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FIELD OF THE INVENTION
This invention relates to medical diagnostic and monitoring apparatus and,
in particular, to apparatus for detecting and monitoring diabetes mellitus
and other abnormalities affecting the lens of an eye.
BACKGROUND OF THE INVENTION
Diabetes mellitus is one of the leading causes of morbidity and mortality
in the United States. Although the disease, once diagnosed, can be
controlled, the diabetic patient faces many complications, some of them
life-threatening. For example, the average life expectancy of the diabetic
patient is one third less than that of the general population; blindness
is twenty five times as common, renal disease is seventeen times more
common, gangrene is five times as common and heart disease is twice as
common in diabetics as compared to the non diabetic.
In addition, the incidence of this disease appears to be
increasing--between 1936 and 1978 there was a six fold increase in the
prevalence of the disease.
It is believed by many researchers in the field that many complications
suffered by diabetic patients can be minimized or avoided by early
detection of the onset of the disease and proper long-term control of the
patient's blood glucose.
Unfortunately, prior art detection and monitoring methods and apparatus has
been unable to either accurately detect the onset of the disease at an
early stage or assess the degree of control on a long-term basis. Such
prior art detection methods, other than interpretation of clinical
symptoms, rely on blood sugar measurements which reflect the presence of
the disease. Prior art monitoring methods involve either spot blood sugar
measurements or more complicated blood tests which reflect blood glucose
levels that existed in the patient's body at a time three to five weeks
prior to the time of measurement. Both prior art measurement methods
require bodily invasion and the results are difficult to interpret.
Accordingly, it is an object of this invention to provide apparatus to
detect the onset of diabetes mellitus prior to the appearance of clinical
symptoms.
It is another object of this invention to provide apparatus for the
detection of abnormalities affecting the lens of the eye.
It is still another object of this invention to provide apparatus which
facilitates assessment of the effectiveness of various methods of diabetic
treatment.
It is yet another object of this invention to provide apparatus which
conduces to the ascertainment of the degree of control required to prevent
the occurrence of diabetic complications.
It is a further object of this invention to provide an apparatus which
enables the effects of systemic disease, trauma, drugs, local inflammatory
conditions of the eye, and aging to be quantified by measurements taken
from the lens of an in vivo eye.
SUMMARY OF THE INVENTION
The foregoing objects are achieved and the foregoing problems are solved in
one illustrative embodiment of the invention in which the diffusion
coefficient of the lens of a patient's eye is measured by directing the
beam from a low-power laser at the patient's lens and measuring the
intensity of the back-scattered light. A number of measurements are taken
of the diffusion coefficient for patients known to be normal to establish
a diffusion coefficient-age relationship. The lens diffusion coefficient
of an unknown patient is compared to the pre-established relationship and
a significant decrease of lens diffusion coefficient over the normal
diffusion coefficient-age relationship indicates a likelihood of diabetes.
The amount of decrease of lens diffusion coefficient over the normal
pre-established diffusion coefficient can be used to indicate the severity
of the disease or monitor the progress and treatment of the disease.
More particularly, the optical system used in illustrative embodiment
consists of a low-power laser and associated optics attached to a
slit-lamp biomicroscope equipped with precision mechanical adjustments to
focus the light beam on a site in the patient's lens. A photomultiplier is
used to detect the intensity of light back-scattered from the site and a
correlator is used to process the output of the photomultiplier to provide
a set of numbers that can be used to calculate the diffusion coefficient.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the slit-lamp biomicroscope and added
equipment used to focus the light beam on a site in the patient's lens.
FIG. 2 shows an overall schematic view of the optical arrangement to
irradiate a site in the patient's lens and the apparatus used to process
the resulting signal.
