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New Quantitative Methods of
Assessing Macular Degeneration
News from the 1999 meeting of ARVO (Association for Research in Vision and Ophthalmology) by Philip Filner, Ph.D. An obstacle to progress on
understanding and treating macular degeneration has been the lack of good objective methods for distinguishing stages of macular degeneration and whether or not a proposed treatment
has an effect on macular degeneration. The usual method: determination of visual acuity The most commonly used method is measurement of visual acuity. This is done with a Snellen eye chart, which has several rows of
progressively smaller characters. The test supervisor determines the line with the smallest characters which the patient can read correctly. Visual acuity is expressed as the ratio of
the distance from the chart at which a person reading the chart is able to read characters in that line correctly, compared to the distance at which a normally sighted person could
correctly read the same line. For example, a determination of a visual acuity of 20/50 means that what the person reading the chart can see at 20 feet could be seen by a normally
sighted person at 50 feet. The major advantages of determining visual acuity are that it is simple, quick and cheap. However, determination of visual acuity has several
shortcomings. First, it is subjective. The patient has to make a conscious effort, and the test supervisor has to make a judgement of when the patient has done his/her best at reading
progressively smaller characters. Second, results can easily vary by +/- a line when the same person is tested on different occasions, so only relatively large changes in visual
acuity can be detected. Third, visual acuity is not a specific test for the amount of macular degeneration which has occurred, but rather is a measure of overall functionality of the
eye in central vision. New methods
Recently two new methods have been developed to objectively, quantitatively measure two important processes in the eye which are involved in macular degeneration. One of these
processes is the flow of blood in the vessels behind the central part of the retina. The other process is the generation of electrical output signals from the central part of the
retina in response to light. Background: Fundus photographs One technique ophthalmologists use to diagnose eye problems is
to shine a light into the eye which illuminates the entire retina, and take a photograph through the lens of the eye. These are called fundus photographs. Some components of the
retina absorb light so appear darkened, while others fluoresce, so appear bright, thereby creating informative details in fundus photographs. Background: Scanning Laser Ophthalmoscope A more advanced
technique for producing an informative representation of the retina involves using a very small laser beam to illuminate individual positions on the retina one at a time, and
detecting how much light is reflected back from only the illuminated spot. The device for doing this is called a Scanning Laser Ophthalmoscope. It sends a precision-positioned laser
beam into the eye to momentarily illuminate a spot on the retina. Some of that laser light is absorbed and some is reflected back out of the eye, to the light-detecting sensor of the
instrument. The signal produced by the detector is recorded, and a computer constructs a "map" of the retina, from the stored information from the many individual points on
the retina. New Method: Laser Doppler Flowmetry If the illuminated point has blood flowing in a vessel behind it, there will be red blood cells moving toward or away from the incoming spot
of laser light. If the cells are moving away, that slightly lengthens the wavelength of the reflected light, while if the cells are moving toward the light source, their movement will
slightly shorten the wavelength of the reflected light. This effect of movement on wavelength is known as the Doppler effect. The amount of lengthening or shortening of the wavelength
increases with the speed of movement of the cells, i.e. blood flow rate.Consequently, the blood flow rate can be calculated from measurements of the Doppler shift in wavelength. In
recent years, accessories for the Scanning Laser Opthalmoscope have been developed which can measure the Doppler shift. These accessories have made it possible for the first time to
determine flow rate in blood vessels behind individual points of the retina. This method is called Laser Doppler Flowmetry. New Findings: Age and foveal blood flow Dr. Juan Grunwald, at
the Sheie Eye institute, U. of Pennsylvania, Philadelphia, has been using Laser Doppler Flowmetry to study the blood volume, blood cell velocity and blood flow behind the foveola,
which is the center of the fovea. The fovea is a very small zone at the center of the macula, in which the light-sensing cones are concentrated. These cones in the fovea play a major
role in our perception of color and detail, a disproportionately large role, when the size of the fovea is compared to the size of the macula or retina. Dr. Grunwald found that in
people with normal vision, blood flow behind the foveola on the average was about 31% lower in an elderly group compared to a younger group (1). This decrease was the result of
decreased blood volume, not decreased blood cell velocity. However, there was substantial variation from individual to individual within each age group, so the 31% difference only
became evident when averages for small groups (11 and 18 individuals) in two age ranges (15 - 45 and 45 - 76) were compared. This finding from dynamic measurements of actual blood
flow was consistent with an earlier finding by another group that the number and diameter of capillaries behind the macula decreased with age by a similar percentage (2).
