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Biomedical subjects

H Lund-Andersen

Publications and source records attributed to H Lund-Andersen.

At least 37 records · Page 2Linked to original sources

Differential spectrofluorometry in the human vitreous: blood-retina barrier permeability to fluorescein and fluorescein glucuronide.

A method is described for the separate quantitation of fluorescein and fluorescein glucuronide in the vitreous by differential spectrofluorometry. An ocular fluorometer was equipped with monochromatic laser excitation at two rapidly interchangeable wavelengths. The data analysis accounts for absorption of light in the cornea, lens, and extrinsic ocular fluorophores. Examination of seven patients with insulin-dependent diabetes and different degrees of diabetic retinopathy demonstrated that both fluorescein and fluorescein glucuronide enter the eye through the blood-retina barrier. The mean ratio between the permeabilities of fluorescein glucuronide and fluorescein was 0.9 (range, 0.3-1.9). Thus, differences in the molecular size and lipid solubility of the two substances appear to be of little or no importance for their inward penetration of the barrier. No association was found between the relative permeability and the degree of retinopathy.

Adult↗

Determination of spatial coordinates in ocular fluorometry.

A method has been developed for the determination of spatial coordinates of ocular fluorescence measurements made by a non-contact-lens type of fluorometer (Fluorotron, Coherent Inc., Palo Alto, Calif., USA). The method is based upon a mathematical model of the instrument and the eye. The model is adapted to the individual eye by the extraction of information from the fluorescence scan and the use of keratometry to determine the radius of curvature of the anterior corneal surface. The validity of the model was examined by comparison of the ocular axial length as measured by fluorometry vs ultrasonometry in 26 eyes of healthy human subjects. The results of fluorometry differed from those of ultrasonometry by less than +/- 2%.

Adult↗

Lens fluorometry: light-attenuation effects and estimation of total lens transmittance.

Front-face fluorometry of the axial fluorescence profile of the lens is influenced by attenuation of light along the optical pathways leading to and from the detection volume. The resulting distortion is evident when the curve is compared with the intrinsic profile that can be recorded by direct measurement on the transected lens. Assuming that attenuation of light by scatter and absorption is proportional to fluorescence, the intrinsic profile can be reconstructed from the non-invasive fluorescence profile. The calculations involve the deduction of total lens transmittance and fluorescence-related absorptivity, parameters that provide essential information about the optical quality of the lens. The method was applied to human lens fluorometry in vivo and in vitro (excitation 430-490 nm, fluorescence 530-630 nm). Even the most anterior lens fluorescence measurements were found to be markedly affected by attenuation of light in the lens. Lens transmittance estimates agreed within +/- 12% with direct measurements of lens transmittance. The differences were due in part to inter-individual variations in the shape of the intrinsic fluorescence profile of the lens.

Absorption↗

Blood-retina barrier permeability in diabetes during acute ACE-inhibition.

We assessed the acute effect of ACE-inhibition (captopril) on blood-retina barrier (BRB) permeability in 10 hypertensive insulin-dependent diabetic patients with background retinopathy in a double-masked placebo controlled cross-over study. All patients underwent ophthalmological examination, fundus photography, fluorescein angiography, vitreous fluorometry, and continuous blood pressure recording within 3 h of the drug/placebo administration. The decrease in mean arterial blood pressure, from placebo treatment 149/92 +/- 17/7 to captopril treatment 132/83 +/- 14/7 mmHg (mean +/- SD), P less than 0.01 was not accompanied by a significant decrease in BRB permeability, which was 2.51 (1.24-9.15) with placebo and 3.02 (1.25-13.93).10(-7) cm/s during captopril treatment (geometric mean and-range), NS. Our study suggests that abnormal leakage through the BRB in hypertensive insulin-dependent diabetic patients with background retinopathy is caused predominantly by structural changes in the retinal vessels whereas hydrostatic forces play a minor role.

Adult↗

Cotton-wool spots and retinal light sensitivity in diabetic retinopathy.

