Synchronous bilateral fluorescein angiography. A new technique

Simultaneous angiography of both eyes allows the synchronous measurement of the arm-retina-time and the retinal circulation time in each eye. The dye-filling pattern of retinal arteries, choroid, disc, and cilioretinal vessels can be compared. A new method of simultaneous fluorescein angiography of both eyes, using two fundus cameras, is demonstrated. Each camera is operated by a separate power unit, thereby providing sufficient light energy for one picture every 0.6 second. The fluorescein is injected by means of an automatic injector in order to create a compact dye bolus. Simultaneous angiograms of a healthy patient and of a patient with unilateral carotid occlusion are shown.     

Late effects of radiotherapy in children

PURPOSE: To examine benzoporphyrin derivative angiography as a modality for studying photosensitizer biodistribution in experimental choroidal melanomas. METHODS: A liposomal preparation of benzoporphyrin derivative was used in this study. Digital benzoporphyrin derivative angiograms were performed in 10 rabbits (six for experimental choroidal melanomas, two for normal choroids, and two for irides) using a Topcon ImageNet H1024 digital imaging system, a Kodak Megaplus video camera, and a Topcon TRC-50-VT fundus camera. Only one eye from each rabbit was used. Filters specifically designed for benzoporphyrin derivative (peak absorption at 580 nm and peak emission at 695 nm) were used. Benzoporphyrin derivative (1 mg/kg) was injected into an ear vein while images of tumor, normal choroid, or iris were being obtained. Follow-up images were obtained during the first 3 hours and at 24 hours after injection. Fluorescence microscopy was performed in all 10 rabbits using 1 mg/kg of benzoporphyrin derivative. Tumor-bearing eyes were enucleated at the same time points that angiograms were performed, and the two sets of results were compared for maximum dye accumulation. RESULTS: Digital angiography demonstrated that maximal benzoporphyrin derivative fluorescence occurred in tumors 15 to 45 minutes after injection. Fluorescence photometry corroborated these results. CONCLUSION: Photosensitizer angiography is a valid modality for determining the optimum treatment time for photodynamic therapy.     

Thyroid angiography

Twelve patients were studied by selective thyroid angiography for the evaluation of solitary thyroid nodule. Under aseptic conditions with local anesthesia a No 7 preshaped catheter was introduced through the femoral artery and guided to the thyrocervical trunk and inferior thyroid artery. Selectively, 2 to 6 cc of the contrast material was injected and a series of radiographs were taken. Striking differences were noticed in vessels in abnormal thyroid gland. In colloid goiter there was no filling of the vessels in the nodule. In fetal adenoma there was unusual branching of the vessels but no arteriovenous communications. In carcinoma, along with increased vascularities and abnormal branching, arteriovenous communications were noted.     

Indocyanine green angiography in choroidal osteoma

BACKGROUND: Choroidal osteoma is a rare choroidal tumor; knowledge of its indocyanine green characteristics is limited. METHODS: The fundus photographs and the fluorescein and indocyanine green angiograms of three patients were reviewed. Each patient was examined at least twice with a follow-up varying from 10 to 60 months. RESULTS: Late-phase fluorescein angiograms allow assessment of the extension of the osteoma as it is variably hyperfluorescent due to tumor staining combined with a variable degree of overlying retinal pigment epithelial changes. The hypofluorescent area observed in the early phase of the indocyanine green angiogram corresponds with the extent of the osteoma but the borders may be difficult to demarcate. In the late phase of the indocyanine green angiogram, hypofluorescence due to choriocapillaris loss and hyperfluorescence due to leakage from abnormal choroidal vessels are combined. Infrared angiography high-lights abnormal choroidal vessels and vascular spiders present on the tumor surface. It is difficult to differentiate these choroidal vascular anomalies from subretinal neovascularization. CONCLUSIONS: We find no homogeneous pattern either on fluorescein or on infrared angiography. The findings may change with follow-up, indicating changes within the tumor or the surrounding tissue that are still poorly understood.     

