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Rods Directly Imaged in Living Eye

Photonics.com
Jun 2011
WASHINGTON, June 10, 2011 — The tiny light-sensing cells known as rods have been clearly and directly imaged in the living eye for the first time. The innovation in adaptive optics will help doctors diagnose degenerative eye disorders sooner, leading to quicker intervention and more effective treatments.

"While therapies are only emerging, the ability to see the cells you are trying to rescue represents a critical first step in the process of restoring sight," said Alfredo Dubra of the University of Rochester in New York, who led the team from Rochester, Marquette University and the Medical College of Wisconsin, Milwaukee. "It's impossible to overemphasize how important early detection is to eye disease."

"One of the major hurdles in detecting retinal disease is that by the time it can be perceived by the patient or detected with clinical tools, significant cellular damage has often already occurred," said Joseph Carroll of Medical College of Wisconsin.

The breakthrough that is ushering in a new era of eye disease research, diagnosis and treatment is an improved design of a noninvasive adaptive optics imaging system. Dubra and his colleagues were able to push the device's resolution to its optical limits of nearly 2 µm, or the approximate diameter of a single rod in the human eye.


The image on the left shows the smallest cones at the center of the retina (the fovea). Whenever we direct our gaze at something, for example to read, the image of what we are looking at is formed over these very important cones. The image on the right shows a more eccentric retinal location, in which the large, bright dots with a dark ring around them are cones, and the surrounding (and far more abundant) smaller spots are rods. (Image: University of Rochester/Biomedical Optics Express)

Rods are much more numerous than cones and are vastly more sensitive to light. With the optical design method successfully demonstrated by Dubra's team, even the smallest cone cells at the center of the retina, known as the foveal center, can be seen very clearly. Rods can be seen clearly in a less central retinal location.

"This is a really exciting breakthrough," said Steve Burns, a professor in the School of Optometry at Indiana University, who was not involved in the research. "Imaging contiguous rod mosaics will allow us to study the impact of a whole new class of blinding disorders on the retina. Since many of the eye diseases most amenable to intervention affect the rods, this should become a major tool for determining what treatments work best for those disorders."

De-twinkling stars, visualizing rods

In astronomy, adaptive optics is able to correct for the blurring effect of Earth's atmosphere, effectively removing the "twinkling" from starlight and rendering cosmic objects as very sharp points of light. To achieve this correction, the adaptive optics system requires a reference point — either a bright, nearby star or an artificial "guide star" produced in the upper atmosphere by lasers mounted on a telescope. By monitoring that reference point, adaptive optics systems use a deformable mirror to create the exact but opposite distortion that is happening in the atmosphere. The result is a clearer image with much greater resolution.

Just as light passing through the atmosphere becomes bent and distorted, so too does light passing through the front part of the eye. This distortion is inconsequential on the scale of human vision but poses a significant barrier in the microscopic realm of medical imaging.

In 1997, David Williams of the University of Rochester led the group that first demonstrated using adaptive optics technology to study the interior of the human eye. In this system, called an adaptive optics ophthalmoscope, a laser creates a reference point that is used to correct the blurring of the image obtained with a fundus camera. Today the fundus camera is commonly replaced by a second laser for imaging, which is known as an adaptive optics scanning laser ophthalmoscope. By moving the laser point across the retina and correcting the distortion along the way, an accurate image emerges line by line, in much the same way that a CRT monitor renders an image.

Breakthrough design

The breakthrough in the design of the adaptive optics instrument that led to clearly visualizing rods was, according to Dubra, "embarrassingly simple and relied on well-known equations and concepts." By simply folding the spherical mirrors that act as lenses in the instrument into a three-dimensional structure, the image quality of the retina was improved sufficiently to clearly resolve the contiguous rod mosaic, as well as the entire cone mosaic at the foveal center.

"By combining careful optical engineering, excellent adaptive optics control and knowledge of the visual system, the authors have made a major advancement in both biomedical imaging and vision science," said Burns.

Improving patient care

The researchers’ next step is to develop a clinical model that could be widely available. A related task is simplifying and teaching the art of interpreting adaptive optics images to guide clinical decisions about diagnosis and treatment.

When that occurs, hopefully in the next five to 10 years, doctors will likely be able to routinely peer into a living human eye with such precision and clarity that they will be able to see and evaluate individual rods — and do three things never before possible: accurately describe the physical presentation of specific rod disorders — the "phenotype" of a disease, intervene with early treatment at the first sign of disease, and even determine how individual cells are responding to a specific treatment.

"That's what's really exciting about this imaging device: It can really make a difference in a patient's life," Carroll said. "The ability to now resolve these cells opens up new possibilities for improving care that researchers have been anticipating for a long time — such as using the information in these retinal images to aid in targeting, delivering and evaluating therapies."

The work is described in the Optical Society's (OSA) open access journal Biomedical Optics Express.

For more information, visit: www.osa.org


GLOSSARY
adaptive optics
Optical components or assemblies whose performance is monitored and controlled so as to compensate for aberrations, static or dynamic perturbations such as thermal, mechanical and acoustical disturbances, or to adapt to changing conditions, needs or missions. The most familiar example is the "rubber mirror,'' whose surface shape, and thus reflective qualities, can be controlled by electromechanical means. See also active optics; phase conjugation.
ophthalmoscope
Also referred to as a funduscope, an ophthalmoscope is a specialized instrument used by ophthalmologists for observing and photographing the fundus (interior) of the eye which includes the retina, macula, fovea, optic disc, macula, and posterior pole. The ophthalmoscope consists of a concave mirror with an orifice at the center through which the viewer examines the eye. A light source is then reflected to the eye from the mirror. A set of lenses are then rotated in front of the hole in the...
retina
1. The photosensitive membrane on the inside of the human eye. 2. A scanning mechanism in optical character generation.
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