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R C Zeimer

Publications and source records attributed to R C Zeimer.

At least 37 records · Page 2Linked to original sources

Ocular fluorophotometry in the normal- and diabetic monkey.

Normal- and diabetic rhesus monkeys without retinopathy demonstrable by ophthalmoscopy or fluorescein angiography were examined with ocular fluorophotometry to detect alterations in their blood-ocular barriers. All vitreous fluorophotometry values were corrected for fluorescence attributable to background levels and then normalized to a blood fluorescein level of 10 micrograms ml-1. Reproducibility studies demonstrated an average coefficient of variation of 0.17 for all animals combined. Insulin-dependent monkeys, both pancreatectomized and streptozotocin-treated, demonstrated significantly higher posterior vitreous fluorescence levels than either control animals or monkeys treated with streptozotocin that were not insulin-dependent. These results cannot be attributed to differences in fluorescein binding or to vitreous abnormalities. However, 14 out of 24 (58%) of the insulin-dependent animals exhibited posterior vitreous fluorescence values within two standard deviations of the control mean. No correlation was apparent between the vitreous values and age or duration of treatment. No difference in anterior chamber concentrations was found between groups after correction. Our results indicate that alterations in blood-retinal barrier can occur in insulin-dependent diabetic monkeys before development of retinopathy.

Aging↗

Fluorescein and fluorescein glucuronide pharmacokinetics after intravenous injection.

The permeability of the blood-retinal and blood-aqueous barriers to fluorescein (F) and the rate of aqueous flow can be estimated by measurements of F in the vitreous, aqueous, and plasma after systemic administration. F is commonly measured by fluorescence, but fluorescein glucuronide (FG), a metabolite of F, also fluoresces. To assess the influence of FG on the quantitation of F by fluorescence, we studied the pharmacokinetics of F and FG for 38 hr in the plasma of five normal subjects given 14 mg/kg of sodium fluorescein intravenously. The plasma and the plasma ultrafiltrate were measured by fluorescence and by high performance liquid chromatography. In our fluorophotometer, FG was 0.124 times as fluorescent as F. F was rapidly converted to FG, and within 10 min the concentration of unbound FG exceeded that of unbound F. The terminal half-lives of F and FG in the plasma ultrafiltrate were 23.5 and 264 min, respectively, so that FG contributed almost all of the plasma fluorescence after 4-5 hr. Because FG was less bound in the plasma than F, the ratio of the fluorescence of the plasma ultrafiltrate to that of the plasma increased with time. The greatest proportion of the total F available to penetrate into the ocular compartments occurred shortly after injection. We concluded that FG is an important contributor to the fluorescence of the plasma ultrafiltrate after intravenous injection and that accurate quantitation of physiologic parameters calculated from the plasma F requires taking this factor into account.

Adult↗

Algorithm for the correction of artifacts.

The sources of vitreous fluorophotometry artifacts are described. An algorithm to define this "spread function" is presented. The use of improved instrumentation and compensation for this artifact by data processing of the "correction" algorithm can improve the results of vitreous fluorophotometry. This algorithm was carried out in 40 eyes and was found to have an error of 0.7 mg/ml at 3 mm from the choroid-retina.

Choroid↗

The performance of a new commercial ocular fluorophotometer in the clinical environment.

Studies using the Fluorotron Master fluorophotometer in vitro and in vivo are presented. The in vitro tests include lower limit of detection and error of measurement, and the in vivo tests include spread function, axial resolution, and reproducibility. Results show that many technical problems have been resolved by this system. Furthermore, this system can be satisfactory handled by technical personnel after short periods of training.

Adult↗

Outward transport of fluorescein from the vitreous in normal human subjects.

Vitreous fluorophotometry was performed on eight normal subjects to compare the outward and inward permeabilities of fluorescein into the vitreous. The results indicate that diffusion alone does not account for the outward flow of fluorescein in the vitreous. The possible underlying factors and significance of these findings are discussed.

Biological Transport, Active↗

Characterization of the early stages of diabetic retinopathy by vitreous fluorophotometry.

