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Vitreous fluorophotometry in patients with no or minimal diabetic retinopathy.

Vitreous fluorophotometry was used to estimate fluorescein leakage into the posterior vitreous of 20 insulin-dependent diabetic patients with no or minimal diabetic retinopathy 60 min after intravenous administration of 14 mg X kg-1 fluorescein. The permeability coefficient (p), a measure of fluorescein penetration through the blood-retinal barrier (BRB) into the vitreous, and the diffusion coefficient (D), a measure of fluorescein dispersion within the vitreous, were obtained by fitting a mathematical model to the vitreous fluorescence scan and plasma free fluorescence curve. A permeability index (PI) was also derived by dividing the area under the fluorescence scan by the area under the plasma free fluorescence time curve. The fluorescence concentrations at discrete distances from the retina were also noted. The mean +/- SD for p, D, and PI were 1.95 +/- 1.03 cm X s-1 X 10(-7), 1.74 +/- 1.53 cm2 X s-1 X 10(-5), and 2.14 +/- 1.21 cm X s-1 X 10(-7), respectively, and were not significantly different from values determined in normal subjects. Diabetic patients and normal subjects also had similar fluorescence measurements at corresponding distances from the retina. Quantitative indices of fluorescein leakage did not correlate with either the microaneurysm counts on fluorescein angiograms or the duration of diabetes. Vitreous fluorophotometry did not detect any abnormality of the BRB in diabetic patients with no or minimal retinopathy on fluorescein angiography.

Adolescent↗

Ocular fluorophotometry in streptozotocin diabetes mellitus in the rat: effect of pancreatic islet isografts.

Fluorophotometry was used to evaluate the integrity of the blood-ocular barriers to fluorescein in experimental diabetes mellitus in rats. This technique allowed quantitation of ocular fluorescein concentrations following intravenous injection. Streptozotacin-induced diabetes resulted in an increased fluorescein accumulation in the anterior chamber (1.52 +/- 0.17 microgram/ml, mean +/- S.E.M.) and vitreous (0.82 +/- 0.11) over baseline nondiabetic levels (0.68 +/- 0.80 and 0.40 +/- 0.03, respectively). Fluorophotometry was repeated at 5, 13, and 20 days following portal vein pancreatic islet transplantation. At 5 days anterior chamber (1.40 +/- 0.17) and vitreous (0.61 +/- 0.08) fluorescein concentrations remained elevated. However, at 13 and 20 days following islet transplantation, ocular fluorescein concentrations were identical to levels observed prior to the induction of diabetes. Intravenous glucose (0.5 gm/kg) tolerance testing was performed 5 and 13 days following transplantation. The glucose responses to the tolerance test were normal and similar at both times. However, at 5 days the insulin response was abnormal with a decreased initial peak and an absent second peak. At 13 days there was a normal biphasic insulin response. In experimental diabetes mellitus ocular vascular permeability was more closely correlated with insulin than blood glucose abnormalities.

Animals↗

Vitreous fluorophotometry: mathematical analysis of the effect of peripheral leakage on axial scans.

Current instrumentation in vitreous fluorophotometry allows the determination of a fluorescein concentration profile along the optical axis of the eye. Based on an assumption of a uniform blood-retinal barrier permeability, several methods have been used for the determination of the permeability from an axial scan. The assumption of a uniform permeability is not realistic and it has been unknown to what extent the calculated common permeability reflects the local permeability in different areas of the retina. Using a mathematical model for a nonuniform permeability, we have investigated the effect of localized leakage on the axial concentrations and thereby on the calculated common permeability under the assumption of free diffusion in the vitreous body. It turns out that leakage outside the large temporal vessels has to be extremely strong to have a noticeable impact on 60 min axial scans. A 100-fold increase of the permeability in the region more than 30 degrees (central angle) from the optical center of the eye leads to just a 2-fold increase of the apparent common permeability. Thus, axial vitreous fluorophotometry almost exclusively measures the condition of the retina in the vicinity of the optical center.

Blood-Retinal Barrier↗

[Tonography and fluorophotometry in the clinical study of aqueous humor dynamics].

We used Grant's tonography and fluorophotometry (the Jones and Maurice method) to study the aqueous humor dynamics in normal and glaucomatous eyes. The results of the two methods were compared. The mean facility and rate of aqueous flow in normal eyes were similar. In glaucomatous eyes the tonographic outflow facility (C-value) varied greatly, and the calculated rate of aqueous flow (F-value) also had a large standard deviation. To study the inflow rate, fluorophotometry is a more accurate method. Further calculation of uveoscleral flow and the "pseudofacility" from the tonographic F-value and fluorophotometric C-value was therefore of only limited accuracy.

