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PubMed1985

Ten years experience with choroidal angiography using indocyanine green dye: a new routine examination or an epilogue?

The choroidal circulation can be studied by an angiographic technique which utilizes near-infrared light wavelengths and a biocompatible dye, indocyanine green (CardiogreenR). Near-infrared light is less absorbed than visible light by the pigment epithelium and the macular xanthophyll, and indocyanine green (ICG) dye doesn't leak from the choriocapillaris as sodium fluorescein dye typically does. Due to the high rate of choroidal blood flow, a fundus camera adapted with special filters and a continuous light source was used in order to make angiograms at the rate of 10 per second. Our experience at the Wilmer Institute and the Eye Clinic at St. Gallen includes 180 choroidal angiograms of normal volunteers and approximately 500 choroidal angiograms of patients with several fundus diseases, mainly senile macular degeneration, diabetic retinopathy and choroidal tumors. Although many of our results are preliminary, we present them to demonstrate the potential applications of this method in ophthalmology. Some factors which may have inhibited an extensive propagation of clinical choroidal angiography in the past are also discussed.

Aged↗
PubMed2002

Inhibitory effects of triamcinolone acetonide on bFGF-induced migration and tube formation in choroidal microvascular endothelial cells.

BACKGROUND: Angiostatic drugs might provide desirable modulation of choroidal angiogenesis-related diseases, including histoplasmosis and the exudative form of age-related macular degeneration. However, the precise effects of this class of compounds in the choroidal neovascularization are still unclear. In the present study, we investigated the effects of triamcinolone acetonide (TA), an angiostatic steroid, on choroidal angiogenesis in vitro. METHODS: Bovine choroidal endothelial cells (CEC), which are the critical cellular component of choroidal angiogenesis in vivo, were isolated with Lycopersicon esculentum agglutinin-coated Dynabeads and cultured in EGM medium. CEC were treated with basic fibroblast growth factor (bFGF) and TA at various concentrations ranging from 50 to 300 mg/l. The capacities for CEC migration and tube formation were evaluated with the modified Boyden chamber and the Vitrogen collagen assay, respectively. The activities of matrix metalloproteinases (MMP)-2 and -9 were examined using gelatin zymography. RESULTS: The stimulation of CEC with 50 ng/ml bFGF resulted in an increase of about 100% in migration activity (P<0.01). Preincubation of CEC with TA at the indicated concentrations for 20 min inhibited the bFGF-stimulated migration in a dose-dependent manner (P<0.01). After 5 days, the bFGF-stimulated tube formation in CEC was inhibited by TA at the concentrations 100, 150 and 300 mg/l (P<0.01). Gelatin zymography of the culture media of CEC showed that the bFGF-induced activation of MMP-2 was attenuated by 300 mg/l TA (P<0.05). CONCLUSION: Downregulation of the activation of MMPs in CEC could be one of the mechanisms by which angiostatic steroids inhibit choroidal angiogenesis.

Animals↗
PubMed2006

The effect of ultraviolet radiation on choroidal melanocytes and melanoma cell lines: cell survival and matrix metalloproteinase production.

BACKGROUND: Ultraviolet radiation (UVR) can induce DNA damage and regulate the expression of factors important for tumour growth and metastasis, including matrix metalloproteinases (MMPs). Epidemiological studies suggest that chronic UVR exposure, especially during early adulthood, may be a risk factor in patients with choroidal melanoma. However, the effects of UV(R)-B on human choroidal melanocyte survival and growth are unknown. In this study, we investigated if UV(R)-B affected the in vitro survival, growth and MMP production of choroidal melanocytes and melanoma cells. METHODS: Cultures of primary choroidal melanocytes and melanoma cell lines (OCM-1 and OCM-8) were exposed to UV(R)-B (0-30 mJ/cm(2)). The cell morphology and growth were examined, and cell viability was assessed using an MTT assay. Gelatin zymography was used to assess the enzymatic activity for MMP-2 and -9 in conditioned media following UV(R)-B treatment. RESULTS: UV(R)-B > or =20 mJ/cm(2) was cytotoxic for choroidal melanocytes. Cytotoxic doses of 5 to 10 mJ/cm(2) were found for OCM-8 and OCM-1 melanoma cell lines. Low levels of UV(R)-B (2.5 and 3.5 mJ/cm(2)) significantly reduced melanoma cell viability after 48 h, although melanocyte viability was not affected by doses of UV(R)-B <10 mJ/cm(2). Conditioned media from melanoma cells and melanocytes displayed pro-MMP-2 activity independent of UV(R)-B. Control and UV(R)-B-treated OCM-1 cells secreted active MMP-2 up to 72 h. Pro-MMP-9 activity was seen from 36 h for control and UV(R)-B-treated OCM-1 and OCM-8 cells. CONCLUSIONS: Melanocytes appeared more resistant to physiological doses of UV(R)-B than melanoma cells; the potential of melanocytes to initially survive DNA damage following UV(R)-B exposure may be relevant to the subsequent transformation of melanocytes to melanomas. Although UV(R)-B did not induce the production and/or activation of MMP-2 and -9 in melanocytes or melanoma cells, we are currently investigating whether DNA damage-response genes such as p53 and p21 can be regulated following UVR exposure, and whether they are important for choroidal melanoma development.

