Intravenous Sodium Fluorescein Research Articles

Real Time Intraoperative Confocal Laser Microscopy-Guided Surgery

To assess the potential utility of in vivo histologic surface and subsurface imaging in real-time using the Optiscan confocal laser microscope to detect diseased tissue at the time of surgery. The goal of surgical treatment of diseases such as cancer is complete microscopic resection of diseased tissue; however, current methods for the assessment of extent of disease at the time of surgery are inadequate. We assessed the potential of the Optiscan confocal laser microscope, a new device developed for real-time in vivo histologic surface and subsurface imaging during surgery. Intravenous Fluorescein Sodium contrast enabled visualization of cellular and architectural morphology of intra-abdominal organs with magnification equivalent to light microscopy and enabled differentiation between normal organs and disease. Real time intraoperative confocal microscopy has significant potential application in detecting disease, and influencing decision-making at the time of surgery.

Intravenous sodium fluorescein enhances the visibility of vitreous during vitrectomy surgery for diabetic retinopathy

OBJETIVO: Observar a eficácia da fluoresceína sódica intravenosa, na visibilidade do vítreo, durante a cirurgia de vitrectomia nos pacientes com retinopatia diabética. MÉTODOS: Quatorze casos consecutivos de cirurgia vitreorretiniana para hemorragia vítrea e descolamento tracional da retina secundário à retinopatia diabética, foram submetidos à injeção de fluoresceína intravenosa a 20%, 1 hora antes da cirurgia.As imagens de todos os passos das cirurgias foram gravadas. RESULTADOS: A fluoresceína corou de verde o vítreo periférico, base vítrea, hialóide posterior melhorando a visibilidade [...]

In vivo confocal laser scanning chromo‐endomicroscopy of colorectal neoplasia: changing the technological paradigm

Recently, miniaturization of a novel confocal laser endomicroscope (Optiscan Pty, Notting Hill, Victoria, Australia) has permitted functional integration into the distal tip of a conventional video colonoscope (Pentax EC3870K; Pentax, Tokyo, Japan) enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. Using endomicroscopy and intravenous sodium fluorescein as a contrast agent, 'virtual histology' can be created, which allows visualization of both the surface epithelium, and some of the lamina propria (down to a quarter of a millimetre), including the microvasculature. Confocal endomicroscopy may have major implications in the future of colonoscopy as uniquely it allows in vivo diagnosis of colonic intraepithelial neoplasia and carcinoma enabling 'smart' biopsy targeting and hence potentially influencing 'on table' management decisions. Initial pilot data have now shown that confocal imaging in vivo using the newly developed EC3870K has high overall accuracy for the immediate diagnosis of intraepithelial neoplasia and carcinoma in sporadic screened cohorts, but also has a role in the detection of intraepithelial neoplasia detection in chronic ulcerative colitis cancer screening when used in conjunction with methylene blue chromoscopy. We discuss the current evidence in support of confocal endomicroscopy in the colorectum and explore the new diagnostic possibilities for this technology.

Influence of bromopride in the prophylaxis of nausea associated with fluorescein angiography

To determine the efficacy of bromopride in the prophylaxis of nausea during fluorescein angiography, when compared with a placebo. The study was a double-masked random clinical trial, between December of 2004 and April of 2005. Examinations were performed with 20% intravenous fluorescein sodium in a single dose of 2.5 ml. The patients were divided into two groups: group 1, patients who received a 2 ml intravenous dose of 5 mg/ml bromopride and group 2, patients who received a 2 ml intravenous dose of 0.9% sodium chloride (placebo), both 20 minutes before the dye injection. Cases of nausea were observed during and after the examination. 352 patients were enrolled, 176 in each group. Cases of nausea were observed in 12 (6.8%) patients of the bromopride group and in 11 (6.3%) patients of the placebo group (p<0.829 - relative risk=1.05). Bromopride did not prevent the occurrence of nausea in fluorescein angiography, when compared with a placebo.

