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Optical coherence tomographic assessment of diabetic macular edema: comparison with fluorescein angiographic and clinical findings.

PURPOSE: To compare the optical coherence tomographic (OCT) features with clinical and fluorescein angiographic (FA) findings in patients with diabetic retinopathy. METHODS: In a retrospective study ophthalmologic examination together with FA and OCT images were obtained from 195 eyes of 110 patients with different stages of diabetic retinopathy and OCT images were obtained from 40 eyes of 20 control subjects. Fluorescein leakage characteristics were organized into five groups: no leakage (1), focal (2), diffuse (3), combined focal+diffuse leakage (4) and cystoid (5). The Pearson correlation test was used to test the correlation between visual acuity and central foveal thickness and ANOVA was used for the statistical comparison between the groups. RESULTS: The OCT images demonstrated retinal swelling in 66.1% of eyes, cystoid macular edema (CME) in 11.8% of eyes, serous foveal detachment + swelling in 6.2% of eyes, serous foveal detachment+swelling+CME in 3.6% of eyes and normal foveal structure in 12.3% of eyes. The best-corrected visual acuity was significantly correlated with central foveal thickness (r:-0.528, p<0.01). There was 77% agreement between clinical examination and OCT results. CME was detected with OCT in 15.4% of eyes in our study, 40% of which was not detected with slit-lamp biomicroscopy and 63.3% of which was not evident in FA. None of the serous foveal detachments could be detected during slit-lamp biomicroscopy or FA. CONCLUSIONS: OCT-3 provided objective documentation of foveal structural changes in eyes with diabetic retinopathy. Best-corrected visual acuity provided a significant correlation with the retinal thickness at the central fovea. These results indicate that OCT can facilitate deciding on the treatment protocol (surgical or medical) and follow-up of diabetic patients, which is especially important in the early stages of diabetic maculopathy when the structural changes are not yet evident with slit-lamp biomicroscopy or angiographically.

Adult↗

Improved reproducibility of the 'large-window' method of assessing transcapillary and interstitial fluorescein diffusion in the skin in healthy subjects and in subjects with insulin-dependent diabetes mellitus.

The transcapillary and interstitial diffusion of intravenously administered sodium fluorescein is used as a marker for capillary permeability. Fluorescein diffusion has been expressed by different parameters with reported coefficients of variation of 14-20%. Aim of the present study is to select a parameter which combines excellent reproducibility with the potential for discriminating insulin-dependent diabetic patients from healthy subjects. We performed three experiments to assess day-to-day reproducibility: 5 healthy subjects were measured twice, 1 healthy subject was measured 6 times and 1 subject with insulin-dependent diabetes mellitus was measured 5 times. We averaged the relative fluorescence light intensity (IREL(t)] from dye arrival until a certain time point [IAV(t)], instead of using the relative intensity at one time point. IAV (7 min) showed markedly improved reproducibility, expressed as geometric mean of the coefficients of variation of the three separate experiments: 10%. In addition, a group of 12 insulin-dependent diabetic subjects was compared with 12 healthy control subjects. Median IAV (7 min) was 69.5% (95% CI: 65.3-78.1%) in the diabetic subjects and 54.9% (95% CI: 52.1-60.0%) in the control subjects (p < 0.001). Since IAV (7 min) combines excellent reproducibility with a good discriminating power, we advise its use in further studies.

Adult↗

In vivo studies of pial vascular permeability to sodium fluorescein: absence of alterations by bradykinin, histamine, serotonin, or arachidonic acid.

We studied pial vessels in vivo in mice, examining under mercury light the permeability of these vessels to sodium fluorescein. Topical application of hypertonic solutions of NaCl caused leakage of fluorescein. However, putative chemical mediators of leakage, such as histamine, serotonin, arachidonic acid, and bradykinin, all failed to increase permeability to the dye. Apparent increases in permeability only accompanied endothelial damage caused by the dye + light combination, as indicated by production of local platelet aggregates. The technique is useful, provided inadvertent endothelial injury is recognized and avoided. The data in mice suggest that pial vessels may not participate in the permeability changes reportedly produced in parenchymal brain vessels by several of the mediators we tested. Therefore, studies of pial vascular permeability are not expected to provide reliable data concerning the actions of agents that might mediate cerebral edema.

Animals↗

Fluorescein-labeled tyramide strongly enhances the detection of low bromodeoxyuridine incorporation levels.