FIG. 3 shows a graph of lens diffusion coefficient versus patient age
developed using the apparatus of the present invention which graph is
useful in detecting and monitoring diabetes.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 shows the mechanical and optical arrangement for an illustrative
embodiment of the inventive diabetic detection device. In particular, a
suitable arrangement consists of a modification of a
commercially-available optical instrument known as a slit-lamp
biomicroscope. This device is well-known to those skilled in the art and
typically is used in ophthalmological studies of the cornea, lens and
retina of the human eye. A device suitable for use with the illustrative
embodiment is manufactured by several companies and its operation and use
are well known to those skilled in the art.
Basically, a slit-lamp biomicroscope consists of a light source, a
microscope and a mechanical supporting arrangement which allows precise
positioning of the light source and microscope relative to the patient to
allow focusing of the light on selected sites in the patient's eye.
Specifically, light produced by source 100 is reflected from mirror 105
and directed as beam 110 to the patient's eye shown schematically as eye
120. The apparatus also includes frame 115 and support 125 which position
and hold the patient's head in a fixed position. Light which is reflected
or scattered by the patient's cornea, lens or retina, shown schematically
as beam 130, is received by a binocular microscope arrangement 150 which
has two eyepieces, 155 and 160. The lamp arrangement and microscope are
supported by arms 140 and 145 from a common post, all in a well-known
manner.
In accordance with the invention, the standard slit-lamp biomicroscope is
modified by the addition of an XYZ positioning apparatus to the microscope
arrangement 150. In particular, the XYZ position apparatus consists of
commercial XYZ positioner 190 which can obtain precise three-dimensional
movement which is controlled by three orthogonal micrometers, 191-193.
Positioner 190 is mounted on plate 194 which is in turn fastened to
microscope arrangement 150 by means of a threaded hole 153 which is
normally found on the arrangement and used for other purposes.
Attached to the movable surface of XYZ positioner 190 are arms 180 and 186
which support a lens arrangement 165. As will be hereinafter further
explained, lens arrangement 165 is connected via fiber optic cable 170 to
a laser and used to illuminate the patient's lens via beam 135. The
back-scattered light shown schematically as beam 130 is detected by a
sensor located in the focal plane of eyepiece 155 and conveyed via cable
195 to a photomultiplier (not shown).
FIG. 2 of the drawing shows a schematic diagram of the entire optical
arrangement of the present invention. The apparatus consists of an
irradiating portion or light source for illuminating the patient's lens
and a detecting or receiving portion for receiving the back-scattered
radiation.
The light source part of the apparatus consists of laser 200, two filters
mounted in housing 215, microscope objective lens 231, fiber optic
termination 235, fiber optic cable 240 and focusing lens arrangement 245.
Laser 200 is a 5 milliwatt helium-neon laser of conventional design which
is commercially available from several companies. A laser suitable for use
with the illustrative embodiment is a model U-1305P manufactured by the
Newport Corporation, 18235 Mount Baldy Circle, Fountain Valley, Calif. The
output of laser 200 passes through two neutral density filters, mounted in
housing 215. One filter is permanently mounted in the laser beam path and
reduced the power output of laser 200 to 1.5 milliwatts. The other filter
is solenoid-controlled so that it can automatically be moved out of the
laser beam path during the measurement operation. When both filters are in
place, they reduce the laser output power to 0.50 milliwatts. The movable
filter is used during premeasurement focusing, as will hereinafter be
described, in order to reduce the patient's exposure to unnecessary laser
irradiation. The movable filter is controlled by solenoid 203 which is
under control of a footswitch operated by the person making the
measurement. When solenoid 203 is operated, arm 220 retracts, in turn,
sliding the movable filter in housing 215 by means of bell-crank 225.
After passing through one or both filters the attenuated laser output light
enters lens 231. Lens 231 is a 40.times. microscope objective lens which
is mounted so that it focuses the laser light on he end of the optical
fiber which transmits the light to the irradiating apparatus. Light
passing through lens 231 falls onto an optical fiber 240 mounted in
termination 235. The end of fiber 240 which enters termination 235 is
attached to an XYZ positioner. The positioner is used to align the end of
the optical fiber with the focusing lens to obtain maximum light
transmission.
