Biomedical subjects

H Lund-Andersen

Publications and source records attributed to H Lund-Andersen.

At least 19 recordsLinked to original sources

PubMed1998

The effect of acetazolamide on passive and active transport of fluorescein across the blood-retina barrier in retinitis pigmentosa complicated by macular oedema.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide (AZM) reduces macular oedema in some patients with retinitis pigmentosa. To better understand the oedema-reducing effect of AZM, the effect of AZM on passive permeability and active transport of fluorescein across the blood-retina barrier was studied in patients with retinitis pigmentosa and varying degrees of macular oedema. METHOD: The selection of patients was based on an introductory examination including vitreous fluorometry for qualitative assessment of the vitreous. Macular oedema was graded by fluorescein angiographic leakage. The effect of AZM on the transport properties of the blood-retina barrier was determined by differential spectrofluorometry, in a randomised, double-masked, cross-over study, comprising 2 weeks' treatment with AZM (500 mg/day) and 2 weeks' treatment with placebo. The penetration ratio, defined as the ratio between vitreous concentration 3 mm in front of the retina and the plasma integral, was determined for fluorescein and its metabolite fluorescein glucuronide at 30-60 min and at 120 min after fluorescein injection. Passive permeability and unidirectional permeability in the direction vitreous to blood, due to outward active transport of fluorescein, were determined in those cases where the curves for vitreous concentration of fluorescein could be fitted to a mathematical model. Visual acuity was tested by use of ETDRS standard logarithmic charts. RESULTS: Twenty-two patients volunteered to participate in the study. Signs of significant vitreous detachment/liquefaction caused the exclusion of ten patients after the introductory examination. Nine patients with approximately intact vitreous and varying degrees of oedema completed the cross-over study. AZM treatment was related to a decrease in the penetration ratio of 21% for fluorescein (P=0.01) and of 22% for fluorescein glucuronide (P=0.004). Passive permeability and unidirectional permeability were determined in seven patients. AZM caused a decrease of 27% in the passive permeability of fluorescein (from 1.1 x 10(1) nm/s, P=0.031), and a 95% increase in unidirectional permeability of fluorescein (from 1.2 x 10(2) nm/s, P=0.047). AZM led to a reduction in the grade of macular oedema as determined by fluorescein angiography in three out of seven patients. Only small improvements (< or =5 letters) in visual acuity were noted. CONCLUSION: The present study indicates that the oedema-reducing effect of AZM is due to decreased leakage and stimulated active transport across the blood-retina barrier.

Acetazolamide↗

PubMed1998

Improved visual function in IDDM patients with unchanged cumulative incidence of sight-threatening diabetic retinopathy.

OBJECTIVE: To evaluate trends in visual acuity and the cumulative incidence of diabetic retinopathy in a clinic-based observational follow-up study. RESEARCH DESIGN AND METHODS: All patients visiting Hvidore Hospital in 1984 whose diagnosis of IDDM had been made before 41 years of age and between 1965 and 1979 (n = 356) were followed until 1994 or until their deaths. All patients were Caucasians and resided in Copenhagen. Patients were divided into three prevalence cohorts based on time of diabetes onset: group A, 1965-1969 (n = 113); group B, 1970-1974 (n = 130); and group C, 1975-1979 (n = 113). RESULTS: Fifteen years after diabetes onset, the visual acuity was significantly improved in patients with increasing calendar year of the disease onset. The median (interquartile range) visual acuity was 1.0 (0.8-1.0), 1.0(0.9-1.0), and 1.0 (1.0-1.0) in groups A, B, and C, respectively (P < 0.01 overall; P = 0.28 for group A vs. group B; and P < 0.01 for group A vs. group C) with 60, 66, and 93 having a visual acuity of 1.0 in groups A, B, and C, respectively. The cumulative incidence (+/-SEM), expressed as a percentage and calculated according to the life-table method, of proliferative retinopathy, maculopathy, and laser-treated retinopathy 15 years after onset of diabetes were, respectively, 13+/-3, 11+/-3, and 12+/-3 in group A; 16+/-3, 12+/-3, and 21+/-4 in group B; 11+/-3, 5+/-2, and 12+/-3 in group C, respectively (NS). The development of proliferative retinopathy was associated with the degree of retinopathy and albuminuria at baseline and the mean HbA1c during follow-up. CONCLUSIONS: The study revealed an improvement in visual acuity with increasing calendar year of diabetes onset but an unchanged cumulative incidence of diabetic retinopathy.

Adult↗

PubMed1996

Lens autofluorescence is increased in newly diagnosed patients with NIDDM.