Adult↗
PubMed2005

Beta 3-adrenergic receptors mediate choroidal endothelial cell invasion, proliferation, and cell elongation.

Beta(3)-adrenergic receptors have been reported to function primarily in adipose tissues to regulate thermogenesis. In this study, we determined if beta-adrenergic receptors are present on human choroidal endothelial cells and examined their ability to promote invasion, proliferation, and/or cell elongation. Using western blotting techniques and assays of cell invasion, cell proliferation, and endothelial cell elongation, we were able to determine that human choroidal endothelial cells do possess all three subtypes of beta-adrenergic receptors. Stimulation of the beta(3)-adrenergic receptor with BRL37344, a specific beta(3)-adrenergic receptor agonist, resulted in phosphorylation of Src, Akt, and ERK1/2. BRL37344 treatment also increased choroidal endothelial cell invasion by 103% above control values; the invasion response was inhibited by PP2 (Src inhibitor), LY294002 (PI3K inhibitor), Akt inhibitor (Akt-I), and matrix metalloproteinase 2/9 inhibitor (MMP-I). Invasion was not affected by PD98059 (mek inhibitor) or KT5823 (protein kinase G inhibitor). BRL37344 produced a significant increase in the total elongation of choroidal endothelial cells formed on Matrigel over a 24hr period. BRL37344 did significantly increase proliferation, although not to the same level as invasion. Stimulation of choroidal endothelial cells with dobutamine to activate beta(1)/beta(2)-adrenergic receptors did not affect invasion, proliferation, or endothelial cell elongation. In conclusion, beta(3)-adrenergic receptors may play a role in choroidal endothelial cell invasion and elongation, while playing a more limited function in regulation of cell proliferation.

Adrenergic beta-Agonists↗
PubMed2006

Variations of disseminated choroid plexus papilloma: 2 case reports and a review of the literature.

BACKGROUND: Choroid plexus papillomas are typically considered benign lesions, but histology is not always predictive of their behavior. These tumors can metastasize anywhere along the neuraxis and may be intraventricular, subarachnoid, or intraparenchymal. We present 2 cases that illustrate the wide diversity with which choroid plexus papillomas can disseminate. CASE DESCRIPTIONS: The patient described in case 1 had a primary fourth ventricular choroid plexus papilloma that produced diffuse cystic subarachnoid and leptomeningeal lesions. Patient 2 also had a primary fourth ventricular tumor but with subsequent suprasellar and spinal drop metastases. Patient 1 was treated with temozolomide, resulting in regression of symptoms including headache and dizziness. Patient 2 has been treated with several modalities, including radiation therapy and chemotherapy, with slowing of symptom progression. CONCLUSIONS: Variations of choroid plexus papilloma dissemination include intraventricular, subarachnoid, and leptomeningeal nodules or cystic lesions, and intraparenchymal locations. There is no consensus on the most effective treatment for choroid plexus papilloma metastases; surgical resection, chemotherapy, and radiation therapy may all yield benefits. The prognosis for patients with disseminated choroid plexus papilloma can range from prolonged stable disease and symptoms to death within months.