In vivo fluorescein staining of SI-30NB silicone intraocular lens

We report a case of a 48-year-old pseudophakic woman who presented 3 weeks after Heidelberg retinal angiography using intravenous sodium fluorescein 2%. Bilateral retinal vasculitis with severe retinal ischemia and extensive capillary dropouts had been diagnosed. Anterior segment examination revealed green staining on the silicone optic of the 3-piece SI-30NB intraocular lens (IOL) (AMO), with no cell or flare in the aqueous humor. The anterior and posterior capsules were not stained. The patient did not report dark vision, double vision, or altered color vision. The anterior and posterior IOL surfaces demonstrated an autofluorescence at the time of fundus photography, which persisted to the 6-week examination although there were no symptoms. This is suggestive of deposits of sodium fluorescein on the IOL surface following angiography.

Confocal Laser Endomicroscopy in the Diagnosis of Celiac Disease

Background: The histological changes of villous atrophy and crypt hypertrophy are key diagnostic features of celiac disease (CD). Whether these changes can be accurately diagnosed in vivo using the confocal laser endomicroscope is unknown. Aims: The aim of this study was to determine the in vivo diagnostic yield of CD using confocal endomicroscopy (CEM) images in comparison with histopathology from endoscopic biopsies. The inter-observer variability in CEM interpretation was also evaluated. Methods: Treated, untreated CD and controls were prospectively recruited to undergo upper gastrointestinal CEM (EC-3870FK, Pentax, Tokyo) aided by intravenous fluorescein sodium plus or minus acriflavine.

Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience

The last major survey of adverse reactions to intravenous fluorescein angiography was performed more than 20 years ago. There have been two recent fatalities involving intravenous fluorescein in Australia. It is important to review the current incidence of adverse reactions and latest literature on the pathogenesis, prophylaxis and alternatives to intravenous fluorescein angiography. A retrospective review of all adverse reactions to intravenous sodium fluorescein in patients undergoing fluorescein angiography between June 1998 and June 2004 was undertaken. The total number of fluorescein angiograms performed and the number of patients with adverse reactions were identified from the photographic department database and the fluorescein adverse reaction register at the Lions Eye Institute. A total of 11 898 fluorescein angiograms were performed during the study period. There were 132 adverse reactions recorded. The commonest adverse reactions were nausea and vomiting. There were no serious adverse reactions or deaths recorded. There was a statistically significant difference in the incidence of adverse reactions between sodium fluorescein used from two manufacturers. Fluorescein angiography is a relative safe procedure and comparable to other intravenous radiocontrast media angiography or investigation. The present results are consistent with previous studies. Prophylactic treatment, fluorescein desensitization or oral fluorescein angiography should be considered in high-risk patients. Safe guards should be in place to manage potential serious adverse reactions. Other imaging techniques, like optical coherence tomography, should be considered as an alternative in selected cases.

Intravenous and indocyanine green angiography

Indocyanine green angiography (ICGA) is an adjunct procedure to intravenous sodium fluorescein angiography (IVFA) for evaluation of disorders of the retina. It has particular application when choroidal pathology is implicated or suspected. Indocyanine green (ICG) dye has been used in the medical field since 1956, when it was approved by the Federal Drug Administration for imaging cardiac and hepatic circulations. Indocyanine green is a well-tolerated, tricarbocyanine dye with a molecular weight of 775 daltons that absorbs light at 790 to 805 nm and has a peak emission at 835 nm. While the substance gives off 4% the fluorescence of sodium fluorescein, its spectral properties allow it to be visualized through ocular pigments, blood, and serous fluids. Using search engines and library resources, clinically relevant ICGA studies were reviewed for their purpose, description, outcome, clinical importance, and compared and contrasted to IVFA. Information is presented that represents the current modalities of ICGA. ICGA still remains an adjunct therapy to traditional IVFA. However, as the technology improves--allowing easier recording and visualization of ICG angiograms--and as more studies are conducted on the best use of the information obtained from ICGA, this technique may emerge as an important diagnostic tool in the fight to prevent the severe vision loss associated with the various retinal disorders mentioned.

The use of dye in ophthalmology.