Lens and cornea autofluorescence has been shown to be increased in patients with insulin-dependent diabetes mellitus and to be positively correlated to glycaemic control and duration of diabetes. We have studied lens and cornea autofluorescence at the clinical onset of non-insulin-dependent diabetes mellitus (NIDDM), in comparison with age-matched subjects with normal glucose tolerance. Fourteen subjects with NIDDM diagnosed less than 6 months prior to the examination were characterised by ocular fluorometry, glycosylated hemoglobin A1c, plasma lipid status, arterial blood pressure, and an oral glucose tolerance test (OGTT). Eleven age- and gender-matched healthy subjects without a family history of diabetes and with a normal glucose tolerance underwent the same examinations. In 11 of the 14 diabetic patients lens autofluorescence was increased to levels higher than the age-related mean + 2SD of healthy subjects. For the entire study population, control and diabetic subjects, lens fluorescence was positively correlated with HbA1c (p < 0.0001, r = 0.73), fasting plasma glucose (p = 0.002, r = 0.60) and the plasma glucose level 2 h after an OGTT (p = 0.004, r = 0.55). Cornea autofluorescence was also significantly increased in the group of newly diagnosed NIDDM patients, but only 9 patients had values above the mean + 2SD of the healthy subjects. NIDDM could be detected by ocular fluorometry with a sensitivity of 79% and a specificity of 100%. We conclude that lens and cornea autofluorescence is abnormally increased in the majority of patients with newly diagnosed NIDDM. The sensitivity and specificity of the method indicate that lens fluorometry may potentially be useful for screening for undiagnosed NIDDM in the general population. Additionally, we propose that the method may be a clinically useful indicator of cumulative glycaemia and risk of development of secondary complications in patients with diabetes.

Adult↗

PubMed1994

Fluorescein transport across the human blood-retina barrier in the direction vitreous to blood. Quantitative assessment in vivo.

Inward and outward movement of flourescein across the human blood-retina barrier was studied in five healthy volunteers, using a differential spectrofluorometry method that eliminates the contribution of fluorescein glucuronide to the total fluorescence in the vitreous and in plasma. The inward permeability across the blood-retina barrier, which is presumed to be passive, and the diffusion coefficient in the vitreous for fluorescein was calculated from data obtained 1 h after intravenous injection of fluorescein. The rate of elimination of fluorescein from the vitreous across the blood-retina barrier was estimated from data obtained 7 to 12 h after injection of fluorescein. The calculations were based upon the free plasma fluorescein decay curve and the preretinal fluorescein gradient in the vitreous. The mean inward permeability of fluorescein was 1.39 x 10(-7) cm/sec (range: 0.70-2.06 x 10(-7) cm/sec), whereas the mean outward permeability was 1.51 x 10(-5) cm/sec (range: 1.14-1.73 x 10(-5) cm/sec). We have thus found that the movement of fluorescein across the blood-retina barrier is highly asymmetric, the outward transport being more than 100 times faster than the passive inward leakage. This could indicate the presence of an active pumping mechanism in the blood-retina barrier, responsible for fluorescein transport in the direction from the vitreous to the blood.

Biological Transport, Active↗

PubMed1994

Probenecid inhibition of the outward transport of fluorescein across the human blood-retina barrier.

The effect of probenecid on the outward transport of fluorescein from vitreous to blood was studied in 13 insulin-dependent diabetic patients with background retinopathy in a randomised double-masked placebo controlled cross-over study. Fluorescein and fluorescein glucuronide was separated in the vitreous and in plasma by differential spectrofluorometry. The data for fluorescein were analysed using a simplified mathematical model of the eye. The inward permeability was estimated from data obtained 1 h after injection and the outward transport from data obtained 7 h after injection. During placebo treatment the mean inward permeability was 3.75 x 10(-7) cm/sec and the mean outward permeability was 2.25 x 10(-5) cm/sec. During probenecid treatment the mean inward permeability was 3.34 x 10(-7) cm/sec and the mean outward permeability was 1.44 x 10(-5) cm/sec. Thus, we found no significant change in inward permeability (p = 0.5879), whereas a significant decrease of 36% was found in the outward permeability of fluorescein (p = 0.0171). The demonstration that the outward permeability, which is more than 100-fold higher than the inward permeability in the healthy eye, is significantly decreased by probenecid, demonstrates that active transport is involved in movement of fluorescein across the blood-retina barrier from the vitreous to the plasma.

Adult↗

PubMed1994

Absence of foveal avascular zone demonstrated by laser scanning fluorescein angiography.

We present laser scanning fluorescein angiograms of abnormal foveal capillary patterns in a healthy subject and an insulin-dependent diabetic patient with mild diabetic retinopathy. In both subjects capillaries were seen to cross the central foveal area where capillaries are usually absent. The flow pattern of the foveal capillaries, which were visualised with the use of a laser scanning ophthalmoscope, was indistinguishable from that of the more peripheral capillaries, indicating that foveal vessels are functionally normal retinal capillaries. The two cases demonstrate that identification of abnormal capillary patterns induced by retinal disease such as diabetic retinopathy is made difficult by the marked interindividual variation in capillary anatomy. In prospective studies, however, the method may be capable of detecting subtle changes in early diabetic retinopathy with a high degree of sensitivity.