In 14 eyes of 14 patients with diabetic retinopathy the light sensitivity of retinal cotton-wool spots was studied by computerised perimetry, and the visual field data were accurately correlated with the corresponding morphology as seen on fundus photographs and fluorescein angiograms. In 12 of the eyes the examinations were repeated within one year in order to follow changes in retinal light sensitivity during the evolution of the lesions. Retinal cotton-wool spots were in all eyes associated with localised non-arcuate scotomata in the visual field. In four eyes the cotton-wool spots disappeared within three months of the first examination, and in two of these cases the corresponding scotomata disappeared together with the morphological lesions. In eight eyes the cotton-wool spots (and the corresponding scotomata) had not resolved one year after the first examination. The mean blood pressure showed no significant difference between the patients in whom the lesions resolved within three months and the patients in whom the lesions persisted longer.

Diabetic Retinopathy↗

Protective effect of captopril on the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy.

The effect of 18 months' inhibition of angiotensin-converting enzyme by captopril on the leakage of fluorescein through the blood-retina barrier was examined in a prospective, randomized control study of 20 normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy. After 18 months, 15 patients remained in the study. Fluorescein leakage remained nearly unchanged in the captopril-treated group, being 4.1 +/- 4.1 (mean +/- SD) x 10(-7) cm/s at baseline and 4.2 +/- 4.1 x 10(-7) cm/s after 18 months' treatment. The permeability increased significantly (P less than 0.01) from 3.3 +/- 2.2 x 10(-7) cm/s to 5.6 +/- 3.5 x 10(-7) cm/s at 18 months in the control group. Arterial blood pressure was nearly constant in both groups throughout the study. The results indicate that angiotensin-converting enzyme inhibition with captopril can arrest or delay a progressive breakdown of the blood-retina barrier in normotensive insulin-dependent diabetic patients with nephropathy and background retinopathy.

Adult↗

A comparative study of microvascular complications in patients with secondary and type 1 diabetes.

The prevalence of retinopathy, albuminuria, and neuropathy were assessed in 25 patients with insulin-requiring diabetes secondary to chronic pancreatitis and in 25 patients with Type 1 (insulin-dependent) diabetes, matched for age at diabetes onset (secondary, 39 +/- 11 (+/- SD) years vs Type 1, 38 +/- 11 years) and duration of diabetes (10 +/- 6 vs 10 +/- 7 years). The prevalence of retinopathy was significantly higher in Type 1 diabetic patients (52%) than those with secondary diabetes (20%) (p less than 0.02). Median urinary excretion of albumin was 9 (range 1-206) mg 24-h-1 in patients with Type 1 diabetes and 7 (1-90) mg 24-h-1 in patients with secondary diabetes (NS). One secondary diabetic patient and five Type 1 diabetic patients had microalbuminuria (NS). Vibration perception threshold (measured at the big toe) was identical in the two groups of patients, and no patient had a threshold indicating somatic neuropathy (biothesiometry greater than 20 V). Retinopathy is more frequent in patients with Type 1 diabetes than in patients with insulin-requiring diabetes secondary to chronic pancreatitis. Retinopathy is so frequent in the latter group, however, that regular ophthalmoscopic examination is still required.

Albuminuria↗

Accurate superimposition of perimetry data onto fundus photographs.

A technique for accurate superimposition of computerized perimetry data onto the corresponding retinal locations seen on fundus photographs was developed. The technique was designed to take into account: 1) that the photographic field of view of the fundus camera varies with ametropia-dependent camera focusing 2) possible distortion by the fundus camera, and 3) that corrective lenses employed during perimetry magnify or minify the visual field. The technique allowed an overlay of perimetry data of the central 60 degrees of the visual field onto fundus photographs with an accuracy of 0.5 degree. The correlation of localized retinal morphology to localized retinal function was therefore limited by the spatial resolution of the computerized perimetry, which was 2.5 degrees in the Dicon AP-2500 perimeter employed for this study. The theoretical assumptions of the technique were confirmed by comparing visual field records to fundus photographs from patients with morphologically well-defined non-functioning lesions in the retina.

Diabetic Retinopathy↗

Localised blood-retinal barrier leakage and retinal light sensitivity in diabetic retinopathy.