Fluorescein pupillary flow in aphakics with intact and spontaneous openings of the vitreous face

The passage of fluorescein dye, injected into the general circulation, from the posterior to the anterior chamber was studied in 60 selected aphakic eyes between 2 days and 4 weeks after an uneventful cataract extraction. In a group of 22 eyes with intact anterior hyaloid, fluorescein was seen to pass only through the pupillary margin, mostly within 20 seconds of the beginning of the eye injection. In 24 eyes with rents in the anterior hyaloid the dye was seen percolating only through the vitreous face openings. No fluorescein passed through the pupillary margin or the peripheral iridectomy in this group of eyes. The appearance time of the dye was delayed to about twice the normal appearance time. In 8 eyes with rents in the anterior hyaloid the dye passed only through the pupillary margin. In 4 eyes with anterior vitreous rents the fluorescein appeared through the anterior vitreous face opening. From the analysis of the data it appears that the spontaneous breaks in the anterior vitreous face may represent a 'self-c,re' of pupillary and iridectomy block by the vitreous in aphakics in a high proportion of cases. It is our impression that 3 peripheral iridectomies and a very tight closure of the wound can prevent the complication of spontaneous breaks of the vitreous face.     

Development of a fluorescein operative microscope for use during malignant glioma surgery: a technical note and preliminary report

BACKGROUND: Fluorescein has been used in the field of neurosurgery; however, fluorescein enhancement or contrast proved to be inadequate because of a lack of appropriate light sources or filters. A new operative microscope system, in which the microscope itself is equipped with excitation and barrier filters, and the application of this system to surgery for malignant glioma are reported. METHODS: BP 450-490, a glass interference filter used as the excitation filter for the light source optical system, and a Kodak Wratten No. 12 filter used as the barrier filter for the microscope optical system, were incorporated in the operative microscope. A switching apparatus was devised so that filters could be inserted instantly when fluorescence was to be observed. Ten cases in which the location of malignant glioma was enhanced by computed tomography (CT) or magnetic resonance imaging (MRI) were selected for this study. After incision of the dura mater, 8 mg/Kg body weight of fluorescein Na was injected intravenously. Tumor removal was begun some 20 min after the injection with the aid of this newly developed fluorescein operative microscope system. RESULTS: Fluorescence enhancement and contrast were remarkable when this system was used. It enabled surgical maneuvering while viewing the fluorescent image of objects. The boundaries between the tumor areas enhanced by CT or MRI and the surrounding brain could be clearly distinguished in the fluorescent image; the tumor was totally removed, except for deep lesions, without any neurological deterioration. When the tumor was relatively hard, the area surrounding the tumor was aspirated with a cavitron ultrasonic surgical aspirator; as a result, the tumor could be removed en bloc; otherwise, the fluorescent tumor was removed piece by piece. CONCLUSIONS: This system provides adequate fluorescent enhancement and contrast and is useful for observing intravenously injected fluorescein during an operation. Though long-term follow-up of such cases is needed, the conditions of our patients immediately after surgery for malignant glioma were satisfactory. These results suggest that our fluorescein operative microscope system is highly effective in surgery for malignant glioma.     

Choroidal vascular lesions in serous retinal detachment viewed with indocyanine green angiography

In serous retinal detachment due to damaged retinal pigment epithelium (RPE), fluorescein angiography shows dye leakage into the subretinal space from the choroid. We performed indocyanine green (ICG) angiography in 110 eyes with serous retinal detachment comprising 71 eyes with central serous chorioretinopathy (CSC), 19 with bullous retinal detachment, 18 with Harada's disease, and 2 with toxemia of pregnancy. Choroidal tissue staining was present around the site of subretinal leakage in late-phase ICG angiograms from 63 eyes with CSC and 18 with bullous retinal detachment. ICG angiography also showed leakage from choroidal vessels in 16 eyes with Harada's disease and 2 with toxemia of pregnancy. As a common feature, ICG angiography showed choroidal vascular hyperpermeability in various types of serous retinal detachment. Choroidal circulation was delayed in Harada's disease and toxemia of pregnancy. Choroidal hypoperfusion and hyperpermeability of choroidal vessels probably contribute to the damage of RPE, and choroidal vascular hyperpermeability probably provides fluid pressure to move fluid into the subretinal space from the choroid.     