Adult↗

Effects of therapy on vitreous fluorophotometry in diabetes mellitus.

Quantitative vitreous fluorophotometry was used to study the alteration of the blood-retinal barrier in 116 patients with diabetes mellitus of adult onset. The patients were in good stable metabolic control on injectable insulin, oral hypoglycaemics, or diet therapy. Vitreous fluorophotometry readings were abnormally high but similar in all three groups and in those with or without early background retinopathy. A higher incidence of systemic hypertension was noted in those patients requiring oral agents compared to those on insulin or diet therapy.

Biological Transport↗

Fluorescein iris angiography and anterior segment fluorophotometry in patients with Behçet's disease.

Fluorescein iris angiography and anterior segment fluorophotometry were performed in 63 eyes of 34 patients with Behçet's disease during its remission stage. Thirty normal eyes were studied as the control. A variety of leakage patterns comprising posterior chamber leakage and paravascular leakage were detected in 32 eyes with Behçet's disease by means of fluorescein iris angiography, while no leakage was detected in the control eyes. These leakage patterns were frequently seen in the posterior type uveitis group of Behçet's patients, but were scarce in the anterior type uveitis group. By anterior segment fluorophotometry, the levels of fluorescein concentration in the anterior chamber were significantly higher in the posterior type uveitis eyes of Behçet's patients than those in either the anterior type uveitis eyes or the controls (P less than 0.05-P less than 0.01). The results indicated that the damage to the vascular system still existed in the remission stage of the disease, and that this abnormality occurred more markedly in the posterior type group than in the anterior type group of Behçet's disease eyes.

Adolescent↗

Ocular fluorophotometry in insulin-treated diabetic patients with and without retinopathy.

To look for possible determinators of the pathological readings of vitreous fluorophotometry in diabetes reported by other groups, we studied 32 insulin-treated patients, 22 of whom had fluorescein angiograms without pathological changes, while 10 had background retinopathy. 14 healthy subjects matched for age and blood pressure served as controls. Sodium fluorescein, 17 mg/kg body weight, was injected intravenously and ocular fluorophotometry performed 60 and 120 minutes later. Blood drawn 5, 45 and 120 minutes after the injection was assayed for total and ultrafiltrable fluorescein and the intraocular readings corrected for average preceding free plasma fluorescein. Patients without retinopathy did not differ from controls in any intraocular measure, while patients with retinopathy showed significantly increased readings in the posterior (60 min: 12 +/- 7 vs. 6 +/- 4, p less than 0.01, 120 min: 26 +/- 35 vs. 11 +/- 5, p less than 0.05) and middle vitreous (60 min: 6 +/- 3 vs. 3 +/- 3, p less than 0.001, 120 min: 11 +/- 5 vs. 8 +/- 5, p less than 0.01 (X 10(-9) g/ml fluorescein, mean +/- SD)). No significant relations to systolic or diastolic blood pressure, blood glucose, hemoglobin Alc or serum creatinine were found in any of the diabetic groups. Re-examination of 7 patients 4-14 days later in a non-fasting state showed no significant changes.

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↗

Vitreous fluorophotometry in children with type I diabetes mellitus.

A clinical, biochemical and ocular study was carried out on 17 children with type I diabetes mellitus. Eight had no clinical or angiographic evidence of retinopathy (Stage 0), seven had stage 1, one had stage 2 background retinopathy (Malone's classification) and one had intraretinal microvascular abnormalities. The vitreous fluorescein concentration 3 to 5 mm in front of the macula in those without retinopathy varied from low to abnormally high, while the concentrations in those with retinopathy were above normal. There was no correlation between haemoglobin A1 estimations taken at the time of the study and the vitreous fluorophotometry readings. This variation in fluorophotometry values obtained in diabetics with stage 0 disease differs from the findings in previous reports and may be of prognostic value in determining those patients at risk of developing retinopathy, and may be an indication for improving diabetic control.

Adolescent↗

The use of vitreous fluorophotometry to distinguish between diabetics with and without observable retinopathy: effect of vitreous abnormalities on the measurement.

Ten age-matched normals, diabetics with retinopathy, and diabetics without observable retinopathy were evaluated by vitreous fluorophotometry (VFL) using a 0.15 mm and a 0.45 fiberoptic probe in a photomultiplier system as well as a commercially available photodiode instrument to determine whether differences in intraocular sodium fluorescein levels could be detected among the three groups. Each subject was injected in the antecubital vein with 7 mg/kg of sodium fluorescein (25% solution) and measurements were taken 1 hr postinjection at 4.5 mm and 7.5 mm from the retina. The influence of choroidal fluorescein and ocular pigmentation are reduced at these locations. We found that a breakdown in the blood-ocular barrier may not be present early in the course of diabetes. Furthermore, no significant difference was found between normals and diabetics without retinopathy. Although the mean value for vitreous fluorescein was significantly higher in diabetics with retinopathy compared to normals, several of the diabetics with retinopathy had values in the normal range. These results differ from those previously reported in the literature. However, our studies took into consideration several factors not considered by other investigators, such as ocular pigmentation, choroidal fluorescence, slit width, and vitreous changes, that may have significant effects on the fluorophotometry values.

