Faculty Bibliography

PURPOSE: To investigate the relationship between choriocapillaris blood flow and blood flow through an overlying choroidal neovascularization, as it relates to photocoagulation-induced changes in the choriocapillaris circulation. METHODS: A theoretical model that simulates the blood flow in the choriocapillaris and choroidal neovascularization of the human eye was developed, based on histologically determined vascular geometry and experimentally measured blood pressure gradients. The choriocapillaris blood pressure and blood flow were examined before and after simulated photocoagulation of various Sattler layer vessels entering the choriocapillaris in the vicinity of the choroidal neovascularization. (The Sattler layer is the inner layer of medium-sized choroidal vessels that includes both arterioles and venules that supply the choriocapillaris.) RESULTS: The theoretical model showed that both partial and complete occlusion of either Sattler arteriole or venous vessels in the vicinity of the capillary-like vessels connecting a choroidal neovascularization to the underlying choriocapillaris results in significant choroidal neovascularization blood flow reduction. These theoretical results are similar to clinically observed changes induced by laser photocoagulation of feeder vessels. (In this discussion, the term 'feeder vessels' refers to those vessels in an indocyanine green angiogram image that appear to supply blood to a choroidal neovascularization; these vessels appear to be Sattler layer vessels, rather than the histologically demonstrated short, capillary-like vessels that form choriocapillaris-choroidal neovascularization communications.) CONCLUSIONS: Reduction of choriocapillaris blood flow underlying a choroidal neovascularization may be sufficient to reduce the blood flow rate in the choroidal neovascularization and thereby reduce the associated retinal edema. The results also suggest that reduction of choriocapillaris blood flow may be the common hemodynamic event associated with the successful application of several currently practiced methods of choroidal neovascularization treatment, including feeder vessel photocoagulation, photodynamic therapy, transpupillary thermotherapy, and prophylactic drusen photocoagulation. Ultimately, this model may be useful in determining optimal placement of laser photocoagulation burns to achieve a desirable perturbation in choroidal blood flow distribution and thereby reduce choroidal neovascularization blood flow to the extent necessary to obliterate associated retinal edema

PURPOSE: To demonstrate an indocyanine green (ICG) angiography-based clinical method for characterizing choroidal blood flow and for detecting changes in choroidal circulation patterns, and by use of that method, to demonstrate that pentoxifylline affects choroidal blood flow. METHODS: High-speed ICG angiography was performed in rhesus monkeys before and after intravenous administration of pentoxifylline or saline (which served as a control) while monitoring blood pressure and heart rate. From these data, three-dimensional surface maps indicating the instantaneous relative distribution of choroidal blood flow during the peak of intra-ocular pressure pulse systole in a 30 degrees field, centered on the macula, were generated to characterize the state of the choroidal circulation at various times during the experiments. RESULTS: Comparisons of the 3-dimentional surface maps consistently indicated an increase in sub-macular choroidal blood flow occurring within 5 to 10 minutes post-pentoxifylline injection, with a gradual return to baseline level 20-40 minutes later. Injection of equal volumes of saline produced no changes in choroidal blood flow. CONCLUSIONS: Posterior-pole choroidal blood flow can be characterized as by a three-dimensional surface representing the instantaneous relative distribution of choroidal blood flow during the peak of intra-ocular pressure pulse systole. Pentoxifylline does, at least transiently, increase sub-macular choroidal blood flow

