Download A Rapid and Affordable Eye Diagnostic Camera Shivam Shah1

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Blast-related ocular trauma wikipedia , lookup

Contact lens wikipedia , lookup

Vision therapy wikipedia , lookup

Visual impairment wikipedia , lookup

Visual impairment due to intracranial pressure wikipedia , lookup

Eyeglass prescription wikipedia , lookup

Dry eye syndrome wikipedia , lookup

Keratoconus wikipedia , lookup

Human eye wikipedia , lookup

Transcript
A Rapid and Affordable Eye Diagnostic Camera
Shivam Shah1, Nitish Thakor1
1
Department of Biomedical Engineering, Johns Hopkins University
3400 North Charles Street
Baltimore, MD 21210
Abstract— Corneal disease is the second leading cause of
blindness in the developing world. Over 314 million people
are visually impaired and nearly 90% live in the
developing world. Better diagnosis of corneal disease
would decrease the number of blindness cases. Fluorescein
sodium is often used to diagnose dry eye, corneal
abrasions, corneal ulcers, and other afflictions. A
diagnostic eye camera that could take naked and
fluorescent images of the cornea would improve
diagnostics in the developing world. A web camera with a
USB 1.0 interface was adapted for fluorescent imaging.
Blue LEDs covered in an additional blue-light filter and a
yellow band-pass filter were used to provide optimal
imaging. The resultant device has the ability to image any
part of the human body, and fluorescently image the eye.
The device can be bulk manufactured for approximately
$10.88 and disseminated in the developing world with
fluorescein sodium dye strips. Initial results show that the
images provided by this device can be used accurately to
diagnose many corneal diseases and some other ocular
diseases as well.
I. INTRODUCTION
The cornea is the eye’s outermost layer and has three
primary functions. With the eye lids, the cornea helps
protect the rest of the eye from germs, dust, and other
harmful objects. The cornea also controls and focuses
the light coming into the eye, and contributes to 65-75%
of the eye’s total focusing power. Additionally, the
cornea filters out some of the damaging ultraviolet light
present in sunlight [1].
The World Health Organization defines blindness as
visual acuity of 3/60 or less [2]. About 45 million
people in the world are blind and 314 million are
visually impaired. Over 87% of the world’s visually
impaired live in developing countries and 85% of
visually impaired cases are preventable [3]. Corneal
disease is second only to cataracts as a major cause of
blindness [3]. Medical conditions involving the cornea
include numerous disorders, infections, and diseases.
Many of these can be diagnosed with the aid of the
camera described here.
layers of corneal tissue include the epithelium,
Bowman’s layer, stroma, Descemet’s membrane, and
the endothelium.
The epithelium is the outermost layer and functions to
block the passage of foreign material into the eye and
provides a smooth surface that absorbs oxygen and cell
nutrients from tears. Thousands of tiny nerve endings
are present in this layer making the cornea extremely
sensitive to pain. Epithelial cells anchor to the
basement membrane part of the epithelium [4].
Below the basement membrane is Bowman’s layer, a
transparent piece of tissue. Injuries involving this
collagen rich layer can lead to significant scar tissue
formation and potential vision loss. The stroma lies
behind Bowman’s layer and accounts for 90% of the
cornea’s thickness. Water and collagen account for 94%
of the stroma layer. Descement’s membrane is a strong
layer of collagen behind the stroma that is regenerated
easily after injury [4].
The endothelium is the innermost layer of the cornea
and functions to pump excess fluid that drains from the
inside of the eye, out of the stroma. Without this
pumping mechanism, the stroma would become hazy
and opaque. If injured, endothelial cells are lost forever.
Corneal edema and blindness can occur if too many
endothelial cells die making a corneal transplant the
only available treatment option [4].
