Improved reproducibility of the 'large-window' method of assessing transcapillary and interstitial fluorescein diffusion in the skin in healthy subjects and in subjects with insulin-dependent diabetes mellitus.

The transcapillary and interstitial diffusion of intravenously administered sodium fluorescein is used as a marker for capillary permeability. Fluorescein diffusion has been expressed by different parameters with reported coefficients of variation of 14-20%. Aim of the present study is to select a parameter which combines excellent reproducibility with the potential for discriminating insulin-dependent diabetic patients from healthy subjects. We performed three experiments to assess day-to-day reproducibility: 5 healthy subjects were measured twice, 1 healthy subject was measured 6 times and 1 subject with insulin-dependent diabetes mellitus was measured 5 times. We averaged the relative fluorescence light intensity (IREL(t)] from dye arrival until a certain time point [IAV(t)], instead of using the relative intensity at one time point. IAV (7 min) showed markedly improved reproducibility, expressed as geometric mean of the coefficients of variation of the three separate experiments: 10%. In addition, a group of 12 insulin-dependent diabetic subjects was compared with 12 healthy control subjects. Median IAV (7 min) was 69.5% (95% CI: 65.3-78.1%) in the diabetic subjects and 54.9% (95% CI: 52.1-60.0%) in the control subjects (p < 0.001). Since IAV (7 min) combines excellent reproducibility with a good discriminating power, we advise its use in further studies.