Adolescent↗

Vitreous fluorophotometry in juvenile diabetes.

A group of 26 juvenile diabetics, 8-22 years old with a mean duration of diabetes of 7.8 +/- 5.7 years were examined by vitreous fluorophotometry. Eleven non-diabetic healthy individuals, 12-27 years old, served as controls. Vitreous fluorescein concentrations one hour after injection of fluorescein were higher in the diabetics than in the controls indicating an abnormal blood-retinal barrier. In diabetes beyond the partial remission period a pronounced leakage of fluorescein into the vitreous body occurred, while diabetics still in partial remission showed no such abnormal leakage. There were no significant correlations between a defect blood-retinal barrier and duration or age at onset of diabetes. Some diabetic patients showed an abnormal leakage with a duration of diabetes less than 2 years, while some other patients with a duration of more than 16 years did not have an abnormal blood-retinal barrier. The diabetics with defect blood-retinal barrier had a lower glucosuria index during the last year, indicating a more inadequate metabolic control than those patients who had a normal barrier. There was no relation between the actual blood-glucose value during the examination and abnormal leakage. In some diabetics, all beyond partial remission significantly elevated fluorescein concentrations were also found in the anterior parts of the vitreous body, indicating a break-down of the blood-aqueous barrier as well. In conclusion, vitreous fluorophotometry provides information about early, functional and possibly reversible retinal changes in juvenile diabetes. The observation that the blood-retinal barrier remained intact during the remission period supports the hypothesis that normoglycemic metabolic control is of importance for the preservation of a normal blood-retinal barrier function.

Adolescent↗

Vitreous fluorophotometry in insulin-dependent diabetes mellitus. Correlation with microalbuminuria and diastolic blood pressure.

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.

Adolescent↗

Determination of the pseudofacility by fluorophotometry in the human eye.

PURPOSE: Pseudofacility (decrease in aqueous humor flow in response to increase in the intraocular pressure (IOP)) has been evaluated in animals and in humans by a combination of different techniques that seriously alter the ocular physiology, such as the cannulation of the eyeballs, use of radioactive isotopes, perilimbic suction cups or tonography. Very different results have been obtained. Our objective is to relate the value of the aqueous humor flow in humans (as measured by fluorometry) with IOP. In order to obtain the widest range of IOP possible, we have performed this study in both normal as well as glaucoma patients. METHODS: 48 eyes were studied, corresponding to 31 subjects (mean age 58 +/- 14 years). Of these, 21 corresponded to normal subjects and 27 to glaucoma patients. The aqueous humor flow (F) was determined by fluorophotometry (Protocol of Yablonsky) and the IOP was measured thereafter. RESULTS: The mean value of F was 2.1 +/- 0.5 microliter/min for healthy eyes and 2.2 +/- 0.7 microliter/min for glaucoma-affected eyes. The values were not different (p > 0.1). The mean value of the IOP was 15.3 +/- 3.1 mmHg in the normal population and 22.1 +/- 4.3 mmHg in the glaucoma patients. A linear relationship between F and IOP was found (r = -0.41, p < 0.05, decrease in F = 0.081 microliter min-1 mmHg-1). CONCLUSIONS: The value of the pseudofacility in the humans can be estimated at 0.081 microliter min-1, mmHg-1, which constitutes 27% of the total outflow facility. This figure also makes it possible to estimate the role of the ultrafiltration in blood in the production of the aqueous humor since it is assumed that active secretion is pressure-independent. The results obtained are concordant with a secondary but no unimportant role of the plasmatic ultrafiltration with respect to the active secretion.

Aqueous Humor↗

Determination of basal tear turnover in insulin-dependent diabetes mellitus patients by fluorophotometry.