Immunocytochemical detection of bromodeoxyuridine (BrdU) labeling can be hampered by low BrdU incorporation levels. We describe here an amplification method for weak BrdU immunosignals. The tyramide signal amplification method based on catalyzed reporter deposition (CARD) uses fluorescein-labeled tyramide as a substrate for horseradish peroxidase. The enzyme catalyzes the formation of highly reactive tyramide radicals with a very short half-life, resulting in the binding of fluorescein-conjugated tyramide only at the site of the enzymatic reaction. MCF-7 cells were grown in vitro in medium containing charcoal-stripped fetal bovine serum supplemented by growth factors. Under these culture conditions, the BrdU immunosignal was hard to detect but could be enhanced specifically by the tyramide signal amplification system, resulting in clear-cut differences between BrdU-negative and BrdU-positive cells. This enabled rapid and objective quantification of the BrdU labeling index without the risk of underestimating the number of cells in S-phase. Therefore, this amplification of BrdU immunosignals might also prove valuable for in vivo cancer prognosis, cell kinetics studies, and computer-assisted image analyses.

Breast Neoplasms↗

Ocular fundus abnormalities detected by fluorescein and indocyanine green angiography in the Royal College of Surgeons dystrophic rat.

The ocular fundi of the Royal College of Surgeons (RCS) dystrophic rats were examined by conventional fundus photography, fluorescein angiography (FA) and indocyanine green angiography (IA). In the fundus, a reddish colored background was observed in the RCS dystrophic rats at 3 weeks of age. At 9 weeks of age, the background had changed to pale in color. In FA, the RCS dystrophic rats at 3 week of age demonstrated background fluorescence with homogeneous brightness. Fluorescent dye leakage was observed in the late phase of the postinjection period at 9 weeks of age. In IA, the RCS dystrophic rats at 3 weeks of age had background fluorescence with homogeneous brightness, and at 5 weeks of age, spots of hyperfluorescence were scattered over the dark background. At 7 weeks of age, numerous delimited, irregular round spots of hyperfluorescence appeared over the dark background. Such hyperfluorescent lesions had further increased in number and size in the RCS dystrophic rats at 9 weeks of age. In this way, ocular findings related to abnormalities in the retinal pigment epithelium and choroid in the RCS dystrophic rat were demonstrated by fundus photography, fluorescein angiography and indocyanine green angiography.

Aging↗

Endoscopic fluorescein flowmetry in the evaluation of gastric and duodenal mucosal blood flow.

Fluorescein flowmetry (FF) implies the measurement of a relative capillary blood flow, expressed as an index--that is, the ratio between the maximum fluorescence, obtained during the first circulatory passage of sodium fluorescein (Na-F), and the rise time, defined as the time interval between 10% and 90% of the maximum fluorescence. The aim of this study was to develop FF to be used during endoscopy for the evaluation of ventricular and duodenal mucosal blood flow. FF was applied during gastroduodenoscopy in 38 patients with normal mucosa, as verified by histopathologic examination. The blood flow index did not differ significantly for the mucosa of the fundus, corpus, and antrum. However, when compared with the duodenal mucosa, the blood flow index of the ventricular mucosa was almost twice as high (P less than 0.01). This, in turn, was due to a significantly higher maximum fluorescence in the ventricular mucosa (P less than 0.01), indicating a denser capillary network than in the duodenal mucosa. Since FF is a reliable method, easy to perform and without complications, it is suitable whenever mucosal blood flow warrants measurement during endoscopy.

Adult↗

[Hypersensitivity to fluorescein].

Intravenous fluorescein angiography is a useful and commonly performed diagnostic procedure. Although relatively rare, hypersensitivity reactions to fluorescein can cause considerable morbidity and even death. The mechanism underlying these reactions is not well understood. We present a case of hypersensitivity reaction. The relevant literature is reviewed and possible mechanisms are discussed.

Aged↗

Indocyanine green dye fluorescence and infrared absorption choroidal angiography performed simultaneously with fluorescein angiography.

The sensory retina of the eye is nourished by two essentially separate blood circulations. The more superficial of these, the retinal circulation, is easily evaluated by direct visualization or routine fluorescein angiography. However, the underlying choroidal circulation, which is attributed with maintenance of the outer layers of the retina is not easily visualized due to the pigment epithelial layer and choroidal pigment. Fluorescence and infrared absorption angiographic techniques using indocyanine green (ICG) dye, which can be used to evaluate the choroidal circulation routinely, are described in this paper. A method is also described which can provide these angiograms simultaneously with standard fluorescein fluorescence angiograms of the retina. Finally, a comparison of all three types of angiograms is made. Limitations to the resolution of fundus details in angiograms imposed by optics of the fundus camera, photographic films, and optics and anatomy of the eye are examined.

Absorption↗

Expansion of microvascular bed and increased solute flux in human Basal cell carcinoma in vivo, measured by fluorescein video angiography.

