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[Central serous chorioretinopathy. Studies of the site of the lesion with indocyanine green].

Indocyanine green angiographies of 33 patients with central serous chorioretinopathy (CSC) were examined in order to find out whether the location of ICG exudation was correlated with other findings. Areas of delayed choroidal filling at the site of the hot spot were found in 27 patients (82%). The hot spot was usually located at the margin of such areas. Furthermore, it seemed correlated to a larger ciliary artery in 19 patients (60.6%). A detachment of the pigment epithelium was detected in 18% and showed a characteristic early hypo- and late hyperfluorescence. There is evidence that the exudation of indocyanine green indicates a primary choroidal disorder as the cause of CSC. Many clinical features, for example pigment epithelial detachments, are easier to explain with this hypothesis. A correlation of the hot spot with variation of choroidal filling has to be interpreted with caution. Yet, it seems feasible that the border between areas of different speed of filling is especially vulnerable and might therefore decompensate in the case of diseased regulation of the choroidal vessels, as has been postulated for CSC.

Adult↗

Functional and non-functional liver blood flow in patients with liver cirrhosis measured by indocyanine green.

Indocyanine green administration was used in a group of ten patients with liver cirrhosis with portal hypertension to estimate hepatic extraction, liver blood flow and the degree of blood shunting. Extraction coefficients obtained by the hepatic catheterization were well correlated with the pharmacokinetic method. Values of the total liver blood flow measured by the classical method based on Fick's principle were always higher than those evaluated by the pharmacokinetic analysis estimating the functional liver blood flow only. Estimates of the degree of shunting varied between 32.0-78.9% of the total liver blood flow. A statistically significant correlation (r = 0.79) was found between the percentage of the functional fraction of the total liver blood flow and albuminemia. It is suggested that in liver cirrhosis with portal hypertension the reduction of the functional fraction of total liver blood flow is combined with partial impairment of hepatic cell metabolism in the remaining functional areas of the liver. In such a case neither the "intact" nor the "sick hepatocyte" hypotheses are appropriate in their strict sense for the interpretation of the findings.

Humans↗

Precise measurement of cerebral blood flow in newborn piglets from the bolus passage of indocyanine green.

Indocyanine green (ICG) is a near-infrared dye that has the potential to be used as a tracer for the minimally invasive measurement of cerebral blood flow (CBF). In order to examine the technique, the arterial and cerebral concentrations of ICG were measured in newborn piglets during the bolus passage of ICG at normocapnia and two levels of mild hypercapnia. The results were analysed by applying the Fick principle in both integral and differential forms using a linear regression technique to improve the precision of calculated values of CBF. It was found that the integral method, which has been used previously, is particularly sensitive to errors in the time registration between the arterial and tissue signals whereas the differential method is less so. In addition, the differential method allows the venous outflow to be calculated which gives further information on the state of the capillary bed. CBF was 39.7 +/- 4.6 ml 100 g(-1) min(-1) at an arterial carbon dioxide tension (PaCO2) of 33.0+/-2.2 mmHg and increased to 53.7+/-9.1 and 75.4+/-15.2 ml 100 g(-1) min(-1) at a PaCO2 of 42.1 +/- 2.6 and 54.2 +/- 3.1 mmHg respectively (mean +/- SD, n = 7). There was no significant change in cerebral metabolic rate for oxygen, validating the value of blood flow to an arbitrary scaling factor. When the inspired CO2 fraction was returned to zero, calculated CBF returned to baseline with a variation of 7% of the mean, indicating that this technique is highly precise.

Animals↗

Kinetics of indocyanine green dye after intraocular surgeries using indocyanine green staining.