II. STRUCTURE OF THE CORNEA
Corneal tissue is arranged in five layers and contains
no blood vessels, a rare characteristic in tissue. The
absence of blood vessels allows the cornea to remain
clear and able to refract light properly. The aqueous
humor held in the anterior chamber directly posterior to
the cornea provides nourishment (Fig. 1). The five
Figure 1: Structure of the Human Eye [4]
III. CORNEAL AFFLICTIONS
Corneal infections can arise when a foreign object
penetrates the tissue from, for example, a poke to the
eye. Bacteria or fungi from a dirty contact lens can also
pass into the cornea. These infections called keratitis
can reduce visual clarity, produce corneal discharge,
erode the corneal, and lead to the formation of scars, a
cause of vision impairment [5].
Another chronic affliction is dry eye, in which the eye
does not produce enough quality tears to keep the
surface lubricated. The uncomfortable feeling and
increased risk of infection make dry eye extremely
unfavorable. Treatment of dry eye ranges from artificial
tears to a surgical procedure preventing the drainage of
tears [5].
Corneal dystrophy occurs when one or more parts of
the cornea lose transparency. Over twenty such
dystrophies have been identified, with each affecting the
eye in a related but slightly different manner. Some lead
to vision impairment, while others lead to severe pain
episodes. Most of the dystrophies identified are
inherited, occur gradually, and originate in one of the
five corneal layers before spreading to others [5].
Keratoconus is the most common corneal dystrophy
in the United States affecting one in every 2000
Americans. This disorder involves the progressive
thinning of the cornea starting with the middle, resulting
in a bulge. The abnormal curvature changes the
refractive properties of the cornea requiring vision
correction or special treatment with contact lenses. In
most cases the cornea heals without any lingering
effects, but in 10-20% of the cases corneal scars form,
preventing the wearing of contact lenses [5].
Other afflictions include lattice dystrophy, map-dotfingerprint dystrophy, pterygium, ocular herpes, and
even shingles. Corneal afflictions can be diagnosed in
different ways including the use of a camera to image
the external eye and simple field tests for visual
impairment [5].
IV. CASE STUDY I: FIELD TESTS
Nearly 90% of the visually impaired live in
developing countries that lack the necessary equipment
to properly diagnose levels of impairment and type of
disease [6]. The issue is further complicated by the fact
that on average there is one ophthalmologist per million
of people living in Africa [6]. A screening test should
require little training to administer or interpret, utilize
easily transportable materials, and not be culturespecific or dependent on literacy.
Screening helps determine those who need further
treatment, but also helps correct for those with a visual
impairment who were falsely classified as blind. The
screening kit developed in a study by Keefe et al.
consists of a visual acuity test card, a pinhole mask to
determine refractive errors, and two manuals describing
how to use the kit and interpret the results [7].
The field tests are completed to screen for normal or
low vision and not to determine the distance visual
acuity accurately. Figure 2 shows an example of a near
vision test card. The letter E was used in four different
orientations as it was believed to be a relatively easy
symbol to describe. Only three different sizes of the
letter were used instead of the standard six sizes for
simplicity.
Distance vision was tested by asking the observer to
identify the smallest sized symbols at a distance of six
meters. If 3 of the 4 orientations were described
correctly, then the patient had normal vision. If not, the
person was asked to identify the largest symbols and if 3
of the 4 orientations were classified correctly, the
patient had low vision. Regardless, of the outcome of
this initial test the patient was asked to identify the
symbols through a pinhole. If vision was improved with
the pinhole, a significant refractive error may be
present. If vision was classified as low vision and did
not improve using the pinhole, then a serious ocular
disease could be present. Appropriate referrals should
be made with screening results. The test card can be
rotated to prevent memorized responses. Further
information about the test protocol can be found on
page 526 of the original published article [8].
Figure 2: Near vision test card [7]
Qualitative feedback from users of this test has been
positive. The test card and testing protocol were found
easy to use and understand. Results from the screening
test were also compared quantitatively with the Snellen
test. The Snellen test is the six optotype test commonly
used by almost all optometrists outside the developing
world [7].
A study involving 123 subjects was performed at the
Royal Victorian Eye and Ear Hospital and 85% were
determined to have the same result for distance visual
acuity in both tests. 93% were determined to be in the
same visual acuity category – normal, low vision, blind.