Adult↗
PubMed2000

Inhibition of experimental choroidal neovascularization by overexpression of tissue inhibitor of metalloproteinases-3 in retinal pigment epithelium cells.

PURPOSE: To evaluate the feasibility of introducing exogenous tissue inhibitor of metalloproteinases-3 gene into the rat retinal pigment epithelium using hemagglutinating virus of Japan liposomes and to assess the effect of tissue inhibitor of metalloproteinases-3 overexpression in retinal pigment epithelium cells on the formation of experimental choroidal neovascularization. METHODS: Hemagglutinating virus of Japan liposomes containing hemagglutin epitope-tagged tissue inhibitor of metalloproteinases-3 gene were injected into the subretinal space in rat eyes. Localization of oligonucleotides was evaluated by fluorescence microscopy. Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression was assessed by reverse transcribed polymerase chain reaction. Exogenous tissue inhibitor of metalloproteinases-3 protein expression was visualized by immunostaining with monoclonal antibody 12CA5 against the hemagglutin epitope. Three days after transfection of tissue inhibitor of metalloproteinases-3 gene into retinal pigment epithelium cells, intense laser photocoagulation was performed and the incidence of choroidal neovascularization was assessed by fluorescein fundus angiography. RESULTS: Exogenous tissue inhibitor of metalloproteinases-3 mRNA expression in the choroid and retina was detected on day 3. The efficiency of tissue inhibitor of metalloproteinases-3 gene transfection into retinal pigment epithelium cells was greatest on day 7 and decreased gradually thereafter. The incidence of choroidal neovascularization in tissue inhibitor of metalloproteinases-3 gene-transfected eyes was markedly decreased compared with controls. CONCLUSIONS: This study shows that tissue inhibitor of metalloproteinases-3 gene can be transferred into rat retinal pigment epithelium using the hemagglutinating virus of Japan-liposome method and that tissue inhibitor of metalloproteinases-3 gene overexpression can inhibit development of experimental choroidal neovascularization. This method may represent a future treatment modality for human macular degeneration associated with choroidal neovascularization.

Animals↗
PubMed2001

Inhibitory effect of losartan on laser-induced choroidal neovascularization in rats.

PURPOSE: To investigate the inhibitory effects of losartan, an angiotensin receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal neovascularization. METHODS: Experimental study. Fifteen Brown-Norway male rats received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown-Norway male rats received unsupplemented drinking water 1 week before photocoagulation, and it was continued to the end of the study. Two weeks after intense laser photocoagulation, choroidal neovascularization was evaluated by fluorescein angiography and histopathologic evaluation. RESULTS: The incidence of choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P <.01). Quantitative morphometric assessment revealed mean choroidal neovascularization lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan-treated rats (P <.01). CONCLUSION: Losartan seems to inhibit development of laser-induced choroidal neovascularization. Angiotensin receptor antagonists may be useful as prophylaxis against choroidal neovascularization associated with age-related macular degeneration.

Angiotensin Receptor Antagonists↗
PubMed2002

Retinal and choroidal arterial occlusion in Wegener's granulomatosis.

PURPOSE: To describe a patient with Wegener's granulomatosis presenting with bilateral retinal and choroidal arterial occlusion. METHODS: A 64-year-old male with Wegener's granulomatosis was examined using ophthalmoscopy and indocyanine green angiography. RESULTS: The patient had central retinal arterial occlusion in the right eye and branch retinal arterial occlusion in the left eye associated with bilateral choroidal infarcts. Early phase wide-angle ICG angiography of left eye revealed widespread choroidal perfusion problems, presumably from the confluence of multiple segmental arterial occlusions. Indocyanine green angiography of the right eye showed similar widespread choroidal arterial occlusions. CONCLUSIONS: This patient developed loss of vision from multiple arterial occlusions of the retina and choroid. Retinal and choroidal ischemia of this patient may have been caused by vasculitis leading to occlusion of retinal arteries and multiple short posterior ciliary arteries.

Choroid↗
PubMedDate not supplied

Rapid injection of indocyanine green dye for evaluation of choroidal venous circulation.