OBJECTIVE: To determine the elimination kinetics of indocyanine green (ICG) after intraocular operations using ICG staining. METHODS: Intraocular fluorescence of ICG was determined using the ICG angiographic mode of a scanning laser ophthalmoscope (in vivo) and fluorescence microscopy (in vitro) after circular curvilinear capsulorhexis with ICG staining during cataract surgery and internal limiting membrane (ILM) peeling with ICG staining during macular hole surgery. SUBJECTS: We studied 9 eyes of 7 patients with white cataracts and 14 eyes of 14 patients with idiopathic macular holes. RESULTS: Scanning laser ophthalmoscopy revealed fluorescence in the anterior segment of patients with cataracts on the first postoperative day, and fluorescence remained for a mean +/- SD of 6.0 +/- 2.2 days postoperatively. Scanning laser ophthalmoscopy also revealed fluorescence in the posterior pole of patients with macular holes, and it remained for a mean +/- SD of 2.7 +/- 1.4 months postoperatively. Fluorescence microscopy showed fluorescence of the entire tissues, suggesting that ICG had stained not only the surface of the membranes but had also entered them. In both operations, visual outcomes were not significantly different from the results obtained without ICG. CONCLUSIONS: Because entire tissues were stained, the differences in ICG kinetics might also be caused by factors other than differences in stainability, such as the environment surrounding the tissues or molecular structural differences between the lens capsule and the ILM. Although we found complete disappearance of fluorescence and good functional recovery, the longer resident time of the dye after macular hole surgery may suggest a potential risk to intraocular tissues.

Adult↗

Toxicity of indocyanine green injected into the subretinal space: subretinal toxicity of indocyanine green.

PURPOSE: To evaluate the toxicity of indocyanine green (ICG) injected into the subretinal space. Indocyanine green may come in contact with photoreceptors and retinal pigment epithelium through a macular hole during ICG-assisted peeling of the internal limiting membrane. METHODS: Balanced salt solution or ICG of various concentrations (0.6, 1.25, 2.5, or 5.0 mg/mL) was injected into the subretinal space of rabbit eyes and removed after 1 minute. After 3 days, 1 week, and 4 weeks, the eyes were enucleated and evaluated by light microscopy and electron microscopy. RESULTS: When the ICG of 1.25 mg/mL or higher concentration was injected into the subretinal space, degenerative changes of the photoreceptors and the retinal pigment epithelial cells were found after 3 days with light and electron microscopy. After 1 week, the outer retina was disintegrated and the photoreceptors were not found. After 4 weeks in the eyes with 1.25 mg/mL ICG, short photoreceptors and a thin outer nuclear layer were seen. In the eyes with 2.5 mg/mL or higher ICG, the photoreceptors and the outer nuclear layer were destroyed completely. CONCLUSION: The results of this study suggest that the ICG of 1.25 mg/mL or higher concentration has toxicity to the outer retina of the rabbit and may cause adverse effects on the functional outcome after macular hole surgery.

Animals↗

The monoethylglycinexylidide test is more useful for evaluating liver function than indocyanine green test: case of a patient with remarkably decreased indocyanine green half-life.

Lidocaine was used for evaluation of hepatic function in a patient undergoing hepatic resection. Preoperatively, half-life of indocyanine green (ICG) was 33 min after intravenous administration. Plasma concentration of the N-dealkylated metabolite of lidocaine, monoethylglycinexylidide (MEGX), was quantitatively determined to evaluate hepatic function. The patient's rate of formation of MEGX at 15 min after administration of lidocaine was within normal limits, at 56 micrograms/L. These findings suggest that in this patient, hepatic cytochrome P-450IIIA activity was not impaired, but selective impairment of uptake of ICG into hepatocytes or excretion into the bile ducts was present. The rate of formation of MEGX was decreased, and plasma concentration of bilirubin was elevated postsurgically; this could have been the result of decreased cytochrome P-450IIIA activity or decreased hepatic blood flow after hepatic resection. We conclude that the rate of formation of MEGX is a better index of hepatic function than is ICG half-life.

Humans↗

Nine cases with marked retention of indocyanine green test and normal sulfobromophthalein test without abnormal liver histology: constitutional indocyanine green excretory defect.