The other end of optical fiber 240 is attached to focusing lens arrangement
245. Lens arrangement 245 consists of a fiber optic holder which is
slidably mounted in a lens holder tube. Lens 248 is a 18 mm focal-length
converging lens which is mounted at the other end of the lens holder tube.
The movable arrangement between the fiber optic holder and the lens allows
small adjustments to be made between the end of the optical fiber and the
lens to permit fine focusing of the laser output beam at a given position
within the patient's lens.
Lens arrangement 245 is connected to the XYZ positioner attached to the
slit-lamp biomicroscope as previously described and is used to focus the
laser beam, 246, such that a sharp focus is achieved at the patient's lens
250. After passing through the focal point in the lens the beam becomes
sharply defocused in order to maintain a low irradiation level at the
retina and prevent any possibility of injury or damage.
The detection optical system uses portions of the optical system of the
slit-lamp biomicroscope. In particular, light back-scattered from the
patient's lens (represented schematically as beam 247) is focused by one
objective of the binocular portion of microscope 255 onto a
commercially-available optical fiber light guide, 260, located at the
center of the focal point of the eyepiece. In the illustrative embodiment,
the end termination of optical fiber light guide 260 replaces the normal
left ocular of slit-lamp biomicroscope 255. The arrangement is such that
the end of fiber cable 260 can be seen when looking through the left
ocular to allow focusing of the back-scattered radiation on the end of the
fiber cable. Scattered light received at microscope 255 is fed by fiber
optic guide 260 to photomultiplier 210 which is a well-known,
commercially-available device. A photomultiplier suitable for use with the
illustrative embodiment is a model number 9863B/350 manufactured by EMI
Gencom, Inc., 80 Express Street, Plainview, N.Y. The output of
photomultiplier 210 is provided to amplifier-discriminator 265 which also
is a well-known device that amplifies the output pulse signals produced by
the photomultiplier and selectively sends to correlator 270 only those
signals which have an amplitude above a preset threshold. A suitable
amplifier-discriminator for use with the illustrative embodiment is a
model number AD6 manufactured by Pacific Photometric Instruments, Inc.,
5675 Landregan Street, Emeryville, Calif.
The output of amplifier-discriminator 265 is, in turn, provided to a
commercial photon correlation spectrometer 270 (a suitable spectrometer is
a model DC64 manufactured by Langly-Ford Instruments, 85 North Whitney
Street, Amherst, Mass.). Correlator 270 counts the number of pulses
received from amplifier-discriminator 265 for a predetermined time
interval and performs a well-known mathematical operation to obtain the
correlation function. In the illustrative embodiment a suitable time
interval is ten microseconds. The correlator utilizes these received
counts to solve the following equation for the autocorrelation function
C.sub.m (t):
##EQU1##
where t=the length of the predetermined time interval
i=an index number whose range is one to the total number of intervals.
p.sub.i =the number of pulses occurring during the ith time interval.
n=the total number of intervals.
m=an integer whose range is one to sixty-four.
In accordance with the above equation, correlator 270 produces solutions or
points (one for each value of m) in a time sequence, each measurement
separated by the value of t. These measurements may be plotted against
time to produce a curve which may then be displayed for examination on
oscilloscope 275. The values of the solutions may also be provided to
computer 280 for further processing to determine the diffusion
coefficient. A computer suitable for use with the illustrative embodiment
is a personal computer manufactured by the International Business Machines
Corporation, Armonk, New York.
In particular, the diffusion coefficient (D) is also related to the
correlation function C.sub.m (t) determined by the correlator by the
following equation:
C.sub.m (t)=A+Be.sup.-2DK.spsp.2.sup.m(t)
where
A, B=constants dependent on the physical details of the measurement
K=the scattering constant for the eye which is
4.pi./.lambda. (sin .theta./2) where .lambda. is the wavelength and .theta.
is the scattering angle
t=the length of the predetermined time interval
m=an integer whose range is one to sixty-four.