PURPOSE: To report a model of choroidal neovascularization feeder vessels that reconciles current histologic, angiographic, and clinical data, and to report experimental studies that investigate the potential of indocyanine-green-dye-enhanced photocoagulation to improve feeder-vessel treatment. METHODS: A model of choroidal neovascularization feeder vessels was conceived to account for current histologic and angiographic data. Based on that model, experimental studies of the efficacy of indocyanine green-dye-enhanced photocoagulation were performed, using pigmented rabbit eyes as a model system. A Zeiss fundus camera was modified to permit visualization of choroidal blood flow by high-speed indocyanine green angiography and to permit simultaneous delivery of 810-nm-wavelength diode laser photocoagulation pulses to specific choroidal vascular targets during indocyanine green-dye bolus transit. RESULTS: Choroidal neovascularization feeder vessels appear to originate in the Sattler layer (that is, that portion of the choroidal vasculature consisting of medium-diameter vessels) and enter the choriocapillaris in close proximity to the small capillary-like vessels that penetrate Bruch membrane and communicate with the choroidal neovascularization. The rabbit eye experiments demonstrated that the presence of high indocyanine green dye concentration in circulating blood enhances uptake of near-infrared laser energy (three eyes); injection of sequential indocyanine green dye boluses results in gradually decreased efficiency of dye-enhanced photocoagulation (two eyes); and by application of laser energy during the initial transit of small-volume, high-concentration indocyanine green dye boluses, dye-enhanced photocoagulation of large diameter choroidal arteries can be accomplished with relatively little concomitant retinal tissue damage (three eyes). CONCLUSIONS: Although future trials will be necessary to substantiate these initial findings in the clinical arena, it appears that the efficiency of choroidal neovascularization feeder-vessel photocoagulation may be enhanced, while minimizing concomitant damage to overlying retinal tissue, by delivery of 810-nm wavelength laser energy immediately upon arrival of a high-concentration indocyanine green dye bolus in a targeted feeder vessel. However, molecules of dye adhering to vessel walls or lying in tissue interstitial spaces appear to divert laser energy from the photocoagulation process, so efficiency of indocyanine green dye-enhanced photocoagulation gradually diminishes as the number of injected dye boluses increases

PURPOSE: Indocyanine green (ICG) angiograms of each of five patients with retinal pigment epithelium (RPE) detachments were made using first a Topcon fundus camera and then a Heidelberg scanning laser ophthalmoscope (SLO); for each patient, both types of angiograms were obtained on the same day. In each case, the serous fluid appeared bright throughout the fundus camera studies and dark throughout the SLO studies. This study sought to explain the disparity in the appearance of the lesions in the two kinds of images and to determine whether there was dye in the serous fluid. METHODS: Simple model eyes were constructed to demonstrate the effects of Mie light scatter and integrating sphere behavior of the sclera on ICG image formation by the fundus camera and SLO optics. Analysis was made of both the clinical angiograms and model eye images to structure an explanation for the disparate RPE detachment angiographic images. RESULTS: Indocyanine green fluorescent light from choroidal vessels adjacent to the lesions and scattered by the turbid serous fluid accounted for the lesion brightness seen in the fundus camera images. The models confirmed that SLOs suppress scattered light. CONCLUSIONS: The apparent fluorescence of serous fluid beneath RPE detachments in fundus camera early-phase ICG angiogram images is not attributable to the presence of dye; rather, it appears to be attributable to serous fluid light scatter of fluorescent light arising from adjacent fluorescent structures. This light scatter is a consequence of the fundus camera illumination and recording optics and is not present in SLO-generated images. The necessity of understanding such phenomena as absorption, diffraction, polarization, and scatter of light and routinely applying them to ICG angiogram interpretation is underscored when it is shown that they offer simple explanations for unusual or unexpected angiographic results, as in the case of the patients with RPE detachment discussed here

PURPOSE. To investigate variability of choriocapillaris blood flow patterns. METHODS. After the intravenous injection of indocyanine green, angiograms were recorded at 30 images per second in rhesus monkey eyes using a fundus camera equipped with a pulsed laser diode light source, synchronized with a gated (5 msec), intensified charge-coupled device, or CCD, video camera. Images of choriocapillaris filling alone were extracted. Plastic corrosion casts were made of two of the monkey's choroidal vasculatures for subsequent scanning electron microscopy examination. RESULTS. Pulsed laser indocyanine green fluorescence excitation produced better definition of choriocapillaris filling than had been achieved using continuous illumination. No correlation was found between the choriocapillaris plexus architecture revealed by the plastic corrosion casts and the observed choriocapillaris lobular filling. Overall posterior pole choriocapillaris dye-filling patterns were relatively stable for periods of days, but they changed gradually for periods of weeks. Localized minor pattern changes occurred on a much shorter time scale. Choriocapillaris filling patterns were altered by acutely elevating intraocular pressure, by O2 and CO2 breathing, and by argon laser retinal photocoagulation of adjacent areas. CONCLUSIONS. Choriocapillaris filling patterns appear to be determined by the network of perfusion pressure gradients that exist among the interspersed feeding arterioles and draining venules connected to the choriocapillaris plexus. Changes in intraocular pressure and in blood PO2 and PCO2 levels can produce marked changes in the distribution of choriocapillaris blood flow. Retinal laser photocoagulation of adjacent fundus areas alters choriocapillaris blood flow to the extent that the altered flow might be an important factor in the beneficial results attributed to retinal laser treatment