Dyes are used in current ophthalmological practice, both as diagnostic and therapeutic aids. Commonly used dyes include sodium fluorescein, indocyanine green, rose bengal and methylene blue. The properties of these agents are outlined, along with indications for their use. The article concentrates mainly on intravenous sodium fluorescein and fundus fluorescein angiography, although topical and intracameral use of other dyes is highlighted. Ocular tissue responses are discussed, in particular those of the retinal vasculature and choroidal circulation. The normal blood-retinal barriers and pathology of abnormal angiography findings is presented. Pharmacokinetics and pharmacodynamics of intravenous dye are discussed, along with potential systemic complications.

Antithrombotic effects of magnesium sulfate in in vivo experiments.

In this study, magnesium sulfate was effective in reducing the mortality of adenosine diphosphate-induced acute pulmonary thromboembolism in mice, when it was administered intravenously at doses of 100 and 200 microg/g body weight. In addition, intravenous injections of magnesium sulfate (100 and 200 microg/g) significantly prolonged bleeding time in the severed mesenteric arteries of rats by approximately 1.7- and 1.9-fold, respectively, compared with normal saline. Continuous infusion of magnesium sulfate (20 microg/g per minute) for 10 minutes also significantly increased the bleeding time by approximately 1.7-fold, and the bleeding time returned to baseline within 60 minutes of cessation of magnesium sulfate infusion. On the other hand, platelet thrombi formation was induced by irradiating mesenteric venules with filtered light in mice pretreated with intravenous fluorescein sodium. When magnesium sulfate was administered at 300 microg/g during induction of platelet plug formation with 10 microg/kg fluorescein sodium, occlusion time was not significantly prolonged, but a dose of 600 microg/g did significantly prolong the occlusion time. Furthermore, aspirin (250 microg/g) also showed a similar activity in this experiment in prolonging the occlusion time. In conclusion, these results suggest that magnesium sulfate has an effective antithrombotic activity in vivo, and treatment with magnesium sulfate may lower the risk of thromboembolic-related disorders.

Mathematical morphology in computerized analysis of angiograms in age-related macular degeneration.

This paper deals with image processing of numerical retinal angiograms in order to facilitate diagnosis and follow-up in age-related macular degeneration (AMD) which is currently the main cause of blindness in industrialized countries. A computerized scheme using principally mathematical morphology operators is proposed for detecting and counting drusen, which are precursor lesions of the ocular fundus. In order to check the feasibility of this approach, results relative to 58 retinal images are compared with those given by three retinal specialists independently. From manual counting measures it is found that interobserver correlation coefficients lie in the range 0.71-0.78. On the other hand, a correlation coefficient of 0.89 is obtained when the average of the three expert countings is compared with the drusen number given by the computerized method. This coefficient is improved from 0.89 to 0.93 by processing only frames captured immediately after the appearance of a dye consecutive to intravenous sodium fluorescein injection. Compared to the manual analysis which is, among other things, tedious and time consuming, the computerized analysis is both quicker and more objective. Validation by the practitioner is however necessary, given possible detection errors. The proposed computerized scheme for detecting and counting drusen may be easily automated and so should prove useful in clinical studies which involve high volume analysis of retinal angiograms.

Platelet-activating factor mediates ischemia-induced leukocyte-endothelial adherence in newborn pig brain.

The authors examined the involvement of platelet-activating factor (PAF) in mediating leukocyte adherence to brain postcapillary pial venules and altering blood-brain barrier (BBB) permeability during basal conditions and during reoxygenation after asphyxia in newborn piglets. Intravital epifluorescence videomicroscopy, closed cranial windows, and labeling of leukocytes with rhodamine 6G allowed us to obtain serial measurements of adherent leukocytes within postcapillary venules. Blood-brain barrier breakdown was determined by optical measures of cortical extravascular fluorescence intensity after intravenous sodium fluorescein. Superfusion of PAF over the cortex induced a dose-dependent increase in leukocyte adherence to cerebral venules and leakage of fluorescein; with 1 micromol/L PAF, the magnitude of adherence and BBB breakdown was similar to that seen during reoxygenation after 9 minutes of asphyxia. Both adherence and loss of BBB integrity resulting from either exogenous PAF or asphyxia-reoxygenation could be significantly attenuated by intravenous administration of WEB 2086, a PAF receptor antagonist. Window superfusion of superoxide dismutase with PAF attenuated PAF-induced increases in adherence and associated fluorescein leakage. These findings indicate that PAF exhibits proinflammatory effects in piglet brain and that PAF contributes to leukocyte adherence and BBB breakdown after cerebral ischemia. These PAF effects are mediated by increases in superoxide radical generation.