Idiopathic polypoidal choroidal vasculopathy of the macula

OBJECTIVE: The authors evaluated the clinical, fluorescein, and indocyanine green (ICG) angiographic characteristics of the macular variant of idiopathic polypoidal choroidal vasculopathy (IPCV). DESIGN: Observational case series. PARTICIPANTS: The records, photographs, and fluorescein and ICG angiograms of eight eyes of seven patients with IPCV lesions confined to the macula were reviewed. MAIN OUTCOME MEASURES: The visual acuity, fundus examination, fluorescein and ICG angiographic characteristics, and clinical course were compared. RESULTS: All patients demonstrated polypoidal lesions arising from macular choroidal vessels on ICG angiography. One patient had bilateral lesions. These lesions appeared hyperfluorescent in the early phases of both fluorescein and ICG angiography. Late-phase leakage was seen in cases associated with subretinal fluid or exudate. None of these patients demonstrated polypoidal lesions arising from the peripapillary choroidal circulation or peripapillary choroidal neovascularization. Three eyes with polypoidal lesions that were associated with subretinal fluid and exudates were treated with photocoagulation. Five eyes were not treated. Final visual acuity ranged from 20/20 to hand motions. Severe visual loss was associated with vitreous and subretinal hemorrhage, but this resolved without permanent severe visual loss in several cases. CONCLUSIONS: In the macular variant of IPCV, ICG and fluorescein angiography demonstrate characteristic macular polypoidal lesions without evidence of peripapillary lesions. The vascular origin of these polypoidal lesions appears to be the macular choroidal circulation. This is distinguished from classic IPCV, in which lesions appear to arise from the peripapillary choroidal circulation. Visual prognosis appears to be good, with most patients retaining visual acuity of 20/80 or better. If subretinal fluid or exudates reduce visual acuity, photocoagulation should be considered.     

A modified technic for local rt-PA catheter-mediated lysis

PURPOSE: To develop an economic and efficient concept for more time-saving local rt-PA thrombolysis therapy. METHOD: 40 patients with peripheral vascular occlusive disease stage IIb-III according to the Fontaine classification and with angiographically proven occluded segments of pelvic and lower limb arteries were treated by a modified concept of local rt-PA catheter thrombolysis. Via a thin guide wire the catheter for thrombolysis is slowly advanced through the thrombus without fluoroscopic control, outside the room in which angiography is performed. In 24 cases a short-term lysis and in 16 cases a long-term lysis was carried out. RESULTS: The initial success rate was 75%, the patency rate in six months' follow-up was 66.7%. The ankle-brachial index decreased from 0.4 +/- 0.3 to 0.8 +/- 0.2 on the average. There were no relevant clinical complications. The average occupancy time of the angiography room or table was 60 +/- 52 min, the average time of fluoroscopy was 17 +/- 13 min. CONCLUSION: In modified local rt-PA thrombolysis, short-term lysis and long-term lysis were mostly performed outside the angiography room, so that the exposure to radiation and there fore the radiation dose were reduced for both the patient and the attending staff. The angiography room is thus available for other patients and can therefore be used more efficiently.     

Physiological side differences in fluorescein inflow into eyes (author's transl)

Rapid-sequence fluorescein angiography was performed simultaneously on both eyes of each of 241 healthy individuals in order to analyze and compare dye inflow patterns in the eyes of each subject. The many uncertainties of successive investigations resulting from uncontrollable changes in systemic circulation parameters between the two angiographies were thus eliminated. In over 90% of the subjects there was no difference between the two eyes in respect of arm-fundus time nor the filling pattern of choroid and retina. A few subjects did show a difference, but this lasted for only one exposure and was normalized on the second exposure of the sequence. It is therefore concluded that side differences of the fluorescein inflow pattern on simultaneous bilateral angiography are highly suggestive of unilateral circulatory disturbances in the cervical, retinal or choroidal vessel. Such disturbances are practically certain if side differences last for more than just one exposure. In contrast, the filling pattern in cilioretinal arteries was very variable and over one third of the subjects presented with side differences between their two eyes. Therefore the filling pattern of these vessels cannot be used for diagnostic purposes.     

