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Johns Hopkins University Researches A New Procedure To Help Prevent Vision Loss or Blindness

Vision loss in people over 50 is commonly caused by the localized excessive new growth of blood vessels in the choroid. These concentrations of blood vessels are called Choroidal NeoVascular Membranes or "CNVM".

Defining The Problem
The choroid is the layer of the eye sandwiched between the retina (the light-registering layer) and the sclera (the tough white outer layer that forms the eyeball). The choroid is a vascular layer rich in blood vessels feeding the retina. A very common disease, Age Related Vascular Degeneration (ARMD) is associated with the pathologic growth of new blood vessels in the choroid (Choroidal Neovascular Membranes or CNVM) which penetrate the retina and cause vision loss or blindness.

Standard Detection Technique
The standard method used for locating CNVM is fluorescein angiography. In this procedure the patient receives an intravenous injection of a fluorescent (fluorescein) dye. The dye is carried through the blood stream and illuminates the translucent blood vessels from within. A camera, peering through the pupil, records the movement of the fluorescent dye as it flows through the blood vessels in the choroid. The problem with this method is that the glowing dye indiscriminately passes through ALL blood vessels. The fluorescence from all these vessels can obscure the view of CNVM, which makes identification and precise location difficult.

LTA -- A New Technique
An experimental method of delineating CNVM is being developed at Johns Hopkins University. It offers new hope for people suffering from ARMD. Laser Targeted Angiography (LTA) is accomplished by encapsulating the fluorescing dye inside heat- sensitive fat cells (liposomes) and releasing the dye with a laser pulse. The laser is positioned so that it can send a pulse through the pupil to the choroid layer. It is targeted at the area of interest by viewing the back of the eye on a video monitor.

LTA Methodology
The method for encapsulating the dye is beyond the scope of this article. Through whichever method, particles of dye are encapsulated in liposomes -- and then the encapsulated dye is injected into a peripheral vein. The dye travels through the blood stream in exactly the same manner as with standard fluorescein angiography -- as long as it remains encapsulated. When the laser sends a low-intensity pulse through the pupil and warms the liposomes to 41 degrees C (106 degrees F), they "open" and release the dye. Once released, the dye glows intensely as it is carried along the blood stream. Of course, this low-intensity laser pulse is administered without damage to the targeted area or surrounding tissues.

Advantages of LTA
Because the laser is aimed locally on a very small area (typically 0.6 millimeter) only a small amount of dye is released and becomes visible. The small amount of visible (glowing) dye is called a "bolus". With the release of the bolus, targeted vessels are illuminated while the background remains dark -- thus enhancing the visualization of CNVM. Once the dye is released by the laser, an angiographic sequence is acquired -- usually for a duration of 2 seconds.

LTA Apparatus
To perform Laser Targeted Angiography, a fundus camera (Zeiss, Germany) is equipped with a high resolution video camera (MC- 1134GN, 1134x480 resolution; Texas Instruments, Dallas, TX). The output of the camera is fed into a video image enhancer and stored on magnetic tape by a high frequency video recorder. For analysis, the tape is played back, and images are digitized with the EPIX 4MEG VIDEO Model 12 imaging board. The capability of the 4MEG VIDEO Model 12, with 16 MB of image memory, to digitize multiple images at video rate, permits acquisition of a complete sequence of angiograms from any one test. Moreover, the presence of the whole sequence in memory permits a consistent and efficient analysis.

Descriptions of Images
Images C-F illustrate a sequence obtained by LTA at the site of the CNVM shown in Images A &B (obtained by conventional fluorescein angiography). The circle indicates the area covered by the releasing laser beam (the area of warming and consequent dye release), which is approximately 600 um in diameter. Once the laser is turned off, the clearance of the dye can be followed. In the area adjacent to the CNVM, patches of fluorescence (arrows in C &D) are seen to dissipate rapidly -- which is expected for normal choriocapillaries (capillaries in the choroid). CNVM display a decidedly different pattern. At the location in which CNVM are observed by conventional fluorescein angiography (Image A) a well delineated pattern of brightly fluorescent vessels (arrowhead in Images C &D) are observed using Laser Targeted Angiography. Typically, this fluorescence pattern evolves slowly as compared to normal choriocapillaries, and some vessels remain filled with dye -- even at the end of the 2 seconds of image acquisition (Image F). This sluggish flow, within the CNVM, further distinguishes the CNVM from the background -- leaving the CNVM illuminated while the surrounding normal choriocapillaries quickly return to darkness. Not only does LTA reveal the location of CNVM with greater precision, it has the added benefit of revealing the pattern of blood flow inside the CNVM. Following the end of the laser pulse, the area of CNVM containing feeder vessels looses fluorescence first (due to the incoming blood devoid of released dye), while draining areas loose fluorescence last (Images D &F). Clinicians have contemplated treatment limited to the feeding vessels. This could dramatically reduce the treatment area and minimize the accompanying potential loss of vision.

Conventional Fluorescein Angiography Fluorescein angiography at (Image A) 14 seconds and (Image B) 2 minutes after injection reveals the presence of a lesion (between the two arrows). Note the lack of sharp delineation of the CNVM. Image A Image B

Laser Targeted Angiography (LTA) In contrast, Laser Targeted Angiography following a release of dye in the area marked by the circle reveals a CNVM with its exact location and flow pattern. Angiograms C, D, and E obtained 17, 165, and 560 msec after the end of the bolus delivery, respectively, depict a brightly flourescent abnormal pattern of CNVM vessels (arrowhead) and diffusely fluorescent patches (arrows) (normal choriocapillaries). In angiogram F, obtained at 2 seconds, the fluorescent bolus has cleared from the choriocapillaries while remaining in the CNVM. The advance of the bolus and direction of flow is seen by the increase in the fluorescence intensity in the area shown by the arrow and a reduction in fluorescence in the area shown by the arrowhead (Images E & F). The pre-release background angiogram was subtracted from Images C - F to highlight the dynamic changes. Image C Image D Image E Image F

Credits
This article is an adaptation of a paper entitled, "Selective Visualization of Choroidal Neovascular Membranes by Laser Targeted Angiography."

EPIX Vision - December 1996 Newsletter

1. PIXCI® DLS Image Capture Board Supports Dalsa Digital Area & Line-Scan Cameras
2. Johns Hopkins University Researches New Procedure to Prevent Vision Loss
3. 4PVINAM -- 4 Input Pixel Clock And Video Multiplexer for 4MEG VIDEO Model 12
4. Image-Pro Plus Drivers (32 Bit) For Win 95 & Win NT
5. Video Rate Real Time Full Resolution Video Display For PIXCI® PCI Board
6. Use EPIX DLLs With Visual Basic 4.0
7. Advances in EPIX Software Include Win 95 & Win NT Support