Focus areas
We strive to improve eye care by advancing the non-invasive visualization of physiological and pathological microscopic retinal structure and function. To achieve this, we focus on the topics listed below.
Wavefront sensing
The Shack-Hartmann wavefront sensor samples a beam of light using an array of lenslets that creates an array of small images on a camera sensor. The position of these images in relation to an ideal (reference) positon, provides information about the distortion of the beam wavefront. Originally conceived for testing optical components, the Shack-Hartmann wavefront sensor is now widely used in ophthalmic research and clinical settings. In eye clinics, this sensor is used to prescribe spectacles or guide laser corneal ablation for vision correction (refractive surgery). When a Shack-Hartmann wavefront sensor is used in combination with wavefront correctors (adjustable optical devices) they form adaptive optics systems, that can: deliver images to the retina that simulate how vision could be after cataract surgery with different intraocular lenses (vision simulators), test vision at a microscopic scale, and capture retinal images that reveal the structure and function of individual cells.
While in our lab, Vyas Akondi, PhD made substantial contributions to the accuracy and dynamic range of Shack-Hartmann wavefront sensing in ophthalmic and other applications, including those summarized in the publications listed below:

- Accounting for focal shift in the Shack–Hartmann wavefront sensor
- Centroid error due to non-uniform lenslet illumination in the Shack–Hartmann wavefront sensor
- Average gradient of Zernike polynomials over polygons
- Multi-layer Shack-Hartmann wavefront sensing in the point source regime
- Shack-Hartmann wavefront sensor optical dynamic range
Optical design
The optical design of ophthalmoscopes is a complex endeavor that requires profound understanding of physiological optics, and advanced optical design techniques and theory. The complexity of these instruments is even higher when incorporating adaptive optics to correct for the blur due to the wavefront aberrations of the eye.
Most of the optical design innovations in our lab stem from work by Armando Gómez-Vieyra, PhD, Yusufu Sulai, PhD, Sam Steven, PhD (for which he received the K.P. Thompson Optical Design Innovator Award), and Xiaojing (Grayce) Huang, through a long-standing collaboration with Julie Bentley, PhD at the University of Rochester. They have produced some of the most advanced and highest resolution adaptive optics ophthalmoscopes to date, which are used by our collaborators in leading academic centers across the North America, Europe and Australia. Their work has also brought rigor and theoretical insight to the field, using both traditional and advanced optical design tools, such as nodal aberration theory, as the publications below illustrate:

- First-order design of off-axis reflective ophthalmic adaptive optics systems using afocal telescopes
- Reflective afocal broadband adaptive optics scanning ophthalmoscope
- Design of two spherical mirror unobscured relay telescopes using nodal aberration theory
- Long eye relief fundus camera and fixation target with partial correction of ocular longitudinal chromatic aberration
- Correction of resonant optical scanner dynamic aberrations using nodal aberration theory
Multiple scattered light imaging

In 2012 Chui, VanNasdale and Burns demonstrated the use of multiple scattered light imaging to reveal the retinal vasculature and capillary network with exquisite detail and non-invasive contrast. This work inspired us and others to explore methods for further improving the contrast of these and other microscopic retinal structures. Borrowing from X-ray differential phase imaging and optical microscopy techniques, we have proposed and demonstrated novel non-invasive imaging methods that reveal non-invasively cellular and sub-cellular retinal structures, such as capillaries, blood cells, photoreceptors, retinal pigment epithelium cells and, more recently, hyalocytes. These techniques also reveal known and previously unredported pathological features, such as the foveal features in persons with multiple sclerosis discovered in collaboration with Heather Moss, MD, PhD.
- In vivo dark-field imaging of the retinal pigment epithelium cell mosaic
- Visualization of retinal vascular structure and perfusion with a nonconfocal adaptive optics scanning light ophthalmoscope
- In vivo imaging of human cone photoreceptor inner segments
- Comparison of confocal and non-confocal split-detection cone photoreceptor imaging
Eye movement
The human eye is in constant involuntary movement (rotation), even when fixating. This movement introduces blur and/or distortion in retinal images. When this eye movement is extreme in amplitude and angular speed, and often repetitive, it is referred to as nystagmus. Because of its detrimental impact in retinal imaging and vision testing, nystagmus presents a challenge to eye care, advancing understanding of blinding eye conditions and the testing of new therapies, such as, gene therapies. To address this clinical and translational need, we are developing a new generation of pupil trackers with very low latency for real-time eye movement compensation in retinal imaging and vision testing instrumentation. The first of such pupil trackers, by Bartlomiej Kowalski, MSc, based on a field-programmable gate array in combination with a desktop computer (CPU), achieved latencies as low as 1-2 ms.
Our next goal is to develop low-cost alternatives for broad dissemination across the scientific community and incorporation in commercial ophthalmoscopes, including optical coherence tomographers, which are both the standard of care and state-of-the-art in eye clinics.