Human basal cell carcinoma (BCC) offers a unique opportunity to assess directly the microvascular abnormalities in a human cancer in vivo. Our objectives were to assess angiogenesis, perfusion, and changes in small solute exchange kinetics. The microcirculation of BCC and a normal (control) skin site was studied in 15 patients by laser Doppler fluximetry and videoangiography after rapid i.v. fluorescein injection. Microvascular morphometry was analyzed off line. Sodium fluorescein accumulation/clearance was recorded for 30 min, and fluorescence intensity (FI) was quantified by computer analysis of videotape image gray levels. In BCCs, the microvascular area fraction was 2.6-fold greater, microvessel length density 2.0-fold greater, average vessel image width 2.1-fold greater, and red cell flux 3.9-fold greater than in control sites (P < 0.01, paired t tests). The initial rate of rise of FI over 10 s was approximately 3-fold greater in BCC than control and correlated with vascular area fraction and red cell flux. Tissue then equilibrated faster in BCC, rate constant -(13.0 +/- 5.6) x 10(-3) s(-1) (mean +/- SD), than controls -(5.3 +/- 1.7) x 10(-3) s(-1), and plasma clearance was 2.6-fold higher in BCC than controls (P < 0.01, paired t test). Similarly, the rate constant of the subsequent clearance phase was approximately 2-fold greater in BCC, -(0.53 +/- 0.19) x 10(-3) s(-1), than controls, -(0.27 +/- 0.22) x 10(-3) s(-1) (P < 0.01). Removal rate constants were an order of magnitude slower than accumulation rate constants. The results demonstrate angiogenesis, increased perfusion, and a more rapid exchange of small solute in human BCC. FI itself is rejected as an index of permeability to small solutes (cf. 29) because it depends also on blood flow, endothelial area, microvascular volume, and interstitial fluid volume.

Aged↗

Enhanced documentation of slit-lamp images of the human vitreous stained with fluorescein sodium.

BACKGROUND AND OBJECTIVE: To develop a new method to document the slit-lamp image of the vitreous body as stained with fluorescein sodium. PATIENTS AND METHODS: The system consists of a Goldmann-type slit-lamp biomicroscope, a highly sensitive monochromatic charge-coupled device camera, and a video attachment for real-time observation and recording. As a standard procedure, observation of the vitreous was conducted 60 minutes after intravenous administration of 500 mg of fluorescein sodium. This method was applied to 19 eyes with various eye diseases. RESULTS: Fine details of the vitreous were observed in all of the eyes. Posterior vitreous detachment could be recorded in 5 of the 19 eyes examined. Vitreoschisis and large lacunae were documented in 11 eyes. CONCLUSION: This method promises to be of value in detecting early age-related and pathological changes of the vitreous such as posterior vitreous detachment and vitreoschisis in clinics.

Adult↗

Clearance of a topically applied fluorescein gel from periodontal pockets.

The clearance of a fluorescein gel applied with an irrigation technique in periodontal pockets was studied. In order to evaluate the time a drug remains in a periodontal pocket, the alteration in concentration of this drug in a given time period was investigated. After application of the gel in 4 pockets of 10 patients, samples were taken from 1 of the 4 pockets at 5, 10, 20 and 40 min. The results show that in the 1st phase, directly after application, most of the gel disappeared from the pocket, while in the 2nd phase, the fluorescein gel is washed out with a calculated 50% reduction time of 12.5 min. The rapid clearance of the gel observed after irrigation might provide a partial explanation of the minor effect of pocket irrigation on the subgingival microflora.

Administration, Topical↗

Variable region primary structures of a high affinity anti-fluorescein immunoglobulin M cryoglobulin exhibiting oxazolone cross-reactivity.

Previous studies of murine IgM hybridoma protein 18-2-3, derived from an (NZB/NZW)F1 mouse following hyperimmunization with fluorescein (Fl)-conjugated keyhole limpet hemocyanin, demonstrated a high affinity for Fl (Ka = 2.9 x 10(10) M-1) and cryoprecipitation that was abrogated upon Fl binding to the antibody-combining site. V region sequences of 18-2-3 were determined by Edman degradation and nucleotide sequence analysis. The VH region of 18-2-3 was encoded by a gene VHI(B) of the Q52 VH family with 96% homology to anti-oxazolone antibody NQ7.5.3 but utilized a larger D region (DQ52 plus N region). The V kappa region of 18-2-3 was encoded by a gene V kappa IV with an amino acid sequence 97% homologous to that of anti-oxazolone antibody NQ11.1.18. Although monoclonal anti-Fl antibodies 18-2-3 and 4-4-20 possessed similar binding affinities and quenched bound fluorescein to the same extent (Qmax greater than 96%), they utilized different VH, D, V kappa, and J kappa genes, but the same JH gene segment (JH4). Solid-phase analyses showed that 18-2-3 was not idiotypically related to 4-4-20 and 9-40, prototypic anti-Fl antibodies. Fine specificity binding patterns of Fl analogues by 18-2-3 IgM and IgMs were distinct from other anti-Fl antibodies. Monoclonal antibody 18-2-3 bound phenyloxazolone bovine serum albumin with a lower affinity than for Fl-bovine serum albumin. The first hypervariable region of the 18-2-3 light chain showed homology to human cryoglobulins. This is the first variable region sequence of a murine IgM which self-aggregates at low temperature.