New Findings: Age related macular degeneration and foveal blood flow Dr. Grunwald also studied people with large drusen, in an early stage of Age Related Macular Degeneration, with only slight deterioration of
central vision. When people with large drusen and dry Age Related Macular Degeneration with only slightly reduced visual acuity were compared to age-matched people without large
drusen and normal visual acuity, the blood flow behind the foveola was found to be decreased an average of 37 % in people with early dry AMD, as a result of decreased blood volume
(3). This could prove to be a very important finding, because it creates the opportunity to determine whether or not proposed treatments, changes in life style, changes in
environmental factors, diet supplements, genetic differences, etc, affect the reduction in blood flow, and whether decreasing the reduction in blood flow stops or slows the progress
of dry macular degeneration. Background: Electroretinography When light strikes the retina, a series of fast and brief changes in electrical potential can be detected by recording electrical potential
at an electrode placed on or near the eye. A plot of the the changing electrical potential with time, on a time scale of milliseconds, is called an electroretinogtram. Typically,
there are three peaks in the electroretinogram. Also, the electroretinogram produced by light of one color may be different from that produced by light of a different color. The
height, duration and/or shape of a peak can change when there is a retinal disorder. Ophthalmologists have learned to interpret such changes. For example, a genetic disorder which
affects one of the cone types, e.g. those which are blue-sensitive, will result in a characteristic electroretinogram with a peak absent or greatly reduced in response to blue light.
New Method: Multi-focal Electroretinography The display of a computer monitor is composed of thousands of small spots of light, each spot being a color and intensity which is specifid
by the computer program which generates the display. The screen is composed of thousands of spots of chemical phosphors, each of which emits one of the spots of light of a specific
color when bombarded by electrons. These spots of chemical phosphors are bombarded in a precise order at precise time intervals by moving the electron beam across one row of spots at
a time, then moving down one row, and repeating the process, thereby "painting" the display line by line, many times per second. The phosphorescent light coming from a spot
persists for only a fraction of a second, so a change of color or intensity at that point in the image can be made the next time the spot is bombarded. Several years ago, Dr. Erich
E. Sutter, of the Smith-Kettlewell Eye Research Institute, in San Francisco, CA realized that the time interval between the bombarding of spots on a monitor was sufficient for
generating and recording an electroretinogram in response to light from a spot. He and collaborators developed a computer program and instrument which could generate and record an
electroretinogram in response to light from each spot, and then construct a map of the retina, showing the variations in some particular aspect of the electroretinograms with position
in the retina. This technique is called Multi-Focal Electroretinography. Others have developed a way to perform Multi-Focal Electroretinography using a scanning laser
ophthalmoscope as the source of the precision-positioned movable spot of exciting light. New Findings: MD and
multi-focal electroretinography The Multi-Focal Electroretinogram obtained from normal eyes has a central peak at the fovea. |
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Recently, Multi-Focal Electroretinography has been performed on people with retinal
disorders, including dry age related macular degeneration or the most common form of inherited macular degeneration - Stargardt's disease, and compared to the results from normal
eyes. On average, the central peak is reduced substanially when recorded from eyes with macular degeneration
(4 -7). This method should be useful for detecting and measuring a
reduction in signal output early in macular degeneration, and determining whether or not proposed treatments prevent the reduction in signal, or restore a signal reduced by the
disease. References
1. Juan E. Grunwald, MD, Seenu M. Hariprasad and Joan DuPont, Effect of Aging on Foveolar Choroidal
Circulation, Archives of Ophthalmology (1998), 116:150 - 154 . 2. R. S. Ramrattan, T. L. Van der Schaft, C.M. Mooy, W.C. de Bruijn, P.G.H. Mulder, P.T.V.M. de Jong, Morphometric
analysis of Bruch's membrane, the choriocapillaris and the choroid in aging, Invest. Ophthalmol. Vis. Sci. (1994) 35: 2857 - 2864. 3. Juan E. Grunwald, Seenu M. Hariprasad, Joan
DuPont, Maureen G. Maguire, Stuart L. Fine, Alexander J. Brucker, Albert M. Maguire, Allen C. Ho, Foveolar Choroid Blood Flow in Age-Rlated Macular Degeneration, Investigative
Ophthalmology & Visual Science (1998) 39: 385 - 390. 4. D, Besch, H. Langrova, K. Steiner, B. H. Weber, E. Zrenner, E. Apfelstedt-Sylla, Distinguishing patterns of multifocal
ERG function loss in stargardt's disease/fundus flavimaculatus, Invest. Ophthalmol. Vis. Sci. (1999) 40: S20, Abstract 105. 5. B. Jurklies, M. Weismann, N. Bornfield, Multifocal
electroretinography in age-related macular degeneration - changes in amplitude of the 1st order kernel, Invest. Ophthalmol. Vis. Sci. (1999) 40:S315 , Abstract 1668. 6. L. Li, J.
Wu, T.T. Lam, M. Tso, Multifocal ERG in the early stage of age-related macular degeneration, Invest. Ophthalmol. Vis. Sci. (1999) 40:S315 , Abstract 1669. 7. G. L. Martinsen, W. A.
Verdon, G. Haegerstrom-Portnoy, The multi-focal ERG in age-related maculopathy, Invest. Ophthalmol. Vis. Sci. (1999) 40:S714 , Abstract 3774 |
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