Retinal oximetry and fractal analysis of capillary maps in sickle cell disease patients and matched healthy volunteers.

PURPOSE: Fractal analysis can be used to quantitatively analyze the retinal microvasculature and might be a suitable method to quantify retinal capillary changes in sickle cell disease (SCD) patients. Retinal oximetry measurements might function as a proxy for the pathophysiology of cerebrovascular diseases. Moreover, hypoxia has an important role in the pathophysiology of diabetic and other retinopathies. However, little is known about the oximetry around the macula in SCD patients. With this study, we explored the feasibility to perform these quantified measurements in SCD patients. METHODS: Retinal microvascular and oximetry measurements were performed in eight SCD patients and eight healthy matched controls. Oximetry pictures and non-invasive capillary perfusion maps (nCPM) were obtained by the retinal function imager. Measurements were conducted twice on two different study days. Measured variables included monofractal dimension (Dbox), relative saturation, deoxygenated hemoglobin (deoxyHb), and oxygenated hemoglobin (oxyHb) concentration. RESULTS: No statistically significant differences in vessel density were found in the different annular zones (large vessels, p = 0.66; small vessels, p = 0.66) and anatomical quadrants (large vessels, p = 0.74; small vessels, p = 0.72). Furthermore, no significant between-group differences were found in the other different anatomical quadrants and annular zones around the fovea for relative saturation levels and deoxygenated Hb. However, the oxyHb levels were significantly lower in SCD patients, compared with those in matched controls in the temporal quadrants (p = 0.04; p = 0.02) and the superior nasal quadrant (p = 0.05). CONCLUSIONS: Our study demonstrated the feasibility of multispectral imaging to measure retinal changes in oxygenation in both SCD patients and matched volunteers. The results suggest that in SCD patients before any structural microvascular changes in the central retina are present, functional abnormalities can be observed with abnormal oximetry measurements.

Correction to: Retinal oximetry and fractal analysis of capillary maps in sickle cell disease patients and matched healthy volunteers.

In the published online PDF version, Figure 3 was incorrectly captured the same as Figure 1.

Retinal microcirculation imaging in sickle cell disease patients.

OBJECTIVES: To explore the feasibility of a new quantitative method for microvascular function: non-invasive retinal function imaging (RFI). in sickle cell disease (SCD) patients and healthy controls and have it benchmarked against Laser Speckle Contrast Imaging (LSCI) measurements. METHODS: The variability of Microvascular measurements was assessed in 8 SCD patients and 8 healthy matched controls. Measurements were conducted twice on two different study days. RFI was performed for assessment of arterial and venous retinal blood flow. LSCI measurements included post occlusive reactive hyperemia and IBH challenges. Measured variables included basal flow, flow upon occlusion-reperfusion and flow during an IBH. RESULTS: RFI arterial flow and venous flow and LSCI basal flow and peak flow showed excellent intra subject repeatability between days (CVC of 8.5% 9.5%, 7.6% and 7.7% respectively) and between measurements on one day (CVC of 7.0%, 7.7%, 7.6% and 4.7% respectively). RFI arterial flow (p<0.002), and RFI venous flow (p=0.007) differed significantly between SCD patients and controls in as did LSCI basal flow, maximal flow and delta flow during IBH (p<0.0001). CONCLUSIONS: RFI showed low variability for all readout measures, comparable with most microvascular measures from LSCI. The discriminating power of the RFI between SCD patients and controls demonstrate the feasibility of this device for quantitative assessment of the microcirculation in clinical research.

Levofloxacin-Induced QTc Prolongation Depends on the Time of Drug Administration.

Understanding the factors influencing a drug's potential to prolong the QTc interval on an electrocardiogram is essential for the correct evaluation of its safety profile. To explore the effect of dosing time on drug-induced QTc prolongation, a randomized, crossover, clinical trial was conducted in which 12 healthy male subjects received levofloxacin at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00. Using a pharmacokinetic-pharmacodynamic (PK-PD) modeling approach to account for variations in PKs, heart rate, and daily variation in baseline QT, we find that the concentration-QT relationship shows a 24-hour sinusoidal rhythm. Simulations show that the extent of levofloxacin-induced QT prolongation depends on dosing time, with the largest effect at 14:00 (1.73 (95% prediction interval: 1.56-1.90) ms per mg/L) and the smallest effect at 06:00 (-0.04 (-0.19 to 0.12) ms per mg/L). These results suggest that a 24-hour variation in the concentration-QT relationship could be a potentially confounding factor in the assessment of drug-induced QTc prolongation.