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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.

Retina Image corrected with adaptive optics
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.

Deformable mirror from Boston Micromachines
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.

Retina Image from a human eye   retinafig3b
Figure 3a   Figure 3b

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.