Therefore, the values of the diffusion coefficient D and the constants A
and B in the above equation can be determined, with the aid of computer
280, from the autocorrelation curve produced by the correlator 270 by
using standard curve fitting and analysis techniques. The calculated
diffusion coefficient can be stored in the computer along with other
patient data including, in accordance with the invention, the patient's
age.
The apparatus shown in FIGS. 1 and 2 is used to perform a measurement of
the lens diffusion coefficient as follows: with a patient sitting at the
slit-lamp biomicroscope, the operator sets up the device in the same way
that the device would be set up during a normal ophthalmic evaluation. In
order to take measurements from various sites within the patient's lens,
it is necessary that the pupil be dilated using routinely-available
dilating drops as normally used during the course of complete ophthalmic
evaluation. Both the light produced by lamp 100 and the laser light with
both filters in place are used to align the laser output as seen through
the ocular 155 and 160 with the end of optical fiber light guide 195 in
left ocular 155. Due to the standard adjustments on the biomicroscope and
XYZ positioner 190, this alignment may be achieved at any desired site
within the patient's lens.
Lamp 100 is then turned off and the operator depresses a foot switch which
operates solenoid 203, sliding the movable filter in housing 215 out of
the way to allow the actual measurement to be made using 1.5 milliwatts
laser light power. A second foot switch adjacent to the first can be used
to turn laser 200 off should any emergency arise.
The back-scattered light output is measured by the photomultiplier through
the optical system previously described and the photomultiplier output is
processed as previously described by the photon correlation spectrometer.
While measurements are in progress, the output of the spectrometer may be
monitored by the oscilloscope connected to it. A measurement is made, for
example, for 5 seconds at which point the first foot switch is released,
reinserting the movable filter into the optical path, and concluding the
measurement.
No contact lens, nor anesthetic drops are necessary to make a measurement.
Although commonly used in eye examinations, anesthetic drops have various
deleterious side effects. Such side effects include stinging, burning and
conjunctival redness as well as severe allergic reactions with resulting
central nervous system stimulation or corneal damage. In addition,
application of a contact lens following the use of a topical anesthetic
requires much patient cooperation as well as experience on the part of the
examiner. Further complications arising from the use of a contact lens
include corneal abrasions and infection as well as recurrent and chronic
corneal erosions. In contrast, the use of the apparatus disclosed herein
is truly "non-invasive".
When employing the foregoing measurement technique to detect or monitor
diabetes, a calculation of the diffusion coefficient s made on a series of
patients whose health is known and are believed to be nondiabetic. The
resulting measurements are compared to the patient's age resulting in a
curve or graph similar to that shown in FIG. 3 (hypothetical measurements
are shown for illustrative purposes). FIG. 3 shows the value of the
diffusion coefficient increasing in an upwards direction along the
vertical axis and patient age increasing rightward in the horizontal
direction.
It has been discovered that patients who do not have diabetes (represented
for example by points 300-305) all lie above a line (marked "normal" on
the graph) while those patients suffering from diabetes lie below the line
(represented by points 306-310). In addition, the severity of the disease
is directly related to the distance below the line at which the
measurement lies which increasing distance indicating increasing severity.
For example, the patient represented by point 308 usually exhibits more
severe symptoms than the patient represented by point 310.
After a curve such as that shown in FIG. 3 is obtained, patients can be
screened for diabetes by making a measurement using the apparatus and
method described above. The result of the measurement is then compared to
FIG. 3. If the measurement is significantly below the "normal" line as
shown in FIG. 3 the patient is likely to have diabetes or a disease which
affects the lens similarly. Known diabetic patients can be monitored by
making repeated measurements over a fixed period of time. The series of
measurements are compared to the graph. An increasing distance from the
"normal" line indicates an acceleration in the disease. A fixed distance
indicates the disease appears to be under reasonable control.
Although only one illustrative embodiment is shown of the invention, other
changes and modifications within the spirit and scope of the invention
will be apparent to those skilled in the art. Such modifications and
changes are intended to be covered by the claims herein.
* * * * *
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