PURPOSE: The purpose of this study was to investigate the effects of rapid intravenous administration of a small bolus of indocyanine green (ICG) dye on early phase findings of ICG angiography. METHODS: Rabbit eyes were used. Ten normal eyes, 5 eyes with occlusion of vortex veins, and 5 eyes with chorioretinal atrophy were examined by ICG angiography, and early-phase findings after a rapid injection of a small bolus of dye were compared with those obtained with an ordinary injection. RESULTS: In normal eyes, after the rapid injection it was possible to visualize some small bright fluorescent boluses in the choroidal veins from 6 to 12 seconds after injection, while with the ordinary injection they were unclear. In eyes with occlusion of vortex veins, the rapid injection resulted in visualization of the choroidal veins with delayed filling against the background, and the region of the choroidal veins with delayed filling could easily be determined. In eyes with chorioretinal atrophy, only the rapid injection clearly revealed the choroidal veins with delayed filling. CONCLUSIONS: The rapid injection made it possible to detect the choroidal veins with delayed filling that were not clearly and easily visible using an ordinary injection. Rapid injection of ICG dye is useful for a detailed examination of choroidal circulation.

Animals↗
PubMedDate not supplied

Indocyanine green videoangiography in macular variant of idiopathic polypoidal choroidal vasculopathy.

BACKGROUND: Fifty patients diagnosed with choroidal neovascularization in age-related macular degeneration were examined by indocyanine green videoangiography. Results were correlated with fundus photographs and fluorescein angiograms. Two patients were diagnosed with the macular variant of idiopathic polypoidal choroidal vasculopathy. CASES: Two middle-aged hypertensive women were diagnosed with macular idiopathic polypoidal choroidal vasculopathy. Throughout the follow-up period, both cases showed improved signs and symptoms without worsening of visual acuity, and despite the absence of definitive therapy. OBSERVATIONS: Indocyanine green videoangiography demonstrated the characteristic polypoidal lesions in idiopathic polypoidal choroidal vasculopathy better than fluorescein angiography, particularly when blood, exudates, or pigment epithelial detachments blocked visualization of the lesions. CONCLUSIONS: Incidence of idiopathic polypoidal choroidal vasculopathy may not be as low as reported, as its presentation mimics choroidal neovascularization in age-related macular degeneration. Differentiation can be made only through indocyanine green videoangiography. Conservative management may be beneficial, as visual prognosis is good.

Choroid↗
PubMed2000

Frequency of choroidal abnormalities in neurofibromatosis type 1.

BACKGROUND: Choroidal neurofibromatosis is thought to be a rare form of neurofibromatosis that involves the eyes. The development of infrared light examination with a scanning laser ophthalmoscope (SLO) and indocyanine-green fundus angiography has allowed examination of the choroid. We studied choroidal abnormalities in patients with neurofibromatosis 1 and compared their frequency with that of other ocular abnormalities. METHODS: We examined 33 eyes of 17 consecutive patients diagnosed with neurofibromatosis 1 by conventional ophthalmoscopy and by non-invasive infrared monochromatic light with confocal SLO. 76 eyes of 39 age-matched controls were examined similarly by confocal SLO. 21 digital fluorescein and indocyanine-green angiographies were obtained from 11 adult patients, and 77 angiograms were obtained from age-matched controls. FINDINGS: Infrared monochromatic light examination by confocal SLO showed bright multiple patchy regions at and around the entire posterior pole of all 33 eyes examined. All bright patchy regions seen in adult patients corresponded to hypofluorescent areas on their indocyanine-green angiograms. However, no abnormalities were noted in any patient at corresponding areas under conventional ophthalmoscopic examination or fluorescein angiography. In SLO and indocyanine-green studies, controls and control angiograms showed no choroidal abnormalities. Iris nodules were noted in 25 eyes (76%) of 14 patients (82%) and eyelid neurofibroma in five patients (29%). INTERPRETATION: The bright patchy regions noted under infrared fundus examination and the corresponding hypofluorescent areas seen on indocyanine-green angiograms are probably of choroidal origin. The high frequency (100%) of these abnormalities suggests that the choroid is one of the structures most commonly affected by neurofibromatosis 1.

Adult↗
PubMed1995

Choroidal hypoperfusion in acute posterior multifocal placoid pigment epitheliopathy. An indocyanine green angiography study.