Intravenous Fluorescein Vascularity Studies of a New Technique: The Subcutaneous Pedicled Extension Flap

To prove the vascularity of the subcutaneous pedicled extension flap through the subcutaneous pedicle. Second, the study was designed to reveal increasing vascularity as a function of time during the intraoperative period. Twenty-six cases of flap utility are presented. The last 11 of these cases were tested for intraoperative vascularity using intravenous fluorescein sodium. Following a 1-mL (100-mg) fluorescein sodium test dose, an additional 900 mg was administered intraoperatively. The fluorescence was observed and photographed at 15-, 30-, and 60-minute intervals. The fluorescence (or lack thereof) was easily visible to the naked eye relative to the surrounding skin, requiring no specialized measurements. Photographic equipment consisted of a 35-mm camera with a UV filter, using 400 ASA-rated film at a 1-second timed setting. A tripod was necessary. All cases were performed in either an ambulatory surgical facility or an in-hospital facility. All patients suffered from skin cancer requiring large resections, necessitating reconstruction via either grafts or flaps. Intravenous 10% fluorescein (Fluorescite) was used as a vascularity testing mode. The method was as described in the "Subjects and Methods" section. The results revealed conclusively the vascularity of the flap through the subcutaneous pedicle. In addition, the secondary goal, ie, of showing increasing vascularity with time, was also proved. The subcutaneous flaps have survived in all cases, with minimal complications. The intravenous fluorescein test, with timed applications intraoperatively, has been reaffirmed as an excellent prognosticator of survivability, as well as a confirmation of the innate vascularity of the subcutaneous pedicle. The subcutaneous pedicled extension is thought to be a new development in random flaps. Its vascularity via the subcutaneous pedicle has been conclusively confirmed using the safe and simple intravenous fluorescein intraoperative study. Second, increasing fluorescence on a timed basis has been reaffirmed and this degree of vascularity related to the ease of survival of the flap.

Laserinduzierte Hornhautgefässokklusion bei variabler Emission und Absorption

Laser light has repeatedly been proposed for the occlusion of corneal neovascularizations. Priority has to be given to minimize laser energy in order to limit side effects such as corneal burns. We investigate the influence of variable emission wavelength using a dye laser or dye-enhanced absorption with intravenous sodium fluorescein. Laser energy can be reduced using intravenous dyes at vessel diameters less than 50 microns. Permanent occlusion is achieved in 43% instead of 28% without dye-enhanced absorption. Vessels measuring greater than 50 microns in diameter can be occluded best at lowest laser energy levels when 575 nm laser light is used, which approximates the absorption maximum of hemoglobin.

Ocular fluorescein phototoxicity

Fluorescein angiography is one of the most commonly used diagnostic techniques in modern ophthalmology. Prior to this study, recommendations on the phototoxicity of this technique were based on light levels alone (i.e., without fluorescein present). Using a rabbit model to demonstrate retinal damage, intravenous sodium fluorescein was found to reduce the amount of blue light needed to cause a phototoxic retinal lesion almost a log unit (from 1.6 to 0.2 W/cm(2)). Intravenous fluorescein also reduced the threshold for light damage to iris and cornea in the rabbit. The results suggest that blue light exposure should be minimized when sodium fluorescein is present in ocular tissue.

Measurement of blood-retinal barrier function in central retinal vein occlusion.

