Precision Targeting with a Tracking Adaptive Optics Scanning Laser Ophthalmoscope

This dual-imaging system could enable selective destruction of diseased cells during the progression of retinal diseases.

Adaptive optics (AO) has become increasingly utilized in research ophthalmic diagnostic instruments since their first use nearly ten years ago. Integration of adaptive optics in scanning laser ophthalmoscopy (SLO) is a flying-spot technique whereby scattered light in images is blocked by placement of an aperture at a back conjugate focal plane. Adaptive optics systems sense perturbations in the detected wavefront and apply corrections to an optical element that flattens the wavefront and allows near diffraction-limited focus.

A possible Precision Targeting of RPE (retinal pigment epithelium) cells for the treatment of advanced macular degeneration (AMD).
In general, very high-resolution imaging of retinal structures can lead to earlier detection of retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Combined with other imaging modalities and functional techniques that can explore metabolic ocular health, AO has high diagnostic potential.

This technology uses AO for the purpose of precision laser targeting. The technology can be applied to studies of vision if the targeting beam is used to stimulate certain retinal structures, such as ganglion cells whose function is yet to be discovered. It can also be used to help study damage mechanisms and determine laser safety thresholds for the use of AO systems. Finally, it can be used for precision delivered laser beams for advanced therapies. The figure shows a possible precision targeting of RPE (retinal pigment epithelium) cells for the treatment of advanced macular degeneration (AMD).

As discussed above, the tracking adaptive optics scanning laser ophthalmoscope (TAOSLO) system used for precision retinal targeting combines scanning laser ophthalmoscopy, adaptive optics, retinal tracking, and ultrashort, pulse-mediated tissue disruption. The system uses a dual-imaging approach that simultaneously displays confocal wide-field and high-magnification retinal views from the front-end TSLO and AOSLO subsystems, respectively. Thus, the position of the AOSLO raster, which often cannot be unambiguously determined from the retinal image information within such a small field, is precisely known, displayed, and controlled by the user. The AO system includes Hartmann-Shack wavefront sensor and deformable mirror wavefront compensator. Diffraction-limited beams are delivered to the eye via a port placed behind the deformable mirror.

The tracking system works with the wide-field line scanning laser opthalmoscope (LSLO) as an independent unit, but drives two galvanometers placed at appropriate conjugates within the path of the adaptive optics scanning laser ophthalmoscope. The input to the “master” control loop is x-y error signals generated from the track beam dithered on a feature and detected from a confocal reflectometer. The input to the “slave” control loop is the scaled position signals from the master galvanometers. The slave tracking mirrors are placed at conjugates to the center of rotation of the eye. This allows line-of-sight tracking because the mirrors pivot about the true axis of rotation of the eye.

In addition to the tracking electronics described briefly above, the instrumentation for the system includes 3 framegrabbers, custom camera and timing boards, digital timing boards to control the DM, and a 8°—8 LED array for fixation controlled via the serial port. The custom timing board provides a non-linear pixel clock to the analog framegrabber to automatically linearize the sinusoidal scan produced by the resonant scanner.

An adaptive optics scanning laser ophthalmoscope with active retinal stabilization was built. The system uses a novel optical arrangement, integrated software platform, and advanced electronics and instrumentation for the generation of high-resolution, aberration- corrected, stabilized scans of the retina. The system was easily configured to acquire advanced scans such as macular montages. The effect of source bandwidth was tested and substantial improvement was found with the use of superluminescent diodes. The retinal tracking system uses a master- slave configuration and further strategies will pursue scalable precision to the level of a single cone. Even for the best fixators, without retinal tracking, eye motion can slew the field of regard to non-overlapping retinal locations reducing useable frames and image correspondence for longer-duration scans and longitudinal studies. In a clinical scenario that includes predominantly elderly patients with limited ability to fixate, retinal tracking may prove invaluable for small AO fields. A significant improvement was demonstrated in the visualization of the retina with retinal tracking.

The TAOSLO system can be used for a wide variety of applications, from the selective destruction of diseased cells during the progression of retinal diseases, to a finer probing of the visual system, to the examination of lesion development and further understanding of the mechanisms of retinal disruption.

This work was done by Daniel X. Hammer, R. Daniel Ferguson, Chad E. Bigelow, Nicusor V. Iftimia, and Teoman E. Ustun of Physical Sciences Inc.; Gary D. Noojin, David J. Stolarski, Harvey M. Hodnett, and Michelle L. Imholte of Northrop Grumman Corp.; Semih S. Kumru and Benjamin A. Rockwell of the Air Force Research Laboratory; and Michelle N. McCall and Cynthia A. Toth of Duke University Medical Center. AFRL-0202