The specificity was found to be 96% (115/119) and
details can be found in Figure 3. The simple test kit
described above contains all of the tools to determine
whether a person has normal vision, should be referred
for refractive error correction, or referred for treatment
of an ocular disease [9]. The overall cost of the device is
primarily determined by printing test cards and
transportation costs. No price was explicitly given, but
the screening test kit is expected to be distributed for
less than $1 per kit.
Figure 4: Virtual Perimetry (VIP) Set-Up [11]
Figure 3: Test results from comparison study involving
described design and Snellen test on 123 patients [7].
The field test described above helps determine who
needs refractive error correction, but does not
sufficiently identify ocular disease. The patient is
referred to an eye specialist if low vision does not
improve with the aid of a pinhole. An ocular disease is
assumed to be the cause, but no specific information
about ocular disease can be provided by the test.
V. CASE STUDY II: VIP - VIRTUAL PERIMETRY
Researchers at Tel Aviv University in Israel have
recently developed goggles called Virtual Perimetry that
simplify eye exams and provide more accurate results.
The goggles prevent the need for a large bulky machine.
Traditionally, patients have been asked to sit with their
chin resting on a ledge and focus their eyes on a center
target. Visual stimuli are provided around the periphery,
and the patient is asked to press a button when the
stimulus is seen.
This test helps determine the health of the retina and
optic nerve. Results can be used to uncover glaucoma
and conditions like optic neuritis. The elderly who
benefit most from routine eye examinations sometimes
have difficulty sitting in the correct position and often
compensate by pressing the button even when the
stimulus is not actually observed.
The goggles can be worn by the patient anywhere
including in the hospital as long as there is a computer
hook-up (Fig. 4). These cost-effective goggles instantly
study a patient’s reflex to an applied visual stimulus.
Pricing for this device was undetermined, but the target
market is hospitals and optometrist’s starting a private
practice [10].
The device might be priced above $100, which would
make it unaffordable for the developing world. The user
of the device must be trained. The goggles test for
refractive error and losses in peripheral vision, but do
not specifically test for an ocular disease.
VI. CASE STUDY III: PERFECT SIGHT
A student group at MIT has identified the need to find
a cheaper and more efficient way to diagnose patients
with refractive error. No diagnosis of visual impairment
or improper diagnosis of visual impairment was found
to lead to a productivity loss of 89-133 billion USD,
which exceeds the annual Gross Domestic Product
(GDP) of 46 out of 52 African countries [12].
The device consists of a retrofitted cell phone, audio
feedback, controls, and a cheap optical piece (Fig 5).
The user is asked to look at the optical piece and
complete some tasks, and the cell phone application
calculates the refractive power needed for myopia,
hyperopia, astigmatism, and presbyopia.
Figure 5: Perfect Sight – The optical piece is attached to
the cell phone. Tasks on the cell phone are completed
with audio feedback and controls. The prescription is
determined by the cell phone application [12].
The device costs only $1 and is significantly cheaper
than traditional lenses (priced over $100) used by
optometrists to determine refractive error. The patient’s
information can be entered into the cell phone providing
electronic storage. The device is also expected to be
safer than some optometric tests completed to determine
refractive error as no lasers or cycloplegic drugs are
used. The easy transportation and manufacturing of the
overall device make it highly scalable.
The current prototype was evaluated and reached a
resolution of 0.22 diopters with the cell phone camera
and 0.16 diopters with a higher resolution camera.
Doctors prescribe refractive correction in 0.25 diopter
increments. With 16 subjects, the average absolute error
was determined to be 0.5 diopters with a standard
deviation of 0.2 diopters for both cylindrical
(astigmatism) and spherical (myopia, hyperopia). A
comparison between estimated and actual values is
shown in Fig. 6. The device is still in the prototype
stage and needs to reduce the average optical error
below 0.25 diopters before widespread dissemination is
possible [13].
Unlike the devices described in the case studies, the
eye diagnostic camera provides information that can be
directly used to diagnose ocular disease. The camera
rapidly obtains images of the naked eye and an eye
stained with fluorescein sodium. The cost of the camera
is minimized to make it affordable for health care
personnel in the developing world.
