Birgitte Moldow

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

Abstract · 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 1.1×101 nm/s, P=0.031), and a 95% increase in unidirectional permeability of fluorescein (from 1.2×102 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 (≤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.

Diabetic macular oedema: a comparison of vitreous fluorometry, angiography, and retinopathy

Aim: To evaluate the relation between the quantitative measurement of vitreous fluorescein with fluorescein angiography and retinopathy in diabetic patients with and without clinically significant macular oedema (CSMO). Methods: In a prospective cross sectional study, passive permeability and active, outward transport of fluorescein across the blood-retinal barrier were quantitated with vitreous fluorometry in 61 eyes from 48 patients with CSMO and 22 fellow eyes without CSMO, after exclusion of eyes with previous macular laser treatment and vitreous liquification. All patients were recruited from the university hospitals outpatient clinic. Retinopathy and fluorescein angiograms were evaluated on 60 degree photographs. Results: The passive permeability in CSMO was significantly correlated with the severity of leakage on fluorescein angiograms (r=0.73), the level of retinopathy (r=0.61), and visual acuity (r=0.45). Significant differences between eyes with CSMO and eyes without CSMO were found for passive permeability (p<0.001), fluorescein leakage (p<0.001), visual acuity (p=0.02), and retinopathy (p=0.002). Conclusion: Passive permeability of fluorescein quantitated with vitreous fluorometry was correlated both with semiquantitative fluorescein angiography and retinopathy, and a significant increase in passive permeability was found when comparing eyes with CSMO to eyes without CSMO. No such pattern was found for the active transport indicating that passive and not the outward, active transport is the factor of most importance in the development of CSMO.

Danish Rural Eye Study: the association of preschool vision screening with the prevalence of amblyopia

To determine the prevalence of amblyopia in Denmark before and after the initiation of the Danish national preschool vision screening programme.

Diabetic macular oedema: the effect of photocoagulation on fluorescein transport across the blood-retinal barrier

Background/aim: The visual loss secondary to diabetic macular oedema can be controlled to some extent by photocoagulation, though the mechanism of action is largely unknown. The purpose of the present study was to quantitate the effect of photocoagulation on the blood-retinal barrier using fluorescein as a tracer of passive and active transport. Methods: A prospective study of 46 eyes in 34 patients with clinically significant macular oedema (CSMO) examined by vitreous fluorometry before and 6 months after macular photocoagulation treatment. Results: In 23 eyes CSMO was not present at follow up (responding eyes), in another 23 other eyes CSMO was still present (non-responding eyes). With reference to the presence or absence of CSMO at follow up, the passive transport (permeability) for responding eyes decreased after photocoagulation in contrast with an increase in non-responding eyes; the difference between the groups at follow up was significant (p=0.03). The active transport for responding eyes decreased slightly at follow up, while it increased for non-responding eyes; the difference between the groups at follow up was not significant (p=0.09). Conclusion: Following photocoagulation a reduction of diabetic macular oedema, defined as disappearance of CSMO, is paralleled by a decrease of the passive permeability while the hypothesis of an increase in the active transport from the retina to the blood could not be supported by this study.

Passive permeability and outward active transport of fluorescein across the blood-retinal barrier in early ARM

AIM To study the passive and active transport of fluorescein across the blood-retina barrier in early age related maculopathy (ARM) (soft drusen > 63 μm, hyperpigmentation and/or hypopigmentation in patients above 50 years of age). METHODS 15 patients and 10 healthy subjects were included. Morphological changes were graded from 30 degrees fundus photographs using a simplified version of the epidemiological ARM study group classification system. Differential vitreous spectrofluorophotometry was used to assess the transport properties of the blood-retina barrier (that is, passive permeability and unidirectional permeability caused by outward active transport from the vitreous to the blood). RESULTS The passive permeability of the patient group was not significantly different from that of the control group. Four patients with passive permeability more than 3 SD above the mean of the control group (mean 1.8 (SD 0.7) nm/s, range 1.0–3.0 nm/s, data normally distributed) all had centrally located drusen >500 μm and superjacent pigment clumps of 63–500 μm in diameter. There was no significant difference between the unidirectional permeabilities for the patient group and for the control group (mean 47.4 (29.3) nm/s, range 12.7–91.1 nm/s). CONCLUSION There was no significant difference in the passive permeability and in the unidirectional permeability of fluorescein. However, the study may indicate that the combination of very large drusen and superjacent pigment clumps in ARM may be associated with a deterioration of the blood-retina barrier.

Corneal autofluorescence in relation to permeability of the blood-aqueous barrier in diabetic patients with clinically significant macular edema and in an age-matched control group.

