Search

Purpose: A fluorophotometer designed to measure aqueous flow in murine eyes was tested with artificial fluorescein chambers and in live mice with different anesthesia regimens, aqueous flow suppressants, and an anterior chamber cannulation method., Methods: Two hours following topical fluorescein application, one group of CD-1 mice was anesthetized with ketamine/xylazine, 2,2,2-tribromoethanol, or ketamine alone. Cornea and anterior chamber fluorescein concentrations were measured periodically for 60 to 90 minutes by fluorophotometric scans to calculate aqueous flow. Later, a subgroup of mice underwent aqueous flow measurement by anterior chamber cannulation. A third group was treated with timolol, dorzolamide, and vehicle in a crossover manner 1 hour prior to fluorophotometric scans., Results: Aqueous flow with ketamine/xylazine anesthesia (0.09 ± 0.05 μL/min, mean ± SD, n = 24) was slower than with tribromoethanol or ketamine alone (P < 0.001). Timolol reduced aqueous flow from 0.20 ± 0.07 μL/min to 0.07 ± 0.03 μL/min (P = 0.001) under tribromoethanol anesthesia and from 0.14 ± 0.03 μL/min to 0.10 ± 0.02 μL/min (P = 0.004) under ketamine anesthesia but not under ketamine/xylazine anesthesia. Dorzolamide reduced aqueous flow from 0.09 ± 0.03 to 0.06 ± 0.03 μL/min (P = 0.04) under ketamine/xylazine anesthesia. Aqueous flow by anterior chamber cannulation (0.20 ± 0.13 μL/min) was greater (P = 0.05) than by fluorophotometry (0.09 ± 0.07 μL/min)., Conclusions: A new noninvasive fluorophotometric method detected effects of general anesthesia and known aqueous suppressants on aqueous flow in mice. Aqueous flow measured by fluorophotometry was slower than by cannulation, and was technically easier with less variability. The mouse fluorophotometer is useful for repeated measurements of aqueous flow in the murine eye making crossover and longitudinal studies possible.

Vitreous fluorophotometry was performed on 240 eyes of 120 young subjects who had insulin-dependent diabetes mellitus (type I) and various grades of retinopathy. The concentration of fluorescein was measured in the anterior chamber and posterior vitreous 1 hour after intravenous injection of fluorescein. There was a significant association (P less than .001) between the grade of retinopathy and the level of posterior vitreous leakage. The amount of posterior vitreous leakage in each eye also had a significant association with borderline elevation of diastolic blood pressure. Subjects with excessive posterior vitreous leakage had significantly higher levels of urinary microalbumin excretion. In a multiple linear regression analysis for posterior vitreous leakage, retinal grade consistently entered the model at a significant level (P less than or equal to .00001 to .003). Blood pressure also entered the model for posterior vitreous leakage at a significant level for retinal grades of the right and left eyes and of the worst eye. These results demonstrate an association between leakage of retinal and renal vessels, possibly linked at least in part to elevation in diastolic blood pressure.

We compared insulin-dependent diabetic patients with minimal (16 eyes of 9 patients) or no retinopathy (45 eyes of 27 patients) to normal volunteers (20 eyes of 12 subjects) using a commercial vitreous fluorophotometer and different procedures for artifact correction. The influence of background autofluorescence was minimized through the use of a software program that subtracted a fluorophotometric scan obtained before administration of fluorescein from that obtained after its injection. We also compared two programs designed to minimize the contribution of the chorioretinal peak spread function to the readings in the vitreous. The fluorescein concentration in the posterior vitreous was then averaged within two different regions. We then assessed the influence of these data-processing methods on the spread of the results of the different groups. The clinical study showed that only the posterior vitreous concentration of fluorescein is relevant in the evaluation of the blood-retinal barrier. However, since there is a gradient of fluorescein concentration in the posterior vitreous, one needs a scanning device so that one can measure at a precise location in front of the retina. The posterior vitreous concentration of fluorescein was significantly increased in diabetic subjects with one or no aneurysms as compared with normals. Moreover, the eyes with minimal retinopathy, as judged by the presence of microaneurysms, had higher values than those without retinopathy. The clear differences among these three groups were not present when the midvitreous values were used.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts related to the wave-spreading phenomenon of fluorescent structures within the eye interfere with interpretation of vitreous fluorophotometric data. A standardized protocol which minimizes such artifacts is desirable in order to reveal actual changes in vitreous fluorescence. We have devised a protocol which reduces artifacts of crystalline lens autofluorescence and "tailing" from both lens and retina by the subtraction of preinjection data from measurements taken one hour after intravenous injection of fluorescein. A method of calculation is presented, performed automatically when programmed into a computerized fluorophotometer. Distinctions among healthy subjects and different kinds of ocular pathology are sharper when artifacts are reduced and the data are normalized to plasma fluorescein concentration. Examples of data from subjects with diabetes and no retinopathy, hypertension, cystoid macular edema, panuveitis and pars planitis are presented.

The technical aspects of fluorophotometry equipment are presented. The sources of artifact are described and a protocol to optimize the use of the "Coherent Fluorotron Master" system is presented. The results of fluorophotometry studies on ten patients indicate that more accurate data evaluation can be achieved using this approach.

We tested the hypothesis that anthracycline-induced cardiac and renal damage is mediated by vasoactive substances. A 1-minute exposure to 5 micrograms per ml. of doxorubicin (DXR, Adriamycin) produced cardiac histamine release in isolated rabbit hearts. Under conditions in which histamine uptake and metabolism were impaired, the administration of DXR, 2 mg. per kg., over 1 minute was associated with elevations in arterial histamine and catecholamines. The chronic weekly administration of DXR produced severe cardiac and renal damage. The administration of combined histaminic and adrenergic blockade with diphenhydramine, cimetidine, phentolamine, and propranolol (DCPP) pre- and immediately post-DXR resulted in near total protection against DXR-mediated cardiac damage and prevented the majority of the renal lesions. The combined administration of diphenhydramine, cimetidine, phentolamine, and propranolol did not appear to be acting by mechanisms other than blockade of vasoactive amine receptors as cardiac uptake of DXR and the DXR antitumor response were not altered by diphenhydramine, cimetidine, phentolamine, and propranolol. This study demonstrates that anthracycline-associated cardiac and renal toxicity may be mediated by vasoactive substances and that anthracycline cardiomyopathy is potentially preventable.