VIII. MATERIALS
A complementary metal oxide semi-conductor
(CMOS)
camera
was
purchased
from
www.epathchina.com. The ¼” inch camera uses a USB
1.0 interface to connect to any desktop or portable
computer. The camera is rated at 15 frames per second
with a resolution of 800x600 pixels. The computer must
have a processing speed greater than 133MHz, a 32 MB
or larger video RAM, and an available USB port.
Two super bright blue LEDs were purchased from
www.sparkfun.com. Each LED is rated at 4,000 mcd.
The forward voltage is 3.4 volts with a maximum
current of 20 mA. Additional circuit elements including
a 9V battery, wires, switch, and resistors were obtained
from the Johns Hopkins University’s BME
Instrumentation supply.
A 545/30 bandpass filter was borrowed from Dr.
Thakor’s laboratory. The bandpass filter passes light
between the wavelength of 530-560 nm. A Dichrofilm
sampler was obtained from www.rosco.com. A primary
blue lightweight plastic color filter was used to coat the
LEDs.
IX. DESIGN
Figure 6: Evaluation of Perfect Sight resolution [13].
VII. CLINICAL NEED
As the previous case studies have identified, there is a
large clinical need for devices that help with eye
diagnosis. Nearly 314 million people are visually
impaired, but 87% of visual impaired cases are
preventable [14]. Corneal disease is the second only to
cataracts in causing blindness. Due to the lack of
optometrists in the developing world, eye diagnosis
needs to be simplified. Eye specialists can use electronic
images of the outer eye to diagnose most corneal
diseases.
Fluorescein sodium is used in some ophthalmic tests
to determine damage to the corneal epithelium. This
protein fluorescent dye binds directly to the basal
membrane of the corneal epithelium. The basal
membrane can only be accessed by the protein dye if
there is damage to the outer layer of cells in the
epithelium. The test is often used to find dry eye
patches, abrasions, ulcers, etc [15].
The goal of this project was to adapt a web camera
with a USB interface for eye diagnostic testing of the
cornea. A simple external image of the eye without any
adaptation also has significant use in the developing
world. Thus, the option to use this device as a simple
imaging camera was maintained. The second use of this
device is fluorescent imaging of the cornea with the use
of fluorescein sodium.
Fluorescein sodium dye is usually applied to the
patient’s eye with the aid of a sterile strip. In 1981,
Grossman found that the dye is best excited with blue
light with a wavelength around 450nm as opposed to
ultraviolet radiation as previously believed [16]. After
excitation, the dye fluoresces in the yellow/green region
of the visible light spectrum at a wavelength around
540nm [16]. Adapting the web camera to eye
diagnostics requires blue light and a yellow filter
(Fig.7).
Camera
spectra provided in Figure 9. The primary assumption is
that the blue light LEDs purchased do not produce any
light in the 700-740nm range, a range of light which the
used filter also passes through.
Figure 7: Schematic of how fluorescein photography
works. A light source covered with a blue filter excites
the fluorophore. Both blue light and yellow light are
reflected towards the camera. A yellow barrier filter
passes only the fluorescent light to the camera [17].
For the blue excitation light, two LEDs were placed
in a circuit as shown in Figure 8. The forward voltage of
the LEDs was 3.4 volts (VL) and the voltage source (Vs)
was 9 volts. The guiding formula was:
RT  (Vs  VL ) / IL
The circuit contained a 360 ohm resistor so the current
through the LEDs was about 15.5 mA, which was below
the 20mA maximum. A toggle switch was placed
between the nine volt battery and resistor.
Figure 8: Schematic of the circuit used in this device.
Once the switch is closed, the voltage drop across the
resistor creates a current of 15.5mA that turns the blue
LEDs on.
Although blue light LEDs were used with a peak
transmission of light at a wavelength of 468 nm, a
dichroic primary blue filter was used to filter out any
additional light with a wavelength above 500nm.
Fluorescent imaging is optimal when the excitation light
source has no overlap with the emitted fluorescence.
The wavelength of any light from the light source must
be below the wavelength of the emitted light [17]. The
Rosco color filter that was used has a transmission
Figure 9: Transmission spectra for the primary blue
filter used in this device [18].