Nine patients revealed marked retention in the indocyanine green (ICG) test and the normal sulfobromophthalein (BSP) test. The results of liver function tests in these cases were within normal limits with the exception of the ICG test. The ICG plasma disappearance rate ranged from 0.017 to 0.025, whereas that of BSP ranged from 0.058 to 0.126. The transfer rate of ICG from plasma to liver markedly decreased on two-compartmental analysis of the ICG decay curve. A transient delay of the ICG plasma disappearance (step formation) on the decay curve was observed over 20 to 25 minutes after an injection in all cases after repeated observation. Binding of ICG to plasma proteins in these cases failed to demonstrate a significant difference from normal subjects. The fasting serum bile acid levels in two cases and postprandial serum bile acid level in one case were normal. Light microscopic findings of the liver revealed normal histology. Electron microscopic findings showed increase of lipofuscin-like lysosomes, modification and paracrystalline-like array of mitochondria, and an increase of reticulum fiber in Disse's space. It is suggested that these cases represent a new type of dye excretory disorder of the liver with impaired hepatic uptake of ICG.

Adenocarcinoma↗

Hepatic transport of serum bilirubin, bromsulfophthalein, and indocyanine green in patients with congenital non-hemolytic hyperbilirubinemia and patients with constitutional indocyanine green excretory defect.

We carried out a retrospective study of 71 patients with congenital non-hemolytic hyperbilirubinemia who had been treated at our institution over the 25 years from 1965 to 1990. Twenty patients had Gilbert's syndrome, 1 had Crigler-Najjar syndrome, 1 had new type unconjugated hyperbilirubinemia, 21 had Dubin-Johnson syndrome, and 28 had Rotor's syndrome. We also reviewed 20 patients with constitutional indocyanine green (ICG) excretory defect. The study focused on the hepatic transport of serum bilirubin, bromsulfophthalein (BSP), and ICG. In Dubin-Johnson syndrome, a defect appeared in late-stage transport, while uptake and storage capacity were normal. In Rotor's syndrome, defects were found in the early stage, and storage capacity was reduced, while excretion into bile was slightly suppressed. A secondary rise in serum ICG was seen in 5 of the 10 patients with Dubin-Johnson syndrome. The transport defect in Gilbert's syndrome was unclear. It could not be considered to be homogeneous, but it may exist at multiple sites, from the conjugation with serum proteins to excretion into bile. Following phenobarbital administration, the ICG secondary rise in the 5 patients with Dubin-Johnson syndrome disappeared, and ICG was rapidly cleared from blood. However, in patients with Dubin-Johnson syndrome, BSP clearance in serum did not show any change before and after phenobarbital administration. ICG excretion in patients with constitutional ICG excretory defect was due only to the impairment o ICG transport, and the defect was suggested to be hepatic uptake. These results indicate that studies of the hepatic transport of bilirubin, BSP, and ICG are useful for determining the etiological factors involved in congenital hyperbilirubinemia and constitutional ICG excretory defect.

Adult↗

Hyperfluorescence associated with serous retinal pigment epithelial detachment on indocyanine green angiography.