BACKGROUND: The pathogenesis of acute posterior multifocal placoid pigment epitheliopathy remains obscure. The placoid lesions and characteristic findings on fluorescein angiography have been interpreted as representing either primary disease of the retinal pigment epithelium or disease of the choroidal vasculature. This study used indocyanine green (ICG) choroidal videoangiography to investigate this controversy. METHODS: Sequential choroidal videoangiography was performed with ICG and a scanning laser ophthalmoscope on patients with acute posterior multifocal placoid pigment epitheliopathy. Image analysis was used to differentiate between masking and ischemia as to the cause of hypofluorescence on the angiograms. RESULTS: Indocyanine green angiograms of acute posterior multifocal placoid pigment epitheliopathy showed areas of hypofluorescence in both the early and late pictures that correlated with the placoid lesions. Image analysis identified these as areas of choroidal hypoperfusion. Successive films showed partial or complete resolution of these hypofluorescent areas. CONCLUSIONS: Indocyanine green choroidal videoangiography has shown choroidal hypoperfusion to underlie the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy.

Acute Disease↗
PubMed1997

[Varix of the vortex ampulla: an unusual differential choroid tumor diagnosis].

UNLABELLED: A raised fundus lesion at the level of the choroid has a high potential of being malignant since choroidal melanoma can appear clinically in many disguises. Final diagnosis may be made only after through investigations with ancillary techniques. We report on a case where--using fluorescein angiography--a suspected choroidal melanoma was diagnosed as having been simulated by a varix of a superior vortex vein ampulla. PATIENT: A 51-year-old woman was referred with the diagnosis of a choroidal melanoma in the upper periphery of the left fundus. Biomicroscopical retinal examination of the left eye revealed at upgaze a raised, slightly darkish lesion at the choroidal level in the peripheral 12 o'clock position. The lesion could not be visualised using the 3-mirror Goldmann contact lens and the area in question appeared flat. Fluorescein angiography showed evident dilatation of the superior vortex vein ampulla at upgaze giving rise to an elevation of both choroid and retina. CONCLUSION: Dilatation of the vortex vein ampulla is a rarely encountered lesion and is most often an incidental finding. Enlargement at up- or downgaze is thought to be evoked by kinking of the vein after leaving the eye through a long intrascleral passage in a very obtuse angle. This explains why the lesion could not be seen using the 3-mirror lens where the globe stays in the primary position. No treatment is indicated.

Choroid↗
PubMed2001

Corrosion casts and scanning electron microscopy of choroidal vasculature in rats with inherited hypercholesterolemia.

PURPOSE: The purpose of the present study is to determine the specific morphological changes in choroidal vasculature due to hypercholesterolemia. METHODS: The choroidal vessels of rats with inherited hypercholesterolemia (RICO) were examined by the corrosion cast technique and electron microscopy. RESULTS: In 18-month-old RICO rats, corrosion casts and scanning electron microscopy showed severe tortuosity, caliber irregularity and generalized dilatation of the large choroidal arteries and veins. The branch arterioles and draining venules were also tortuous and dilated. The ampullae of the vortex veins were wide, but no arteriovenous anastomoses, crossing defects or obstruction were seen. However, there were many venular collateral channels and venulo-venular anastomoses. The choriocapillaries appeared normal. Transmission electron microscopy of the choroidal vessels showed hypertrophy of smooth muscle cells and irregular thickening of the basement membrane. The RPE and Bruch's membrane were intact. CONCLUSION: These findings indicate that the choroidal vascular changes are probably related to hypercholesterolemia. The results of the present study will be useful in the interpretation of the changes seen in hypertensive, diabetic and aged choroids.

Animals↗
PubMed1997

Choroidal osteoma.

The choroidal osteoma is a benign, ossifying tumor of the choroid that typically is found in young, healthy women in the second or third decade of life. Its pathogenesis is unknown. This tumor is clinically unilateral in 75% of cases and tends to be located in the juxtapapillary region. Choroidal neovascularization may occur in up to one-third of cases. The choroidal osteoma must be differentiated from other intraocular tumors as well as cases of dystrophic and metastatic calcification. Ultrasonography and computed tomography may help in the diagnosis by demonstrating a calcified plaque at the level of the choroid. Fluorescein angiography and ICG videoangiography may demonstrate choroidal neovascularization, which may be amenable to treatment by laser photocoagulation.

