Retinal vascular permeability determined by dual-tracer fluorescence angiography

Diabetic retinopathy is the leading cause of blindness in working age indiv iduals in the United States. Breakdown of the blood-retinal barrier is one of the earliest events in the proggression of diabetic retinopathy. Ideally , therapeutic measures would be directed at this early stage, but there are few sensitive, quantitative methods to assess the retinal vascular barrier in vivo. We present here a method that combines fluorescence microangiogra phy and the simultaneous use of two: fluorescent tracers to quantitatively assess the retinal vascular barrier. PS/F (permeability X surface area flow ) describing the retinal vasculature of Long Evans rats was found to be 0.0 86 +/- 0.031 (n = 13, avg. +/- s.d.). Based on estimates of flow and surfac e area, we estimate the permeability of sodium fluorescein to be approximat e to 1.2 X 10(-5) cm/s. Infusion of a hyperosmolar solution of 1.6 M mannit ol for 5 min significantly increased PS/F in individual veins and significa ntly increased a flow weighted PS/F from 0.073 +/- 0.028 to 0.16 +/- 0.034 (n = 3). In conclusion, we have adapted indicator dilution techniques to qu antitatively assess the retinal vasculature in vivo. We have found dual-tra cer fluorescence angiography to be a sensitive indicator of increases in th e blood-retinal barrier produced by hyperosmolar mannitol. This methodology is a promising new minimally invasive strategy which may be adapted to qua ntitatively track retinal vascular permeability. (C) 2001 Biomedical Engine ering Society.