PURPOSE: Indocyanine green angiography has been reported to improve detection and delineation of occult choroidal neovascularisation in serous pigment epithelium detachment in age-related macular degeneration. The study aims to evaluate the visual acuity results of eyes affected by serous pigment epithelium detachment in age-related macular degeneration, having had indocyanine green-directed laser photocoagulation, and to correlate them to the pattern of serous pigment epithelium detachment on indocyanine green angiography. METHODS: Thirty-four eyes of 31 patients affected by serous pigment epithelium detachment in age-related macular degeneration were prospectively considered. Each patient underwent an ophthalmological examination including fluorescein and indocyanine green angiography one day before, and 6 weeks, 3 months, 6 months, 9 months, 12 months and 24 months after krypton-laser treatment. The serous pigment epithelium detachment was classified in the late-phases angiograms as either hypofluorescent, isofluorescent or hyperfluorescent comparing the fluorescence of the serous pigment epithelium detachment with the choroidal background fluorescence. RESULTS: The indocyanine green-guided laser treatment was associated with a temporary stabilization and a long-term progressive reduction of visual acuity: after 24 months visual acuity improved in 2.9%, stabilized in 26.5% and worsened in 70.5% of cases. Serous pigment epithelium detachment presenting a pretreatment hyperfluorescence had a final visual acuity of 0.06, with subfoveal choroidal neovascularisation development in 100% of cases, whereas serous pigment epithelium detachment presenting a pretreatment hypofluorescence and isofluorescence showed a final visual acuity of 0.12, with subfoveal choroidal neovascularisation development in 43.5% of eyes, with statistically significant difference. CONCLUSION: Overall visual acuity decreases with time after indocyanine green-guided laser treatment of choroidal neovascularisation in serous pigment epithelium detachment, and serous pigment epithelium detachment becoming hyperfluorescent in the late-phases of indocyanine green angiography has the worst functional outcome.

Aged↗

Indocyanine-green angiography.

Indocyanine-green angiography represents a major advance in imaging of the choroidal circulation. Recent technical innovations have permitted this diagnostic technique to find clinical application in many chorioretinal conditions. The indocyanine-green molecule has proven to be safe for human study. In age-related macular degeneration, indocyanine-green angiography may play an important role in the diagnosis of patients with occult choroidal neovascularization, leading to eventual increased efficacy with laser photocoagulation treatment. Histopathologic confirmation of a lesion noted by ICG angiography has been made. In multiple inflammatory conditions, as well as with central serous chorioretinopathy, distinct ICG patterns have emerged that may facilitate better understanding of the disease processes. With greater experience, ICG angiography may provide improved imaging, a better understanding of the pathogenesis, and new treatment approaches for various chorioretinal conditions.

Chorioretinitis↗

Intravenous and indocyanine green angiography.

BACKGROUND: 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. METHODS: 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. RESULTS: Information is presented that represents the current modalities of ICGA. CONCLUSION: 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.

Choroid Diseases↗

Intraretinal leakage of indocyanine green dye.

PURPOSE: Indocyanine green (ICG) dye is known to remain selectively in and around choroidal neovascularization (CNV) associated with age-related macular degeneration, and is thought to be cleared from the overlying retinal circulation without leakage. This is the basis of ICG dye-enhanced laser photocoagulation. The authors have observed, however, leakage of ICG dye into cystoid spaces within the retinal and have determined the incidence, clinical features, and angiographic characteristics of this newly described phenomenon. METHODS: The digital ICG videoangiograms of 149 consecutive patients with exudative age-related macular degeneration and occult CNV were reviewed independently to determine the characteristics of intraretinal ICG dye leakage. RESULTS: Of the 149 patients with occult CNV, 16 (11%) demonstrated intraretinal leakage of ICG dye between 14 and 34 minutes (median = 20 minutes). The clinical features most commonly associated with this phenomenon are: subretinal fluid (88%), subretinal hemorrhage (88%), subretinal lipid (63%), and retinal pigment epithelial detachment (56%). CONCLUSIONS: Indocyanine green dye may not be as concentrated in and around CNV as previously reported. The delayed onset of its appearance within intraretinal cystoid spaces may suggest a diffusible choroidal source of leakage. Intraretinal ICG dye may be a relative contraindication for ICG dye-enhanced laser photocoagulation.

Aged↗

Increase in the relative amount of bilirubin diconjugates in rat bile and serum under infusion of phthaleins and indocyanine green.