Twenty patients with insulin dependent diabetes mellitus were selected on the basis of morphological signs of blood-retinal barrier leakage--namely, hard exudates seen on fundus photographs and/or localised leakage of fluorescein seen on fluorescein angiograms. Computerised perimetry was carried out in visual field areas that corresponded to the morphological lesions, and the visual field data were accurately correlated with the morphology as seen on fundus photographs and fluorescein angiograms. In addition, in seven of the patients who represented the range of leakage among the patients studied, the blood-retinal barrier leakage was quantitated by vitreous fluorophotometry. In 16 cases normal light sensitivity was found in retinal areas showing localised leakage as studied on fluorescein angiograms. In four cases with pronounced maculopathy, where scotomata occurred, there was no topographical correlation between the scotomata and barrier leakage. Furthermore hard exudates often, but not consistently, caused localised scotomata when arranged in dense conglomerates. The permeability values correlated with angiographically observed hyperfluorescence in the macular area. On the basis of the techniques employed in the present study it seems that breakdown of the blood-retinal barrier is an earlier event than disturbance of neurosensory function in the development of diabetic retinopathy. However, the findings give no evidence of a causal relationship between barrier leakage and damage to sensory cell function.

Blood-Retinal Barrier↗

Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus.

Growth hormone is assumed to be involved in the development of diabetic retinopathy. In a randomized study we evaluated the possible effects of one year treatment with a somatostatin (SRIH) analogue, octreotide, on early retinopathy and on metabolism in Type I (insulin-dependent) diabetes mellitus. Eleven patients were allocated to treatment with a continuous sc infusion of 400 micrograms octreotide per day and 9 served as controls. Only 7 patients from each group completed the study. Three octreotide-treated patients left the study owing to severe diarrhea. The subjects were evaluated at entry, after 2, 6 and 12 months treatment, and 2 months after withdrawal. Octreotide induced a decrease in GH secretion, expressed as the area under the 24 h serum GH profiles (p less than 0.05), and of the serum levels of IGF-I (p less than 0.05). The entire decline in GH levels occurred during the daytime, whereas the nocturnal levels were unaffected. Retinopathy, as assessed by determination of the blood retina barrier permeability, by colour fundus photography, and flurescein angiography was unchanged in both groups. Apart from a decline in insulin requirements, octreotide had no major effect on glycemic control, but induced a mild transient pituitary hypothyroidism, not clinically relevant. We conclude that treatment with octreotide for one year has modest effects on GH, IGF-I, and glucose metabolism, but has no significant effect on early retinopathy in Type I (insulin-dependent) diabetes.

Adult↗

Lens fluorescence in relation to metabolic control of insulin-dependent diabetes mellitus.

The correlation of blue-green lens fluorescence to the metabolic control of insulin-dependent diabetes mellitus was studied in 36 patients in whom the level of glycosylated hemoglobin A1c (HbA1c) had been followed from the onset of diabetes. Good metabolic control (22 patients, all with mean HbA1c levels, less than 7.0% and, thus, low blood glucose concentrations) was associated with less lens fluorescence and a higher lens transmittance than poor metabolic control (14 patients, all with mean HbA1c levels, greater than 9.7%). It appears that in diabetes, an increase in lens fluorescence and a decrease in lens transmittance are delayed by good metabolic control, and that the determination of lens fluorescence provides information about the long-term control of diabetes.

Adolescent↗

Effect of antihypertensive treatment on blood-retinal barrier permeability to fluorescein in hypertensive type 1 (insulin-dependent) diabetic patients with background retinopathy.

The effect of antihypertensive treatment on blood-retinal barrier leakage of fluorescein in background retinopathy was studied in nine hypertensive Type 1 (insulin-dependent) diabetic patients suffering from nephropathy. The patients were investigated before and after 7 (3 to 13) months of treatment with captopril (n = 8; 25 to 100 mg daily) and a diuretic, either frusemide (n = 4; 80 to 200 mg daily) or bendrofluazide (n = 2; 2.5 mg daily). Retinal function was assessed by fundus photography, fluorescein angiography, vitreous fluorometry, and renal function by glomerular filtration rate, and albuminuria. The antihypertensive treatment induced a significant reduction (p less than 0.05) in: blood pressure from 152/97 +/- 14/8 mmHg to 134/82 +/- 11/6 mmHg; blood-retinal barrier leakage of fluorescein from 2.4 +/- 1.1 to 1.4 +/- 0.5.10(-7) cm/second; albuminuria from 1391 (range: 168-4852) micrograms/min to 793 (range: 35-2081) micrograms/min. Glomerular filtration rate declined from 88 +/- 15 to 78 +/- 23 ml.min-1.1.73 m2 (0.05 less than p less than 0.10). The metabolic control of the patients as reflected by their blood glucose and HbA1c levels remained stable during the study. Our study suggests that systemic blood pressure elevation contributes to the abnormal blood-retinal barrier permeability to fluorescein characteristically found in diabetic background retinopathy and that this abnormality can be reversed during antihypertensive treatment.

