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Adaptive optics could allow clinicians to monitor the progression of retinal diseases cell-by-cell, according to Jacque Duncan, MD.
Adaptive optics could allow clinicians to monitor the progression of retinal diseases cell by cell, according to Jacque Duncan, MD.
“We’re able to identify the source of vision loss when there is a problem with patients’ cones,” said Dr. Duncan, professor of clinical ophthalmology, University of California, San Francisco.
The technology compensates for optical aberrations allowing any ophthalmoscope modality, including flood-illuminated fundus cameras, scanning laser ophthalmoscopes, and optical coherence tomography (OCT), to produce sharper images. It can yield new understanding of retinal diseases, and could be used to evaluate the effects of treatments on photoreceptors, Dr. Duncan said.
Astronomers developed adaptive optics to compensate for the aberrations caused by turbulence in the earth’s atmosphere.
Similarly, the technique can measure and correct for the optical imperfections of the eye. Current systems use the Shack-Hartmann wavefront sensor, an approach pioneered for ophthalmology in the 1990s, Dr. Duncan pointed out.
The sensor measures the aberrations introduced into light exiting the eye using an array of lenslets, where each lenslet samples a local portion of the incidence wavefront and focuses light on a charge-coupled device. Based on software algorithms, a series of actuators deflect the surface of a deformable mirror to compensate for these aberrations so light exits the surface of the mirror in parallel planes.
“You can apply this technology to all forms of imaging,” said Dr. Duncan. Already one adaptive optics fundus camera is commercially available: the rtx1 by Imagine Eyes, she said. However, the fundus camera “doesn’t allow you to see individual cones within the central 1º from the fovea,” she added.
However, scanning laser ophthalmoscopes are suited to adaptive optics, Dr. Duncan said. These systems form images by recording the light scattered from a focused beam as it is scanned across the retina. Continuous scanning in a raster fashion allows it to sample large areas at a faster rate than conventional flash fundus imaging using less exposure to visible light.
With adaptive optics, scanning laser ophthalmoscopes can distinguish features as small as 2 µm, said Dr. Duncan. “We’re able to identify individual cones within a mosaic that are difficult to see using other methods,” Dr. Duncan added.
Scanning laser ophthalmoscopes typically use confocal imaging in which a pinhole is positioned close to the detector, optically conjugate to the focused spot on the retina. Light not originating from the focal plane of the retina is excluded. This results in an image with a higher contrast and allows axial sectioning of the retina and visualization of various layers.
Dr. Duncan and her colleagues have superimposed images produced by scanning laser ophthalmoscopes on images produced by spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FA) to create cross-sectional images in three dimensions. In this way, they can follow changes in individual cones over time, noting their spacing, packing, and density.
Such measures as the average distance between cones in a mosaic can provide a sensitive, reliable, repeatable outcome measures for disease progression in eyes with inherited retinal degeneration, said Dr. Duncan.
The confocal system provides images of photoreceptors with intact inner and outer segments that are in contact with retinal pigment epithelial (RPE) cells. But photoreceptors with outer segments that are disrupted, detached, or misaligned may not be visible in confocal images, she said.
For this reason, Dr. Duncan and other researchers are exploring the use of non-confocal techniques. One such technique using split detection to capture non-confocal images can resolve intervening rods, show cone inner segments even in the absence of outer segments, and can reveal RPE cells, allowing them to be reliably identified.
Since the technique does not rely on confocal images of direct, backscattered light, a split detector adaptive optics image might reveal structures even when cones are not wave-guiding and scattering normally. Images produced this way might reveal the photoreceptor inner segments in cases where the outer segments are disrupted, misaligned, or absent, which would not give rise to a confocal, wave-guided image.
Another non-confocal technique, dark-field adaptive optics scanning laser ophthalmoscopy (AOSLO), can attenuate backscatter light from photoreceptors to show RPE cells.
A third non-confocal technique, multiple offset detection, can reveal cone inner segments at the margins of geographic atrophy in age-related macular degeneration.
Applied to microperimetry, AOSLO can deliver small visual stimuli precisely to individual cones or small groups of cones. Combined with high-speed fundus tracking, this technique can be used to test cone function in areas where cones are not visible in confocal images.
An example of the way the AOSLO can be used, acute foveolitis reduced the visual acuity of a 21-year-old woman to 20/80. No cones were visible in her fovea. Five years later, her visual acuity had recovered to 20/25, with improved visual function in regions where cones were still not visible, but the external limiting membrane was slightly hyper-reflective in cross-sectional OCT scans through the fovea.
AOSLO was used to deliver spots of light precisely to regions where cones were not visible using confocal images, and measures of visual function provided evidence of residual cones that could not be seen with other imaging modalities.
Jacque Duncan, MD
This article was adapted from a presentation that Dr. Duncan delivered at the Retina Subspecialty Day held prior to the 2016 American Academy of Ophthalmology meeting. Dr. Duncan had no financial disclosures to declare relevant to this topic.