The effect of organic anions on bilirubin metabolism and excretion was investigated in rats. Biliary excretion of bromosulfophthalein, bromcresol green and indocyanine green led to a significant decrease in excretion of bilirubin pigments and to an increase of their concentration in serum. This was concomitant with a marked increase in the ratio of bilirubin diconjugates to monoconjugates in bile and serum. These changes were unrelated to either bile flow, biliary lipid output, or hepatic activity of bilirubin UDP-glucuronyl transferase. Following bolus injection of [14C]bilirubin, peak excretory rate of radioactivity was markedly delayed in rats infused with bromosulfophthalein, as compared to controls. It is concluded that administration of the organic anions increased the ratio of bilirubin diconjugates to monoconjugates in bile and serum, by slowing down the intrahepatic transit of bilirubin pigments. This, in turn, allowed more efficient enzyme-catalyzed formation of bilirubin diconjugates from the intermediate bilirubin monoconjugates.

Animals↗

Light-absorbing properties, stability, and spectral stabilization of indocyanine green.

The absorption spectrum of indocyanine green depends on the nature of the solvent medium and on the dye concentration. Binding to plasma proteins causes the principal peaks in the absorption spectrum to shift about 25 nm toward the higher wavelengths. The much greater influence on the spectrum of the dye concentration results from progressive aggregate formation with increasing concentration. Indocyanine green solutions therefore do not follow Lambert-Beer's law above 15 mg-I-1 (in plasma). Indocyanine green solutions in plasma and concentrated (1,000 mg-I-1) solutions in distilled water are stable for at least 4 h. In long-term experiments the optical density of indocyanine green solutions in plasma as well as in distilled water generally diminishes, even in the dark. On the 7th day a new absorption maximum starts to appear at gamma=900 nm, possibly caused by further aggregate formation leading to much larger particles. Spectral stabilization after injection of a concentrated solution into the blood is most rapid when the dye is dissolved in distilled water. Spectral stabilization slows down with decreasing temperature. As rapid spectral stabilization is essential in quantitative dye dilution studies, the practice of adding a albumin and/or isotonic saline solution to the injectate should be discontinued. When a 10 g-1(-1) aqueous solution of indocyanine green is used, spectral stabilization takes less than 1.5 a (at 37 degrees C), which is sufficiently fast for almost any application.

Blood↗

Detection of choroidal neovascularization by subtraction indocyanine green angiography.

BACKGROUND: Indocyanine green (ICG) angiography is considered to be an effective clinical tool to detect choroidal neovascularization (CNV) in age-related macular degeneration. However, CNV detection by angiography becomes difficult when a thick hemorrhagic lesion exists. METHODS: CNV was analyzed in 20 eyes (20 patients) showing age-related macular degeneration and accompanying subretinal hemorrhage using the subtraction method of ICG angiography. RESULTS: Subtraction ICG angiography revealed hyperfluorescent areas determined as dye leakage from CNV in all 20 cases. In 6 of the 20 cases, ill-defined fluorescence-increasing areas were observed which expanded during continuing angiography. On the other hand, the remaining 7 cases showed well-defined fluorescence-increasing areas which did not expand over time. CONCLUSIONS: The subtraction method is an effective clinical tool to detect CNV concomitant with subretinal hemorrhage. Moreover, this method provides information to elucidate an increasing pattern of fluorescence surrounding CNV.

Aged↗

Indocyanine green fluorescence angiography.

Indocyanine green (ICG) fluorescence angiography has been further refined for use in both laboratory and clinical investigations. In the present modification of the Zeiss fundus camera all lenses except the aspherical objective lens have been specially antireflection coated to increase light transmission in the spectral region around 800 nm. A 300 watt indium iodide lamp continuous light source has replaced the conventional xenon flash lamp. This light source produces a retinal irradiance of 265 mw, and therefore restricts retinal exposure time to 11.9 seconds, but that time is more than adequate to record passage of dye through the choroid. Spatial resolution of the fundus on the film has been increased from 11.7 microns to 7.4 microns. With these technical refinements the choroidal circulation can be studied at 20 frames per second, which is adequate to document the very rapid movement of blood through the vasculature. ICG angiography may change our interpretations of choroidal circulatory phenomena which are now based on fluorescein angiography, and it clearly is an effective tool in laboratory (experimental) investigations.

Animals↗