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.     

Digital indocyanine green angiography in chorioretinal diseases

BACKGROUND: Fluorescein angiography (FA) is important in the diagnosis of chorioretinal diseases; however, it has some limitations. We conducted this study to evaluate whether digital indocyanine green (ICG) angiography can offer enhanced image in chorioretinal diseases. METHODS: Digital indocyanine green angiography with scanning laser ophthalmoscope (SLO) was performed in 314 patients with various chorioretinal diseases. This coupled digital imaging system can offer instant images, process and store data by computer, and give convenient hardcopy generation. RESULTS: The digital ICG angiography provided enhanced image resolution of the choroid compared with FA. The disease categories included choroidal neovascularization (CNV), choroidal tumor, inflammatory choroidal disease, ischemic choroidal disorder, idiopathic central serous chorioretinopathy and retinal macroaneurysm. CONCLUSIONS: ICG angiography is a useful adjunctive diagnostic technique to fluorescein angiography for various chorioretinal diseases. It is especially useful in the diagnosis of occult and recurrent CNV, as well as choroidal tumor and choroiditis. With greater clinical experience, ICG angiography is promising in giving additional clinical information for many other chorioretinal diseases.     

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.     

Indocyanine green angiography of multifocal choroiditis

PURPOSE: The purpose of the study is to determine indocyanine green (ICG) angiographic characteristics of patients with multifocal choroiditis (MC) and to identify features that may assist in the differentiation of MC from other ocular inflammatory diseases. METHODS: After complete ophthalmologic examination, fluorescein angiography and ICG angiography were performed in a series of 14 patients with MC. The ICG findings were then correlated with the clinical and fluorescein angiographic appearance of these patients to determine specific characteristics and distinguishing features of the entity. These findings then were compared with those of angiographic patterns observed in patients with ocular histoplasmosis syndrome to determine whether differentiating features could be identified. RESULTS: Fourteen (50%) of the 28 eyes were found to have large hypofluorescent spots in the posterior pole on ICG angiography, which, in most cases, did not correspond to clinically or fluorescein angiographically detectable lesions. Seventeen (61%) had smaller hypofluorescent lesions (approximately 50 pm in size) in the posterior pole on the ICG study. In seven eyes exhibiting enlarged blind spots on visual field testing, ICG angiography showed confluent hypofluorescence surrounding the optic nerve. The ICG angiogram was found useful in evaluating the natural course in two patients with MC as well as a response to oral prednisone therapy in four others. The ICG angiographic findings differed from those seen in patients with ocular histoplasmosis. CONCLUSIONS: Indocyanine green angiography can provide information that is not detectable by clinical or fluorescein angiographic examination in patients with MC. This information may prove useful in differentiating this condition from the ocular histoplasmosis syndrome, provide a better understanding of the natural course and progression of the disease, and provide a potential adjunct in the clinical evaluation of patients undergoing therapeutic regimens for active inflammatory lesions.     

Visualization of leukocyte dynamics in the choroid with indocyanine green

PURPOSE: To report a method to evaluate leukocyte dynamics in the choroidal circulation with indocyanine green (ICG) angiography. METHODS: Nonpigmented and pigmented rats were administered ICG solution intravenously. The fundus image was obtained with a scanning laser ophthalmoscope and recorded on magnetic tapes at a video rate (30 frames/second). The images were analyzed with a personal computer-based image analysis system. RESULTS: On ICG angiography, hyperfluorescent dots were seen moving along the choroidal vessels and in the retinal vessels several minutes after injection. These fluorescent dots were thought to be circulating leukocytes stained with ICG. The micrographs of blood smears after ICG injection showed intense fluorescence of leukocytes. Computer-assisted image analysis allowed tracing of these fluorescent dots using a frame-by frame method. CONCLUSIONS: Results of this study indicated that ICG can be used for vital staining of leukocytes and that it is possible to evaluate leukocyte movement in the choroidal circulation in vivo in rats.     

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.     

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.     