Adult↗
PubMed1997

Choroid plexus papilloma in the posterior third ventricle: case report.

OBJECTIVE AND IMPORTANCE: The case of a 42-year-old woman with a choroid plexus papilloma (CPP) arising from the posterior wall of the third ventricle is described. This case is very unusual because the tumor did not have any connection with the choroid plexus but was attached to the normal brain parenchyma. CLINICAL PRESENTATION: The patient presented with the symptoms of increasing intracranial pressure. Magnetic resonance imaging revealed hydrocephalus related to a small mass in the posterior third ventricle, occluding the aqueduct. INTERVENTION: Surgery confirmed that the tumor was located at the surface of the posterior commissure without having any connection to the normal choroid plexus. A histopathological examination revealed a CPP with no attachment to the choroidal tissue. CONCLUSION: A review of the literature demonstrates that CPPs without any connection to the choroid plexus are very unusual. To our knowledge, this is the first reported case of such a CPP that developed on the posterior wall of the third ventricle in which no choroid plexus was present. Furthermore, this tumor, to our knowledge, is also the smallest intraventricular CPP to be verified at surgery.

Adult↗
PubMed1997

Choroidal findings in the course of idiopathic serous pigment epithelium detachment detected by indocyanine green videoangiography.

PURPOSE: To analyze the choroidal alterations associated with idiopathic serous pigment epithelium detachment. METHODS: Twenty-five consecutive patients affected by idiopathic serous pigment epithelium detachment underwent ophthalmoscopy, fluorescein angiography, and indocyanine green videoangiography. RESULTS: On indocyanine green videoangiography an early, complete, and homogeneous filling of the pigment epithelium detachment was always observed. In the late phases, the indocyanine green pattern depended on the size of the detachment. An idiopathic serous pigment epithelium detachment larger than the diameter of one optic disk was still hyperfluorescent in the late phases of indocyanine green videoangiography and was surrounded by a ring of brighter hyperfluorescence. An idiopathic serous pigment epithelium detachment smaller than the diameter of one optic disk usually could be visualized in the late phases as a hypofluorescent area surrounded by a hyperfluorescent ring. In 30 eyes (83.3%), choroidal hyperpermeability was observed. An irregular dilatation of the choroidal veins at the site or within an area the size of one disk diameter from the detachments could be visualized on indocyanine green videoangiography in 12 of 36 affected eyes (33.3%); in three cases an active focus of central serous chorioretinopathy with subretinal leakage developed in the follow-up period. CONCLUSION: The observation that pigment epithelium detachments frequently are associated with choroidal leakage and venous dilatation supports the hypothesis that an idiopathic serous pigment epithelium detachment is a variant of central serous chorioretinopathy. Moreover, the choroidal permeability alterations detected by indocyanine green videoangiography would support the theory of Gass that idiopathic serous pigment epithelium detachments could be caused by exudation of fluids from the choroidal vessels.

Adult↗
PubMed2005

Midperipheral mottling pigmentation with familial choroidal osteoma.

PURPOSE: To describe a rare presentation of familial choroidal osteoma in two siblings. METHODS: The clinical findings in two siblings over 4 years' follow-up. RESULTS: Two brothers (15 and 12 years old) had bilateral choroidal osteomas. Both had bilateral peripapillary yellowish-white lesions and midperipheral mottling pigment appearance, which are not seen in sporadic cases. Extensive midperipheral area with mottling pigment appearance was noted by fluorescein angiography (FA) as scattered multiple hyperfluorescent dots. The yellowish-white lesions showed diffuse hyperfluorescence with FA and hypofluorescence with indocyanine green angiography (ICG). ICG also revealed irregular hyperfluorescent areas within the tumor, indicating abnormal choroidal vessels on the tumor. In the left eye of the younger brother, the subretinal fibrosis due to choroidal neovascularization superior to the macula extended down toward the foveal region over 2 years, resulting in visual deterioration. CONCLUSION: The midperipheral mottling pigment appearance of familial choroidal osteoma cases is unique and different from most sporadic cases, suggesting that familial choroidal osteoma might have separate etiologic or modified factors.

Adolescent↗