The yellow light filter transmission spectra could not
be obtained, but this filter passes light between 530-560
nm. Optimal fluorescence is obtained with the use of
these filters as the excitation light is around 450nm and
the yellow filter passes light with wavelength of 540nm,
the expected wavelength of the emitted light.
The purchased web camera needed to be removed
from a plastic clip and placed into a rapid prototyped
adapter. The adapting device included a grip and a head
with a removable back piece. The pieces were designed
using a Pro/ENGINEER and SolidWorks, and printed
using a rapid prototyping machine. The adapter and
dimensions can be seen in Figure 10.
The grip was cylindrical with a height of 4.5 in. and
internal radius of 0.6 in. The wall thickness of the grip
and the head were 0.15 in. The primary box in the head
of the device had overall dimensions of 2.55 x 2.33 x
1.90 in. The head also included a protruding rectangular
box with dimensions of 1.475 x 1.15 x 0.60 in. Two
holes for the filter and camera head with radii of 0.488
and 0.438 in., respectively, were placed in both
aforementioned boxes in the head of the device. More
dimensions can be seen in the figure provided.
Figure 10: 3D views and dimensions of camera adapter.
X. RESULTS
The working device is depicted in Figure 11.
Figure 11: The top figure show a frontal view of the
device, the middle figure shows a side view, and the
bottom figure shows a back view of the device.
Images were taken of the eye without the yellow filter
on the camera lens and with the yellow filter (Fig. 12).
There was no fluorescent staining in the first round of
images. The effect of the yellow filter was tested. The
images with the filter appear to be significantly darker
because less yellow light was reflected from the eye.
The next set of images was of a paper dyed with
fluorescein sodium (Fig.13). The images were taken to
show that the darkness of the bottom image in Figure 12
is eliminated when a fluorescent image is present. This
validates that the emitted light is in the yellow region
passed by the filter.
Figure 12: The first figure is of a healthy eye without
the filter, and the second figure is of a healthy eye with
the yellow filter.
Figure 13: The left figure is of the fluorescently dyed
paper imaged without a yellow filter, and the right
figure is the same dyed paper imaged with the yellow
filter.
Another round of images was taken of a healthy eye
dyed with fluorescein sodium. The first image was
taken with the yellow filter to catch the time sensitive
fluorescence and the second image was taken without
the yellow filter. The images shown in Figure 14
confirm that the eye is healthy. No fluorescein sodium
molecules bound to the basal membrane beneath the
corneal epithelium. This means that no cells in the
corneal epithelium were damaged, exposing the basal
membrane to the surface.
roughly $10,000, and a used one can be purchased
online for around $3,000. An eye specialist can use this
large, bulky instrument to observe the anterior segment
of the patient’s eye which includes the cornea. The
instrument can be adapted for use with fluorescent
imaging. Heine also has a handheld slit-lamp
biomicroscope (model HSL 150) that can be purchased
for $750 and adapted for use in fluorescent imaging
[20].
The cost breakdown for building the prototype device
and bulk manufacturing the device are shown in Figure
15. Circuit elements include resistors, wires, solder,
electrical tape etc. The cost of the device for
dissemination is expected to be $11.88. Only one
device is needed to serve a community in the
developing world. Conservatively, 50 families in one
community can benefit from one device. Assuming that
families in Africa live on the equivalent of a $0.50 per
day, the community of 50 families survives on $25 per
day [12]. Hence, this device is affordable as it is less
than half of what a community survives on daily.
Figure 14: The first image is of a stained healthy eye
with a yellow filter and dark due to the absence of
corneal damage. The second image is of a stained
healthy eye without the yellow filter.
XI. SAFETY
The LEDs that are utilized in this device are bright,
but not harmful if the device is used properly. The
maximum permissible exposure (MPE) to the eye was
determined to be 2.92J/cm2 [19]. The power generated
by one LED is the current multiplied by the voltage or
0.016 A*3.4 V= 0.0544 W. The total power of both
LEDs is 0.1088 W. Assuming that the area of the eye is
2 cm2, the LEDs provide 0.0544 W/cm2 [19]. Dividing
the MPE of 2.92 J/cm2 by 0.0544 W/cm2 gives the
maximum exposure time of the device – 53s. Therefore,
the device should not be used to image the eye for a
continuous span longer than 53s. However, images of
the eye can easily be obtained in this time period, and
the patient can be exposed to the LEDs for cumulatively
more than 53s if the exposure is discontinuous.
