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.

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 hospital's 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.

Diabetic macular edema: passive and active transport of fluorescein through the blood-retina barrier.

PURPOSE: To investigate the passive bidirectional and active outward transport of fluorescein through the blood-retina barrier (BRB) in diabetic patients with clinically significant macular edema and in healthy controls. METHODS: The passive and active transport of fluorescein through the BRB was quantitated by vitreous fluorometry. A previously developed method was used to model passive transport. A new simulation model was developed and evaluated for estimation of active transport. The study included 10 eyes of 5 healthy controls and 31 eyes of 20 diabetic patients with clinically significant diabetic macular edema (CSME) in at least one eye, totalling 25 eyes with CSME. RESULTS: Passive permeability of fluorescein was increased by a factor of 12 in eyes with edema compared to healthy controls (edema, 23.7 nm/sec; healthy subjects, 1.9 nm/sec, P < 0.01), whereas the active transport was doubled (edema, 84.1 nm/sec; healthy subjects, 43.5 nm/sec, P < 0.01). Unlike active transport, passive permeability was related to the degree of retinopathy, in that eyes with severe non-proliferative diabetic retinopathy had a passive permeability that was significantly increased compared to moderate retinopathy (32.1 nm/sec and 14.6 nm/sec, respectively, P: < 0.05). The passive movement quantitated with vitreous fluorometry was larger for diffuse and mixed leakage compared to focal (P = 0.07). CONCLUSIONS: Insofar as the movement of fluorescein can be taken as a probe for the movement of electrolytes and water, the pathogenesis of diabetic macular edema seems to involve a disruption of the BRB, presumably its inner component. The active resorptive functions of the blood-retina barrier appear to be compensatorily increased to counteract edema formation, although the increase is too small to prevent edema in the face of severe leakage through the blood-retina barrier.

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.

[Chronic radiation enteropathy. A retrospective study]. / Kronisk stråleenteropati. En retrospektiv undersøgelse.

In the period 1968-1989 50 patients, 38 women and 12 men, aged 30-76 years, median 58 years, were referred to the Department of Gastroenterology, Rigshospitalet for severe chronic radiation enteropathy. Most women had received radiation for gynaecological cancer, and most men for urogenital cancer. The initial symptoms of the enteropathy were diarrhoea in 74%, abdominal pain in 62% and weight loss in 52%. Twelve per cent had visible blood in the stools. Ten per cent had fistulas. The symptoms occurred 0-37 years, median ten months after the radiation. The radiation enteropathy had necessitated one or more laparotomies in 35 patients, most often because of subileus/ileus, including resection of the small bowel or the colon in 25 patients, and establishment of an ileostomy or a colostomy in 11. Seven patients developed new fistulas postoperatively. In 32 patients one or more tests for malabsorption were performed as a guidance for therapy: stool mass (26 patients), faecal fat excretion (26 patients), Schilling test (22 patients), lactose absorption (11 patients) and bile acid breath test (seven patients). Half of the patients had diarrhoea, including one third of the patients without intestinal resection. Two thirds had steatorrhoea, including half of the patients without small bowel resection. Three fourths showed decreased absorption of vitamin B12, including half of the patients without ileal resection. All patients studied had abnormal deconjugation of bile acids and more than half of them had bile acid malabsorption. Malabsorption of lactose was found in only one patient. There was no correlation between the radiological and functional abnormalities of the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)