Image processing
Retinal images have to be prepared, or processed, for the calculation of biomarkers that can be used for diagnosing disease, quantifying disease progression or testing vision. We develop image processing algorithms for: removing image distortions caused by eye movement, ophthalmoscopes and the optics of the eye; subtracting background; correcting for non-uniform illumination; combining images to create new imaging modalities; etc. Our long term goal is to provide a suite of open-source algorithms and applications for automating and improving the rigor and reproducibility of ophthalmic image processing.
Our initial contribution, by Zachary Harvey, MSc, was a strip-based image registration application that has been deployed to and been used by a large fraction of the adaptive optics scanning light ophthalmoscopy community. More recently, Grayce Huang, PhD proposed two new methods for improved scaling of retinal images by using a new generation of clinical ocular biometers used for selecting intraocular lenses before cataract surgery. These methods can be applied to improve the accurary of all retinal imaging biomarkers that are derived from retinal layer or pathological feature thickness and/or size. In her work, Grayce also provided a first theoretical derivation of how retinal images scale with the distance between any ophthalmoscope and the eye, which is currently not recorded by any ophthalmoscope, thus injecting a substantial source of biomarker error in eyes with strong spectacle presciption.

- Robust real-time estimation of non-uniform angular velocity and sub-pixel jitter in images captured with resonant scanners
- Correction of non-uniform angular velocity and sub-pixel jitter in optical scanning
- Retinal magnification factors at the fixation locus derived from schematic eyes with four individualized surfaces
- Registration of 2D images from fast scanning ophthalmic instruments
Ophthalmic instrumentation
We are continually exploring methods for improving the performance and capabilities of ophthalmoscopes, catering for both current and future technical needs. Examples of that are:
- Annular illumination and/or imaging pupils to improve transverse image resolution. Adaptive optics scanning ophthalmoscopy with annular pupils.
- Sub-Airy disk-sized light detection pinholes to improve transverse image resolution. Sub-Airy Confocal Adaptive Optics Scanning Ophthalmoscopy.
- Reduction of retinal area that can be imaged with negligible image blur (isoplanatic patch) due to dynamic distortion in optical scanners. Dynamic wavefront distortion in resonant scanners
- Low-cost low-complexity correction of image jitter and distortion due to non-uniform angular scanning velocity in resonant scanners. Correction of non-uniform angular velocity and sub-pixel jitter in optical scanning
Dynamic distortion in resonant galvanometric optical scanners
Robust real-time estimation of non-uniform angular velocity and sub-pixel jitter in images captured with resonant scanners

Dissemination
Our lab is committed to the translation of the dissemination of
our technology and expertise for the benefit of patients with
conditions that lead to vision loss.
We have deployed our adaptive optics ophthalmoscopes to leading
academic centers worldwide, including: University College
London & Moorfields Eye Hospital (UK), the National Eye
Institute Intramural Research Program, Univ. of California San
Diego, the Medical College of Wisconsin, the University of
Pennsylvania, New York Eye and Ear Infirmary, University of
Melbourne (Australia) and Univresity of Waterloo (Canada).
These instruments have contributed to numerous peer-reviewed
publications and conference presentations about ocular,
neurological and systemic diseases.
We have also provided optical designs, image registration
software, alignment software, adaptive optics control software
and training to colleagues at many academice centers.

Translational uses of our technology
We see the use of our technology to addressing clinical needs and basic science questions as the ultimate measure of success and impact. The number of examples of our technology applied to the study of eye, neurological and systemic disease is constantly growing, with a few examples of work with our collaborators listed below:

- Imaging of vitreous cortex hyalocyte dynamics using non-confocal quadrant-detection adaptive optics scanning light ophthalmoscopy in human subjects
- Photoreceptor inner segment morphology in best vitelliform macular dystrophy
- Novel Foveal Features Associated With Vision Impairment in Multiple Sclerosis
- Discovery and clinical translation of novel glaucoma biomarkers
- Cellular imaging reveals origin of the tapetal-like reflex in carriers of RPGR-associated retinopathy
- Assessing photoreceptor structure associated with ellipsoid zone disruptions visualized with optical coherence tomography
- The effect of cone opsin mutations on retinal structure and the integrity of the photoreceptor mosaic
- Assessing retinal structure in complete congenital stationary night blindness and Oguchi disease
- Adaptive optics imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma