THE USE OF DYE DILUTION CURVE ANALYSIS IN THE QUANTIFICATION OF INDOCYANINE GREEN ANGIOGRAMS OF THE HUMAN CHOROID

Abstract

The choroidal circulation supplies most of the intraocular blood flow. The macula and optic nerve depend almost entirely on the choroidal blood flow. Most of the studies for the ocular blood flow have been performed for retinal circulation. Therefore, choroidal anatomy and hemodynamics, and the role of the choroid in the pathogenesis of several important ocular disorders, such as age-related macular degeneration, diabetic retinopathy, glaucoma and so forth are poorly understood. Since Flower and Hochheimer first successfully performed indocyanine green (ICG) angiography in humans in the early 1970s, 9,6 clinicians and researchers have attempted to image the choroid with high resolution. Compared with sodium fluorescein dye, ICG dye has greater advantages for angiographic study of the choroid for several reasons. First, the near-infrared light absorbed by ICG 13 is much more efficient in its penetration of pigmented layers of the fundus compared with the shorter wavelength used in fluorescein angiography. A second advantage is ICG dye's tendency to bind to plasma proteins. Approximately 98% of the ICG dye is bound to plasma albumin 4 (the sodium fluorescein dye molecules are far less completely bound). As a result, ICG diffuses slowly out of the fenestrated choriocapillaris in contrast to the rapid leakage of fluorescein dye, which prevents visualization of choroidal details. Guyer and others reported the largest series of digital ICG videoangiography of occult choroidal neovascularization as determined by fluorescein angiography; in 1000 consecutive cases, they found that ICG could better image the occult choroidal neovascular membrane (CNVM) over fluorescein angiography with ICG angiography yielding 283 cases (29%) of focal hyperfluorescent spots; 597 cases (61%) of hyperfluorescent plaques (consisting of 265 cases [27%] of well-defined plaques and 332 cases [34%] of poorly defined plaques); and 84 cases (8%) of combination lesions (consisting of 35 cases [3%] of marginal spots, 37 cases [4%] of overlying spots, and 12 cases [1%] of remote spots). 7 Scanning laser ophthalmoscopy, with its high resolution and contrast, further enhances this technique, and a number of investigators have described ICG angiography of choroidal neovascular membranes using scanning laser videoangiography.* *References 1,2,3,4,5,7,8,10,13,15,16,17,18,21,22,23 and 25 Scanning ophthalmoscopy is also an extremely versatile adjunct to ICG angiography. Bischoff et al 3 described the use of a two wavelength scanning laser ophthalmoscope to facilitate simultaneous recording of ICG and fluorescein angiography in 340 cases, two thirds of which had well-defined or occult choroidal neovascularization in age-related macular degeneration. The angiograms are displayed as one combined red-green picture. They note that this method allowed a precise comparison of the transit of both dyes through both vascular beds with perfect alignment of the critical retinal vascular landmarks provided by the fluorescein images onto the ICG angiogram. 3 Holtz et al 10 later reported similar experience in 295 simultaneous angiograms on 268 patients with various retinal and choroidal diseases, including exudative age-related macular degeneration with occult and classic choroidal neovascularization. 10 Schneider described ICG angiography with simultaneous microperimetry using the scanning laser ophthalmoscope (SLO) to facilitate precise point-to-point correlation between visual function and the macular pathology. They detected a relative scotoma in 19 and an absolute scotoma in 21 out of 40 eyes, and they noted that eyes with well-defined CNVM had significantly deeper scotomas than eyes with occult CNVM. They suggested that the depth of the scotoma may guide physicians in selecting appropriate treatment for the CNVM. 17 The recent introduction of the SLO has brought quantitative angiography to new heights. This instrument overcomes many of the limitations of traditional photographic or video angiography. The SLO is a confocal laser device. Reflected light exits the eye through the pupil and must pass through a confocal aperture before reaching a solid-state detector. This detector generates a voltage level based on the intensity of incoming light. The detector voltage level, measured in real time, creates the standard video signal. Scattered light and light reflected from sources outside of the focal plane are blocked by the confocal aperture. Overall retinal illumination is reduced, and contrast is improved as only a single spot is illuminated by the laser beam at any moment. The signal is generally passed through a video timer and then directed to an S-VHS video recorder. The resulting images are similar to those obtained with standard video angiography but with improved spatial resolution and contrast. A SLO is available for fluorescein angiography and ICG angiography. The examiner can select an integrated argon-blue laser (488 nm) with barrier filter (530 nm) for fluorescein angiography and an infrared diode laser (790 nm) with a barrier filter (830 mm) for ICG angiography. Glaucoma should be another promising study field for ICG angiography with SLO technique. Although the superficial optic nerve head is supplied by branches of the central retinal artery, the laminar and prelaminar portions, which are important for optic nerve perfusion and pathogenesis of glaucoma, are supplied by the intrascleral arterial circle of Zinn. The main supply to the circle of Zinn is provided by the posterior ciliary arteries, which branches to the choroid. Because the blood supply for the optic nerve head comes mainly from choroidal circulation, choroidal circulation insufficiency is a possible causal factor for glaucoma. Recently the study using ICG angiography with SLO showed that glaucoma eyes have more peripapillary hypofluorescent areas in late phase. 14 Although these morphologic data are valuable, the data have limitation to document hemodynamic changes that is essential to evaluate blood perfusion pressure and autoregulation of blood supply. Scanning-laser ICG angiography has also been used to investigate ocular hemodynamics. Several authors have attempted to quantify morphologic and dynamic parameters in the choroidal circulation. In a recent pilot study by Harris and associates, a new area dilution analysis technique for scanning-laser ICG angiography showed that normal tension glaucoma (NTG) patients have peripapillary choroidal filling deficits when compared with the macular area of the same patients. 11 This new analysis software is based on dye-dilution curve analysis, which has been studied, surprisingly, since 1920. It can provide various hemodynamic parameters for scanning-laser ICG angiography which were previously unavailable.