Purpose. Corneal autofluorescence is related to advanced glycation end products formed by glucose that reaches the cornea via the aqueous humour. The aim of the study was to examine the influence on autofluorescence of changes in permeability of the blood aqueous barrier. Methods. Corneal autofluorescence was measured in 50 diabetic patients with clinically significant macular edema and in 28 age-matched control subjects. Permeability of the blood aqueous barrier was assessed using the diffusion coefficient of fluorescein. Results. Corneal autofluorescence was higher in diabetic subjects than in the control group, mean (SD) at an excitation wavelength of 458nm was 41.2 ng f-eq/ml (11.7) in diabetic patients and 26.5 ng f-eq/ml (7.3) in the control group, p < 0.001. The mean permeability of the blood aqueous barrier, Kd(F), was 492.0 · 10 -6 min -1 in the diabetic patients and 484.2 10 -6 min -1 in the control group. There was no association between permeability of the blood aqueous barrier and corneal autofluorescence, p = 0.99 for the diabetic patients and p = 0.15 for the control group (458 nm). Conclusions. Corneal autofluorescence was unaffected by permeability of the blood aqueous barrier suggesting that formation of advanced glycation products is limited by other factors than the concentration of glucose in the aqueous humour, or that other factors unrelated to nonenzymatic glycation of stromal proteins are involved.

Danish Rural Eye Study: Epidemiology of Adult Visual Impairment

ABSTRACT Purpose: To examine the frequency and causes of visual impairment (VI) in a select population of Danish adults. Methods: A total of 3843 adults aged 20–94 years from the Danish General Suburban Population Study (GESUS) were included in the population-based, cross-sectional ophthalmological study, Danish Rural Eye Study (DRES). All DRES participants received a comprehensive general health examination preceding their eye examination, including measurement of best-corrected visual acuity (BCVA) for each eye, bilateral 45° retinal fundus photographs and further ophthalmological examination where indicated. Results: Overall, 3826 of 3843 participants (99.6%) had bilateral visual acuity measurements. The overall frequency of VI (BCVA <20/40 in the better-seeing eye) was 0.4% (95% confidence interval, CI, 0.2–0.7%; n = 15) among all DRES participants, 0.6% (95% CI 0.3–1.0%; n = 15) among participants >50 years and 3.7% (95% CI 2.1–6.5%; n = 11) in participants >80 years. The primary causes of VI in the better-seeing eye were age-related macular degeneration (AMD) in 46.7% (7/15) and cataract in 26.7% (4/15). A total of 43.3% (n = 115) of participants >80 years were pseudophakic in one or both eyes. The frequency of diabetes (HbA1c ≥48 mmol/mol or self-reported diagnosis) was 5.9% (n = 227), including 1.3% (n = 51) newly diagnosed in the GESUS. Of participants determined to have VI due to exudative AMD, 50% had received anti-vascular endothelial growth factor (VEGF) treatment. Conclusion: We report a relatively low frequency of VI among Danish adults over 59 years of age compared with that observed 10–15 years ago, which is both consistent with other recent Scandinavian studies and reflective of our relatively healthy and mobile population sample.

An evaluation of fundus photography and fundus autofluorescence in the diagnosis of cuticular drusen

Purpose To examine non-mydriatic fundus photography (FP) and fundus autofluorescence (FAF) as alternative non-invasive imaging modalities to fluorescein angiography (FA) in the detection of cuticular drusen (CD). Methods Among 2953 adults from the Danish Rural Eye Study (DRES) with gradable FP, three study groups were selected: (1) All those with suspected CD without age-related macular degeneration (AMD) on FP, (2) all those with suspected CD with AMD on FP and (3) a randomly selected group with early AMD. Groups 1, 2 and 3 underwent FA and FAF and group 4 underwent FAF only as part of DRES CD substudy. Main outcome measures included percentage of correct positive and correct negative diagnoses, Cohens κ and prevalence-adjusted and bias-adjusted κ (PABAK) coefficients of test and grader reliability. Results CD was correctly identified on FP 88.9% of the time and correctly identified as not being present 83.3% of the time. CD was correctly identified on FAF 62.0% of the time and correctly identified as not being present 100.0% of the time. Compared with FA, FP has a PABAK of 0.75 (0.60 to 1.5) and FAF a PABAK of 0.44 (0.23 to 0.95). Conclusions FP is a promising, non-invasive substitute for FA in the diagnosis of CD. FAF was less reliable than FP to detect CD.

THE ASSOCIATION BETWEEN CUTICULAR DRUSEN AND KIDNEY FUNCTION: A Population-Based Case-Control Study.

Purpose: To determine the association between cuticular drusen (CD) and kidney function. Design: observational case-control study. Methods: Setting: Population-based. Patients or Study Population: 53 participants with (CD) and 53 age- and sex-matched controls, selected from the Danish Rural Eye Study. Cuticular drusen participants were diagnosed using fluorescein angiography and controls were excluded if the patients were suspected of having CD on fundus photography or did not have an available estimated glomerular filtration rate. Main Outcome Measures: creatinine and estimated glomerular filtration rate. Results: The mean estimated glomerular filtration rate of those with CD was 73.3 mL·min·1.73 m−2 (95% confidence interval [CI]: 70.0–76.6) and 73.4 mL·minute−1·1.73 m−2 (95% CI: 69.5–77.3) in controls. The difference was not significant (P: 0.970). The mean creatinine among those with CD was 72.8 &mgr;mol/L (69.3–76.4) and 73.5 &mgr;mol/L (95% CI: 69.3–77.6) among controls. The difference was not significant (P = 0.820). Conclusion: The authors did not find an association between a (CD) diagnosis and decreased kidney function at a population level.