Adult↗

The influence of stimulus size on perimetric detection of small scotomata.

The influence of perimetric stimulus size on the detection of small scotomata was examined, and the blind spot was used as a paradigm of a small scotoma. A customized point pattern for perimetry was created on a Humphrey field analyzer. The point pattern had a density of 1.4 degrees and was arranged in a grid in the area of the blind spot. Four normal persons were tested with full-threshold strategy in the points of this grid using Goldmann stimulus sizes ranging from I to V. The delimitation of the blind spot was found to depend strongly on stimulus size. For small stimulus sizes, the blind spot could be delimited as an absolute scotoma with almost sharp borders. However, with larger spot sizes a relative scotoma zone gradually developed, extending centrally from the borders of the blind spot. The central absolute scotoma component of the blind spot totally disappeared for the largest stimulus sizes. We could establish that some of these larger stimuli would be projected totally within the optic nerve head, if perfect imaging through the refractive media of the eye, was assumed. We interpret our findings to be a result of light scattering in the refractive media of the eye, causing a blur to appear around the image of the light stimulus at the retinal plane. We conclude that perimetric resolution power is highly dependent on stimulus size. The smallest stimulus size possible should be used when dense stimulus patterns are used for perimetric detection of small scotomata.

Adult↗

Fluorescein and fluorescein glucuronide in vitreous: fluorescence and binding properties in vitro.

The total and ultrafiltrable fluorescence were measured after disodium fluorescein and fluorescein monoglucuronide were added to aliquots of human and porcine vitreous, and to aliquots of phosphate buffer with and without 0.2% sodium hyaluronate. No significant binding or quenching of F or FG by vitreous or sodium hyaluronate could be found, indicating that vitreous binding is not a source of error in vitreous fluorometry.

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↗

Fluorescein and fluorescein glucuronide in plasma after intravenous injection of fluorescein.

After intravenous injection of fluorescein the time-course of the plasma concentrations of fluorescein (F) and fluorescein glucuronide (FG) was studied in 18 insulin-dependent diabetics with various degrees of nephropathy, and in two non-diabetic subjects. Fifteen minutes after injection the molar concentrations of free (non-protein bound) F and FG were almost identical. After one hour the concentration curve integrals of the two substances were of the same magnitude. There was, however, considerable interindividual variation. In diabetic patients with renal insufficiency an increase was found in both integrals, the F integral being less increased (27%) than the FG integral (44%). It appears from the variation in absolute and relative concentrations of F and FG that a separate determination of the two fluorophores in plasma is desirable, when F is used by intravenous administration as an indicator of blood-ocular barrier function. Previous observations of an increase with time after injection of the free fraction of plasma fluorescence are explained by the finding of a higher free fraction of FG (34%) than of F (11%) and a change in relative concentrations of the two fluorophores.

Adult↗

Fluorescein and fluorescein glucuronide in the vitreous body of diabetic patients.

Fluorescein (F) and fluorescein glucuronide (FG) were determined in the vitreous of four diabetic patients by a double-filter slit-lamp fluorophotometric technique. Determinations were performed 60-80 min after i.v. injection of fluorescein. F and FG were also determined in plasma ultrafiltrate 5, 15, 30, 60 and 120 min after injection by high-pressure liquid chromatography. The concentration of FG in the vitreous was 3 times that of F. After correction for plasma concentrations of FG higher than those of F, the penetration index of FG through the blood-retinal barrier was found to be twice the penetration index of F. This is not what would be expected if passive transport alone were involved. Accordingly, it is suggested that active transport mechanisms contribute to the movement of F and FG across the blood-retinal barrier.

Blood-Retinal Barrier↗

Lens autofluorescence in diabetes compared with the level of glycosylated hemoglobin A1c.

The autofluorescence of the crystalline lens has been measured by an ocular fluorophotometer in two comparable groups of patients with insulin-dependent diabetes mellitus. One group has had a high level of HbA1c since the onset of diabetes (mean 10.1 per cent) and the other group a very low level (mean 6.5 per cent). The group with low HbA1c during the disease period showed a significantly lower lens fluorescence than the group with high HbA1c.

Diabetes Mellitus, Type 1↗