Adult↗

PubMed1994

Early changes in diabetic retinopathy: capillary loss and blood-retina barrier permeability in relation to metabolic control.

In diabetic retinopathy capillary loss and blood-retina barrier leakage are prominent factors. We present a study with quantitative measurements of both capillary loss and leakage and their relation to cumulative metabolic control. Seventeen insulin-dependent diabetic patients with no retinopathy or only mild background retinopathy and 10 years' duration of the disease were included in the study. Status of metabolic regulation had been followed for at least 6 years. Seven healthy subjects were included as controls. In diabetic patients the perifoveal intervascular areas were found to increase significantly with the cumulative HbA1c index (p = 0.02) and in relation to the presence of moderate background retinopathy (p < 0.02). The blood-retina barrier leakage and the area of the foveal avascular zone were not significantly different from healthy subjects and no correlation was found between the HbA1c index and blood-retina barrier permeability. We conclude that perifoveal capillary loss occurs early in the course of diabetic retinopathy and that this loss is related to prior glycemic control and to the ophthalmoscopic retinopathy level.

Adult↗

PubMed1994

Interferon alfa-2a modifies the course of subfoveal and juxtafoveal choroidal neovascularisation.

The first double masked placebo controlled trial of interferon alfa-2a for the treatment of overt choroidal neovascular membranes is presented. A total of 43 consecutive patients were randomised to double masked treatment with either interferon alfa-2a, 3 million IU subcutaneously three times a week or matching placebo, for a period of 8 weeks. End of study changes from baseline in distance and near visual acuity, macular visual field, contrast sensitivity, and macular morphology (fluorescein angiography) were assessed. The between group difference in distance visual acuity, the primary efficacy variable, was significant in favour of interferon alfa-2a (p = 0.023). Fluorescein angiograms, macular visual fields, and near vision all showed a trend in favour of interferon alfa-2a. It was concluded that, at the dosage used in this study, interferon alfa-2a is a reasonably well tolerated and apparently effective short term treatment of subfoveal and juxtafoveal choroidal neovascularisations.

Adult↗

PubMed1993

Interferon alpha-2a treatment of patients with subfoveal neovascular macular degeneration. A pilot investigation.

It has recently been suggested that interferon alpha-2a has a beneficial effect on exudative age-related macular degeneration (AMD). So far, results are controversial, and masked, placebo controlled, randomized studies with well-defined inclusion criteria are required to assess the effect of interferon alpha-2a. In preparation for such a study we performed a pilot investigation that included 5 patients with subfoveal neovascularizations. All patients received interferon alpha-2a (Roferon-A, Hoffmann La-Roche) 1.5 mio, IU subcutaneously every second day for 8 weeks. Improved visual acuity was subjectively observed by 4 patients and objectively by 3 patients. Two patients showed decreased central visual field defect. Fluorescein angiography and fundus photography showed ambiguous changes. Amsler chart and contrast sensitivity also showed heterogenous results. Even though the treatment with interferon alpha-2a may show some positive effect, our results are not unequivocal and serve to underline the need for controlled studies before the effect of interferon alpha-2a on neovascular AMD can be reliably assessed.

Adult↗

PubMed1992

Lens fluorescence in relation to nephropathy in insulin-dependent diabetes mellitus.

The relationship between diabetic nephropathy and blue-green lens fluorescence, lens transmittance, and other lens fluorometry parameters was studied in patients with long-term insulin-dependent diabetes mellitus. The findings in 10 patients who presented with diabetic nephropathy were compared with those of 11 patients of comparable age and duration of diabetes but without nephropathy. Diabetic nephropathy was associated with increased lens fluorescence (P = 0.04) and decreased lens transmittance (P = 0.045). We propose that lens changes may be responsible for various psychophysical abnormalities in diabetic patients and that our results explain the correlation of these abnormalities with the degree of microangiopathy.

Adult↗

PubMed1991

Blood-retina barrier permeability and its relation to the progression of diabetic retinopathy in type 1 diabetics. An 8-year follow-up study.

Blood-retina barrier (BRB) permeability and its relation to the progression of diabetic retinopathy was studied over an 8-year period in 50 insulin-dependent diabetic patients. Initially, the patients underwent an ophthalmological examination, including measurement of best corrected visual acuity, fundus photography and vitreous fluorometry for determination of BRB permeability. After 8 years the patients were reexamined and their retinal status and clinical course were evaluated. We found a positive correlation between a high initial permeability value and an unfavorable clinical course using the parameter photocoagulation. A decrease in follow-up visual acuity was also associated with high initial permeability; however, this correlation was not statistically significant. A significant difference in mean blood pressure was found between values measured in laser-treated patients vs a group that did not undergo such therapy. Thus, in patients showing the same initial retinal morphology, high permeability seems to indicate an unfavorable disease course. The extent to which BRB permeability can be a valuable supplement to fluorescein angiography and three-mirror examination in the clinical decision process needs to be further evaluated.

Adolescent↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1991

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↗

PubMed1990

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↗

PubMed1990

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↗