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)

Adolescent↗

Transport of fluorescein in the ocular posterior segment in retinitis pigmentosa.

The function of the blood-retinal barrier was assessed by vitreous fluorophotometry in 12 patients with various genetic types of retinitis pigmentosa and in 11 normal subjects. The measurements were corrected to minimize the effect of artifacts. We evaluated the inward penetration of fluorescein sodium across the blood-retinal barrier and determined the outward permeability coefficient for fluorescein by interpreting the data with a pharmacokinetic computer model. Patients with retinitis pigmentosa had increased inward permeability and decreased outward permeability to fluorescein in comparison with values of normal subjects.

Adolescent↗

A new method of measuring in vivo the lens transmittance, and study of lens scatter, fluorescence and transmittance.

We propose a new method to measure in vivo nuclear transmittance using scanning photometry, thus complementing its present application in measuring lens scatter and fluorescence. We compared our method of measuring the transmittance with a previously reported in vivo method and found an adequate correlation. We then measured the fluorescence, scatter and transmittance of lenses without cataract and those with as much as a mild yellowing. The three phenomena correlated with age. In addition, this study allowed a correlation of the three phenomena with each other, indicating that the loss of transmittance of the nucleus cannot be explained by its thickening alone but that changes in its composition must take place. Finally, a preliminary study on diabetics showed early onset of the process responsible for the increase in lens fluorescence. This process did not seem to be accelerated in diabetics in comparison with normals. The nuclear scatter appeared to increase more rapidly with age in nondiabetics as compared to diabetics. This preliminary study suggests mainly that scanning photometry can be used to study aging and pathologic changes in the lens.

Absorption↗

Noninvasive measurement of optic nervehead mechanical compliance in normal and ocular hypertensive beagles.

We have proposed that the susceptibility of some eyes to glaucomatous damage is due to an abnormal weakness of the structural support of the optic nervehead. To verify this hypothesis and, if it proves correct, to provide an early test of glaucoma, we have developed a noninvasive method of measuring the optic nervehead compliance. We present here the first in-vivo measurements that were performed in a normal beagle dog and dogs with congenitally elevated intraocular pressure (IOP) over different periods of time. The quality of the measurements was tested and the reproducibility of the optic nervehead displacement was +/- 15 microns. The optic nervehead displacement was found to be higher in the older dogs that also sustained ocular hypertension for a longer period. These results were compared with ophthalmoscopic observations of the optic disc. The present study indicates that the method is applicable to the measurement of the optic nervehead compliance and that the structural support of the optic nervehead may vary.

Animals↗

Outward transport of fluorescein from the vitreous in normal human subjects.

The permeability of the blood-vitreous barrier to fluorescein passing out of the vitreous does not necessarily equal the permeability to fluorescein passing into it. We calculated the ratio between the outward and inward permeability coefficients of the blood-vitreous barrier in eight normal men who ingested 3-g of sodium fluorescein. The calculation was based on the ratio between the serum free fluorescein and the vitreous fluorescein concentrations (as determined by fluorophotometry) when the net transport across the barrier was zero. The outward permeability to fluorescein was 31 +/- 18 times (mean +/- SD) the inward permeability. To our knowledge, this article provides the first direct evidence for a specialized transport mechanism in humans whereby fluorescein is removed from the vitreous into the blood. The malfunction of this process may be important in human diseases. Pharmacologic manipulation of this process may be possible.

Adult↗

A practical venomanometer. Measurement of episcleral venous pressure and assessment of the normal range.

Glaucomatous damage develops in certain patients because of elevated episcleral venous pressure (EVP). To measure the EVP in typical clinical settings, a practical and reliable instrument is needed. We have developed such an instrument, the venomanometer, and present tests of its reproducibility. The intraobserver reproducibility was 0.7 mm Hg, and the mean difference between the readings of two observers was 0.7 +/- 1.2 mm Hg. We then used the venomanometer to study the EVP in 122 eyes of 68 normal subjects distributed in seven age groups between 10 and 80 years. The EVP did not vary with age (mean, 7.6 +/- 1.3 mm Hg). This value is compared with those obtained with other instruments.