Photocoagulation of well-defined choroidal neovascularization in age-related macular degeneration: clinicopathologic correlation

PURPOSE: To present the clinicopathologic features of the eyes of a patient with age-related macular degeneration (ARMD): the right eye was treated for well-defined extrafoveal choroidal neovascularization (CNV), and the left eye had an untreated disciform scar. METHODS: The patient was studied ophthalmoscopically and by fluorescein angiography at the time of presentation and on follow-up examinations up to 54 days after laser treatment, when he died. The posterior portions of both eyes (obtained postmortem), including the macula and optic nerve head, were sectioned serially for light microscopy. Tissue sections from both eyes were removed from glass slides and studied by transmission electron microscopy. RESULTS: Histopathologic study of the right eye disclosed a thin layer of basal laminar deposit throughout the posterior pole. Two defects in Bruch's membrane without CNV were present within the area of laser photocoagulation located superior to the fovea. No CNV was present in the scar. Eleven areas of early CNV were present in the posterior pole. Histopathologic study of the left eye showed a prominent basal laminar deposit throughout the posterior pole. A 2.6 x 2.7 mm disciform scar was present that was located mostly in the subretinal space. Four sources of CNV were present. CONCLUSIONS: The clinicopathologic features of a treated eye with well-defined extrafoveal CNV, and the fellow eye with a disciform scar, both associated with ARMD, are presented. Although laser treatment obliterated a choroidal neovascular membrane, 11 additional areas of early, subclinical CNV were present.     

External beam radiotherapy (20 Gy, 2 Gy fractions) fails to control the growth of choroidal neovascularization in age-related macular degeneration: a review of 111 cases

BACKGROUND: Control of the natural course of choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) is difficult, and laser photocoagulation is recommended in only a subset of patients. Alternative modalities of treatment are under investigation. METHODS: We have used external beam radiotherapy (20 gray radiation units [Gy], 2 Gy fractions) to treat CNV in ARMD. A total of 111 patients have been followed for 12-30 months after radiotherapy. This study evaluates the effect of radiotherapy on the size of CNV, which was digitally measured on serial fluorescein angiograms. RESULTS: Analysis of results in the classic (or mixed classic and occult) CNV group was conclusive for fast growth of CNV and continuous increase of size during follow up. In the occult CNV group, a slowly progressive growth of CNV was demonstrated. In patients with vascularized pigment epithelium detachments, "hot spots" persisted; in a few patients, flattening of the macula was observed. Nearly all treated patients experienced further loss of vision. CNV growth in the radiotherapy treated eye was usually similar to growth in the untreated fellow eye, and in some, even worse. CONCLUSION: External beam radiotherapy (20 Gy, 2 Gy fractions) failed to control growth of CNV and was ineffective in stabilizing vision.     

Expression of cell adhesion molecules and vascular endothelial growth factor in experimental choroidal neovascularisation in the rat

AIMS: To investigate the longevity and reproducibility of choroidal neovascularisation (CNV) induced by krypton laser photocoagulation in the rat. The presence of cell adhesion molecules (CAMs) and vascular endothelial growth factor (VEGF) during the development of CNV was also studied. METHODS: 67 pigmented rats underwent retinal photocoagulation by krypton laser. The eyes were examined by either single or serial fluorescein angiography at 3 days, 1, 2-3, 4-5, 7-8, and 12 weeks post photocoagulation. The expression of CAMs (ICAM-1, E-selectin, and CD44) and VEGF post photocoagulation was studied by immunohistochemistry. RESULTS: CNV related fluorescein leakage appeared in 46.4% of 766 laser spots delivered to the 58 eyes that were tested at 2-3 weeks post treatment. The ratio of hyperfluorescent laser sites did not change significantly at 8 weeks post laser. The number of leaky spots was independent of the total number of lesions delivered to each eye (at 2-3 weeks post laser 10-15 spots/eye: 44% and 25-30 spots/eye: 49%; t = 0.7673; p = 0.3903). Nine eyes were followed by serial angiography between 2 and 12 weeks. The laser spots with fluorescein leakage at 2 weeks (51.5%) remained leaky at 12 weeks (51.5%). Histopathologically, macrophage accumulation peaked at 5 days and CNV was firstly observed at 1 week post photocoagulation. ICAM-1, E-selectin, CD44, and VEGF were maximally induced at 3-5 days post laser photocoagulation, and were localised to RPE, choroidal vascular endothelial, and inflammatory cells. VEGF was also detected in intravascular leucocytes at the sites of laser lesions. CONCLUSIONS: These studies demonstrated that krypton laser photocoagulation can be successfully used to produce lesions similar to those of human CNV. The response induced remained present for an extended period of time (12 weeks), thus offering a potential model to screen candidate CNV inhibitory agents. In addition, it is proposed that the expression of ICAM-1, E-selectin, CD44, and VEGF before new vessel formation might be linked to the initiation of CNV.     

Indocyanine green fluorescence angiography of the choroid

Indocyanine green fluorescence (ICG) angiography of the choroid gives better visualization of the choroidal vessels than does fluorescein angiography. We found that the detachment of the pigment epithelium seems bigger on ICG than on fluorescein angiograms, and pigmented lesions are more clearly delineated.     

Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model

Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast growth factor (FGF2) plays a role in stimulating CNV. In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CNV. One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV. At 2 weeks, CNV was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.     

Pre-injection fluorescence in indocyanine green angiography

PURPOSE: To verify whether infrared pre-injection fluorescence can be observed in patients undergoing indocyanine green (ICG) angiography. METHODS: Infrared fundus photographs were taken before dye injection for 450 consecutive patients undergoing ICG angiography for different chorioretinal disorders. The authors used a high-resolution videoangiography system with the standard ICG filters inserted (overlap, < 0.5%) and the highest flash intensity. RESULTS: Pre-injection fluorescence was detected in 184 patients (40.8%). It was a strong fluorescence in 75 patients (40.7%) and a faint fluorescence in 109 (59.2%). When fluorescence was strong, it simulated vascular filling on the ICG angiogram. Pre-injection fluorescence resulted from the following lesions: (1) old grayish subretinal hemorrhages (35 patients); (2) lipofuscin-like deposits (65 patients); (3) pigmented choroidal neovascular membranes (72 patients); and (4) serous retinal detachments lasting from several months or years (12 patients). Highly reflecting white lesions were not fluorescent. CONCLUSION: Pre-injection fluorescence of chorioretinal lesions is frequently detectable in patients with diseases requiring ICG examination. A pre-injection photograph may help to avoid misinterpretation of the angiograms. The authors' findings may be interpreted as pseudofluorescence or autofluorescence. Pigments contained in pathologic structures of the ocular fundus may be the source of autofluorescence emissions in the near-infrared range.     

Prevalence of positive urinary dipstick analysis (leucocyte esterase, nitrite, haemoglobin, or glucose) in a population of 3645 adult subjects--consequence for measurement of urinary albumin excretion rate

A 10-year-old boy presented with typical fundus findings of frosted branch angitis in both eyes. Fluorescein angiography showed late-phase hyperfluorescence in some active areas of vascular lesions. Indo-cyanine green (ICG) angiography showed similar but less extensive hyperfluorescence along the frosted vessels and in the disc. ICG angiography also showed filling delay in the choriocapillaris. These findings suggest that frosted branch angitis is a manifestation of inflammation in the retina and the choroid. Laboratory studies showed increase in the toxoplasma titer at 1:10,240 and in the serum levels of alpha 1 and alpha 2 globulin. Frosted branch angitis in this case seemed to be the consequence of local allergic reaction, or immune complex deposition, presumably due to toxoplasma infections.     

Digital subtraction indocyanine green angiography of occult choroidal neovascularization

OBJECTIVE: This study aimed to use a new technique for ocular imaging, digital subtraction indocyanine green angiography (DS-ICGA), to evaluate patients with occult choroidal neovascularization (CNV). DESIGN: The design was a cross-sectional study of patients with occult CNV. PARTICIPANTS: A total of 31 eyes of 31 patients were studied. INTERVENTION: Digital subtraction of sequentially acquired indocyanine green angiographic frames was used to image the progression of the dye front in eyes with occult CNV. A method of pseudocolor imaging of the choroid was developed that allows differentiation and identification of underlying choroidal arteries and veins. RESULTS: The DS-ICGA of occult CNV showed consistent findings. Occult CNV was imaged with greater detail and in a shorter period of time than with conventional indocyanine green angiography. The fundus landmarks were retained with DS-ICGA much better than with conventional indocyanine green angiography. CONCLUSIONS: The DS-ICGA uses time to dissect the choroidal circulation. With DS-ICGA, occult CNV could be imaged more quickly and in greater detail than with conventional imaging techniques. The DS-ICGA may improve the authors ability to image, and subsequently treat, occult CNV.     

MRI arthrography in labrum lesions of the hip joint. Method and diagnostic value

PURPOSE: Several pilot studies have indicated that low-dose radiation therapy might have a beneficial effect on the course of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). This study aimed to ascertain whether such treatment might halt the progression of neovascular AMD and whether a low or a high radiation dose should be applied. PATIENTS: The patients comprised some randomized to 0 vs 10 vs 36 Gy of radiation and (after a change of the study protocol became necessary) others who participated in a prospective, controlled non-randomized pilot study. Enclosed were eyes with visual acuity of > or = 0.1 and < or = 0.6 revealing a juxta-subfoveal CNV either of the occult type (type 1) or the classic type (isolated or as part of a predominantly occult lesion). RESULTS: Eyes treated with 10 Gy for occult CNV (n = 12) were subject to severe visual loss in 41.6% of the cases compared to 38.5% in the control group (n = 13) at 12 months of follow-up. For eyes treated with 10 Gy because of classic CNV, the corresponding figures were 33% (n = 18) and 57% (n = 14) respectively. At 18 months of follow-up, the percentages were 63% and 75% respectively. Fluorescein angiographic growth of classic and occult CNV could not be halted by 10 Gy, while a temporary growth retardation was observed in cases irradiated with 36 Gy. CONCLUSION: In the study presented, the natural course of occult CNV could not be improved by irradiation with 10 or 36 Gy. In cases of classic CNV, low-dose irradiation with 10 Gy postponed severe visual loss by a maximum of 18 months. A positive treatment effect was also observed in cases irradiated with 36 Gy; however, a 25% incidence of radiation retinopathy seems unacceptable.     