Vitreous fluorophotometry was used to measure blood-retinal barrier permeability to fluorescein in eight patients (mean age, 42.9 years; range, 30 to 55 years) with central retinal vein occlusion (CRVO). Permeability coefficient was derived by fitting a mathematical model to the posterior vitreous fluorescence scan and plasma-free fluorescein concentration curve at 60 minutes after intravenous fluorescein sodium (14 mg X kg-1). A permeability index (PI) was estimated by dividing the area under the vitreous fluorescence scan by the area under the plasma-free fluorescein curve. The permeability coefficient and PI were comparable and highly correlated. Initial mean permeability coefficient was 28.78 X 10(-7) cm X s-1 (range, 14.42 X 10(-7) to 41.10 X 10(-7) and 1.89 X 10(-7) cm X s-2 (range, 0.96 X 10(-7) to 2.76 X 10(-7) in eight affected and seven unaffected eyes, respectively. The permeability coefficient and PI in unaffected eyes did not differ significantly from 18 eyes of ten normal subjects. After three to 12 months, permeability coefficient and PI in affected eyes approached the values in the contralateral eyes of four patients with mild and one patient with moderate CRVO but remained elevated in the remaining patients. The permeability coefficient and PI correlated well with changes in severity of retinal appearances on color photographs and fluorescein angiograms. Vitreous fluorophotometry quantitated changes in blood-retinal barrier permeability in CRVO.

Report on the presence of a toxic substance, dimethyl formamide, in sodium fluorescein used for fluorescein angiography.

The revelation that intravenous sodium fluorescein is not all that it might seem to be may be a significant finding in the light of the adverse reactions to fluorescein that have been previously reported. Analysis of commercially prepared intravenous sodium fluorescein by mass spectroscopy and nuclear magnetic resonance has indicated that an industrial solvent used in the manufacturing process has not been eliminated. Dimethyl formamide is an industrial solvent with a maximum acceptable exposure level of 10 parts per million for dermal contact. It has been found in quantities of 5000 parts per million in the fluorescein for intravenous use. This investigation was prompted by a significant increase in the adverse reactions in patients receiving intravenous fluorescein in the retinal photographic unit at the Manchester Royal Eye Hospital.

Qualitative measurement of cerebral infarction using ultraviolet fluorescence

A reliable method of macroscopically determining the volume of cerebral infarction using ultraviolet fluorescence was developed in an animal model. Cerebral infarction was induced in 40 dogs by occluding the distal internal carotid and middle cerebral arteries. No barbiturates were administered. Intravenous sodium fluorescein was given before the animal was killed. Following fixation, 1 cm coronal sections were evaluated with ultraviolet light of 366 nm wavelength. The area of induced fluorescence for each section was determined using a grid overlay. Microscopic examination revealed that the areas of ischemic cell necrosis corresponded to areas of maximal fluorescence. This is an easily reproducible method to determine the volume of cerebral infarction.

Topical prostacyclin (PGI2) inhibits platelet aggregation in pial venules of the mouse.

Local application of prostacyclin (PGI2) to cerebral (pial) microvessels, inhibited the aggregation of platelets induced in the vessels by exposing them to a filtered mercury light source following intravenous sodium fluorescein. The inhibition was consistantly observed in venules rather than arterioles and was manifest by a lengthening of the time required for the noxious stimulus to produce an initial aggregate, and/or by a lengthening of the time required for enlarging aggregates to totally block the venule. The consistency of the inhibition diminished at doses below 100 microgram/ml. Inhibition was observed whether or not alcohol was used as the vehicle for PGI2 and whether or not the body temperature of the anesthetized mouse was permitted to fall.

Clinical Comparison of 10% and 25% Intravenous Sodium Fluorescein Solutions

Sodium fluorescein solutions, 3 ml of 25% solution and 5 ml of 10% solution, were compared with a double-blind crossover method in a group of 41 normal volunteers and in a group of 42 patients who had diverse ophthalmic disorders. Following injection of the solutions into the antecubital vein, visualization, serial fluorescein angiograms, and five-minute phase angiograms were studied and compared. The untoward reactions reported in both studies were of types usually associated with sodium fluorescein, the most common of which was a mild, transient nausea. On the basis of our results, there is no significant difference in the incidence and severity of adverse reactions between the 10% and 25% solutions. In the volunteer study, the 25% solution was significantly superior in visualization and paired comparison (P less than .001) in the patient study, the 25% solution was significantly superior in angiogram quality (P less than .01), five-minute phase angiogram (P less than .05), and paired comparison (P less than .005). The overall superiority of the 25% concentration in a 3-ml volume was demonstrated both subjectively and objectively in the volunteer study and in the patient study.