Figure 15: Cost breakdown for prototype and bulk
manufacturing this device. The cost per device
decreases with bulk manufacturing primarily because
supplies are cheaper when purchased in bulk.
XII. COST EFFECTIVENESS
XIII. ADVANTAGES
The ophthalmic test using fluorescein sodium is
usually completed with a camera already purchased for
viewing the eye. A new slit-lamp biomicroscope costs
The described device provides medical personnel in
the developing world the ability to screen corneal
diseases in a high-throughput manner. The device
allows for images to be saved to a computer to be
evaluated by an eye specialist later if none is present at
the time. Saved images provide a record of a patient’s
development of or recovery from an ocular disease.
The device is cost-effective and requires little training
to use. The ability to remove the yellow filter allows the
camera to be used for any imaging of the body including
wounds and skin moles. Tracking the healing process of
a wound and diagnosing skin cancer better would
decrease the great health divide between the developing
world and countries like the United States, Russia, and
United Kingdom.
XIV. FUTURE CONSIDERATIONS
More testing of the device should be completed to
understand its limitations as a diagnostic eye camera.
The differences between images of diseases eyes taken
by adapted slit lamp biomicroscopes and the eye
diagnostic camera described here need to be compared
in a clinical study (Fig.16). Most limitations are
expected to arise from the image quality provided by the
purchased web camera. However, if this device is found
satisfactory by three clinicians at the Wilmer Eye
Institute, the device can be deemed ready for
dissemination in the developing world. Fluorescein
sodium strips or drops must also be disseminated with
the device. Fluorescein sodium strips cost
approximately $0.20 per strip. These strips are better
suited for the developing world because they require
less training and cannot apply a harmful dose to the eye.
Figure 16: The corneal abrasion is visible due to
staining and imaging with fluorescein sodium [21].
XV. ACKNOWLEDGEMENTS
Kartikeya Murari, Heather Benz, and Chris Browne
helped in the making of this device. The funding for the
prototype and laboratory space was provided by Dr.
Nitish Thakor and the Department of Biomedical
Engineering at Johns Hopkins University.
XVI. REFERENCES
[1]
[2]
[3]
[4]
“Facts about the Cornea and Corneal Disease.” National Eye
Institute (2010).
“The prevention of blindness: report of a WHO Study Group.”
World Health Organization (1973):10-11.
“Visual impairment and blindness.” World Health Organization
(2009).
Ibid. 1.
[5]
[6]
Ibid. 1.
Foster A, Johnson G. “Blindness in the developing world.”
British Journal of Ophthalmology 77 (1993):398-399.
[7] Keefe JE, et al. “A simplified screening test for identifying
people with low vision in developing countries.” Bulletin of the
World Health Organization 74(5) (1996):525-532.
[8] Ibid. 7.
[9] Ibid. 7.
[10] “New goggles take hassle out of eye test.” Indo-Asian News
Service August 9, 2008.
[11] Ibid. 10.
[12] “Perfect Sight – Increasing global accessibility to diagnostic
services for eye care.” MIT Media Lab (2010).
[13] Ibid. 12.
[14] Ibid. 3.
[15] Williams R. “The Sodium Fluorescein Technique.” Medical and
Science Photography (2002).
[16] Grossman J. “A simple technique for fluorescein photography.”
Plastic and Reconstructive Surgery 67(2) (1981):257-258.
[17] Ibid. 15.
[18] “Color filter technical data spreadsheet” access:
http://www.rosco.com/us/filters/permacolor.asp
[19] Calkins JE. “Retinal light exposures from ophthalmoscopes, slit
lamps and overhead surgical lamps.”
[20] Heine HSL 150 Hand-Held Slit Lamp - www.heine.com
[21] Sowka J, et al. Handbook of Ocular Disease Management
Jobson. Publishing LLC. (2001).