The tear turnover was determined by fluorophotometry in 25 insulin-dependent diabetes mellitus (IDDM) patients without retinopathy and 29 IDDM patients with (pre-)proliferative retinopathy. The results were compared with those in 34 healthy controls, to investigate the lacrimal gland function in diabetic patients. The tear turnover was calculated from the decay of the relative tear fluorescein concentration values measured after instillation of one microliters of fluorescein. The tear turnover values in both patient groups did not correlate significantly with age or diabetes duration (linear correlation coefficients: r less than 0.3). The tear turnover values in patients both without retinoplathy and with (pre-)proliferative retinopathy did not differ significantly from those in healthy controls (mean +/- SD in %/min: 13.7 +/- 4.5, 14.7 +/- 5.8 and 15.5 +/- 5.1, respectively; P greater than 0.16). The tear turnover was significantly decreased in eyes having a BUT shorter than 10 seconds compared with eyes having a BUT longer than 10 seconds (P less than 0.05). The tear turnover values correlated significantly with the HbA1c and Schirmer-test values in patients with (pre-)proliferative retinopathy (r = 0.7 and r = 0.4, respectively; P less than 0.02) and with the blood glucose values in patients without retinopathy (r = 0.41, P = 0.04). Since the tear turnover was not significantly decreased in IDDM patients in comparison with healthy controls the corneal disorders which are more frequently seen in these patients than in a healthy population may not be attributed to a decrease in tear production.

Adult↗

The permeability of the corneal epithelium of Graves' ophthalmopathy as determined by fluorophotometry.

The function of the corneal epithelium was evaluated in 30 patients with Graves' ophthalmopathy in whom no signs of corneal disease were observed. This function was evaluated by determining the permeability values of the corneal epithelium for fluorescein using fluorophotometry. The permeability values of the patients were compared with those of 46 healthy individuals. A significant increase in the permeability values was seen in 11 (37%) patients and in two (4%) controls (p less than 0.05). The difference in the mean permeability values between patients en controls was statistically significant (0.053 nm/sec. +/- 0.043 SD and 0.038 nm/sec. +/- 0.017 SD, respectively, p less than 0.05). No relation was found between the permeability values of the corneal epithelium and the NOSPECS classification or the duration of the disease. There was a tendency for increased permeability values in patients having an exophthalmos larger than 20 mm. (correl. coeff. = + 0.3, p less than 0.05).

Adult↗

Topical timolol, corneal epithelial permeability and autofluorescence in glaucoma by fluorophotometry.

UNLABELLED: Corneal epithelial permeability and autofluorescence were measured by fluorophotometry in patients with open-angle glaucoma or ocular hypertension to quantify the epithelial function of the cornea and to evaluate its metabolic activity in 24 patients using daily timolol and 11 not using timolol. The findings were compared with those in age-matched healthy controls. Permeability values in patients using timolol were 1.9 times higher than in patients not using timolol and 2.5 times higher than in healthy controls (Mann-Whitney test P < 0.001). Values for patients not using timolol did not differ from those for healthy controls (P = 0.15). Corneal autofluorescence values in each patient group were higher than in healthy controls (P = 0.002). CONCLUSIONS: (1) open-angle glaucoma or ocular hypertension alone does not affect corneal epithelial permeability; (2) daily instillation of timolol causes impairment of the corneal epithelial barrier; (3) open-angle glaucoma or ocular hypertension are likely to induce an increase of corneal autofluorescence.

Administration, Topical↗

Epithelial permeability in corneal grafts by fluorophotometry.

The epithelial permeability to fluorescein of 27 clear corneal grafts in 23 patients was determined by fluorophotometry at greater than 1 year after penetrating keratoplasty (PKP) so as to study the recovery of corneal epithelial function. The mean epithelial permeability of the corneal grafts did not differ significantly from that of normal corneas (0.042 +/- 0.016 and 0.038 +/- 0.017 nm/s, respectively; P greater than 0.3). Multiple linear regression analysis showed that permeability correlated with recipient age but not with donor age (permeability increase, 0.00054 nm/s per year; r = 0.6, P less than 0.005 and r = 0.1, P greater than 0.5, respectively). These results indicate that corneal grafts can regain a normal epithelial barrier function and that recovery of epithelial function is better in young than in old recipients.

Adult↗

Effect of eledoisin on tear volume and tear flow in humans as assessed by fluorophotometry.

Topical application of the endekapeptide eledoisin has been reported to increase tear secretion in patients with dry eye. However, to date the efficacy of eledoisin has been proved only by methods that are not easily reproduced and have an enormous intraindividual scatter range (Schirmer test, basic secretion test). In the present study the effect of topically applied eledoisin on tear volume and tear flow was determined quantitatively by means of objective fluorophotometry in 40 subjects, 20 of whom suffered from severe dry eyes. Both tear volume and tear flow were found to be significantly increased up to 2 h after instillation, reaching a maximum 1 h after application (tear volume: +87% and +35% for dry eyes and healthy controls, respectively; tear flow: +250% and +27% for dry eyes and healthy controls, respectively).

Administration, Topical↗