Perifoveal laser treatment for subfoveal choroidal neovascularization in age-related macular degeneration

The management of subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration presents a major therapeutic dilemma. No treatment may lead to severe visual loss, and direct laser treatment to the entire subfoveal lesion results in acute loss of visual acuity. Encouraging results have been described with a foveal-sparing laser technique for subfoveal CNV. The authors performed perifoveal confluent laser treatment on a relatively well-defined occult CNV, sparing the foveal avascular zone. One month after treatment, the visual acuity had improved from 20/400 to 20/30. At 24 months, the visual acuity was 20/40 with no recurrence. Confluent perifoveal laser treatment for subfoveal CNV may be useful in preserving central visual acuity in selected patients.     

Choroidal neovascularization in second eyes of patients with unilateral exudative age-related macular degeneration

PURPOSE: To evaluate patients with unilateral occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) for the nature of the neovascularization which develops in the fellow eyes. METHODS: Patients with newly diagnosed unilateral occult CNV were followed prospectively for the development of CNV in the fellow eye. Patients were classified based on the type of occult CNV in the first eye: (1) those with associated serous pigment epithelial detachment (serous PED) and (2) those without. Demographic and clinical data, including the type of CNV in the second eyes, were compared. RESULTS: Choroidal neovascularization developed in 115 patients in the second eye. Fifty-six patients had occult CNV with a serous PED (also termed vascularized PED) in the first eye, and 59 patients had occult CNV without serous PED. The two groups did not differ significantly in the demographic and the clinical features evaluated. Well-delineated (or classic) CNV developed in the fellow eye of one patient in each group. Of the remaining 55 patients with vascularized PED in the first eye, the same type of occult CNV developed in 48 (87%) patients in the second eye. Of 58 (84%) patients in the second group, the same type of occult CNV developed in the second eye of 49 patients. This symmetric distribution of type of CNV between eyes is highly significant (P < 0.001). CONCLUSIONS: Eyes with occult CNV secondary to AMD can be classified by the presence or absence of an associated serous PED. Patients with unilateral occult CNV have a significant risk of occult CNV developing in the second eye, and the type of occult disease in the first eye is highly predictive of the type of neovascularized disease in the second eye. These findings are important with respect to natural history, and possibly to the treatment response and visual prognosis of patients with neovascularized AMD.     

Magnetic resonance angiography demonstrates vascular healing of carotid and vertebral artery dissections

BACKGROUND AND PURPOSE: Dissection of the carotid and vertebral arteries is most accurately diagnosed with conventional angiography. MR techniques are sensitive for detecting the abnormalities associated with dissection but may lack specificity. We hypothesized that MR may be useful for serial monitoring of dissection and may therefore guide therapy. METHODS: All patients with angiographically proven carotid and/or vertebral artery dissection from July 1994 to June 1996 were followed for a median duration of 10.5 months. Of these 29 patients (44 vessels), 18 were concurrently evaluated with MR, and a target group of 9 patients (17 vessels) was prospectively followed with MR at 3-month intervals. RESULTS: In the 18 patients with both imaging studies at baseline, angiography revealed 30 dissected vessels while MR detected 27 (90%). In the target group of 9 patients, initial MR identified 15 of the 17 dissections diagnosed with angiography. Serial MR revealed complete healing in 5 vessels, improvement in 6 vessels, no change in 4 vessels, and worsening in 2 vessels. The radiographic features most likely to resolve were stenosis and mural hematoma, while occlusion and luminal irregularity tended to persist. Late ischemic events occurred in 2 patients, both with persistent MR evidence of dissection, one while subtherapeutic on warfarin therapy and the other occurring 1 week after warfarin was discontinued. CONCLUSIONS: MR is a reliable noninvasive method for following the vascular response to treatment and may guide the course of a clinical trial comparing medical therapies for carotid and vertebral artery dissection.