations and rat experiments to estimate extraction fraction within a 20%-error for physiological ranges of vascular permeability expected in nonproliferative DR, even in low-dynamic-range (8-bit) fluorescein imaging systems that are standard in many institutes.

Clinical symptoms of diabetic retinopathy are not detectable until damage to the retina reaches an irreversible stage, at least by today’s treatment standards. As a result, there is a push to develop new, “sub-clinical” methods of predicting the onset of diabetic retinopathy before the onset of irreversible damage. With diabetic retinopathy being associated with the accumulation of long-term mild damage to the retinal vasculature, retinal blood vessel permeability has been proposed as a key parameter for detecting preclinical stages of retinopathy. In this study, a kinetic modeling approach used to quantify vascular permeability in dynamic contrast-enhanced medical imaging was evaluated in noise simulations and then applied to retinal videoangiography data in a diabetic rat for the first time to determine the potential for this approach to be employed clinically as an early indicator of diabetic retinopathy. Experimental levels of noise were found to introduce errors of less than 15% in estimates of blood flow and extraction fraction (a marker of vascular permeability), and fitting of rat retinal fluorescein angiography data provided stable maps of both parameters.