Comparison of indocyanine green and fluorescein angiography of choroidal neovascularization

We compared indocyanine green (ICG) and fluorescein angiography for evaluation of choroidal neovascularization (CNV). Cast preparations of CNV induced in monkey eyes by laser photocoagulation were correlated with ICG and fluorescein angiographies of the same CNV formations. Fluorescein angiography was more effective, in general, than ICG angiography in detecting CNV; however, CNVs with subretinal hemorrhage (2 of 35 sites) were visible only with ICG angiography. In early phase ICG angiography, CNV formations that casts showed to be dense or composed of thick vessels were seen, but less dense areas were not visible. Lesions that ICG angiography revealed as leaking were not differentiated morphologically from non-leaking areas by the CNV casts. This study confirms that only ICG angiography can identify CNV hidden by subretinal hemorrhage, although fluorescein angiography is otherwise superior. Indocyanine green angiography is indicated as a valuable complement to fluorescein angiography for evaluation of CNV.     

Cholelithiasis following gastric surgery]

"Classic" choroidal neovascularization (CNV) has a relatively uniform appearance in fluorescein angiography. In contrast, indocyanine green (ICG) angiography shows variable features of well-defined CNV. We examined 31 classic CNV patients secondary to age-related macular degeneration using a confocal laser scanning ophthalmoscope (Heidelberg Retina Angiograph) in order to determine ICG characteristics of classic CNV. Vascular patterns (97%), a hypofluorescent rim (84%), a hyperfluorescent margin (42%), late ICG leakage (32%) and "feeder vessels" were identified in variable frequency. Some of the ICG characteristics may correlate with histological features of the membrane and reflect proliferative activity. Extrafoveal "feeder vessels" may be amenable to laser photocoagulation in the presence of subfoveal CNV.     

Cilioretinal arteries. A study based on review of stereo fundus photographs and fluorescein angiographic findings

The incidence of cilioretinal arteries in 2,000 eyes of 1,000 consecutive patients was determined by review of stereo color fundus photographs and fluorescein angiographs. One or more cilioretinal arteries were present in 49.5% of all patients or in 32.1% of the eyes. The arteries occurred bilaterally in 14.6% and contributed to some portion of the macular circulation in 18.7% of the patients. A great deal of variability of size, number, and distribution of cilioretinal vessels was observed. Prior studies that were based on direct visualization of the fundus have reported cilioretinal arteries in 7% to 29.6% of patients examined. Careful review of stereo fundus photographs and early phase fluorescein angiographs aided in the observation of these vessels that might otherwise have been unrecognized. We believe the method of review accounts for the high incidence of cilioretinal arteries in our series.     

Digital subtraction rotational angiography for aneurysms of the intracranial anterior circulation: injection method and optimization

PURPOSE: To optimize parameters of rotational angiography for examination of the internal carotid circulation; to compare rotational angiography with standard digital subtraction angiography (DSA) in the evaluation of aneurysms of the intracranial internal carotid circulation; and to determine tolerance and safety limits of prolonged internal carotid injection angiography. METHODS: Rotational angiograms were obtained during injection of the internal carotid circulation as part of the clinical angiographic evaluation of aneurysms in 41 patients. Injection rates, X-ray delays, and fields of view were studied retrospectively. Findings at rotational angiography and standard DSA were compared. Nonionic contrast material was injected over 6 seconds, and patients were studied before and after prolonged injection angiography by physical and laboratory examination, including measurement of blood pressure, pulse, and intracranial pressure. RESULTS: Vascular conspicuity was equivalent at carotid injection rates of 4 and 5 mL/s delivered over 6 seconds. At 3 mL/s, more image manipulation was required to see small vascular structures. One-second X-ray delay combined with 6-second injection duration provided the best arterial depiction of intracranial vessels from start to end of rotational angiography. Maximal rotational resolution was with a 17-cm field of view. Identification of aneurysms and small vessels was equivalent at all injection rates. Aneurysm detection was equivalent with rotational angiography and DSA. In 9 of 31 aneurysms, the neck was defined more clearly with rotational angiography than with DSA, compared with 2 of 31 that were seen better with DSA. Aneurysms of the intracranial internal carotid circulation were seen with rotational angiography and not DSA in 12 of 41 cases. No change was noted in clinical or laboratory findings. CONCLUSION: Rotational angiography provided better definition of the aneurysmal neck and greater clarity of aneurysms than did DSA; it also improved the level of confidence in predicting the presence or absence of aneurysms, especially in the anterior communicating artery; however, in our small series it did not significantly increase the detection of aneurysms. Prolonged injection angiography was well tolerated in all patients.     

Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate

PURPOSE: The purpose of the study is to determine the effect of exogenous vascular endothelial growth factor (VEGF) on the primate retina and its vasculature. METHODS: Ten eyes of five animals were studied. Physiologically relevant amounts of the 165 amino acid isoform of human recombinant VEGF were injected into the vitreous of six healthy cynomolgus monkey eyes. Inactivated human recombinant VEGF or vehicle was injected into four contralateral control subject eyes. Eyes were assessed by slit-lamp biomicroscopy, tonometry, fundus color photography, fundus fluorescein angiography, light microscopy, and immunostaining with antibodies against proliferating cell nuclear antigen and factor VIII antigen. RESULTS: All six bioactive VEGF-injected eyes developed dilated, tortuous retinal vessels that leaked fluorescein. Eyes receiving multiple injections of VEGF developed progressively dilated and tortuous vessels, venous beading, edema, microaneurysms, intraretinal hemorrhages and capillary closure with ischemia. The severity of the retinopathy correlated with the number of VEGF injections. None of the four control eyes exhibited any abnormal retinal vascular changes. The endothelial cells of retinal blood vessels were proliferating cell nuclear antigen positive only in the bioactive VEGF-injected eyes. CONCLUSION: Vascular endothelial growth factor is sufficient to produce many of the vascular abnormalities common to diabetic retinopathy and other ischemic retinopathies, such as hemorrhage, edema, venous beading, capillary occlusion with ischemia, microaneurysm formation, and intraretinal vascular proliferation.     

Recombinant GM2-activator protein stimulates in vivo degradation of GA2 in GM2 gangliosidosis AB variant fibroblasts but exhibits no detectable binding of GA2 in an in vitro assay

OBJECTIVE: To examine choroidopathy in patients with Beh?et disease. DESIGN: Prospective clinical study. PARTICIPANTS: Thirty-three patients (63 eyes) with Beh?et disease. INTERVENTION: Patients underwent simultaneous indocyanine green (ICG) and fluorescein angiography with a double detector of scanning laser ophthalmoscopy. MAIN OUTCOME MEASURES: Angiographic findings recorded on videotapes were evaluated. The relation of angiographic findings with systemic activity and aqueous inflammation was also analyzed. RESULTS: Fluorescein angiography showed leakage in varying degrees from retinal vessels in 30 patients (53 eyes, 84%). The ICG angiographic findings were choroidal vascular wall staining in 16 eyes (25%), hyperfluorescent spots in 42 eyes (66%) and hypofluorescent plaques in 22 eyes (35%), both of which were not evident with fluorescein, leakage from choroidal vessels in 3 eyes (5%), and irregular filling of choriocapillaris in 11 eyes (17%). These findings did not have a statistically significant correlation with the presence or absence of aqueous inflammation or oral aphthous ulcerations. CONCLUSIONS: The patients with Beh?et disease showed choroidal abnormalities, which could be revealed only by ICG angiography, but not with funduscopy or fluorescein angiography. Simultaneous ICG and fluorescein angiography would be useful for examining choroidal lesions in Beh?et disease.     

Comparison of nerves to cerebral and extracerebral blood vessels: a differential effect of alpha methyl tyrosine on norepinephrine content

Alpha methyl tryosine (AMT), and inhibitor of norepinephrine (NOR) synthesis, was injected intraperitoneally (200 mg/kg) in Sprague Dawley rats, kept in a cold room, or at room temperature for 16 hours. Using formaldehyde induced NOR fluorescence, nerve counts were made on whole mounts of cerebral and femoral arterioles 14-300 micronm in diameter, utilizing a grid superimposed on the vessels. Cold had no effect on the number of visible (i.e. fluorescing) nerves. AMT had an appreciable effect but only on nerves to femoral arterioles, where a significant reduction in nerve count was observed in both cold stressed and non stressed rates, when compared with animals not given AMT. Since the counting technique is sensitive only to large depletions of NOR, we cannot conclude that AMT failed to affect NOR content in cerebrovascular nerves. However, if such an effect was present, it was much less than the effect of AMT on nerves to femoral vessels. We suggest that the differential effect of AMT on these 2 vascular beds may indicate a lower basal level of NOR release from cerebrovascular nerves, which would correlate with the difficulty of demonstrating basal sympathetic tone in this vascular bed.     