Amino Acid Sequence↗

Seizures associated with fluorescein angiography.

We describe a case of grand mal generalized tonic-clonic seizure after fluorescein angiography. The patient had a history of seizure disorders and had been controlled with proper medication before the test. We advocate the need to include diazepam and phenytoin in the list of emergency medications needed to control adverse reactions of fluorescein angiography.

Adult↗

Microscopic fluorometric analysis of Na-fluorescein transport in the smallest secretory unit (couplet hepatocytes) and the effects of cytochalasin B.

The uptake and secretion of sodium fluorescein by couplet hepatocytes was examined in primary culture. When sodium fluorescein was added at an early stage of primary couplet hepatocytes culture, this resulted in a rapid uptake of the dye and its subsequent accumulation in bile canaliculi. From microscopic fluorometry observations, cytochalasin B pretreatment of the couplet hepatocytes caused much more rapid uptake and secretion of the dye in bile canaliculi. The present study indicates that the cholestatic agent cytochalasin B causes choleresis at the bile canalicular level of cultured couplet hepatocytes and also indicates that a defect in canalicular secretion plays no role in the cytochalasin B-induced impairment of bile flow.

Animals↗

Evaluation of fluorescein dye as an indicator of small intestinal viability in the horse.

In 6 horses, 2 types of ischemic lesions were created in small intestinal segments by selective ligation of vessels and intestinal wall for 1, 2, or 3 hours. After confirming the ischemia by IV injection of sodium fluorescein, the ligatures were released. Five minutes later, the fluorescent patterns were documented photographically. Observed patterns ranged from normal (identical to that observed in unaffected bowel) to a patchy distribution of non-fluorescence (indicating incomplete perfusion). None of the experimental segments was normal when reevaluated 1 month later. The typical appearance included fibrosis, adhesions, and thickening of the bowel wall. It was concluded that IV injection of fluorescein can be used to indicate perfusion of the intestine, but that this is not the only criterion for determining clinical outcome in cases of intestinal ischemia in horses.

Animals↗

Pharmacokinetics and distribution of a fluoresceinated glycosaminoglycan, sulodexide, in rats. Part I: Pharmacokinetics in rats.

Fluorescein-labelled sulodexide pharmacokinetics and urinary excretion were studied in the rat after intravenous administration. The compound showed a pharmacokinetic pattern similar to that of heparin and the plasmatic levels were linearly correlated with anti-factor Xa activity and logarithmically with lipoprotein lipase activation. The compound is well eliminated by urinary route; the urinary recovery was 50% in 24 h and 67% 48 h after administration. The results obtained indicate that fluorescein labelling of glycosaminoglycans may be a valid tool for pharmacokinetics and distribution studies in the laboratory animals.

Animals↗

Acute myocardial infarction following fluorescein angiography.

A 64-year-old woman with diabetes mellitus as well as hypertensive retinopathy developed an acute myocardial infarction and hypertensive crisis following the injection of 5 ml. of 10 per cent sodium fluorescein for fundus angiography. This is the first time this complication has been documented. Possible mechanisms for such an occurrence are discussed. Recommendations for recognizing and dealing with patients at high risk for cardiovascular complications of fluorescein angiography are emphasized.

Diabetes Complications↗

Preinjection with sodium fluorescein aids discrimination in vitreous surgery.

To discriminate formed and opacified vitreous from lacunae and irrigating solution during closed vitrectomy, sodium fluorescein solution was injected intravenously 18 to 20 hours prior to the operation. Vitreous gel became yellowish-green and helped in the resection of opacified vitreous, especially when ultraviolet light was used. The higher the total amount of fluorescein in the vitreous of patients with impaired blood-retinal barriers, the stronger the vitreous gel was stained. Neurosensory retina and hard proliferative vitreous membrane, however, did not stain well. This method can be useful to the beginning vitreous surgeon and in teaching surgical procedures.

Adult↗