Adolescent↗

Vitreous fluorophotometry for clinical research. I. Description and evaluation of a new fluorophotometer.

In vitro and in vivo tests of a new commercial fluorophotometer showed that the instrument is capable of measuring fluorescein concentrations of 1 to 1,000 ng/mL accurately. The in vivo estimate of the spread functions of the lens and chorioretinal peaks yielded values of about 1% and 0.5% 3 and 6 mm, respectively, from the peak. Pigmentation did not influence the chorioretinal spread function. Reproducibility in vivo was evaluated to be 12%. Furthermore, when compared with other existing fluorophotometers, the new instrument performed superiorly.

Choroid↗

Vitreous fluorophotometry for clinical research. II. Method of data acquisition and processing.

Several methods of data analysis permit improved evaluation of the blood-retinal barrier (BRB) by vitreous fluorophotometry. With the use of an algorithm for artifact correction, tested in vivo in situations in which large artifacts are expected, artifacts were reduced to less than the equivalent of 1 ng/mL in normal eyes 3 mm from the chorioretinal and lens peaks. A procedure developed to evaluate the lens transmittance was found to have a 12% reproducibility. In addition, the anterior and posterior sources of leakage could be separated by choosing the appropriate time of measurement after injection of the dye. Moreover, a procedure to estimate quantitatively the inward permeability of the BRB yielded a preliminary estimate of 7.2 X 10(-8) cm/s in normal subjects.

Blood Physiological Phenomena↗

Evaluation of a self tonometer for home use.

It has been repeatedly stated that home monitoring of the intraocular pressure of glaucomatous patients could be of clinical significance. However, home tonometry has not been implemented due to the lack of an appropriate instrument. We present herein an upgraded version of a home tonometer that can be used by the patient alone. When it was tested on 37 eyes of 22 glaucomatous patients, the reproducibility was 1.7 mm Hg at IOPs of 20 mm Hg. The IOP was also measured with a Goldmann applanation tonometer. The two measurements were well correlated (r = .89) and the accuracy of the home tonometer, namely the variation of the data from the regression curve, was 2.5 mm Hg. This accuracy is compared with that of conventional tonometers. Moreover, the study showed that the home tonometer yielded reliable results in the hands of a substantial portion of the potential population.

Adult↗

Pharmacokinetic interpretation of vitreous fluorophotometry.

Vitreous fluorophotometry is producing an increasing amount of clinical and experimental data. In order to interpret these data and obtain quantitative values for the permeability of the blood ocular barriers, there is a need to understand better the basic phenomena governing the transport of fluorescein. We present here a refined mathematical model that we use to interpret a large body of clinical data yielding values for the inward (6.9 x 10(-6) cm/min) and outward (210 x 10(-6) cm/min) posterior permeability coefficients, the effective diffusion coefficient in the vitreous (8 x 10(-4) cm2/min), and the plasma fluorescein decay constants (1.17, 0.34, and 0.044 per hour). Moreover, we utilize the model to make predictions related to kinetic vitreous fluorophotometry and to the reliability of the procedure to calculate the permeability coefficients.

Adult↗

Studies on the technique of vitreous fluorophotometry.

We examined the sources of artifacts of vitreous fluorophotometry (VF), a technique used to assess the permeability of the blood-retinal barrier. By performing in vitro measurements in a model eye and in vivo readings in humans, we investigated the influence of various concentrations of fluorescein in the anterior chamber and in the retina on the measurements performed in the vitreous. Upper limits for the artifactual effects are set under clinical conditions, and a way to account for them is proposed. Special attention is given to depth resolution, which was investigated as a function of the region being scanned, the beam width, and the probe size. Further, preliminary results indicate that a procedure to account for light attenuation by the lens is feasible. It appears that reliable quantitative results can be obtained by VF, provided that the artifacts are acknowledged, minimized, and corrected.

Anterior Chamber↗