Arterio-venous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis)

Insulin neuritis, or painful neuropathy following rapid improvement in glycaemic control, is well recognised but its aetiology is unclear. An understanding of the processes involved in the genesis of acute painful neuropathy of rapid glycaemic control may give an insight into the early pathogenetic factors leading to diabetic nerve damage in general. We have identified five subjects with insulin neuritis including one who developed severe autonomic neuropathy following treatment with insulin. Subjects underwent: 1) assessment of neuropathic symptom and deficit scores; 2) quantitative sensory and electrophysiological studies and 3) sural nerve epineurial vessel photography and fluorescein angiography in vivo. The sural nerve photographs were independently graded by an ophthalmologist. All subjects with insulin neuritis presented with severe sensory symptoms but clinical examination and electrophysiological tests were normal except in the subject with the severe autonomic neuropathy in whom all the tests were abnormal. On nerve photography, there was an abundance of epineurial nutrient vessels although these showed severe abnormalities including arteriolar attenuation, tortuosity and arterio-venous shunting in all subjects. Proliferating neural 'new vessels' which bear striking similarities to those found in the retina and that were more leaky to fluorescein than normal vessels, were observed in three subjects. Venous distension and/or tortuosity was also observed in three subjects and this was most marked in the subject with severe autonomic neuropathy. This study shows that epineurial nutrient vessel anatomy is abnormal in subjects with acute painful neuropathy of rapid glycaemic control, a condition previously thought to be purely metabolic in origin. The presence of epineurial arterio-venous shunting and a fine network of vessels resembling the new vessels of the retina, may lead to a 'steal' effect rendering the endoneurium ischaemic. This process may be important in the genesis of neuropathic pain, and further supports the importance of vascular factors in the pathogenesis of diabetic neuropathy.     

Prefabrication of bilaminar-epithelialized composite flap with tissue expander and cultured keratinocytes

This study investigated the feasibility of prefabrication of a bilaminar-epithelialized flap by using a tissue expander and cultured keratinocytes, for reconstruction of perforate defects in the oral cavity and upper aerodigestive tract. In each of six rats, a 10-ml volume expander was implanted under the inferior epigastric flap and a thin silicon catheter was introduced into periexpander space. Seven days after implantation, 10 x 10(6) cultured keratinocytes, isolated from inbred donor rats, were suspended in fibrin glue and injected into the periexpander space through the catheter (n = 4 of 6). The expansion was started immediately after cell inoculation and lasted at least 3 weeks at the speed of 2 to 3 ml every 5 to 7 days. At the end of expansion, the periexpander space was opened and the capsule around the tissue expander was found to be covered completely with a neoepithelium. Thus, a bilaminar-epithelialized flap based on femoral vessels was elevated and successfully transferred to cover the excisional perforate defect in the oral cavity with the neoepithelial side as inner lining. All flaps treated with 10 x 10(6) cultured keratinocytes survived with complete wound healing during a 1-week follow-up (n = 4 of 6). Both macroscopic and histologic findings demonstrated that a bilaminar-epithelialized composite flap can be fabricated by using a tissue expander and keratinocyte-fibrin glue suspension.     

A case of nonarteritic anterior ischemic optic neuropathy with cilioretinal artery occlusion

We report a case of nonarteritic anterior ischemic optic neuropathy (AION) with cilioretinal artery occlusion. The patient was a 61-year-old man with sudden visual loss in his right eye. Funduscopy showed pale swelling of the entire optic disc with retinal ischemic edema of the upper half of the retina, and fluorescein angiography revealed faint filling of the dye in the optic disc in the retinal arterial phase, and dye staining of the optic disc in the late phase. We initially diagnosed the disease as AION with branch retinal artery occlusion, but systemic administration of a corticosteroid and urokinase were ineffective and the optic disc became atrophic. As the optic disc swelling decreased and the course of arteries in the optic disc became clear, we repeated fluorescein angiography which proved that the involved upper retinal artery was a cilioretinal artery having earlier dye appearance than the lower retinal artery. Thus, we finally diagnosed the disease as AION with cilioretinal artery occlusion. We believe that Hayreh's view that AION may result from occlusion of the posterior ciliary artery is supported by the intraocular findings in this case.