Ophthalmology Times | Cover
Story | November 2006
Adaptive
Optics Creating a Clearer View of Retina
by Paul Bierden and Steven Menn, Boston Micromachines Corp.
Introduction
For vision scientists, the human retina promises
to be a window into the health of a patient. A clear
view of the retina in-vivo with high resolution
detail of photoreceptors and vascular flow could
give the vital detail that would enable clinicians
to make early and accurate diagnosis of diseases.
This window is blurred, however, by imperfections
in the eye itself: the cornea and crystalline lens,
as well as the viscous and non-uniform nature of
the vitreous humor, keeps clinicians from viewing
the important cellular structures. Optically, this
blurring, or image distortion, is caused by tissue-induced
wavefront aberration in the light that images the
retina and results in a low-resolution image. By
actively correcting for wavefront aberration in
the optical path between the imaging camera and
the retina, adaptive optics (AO) technology has
emerged as an enabling technology for cellular-level
resolution and extracting vital information from
the human retina.
Today's Optical Instrumentation (Current
Methods)
Clinical retinal imaging methods vary widely from
traditional Fundus cameras to advanced microscopic
techniques, ultrasound immersion, fluorescence angiograms,
and electroretinogram.
The Fundus film camera is still considered the gold
standard for retinal imaging instrumentation according
to Dr. Richard Calderon, Chief of the Advanced Diagnostic
Imaging Center at Joslin Diabetes Center, "Digital
Fundus images may have the convenience factor for
emailing images etc., but film often offers greater
resolution, especially when looking at gray scale."
The strengths of the scanning
laser ophthalmoscope (SLO) lie in the ability
to create video-rate images using a low energy
light source while the main advantage afforded
by optical coherence tomography (OCT) is its high
axial resolution. The high resolution images come
at a cost of slow image acquisition. "Loss
in resolution is due to the long image acquisition
time which is slower than eye movement,"
notes Dr. Joseph Izatt, Professor of Ophthalmology
at Duke University.
While clinical retinal
imaging instruments are achieving ever-greater
resolution capabilities, the eye itself imparts
the final obstacle in ultra-high resolution imaging.
Ophthalmologists have long been interested in
imaging cellular structures in the retina to examine
photoreceptor properties in vivo and to more precisely
characterize retinal disease. A number of vision
science researchers have recently succeeded in
cellular-level resolution by actively correcting
light distorted by the cornea and crystalline
lens.
Adaptive Optics 101
The purpose of AO is to compensate for wavefront
aberrations caused by a distorting medium in the
optical path. AO systems are comprised of three
main elements: a wavefront sensor that measures
distortion as the light reflects off the retina
and exits the eye, a wavefront corrector that
compensates for this distortion, and a control
system to measure the distortion from the sensor
and correct the mirror accordingly. Figure 1 shows
a schematic diagram of the system with each of
these elements.
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| Figure 1 |
The sensor, called a Shack
Hartmann, works by breaking up the incoming wavefront
into a number of small pieces using an array of
miniature lenses, (called lenslets) which then
focus the light onto CCD array camera. Changes
in wavefront result in changes in spot location
on the camera - thus measuring the wavefront.
The wavefront corrector
is the adaptive element of the AO system. The
most commonly used wavefront corrector is a deformable
mirror (DM): a thin, flexible mirror with a number
of control points behind its surface to adjust
shape and position. Based on information provided
by the controller, the DM will change its shape
to correct for the aberration in the wavefront
thus cleaning up the image. Originally developed
for astronomy, the first DMs were large devices,
approximately 150 mm in diameter, using piezo-electrics
for actuation. While these mirrors worked well
for adaptive optics in a number of research laboratories,
their size and cost excluded them from clinical
instrumentation.
The advent of the MEMS
(micro electromechanical systems) DM opened up
the possibility for AO in clinical retinal imaging.
The combination of small size, low cost, and high
spatial resolution control make them well suited
for instrumentation. MEMS DMs for retinal imaging
have aperture size on the order of 5-10mm and
actuator count from 19- 200. An example of a MEMS
mirror that has been used on a number of retinal
imaging instruments can be seen in Figure 2.
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| Figure 2 |
Ultra-high Resolution Retinal Imaging
To vision scientists and ophthalmologists, cellular-level
resolution of the retina gives the ability to
study vasculature and photoreceptor properties
and changes and holds promise for earlier diagnosis
and treatment of the "big three" diseases:
glaucoma, diabetic retinopathy, and age-related
macular degeneration. The first use of adaptive
optics to achieve this level of resolution was
in 1996, Miller et al. used a low resolution deformable
mirror in an OCT system to correct low order aberration.
This system was able to resolve photoreceptor
cones, but only in excellent eyes with minimal
cornea and crystalline lens defect. In 2006, Zhang,
Roorda, et. al used a 140 actuator DM to 70 µm
axial, and 2.5 µm lateral resolution with
the their AOSLO system. This dramatic improvement
over commercial SLO enabled visualization of 3
µm photoreceptor cones and individual white
blood cells flow through vessels. Figure 3 shows
the dramatic increase in signal strength, contrast,
and resolution obtained from when turning on the
AO system. Vascular attenuation is telltale of
many retinal diseases, and earlier detection of
attenuation through higher resolution images,
as seen in Figure 4, will allow earlier diagnosis.
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| Figure 3a |
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Figure 3b |
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| Figure 4 |
Future
Today, ophthalmologists detect eye pathology once
the disease has set-in. Dr. Lloyd P. Aiello, Director
of the Joslin Diabetes Center says, "If we
can see disease or damage that is currently sub
clinical we may be able to show that these changes
are predictive of future outcome and would know
better when to begin therapy." He believes
that the future generations of retinal imaging
instrumentation should enable high resolution
with applicability to a wide range of anatomy
for detailed evaluation of individual lesions,
terminal vasculature, and overall cellular health.
A clearer retinal image
would assist not only clinicians, but in automated
pathology detection. As advanced eye disease analysis
moves from individual clinics towards retinal
image analysis at a centralized location by experts
in the field, automated software recognition of
pathologies will become increasingly important.
Clear, high contrast imaging will be vital for
this future analysis.
Finally, recent, highly
publicized research by Prof. Tien Wong, Director
of The Retinal Vascular Imaging Centre, University
of Melbourne, Australia has shown a link from
retinal vasculature damage to coronary heart disease, stroke, and diabetes . His work uses new retinal
imaging technology to predict diabetes stroke,
heart disease, hypertension and other risk factors.
According to Wong, an increase in imaging resolution,
such as would be provided by AO, "May address
a major limitation with the prediction of cardiovascular
disease using imaging from standard retinal photography
in its inability to detect subtle changes, on
the scale of a few microns, between healthy and
diseased vessels." A clearer view of the
retina may someday help doctors non-invasively
diagnose the diseases that cause the most hospitalization
and death worldwide.
Meet the authors
Paul Bierden is president and CEO of Boston Micromachines
Corp. in Watertown, Mass.
Steven Menn is director of product marketing at
Boston Micromachines Corp. |
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