Wide-field optical eye models for emmetropic and myopic eyes.

Ocular wavefront aberrations are used to describe retinal image formation in the study and modeling of foveal and peripheral visual functions and visual development. However, classical eye models generate aberration structures that generally do not resemble those of actual eyes, and simplifications such as rotationally symmetric and coaxial surfaces limit the usefulness of many modern eye models. Drawing on wide-field ocular wavefront aberrations measured previously by five laboratories, 28 emmetropic (-0.50 to +0.50 D) and 20 myopic (-1.50 to -4.50 D) individual optical eye models were reverse-engineered by optical design ray-tracing software. This involved an error function that manipulated 27 anatomical parameters, such as curvatures, asphericities, thicknesses, tilts, and translations-constrained within anatomical limits-to drive the output aberrations of each model to agree with the input (measured) aberrations. From those resultant anatomical parameters, three representative eye models were also defined: an ideal emmetropic eye with minimal aberrations (0.00 D), as well as a typical emmetropic eye (-0.02 D) and myopic eye (-2.75 D). The cohorts and individual models are presented and evaluated in terms of output aberrations and established population expectations, such as Seidel aberration theory and ocular chromatic aberrations. Presented applications of the models include the effect of dual focus contact lenses on peripheral optical quality, the comparison of ophthalmic correction modalities, and the projection of object space across the retina during accommodation.

Label-Free Imaging of Inflammation at the Level of Single Cells in the Living Human Eye.

Purpose: Putative microglia were recently detected using adaptive optics ophthalmoscopy in healthy eyes. Here we evaluate the use of nonconfocal adaptive optics scanning light ophthalmoscopy (AOSLO) for quantifying the morphology and motility of presumed microglia and other immune cells in eyes with retinal inflammation from uveitis and healthy eyes. Design: Observational exploratory study. Participants: Twelve participants were imaged, including 8 healthy participants and 4 posterior uveitis patients recruited from the clinic of 1 of the authors (M.H.E.). Methods: The Pittsburgh AOSLO imaging system was used with a custom-designed 7-fiber optical fiber bundle for simultaneous confocal and nonconfocal multioffset detection. The inner retina was imaged at several locations at multiple timepoints in healthy participants and uveitis patients to generate time-lapse images. Main Outcome Measures: Microglia and macrophages were manually segmented from nonconfocal AOSLO images, and their morphological characteristics quantified (including soma size, diameter, and circularity). Cell soma motion was quantified across time for periods of up to 30 minutes and their speeds were calculated by measuring their displacement over time. Results: A spectrum of cell morphologies was detected in healthy eyes from circular amoeboid cells to elongated cells with visible processes, resembling activated and ramified microglia, respectively. Average soma diameter was 16.1 ± 0.9 µm. Cell movement was slow in healthy eyes (0.02 µm/sec on average), but macrophage-like cells moved rapidly in some uveitis patients (up to 3 µm/sec). In an eye with infectious uveitis, many macrophage-like cells were detected; during treatment their quantity and motility decreased as vision improved. Conclusions: In vivo adaptive optics ophthalmoscopy offers promise as a potentially powerful tool for detecting and monitoring inflammation and response to treatment at a cellular level in the living eye. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A paradoxical misperception of relative motion.

Motion perception is considered a hyperacuity. The presence of a visual frame of reference to compute relative motion is necessary to achieve this sensitivity [Legge, Gordon E., and F. W. Campbell. "Displacement detection in human vision." Vision Research 21.2 (1981): 205-213.]. However, there is a special condition where humans are unable to accurately detect relative motion: images moving in a direction consistent with retinal slip where the motion is unnaturally amplified can, under some conditions, appear stable [Arathorn, David W., et al. "How the unstable eye sees a stable and moving world." Journal of Vision 13.10.22 (2013)]. In this study, we asked: Is world-fixed retinal image background content necessary for the visual system to compute the direction of eye motion to render in the percept images moving with amplified slip as stable? Or, are non-visual cues sufficient? Subjects adjusted the parameters of a stimulus moving in a random trajectory to match the perceived motion of images moving contingent to the retina. Experiments were done with and without retinal image background content. The perceived motion of stimuli moving with amplified retinal slip was suppressed in the presence of visual content; however, higher magnitudes of motion were perceived under conditions with no visual cues. Our results demonstrate that the presence of retinal image background content is essential for the visual system to compute its direction of motion. The visual content that might be thought to provide a strong frame of reference to detect amplified retinal slips, instead paradoxically drives the misperception of relative motion.

Alignment, calibration, and validation of an adaptive optics scanning laser ophthalmoscope for high-resolution human foveal imaging.

In prior art, advances in adaptive optics scanning laser ophthalmoscope (AOSLO) technology have enabled cones in the human fovea to be resolved in healthy eyes with normal vision and low to moderate refractive errors, providing new insight into human foveal anatomy, visual perception, and retinal degenerative diseases. These high-resolution ophthalmoscopes require careful alignment of each optical subsystem to ensure diffraction-limited imaging performance, which is necessary for resolving the smallest foveal cones. This paper presents a systematic and rigorous methodology for building, aligning, calibrating, and testing an AOSLO designed for imaging the cone mosaic of the central fovea in humans with cellular resolution. This methodology uses a two-stage alignment procedure and thorough system testing to achieve diffraction-limited performance. Results from retinal imaging of healthy human subjects under 30 years of age with refractive errors of less than 3.5 diopters using either 680 nm or 840 nm light show that the system can resolve cones at the very center of the fovea, the region where the cones are smallest and most densely packed.

FIAT: A Device for Objective, Optical Measures of Accommodation in Phakic and Pseudophakic Eyes.

Purpose: To present FIAT, a novel optical instrument and analysis package that is designed to elicit and optically record accommodation in human eyes. Methods: FIAT employs a Shack-Hartmann wavefront sensor and a retro-illumination pupil camera that records from a single eye at video rates. It is effective at eliciting accommodation by offering the subject a full-field binocular view of an alternating distant target and a near-eye display. FIAT analysis software computes wave aberrations for each video frame over full- or subpupil sizes and computes accommodative dynamics and accommodative range. Results: The system is validated by showing accurate refraction measurements in model eyes and human eyes with trial lenses. Robust accommodative responses are shown for young eyes, and a lack of accommodative response is shown for a known presbyopes. Accommodative stimulus-response curves from five phakic subjects over a range of ages show expected results. Results from two individuals with monofocal intraocular lenses are shown. Conclusions: FIAT is an effective instrument for making accurate, objective measures of accommodation in phakic and pseudophakic eyes. Translational Relevance: We present a device that can play an important role in the development and testing of accommodating intraocular lenses.

Retinal imaging using adaptive optics optical coherence tomography with fast and accurate real-time tracking.

One of the main obstacles in high-resolution 3-D retinal imaging is eye motion, which causes blur and distortion artifacts that require extensive post-processing to be corrected. Here, an adaptive optics optical coherence tomography (AOOCT) system with real-time active eye motion correction is presented. Correction of ocular aberrations and of retinal motion is provided by an adaptive optics scanning laser ophthalmoscope (AOSLO) that is optically and electronically combined with the AOOCT system. We describe the system design and quantify its performance. The AOOCT system features an independent focus adjustment that allows focusing on different retinal layers while maintaining the AOSLO focus on the photoreceptor mosaic for high fidelity active motion correction. The use of a high-quality reference frame for eye tracking increases revisitation accuracy between successive imaging sessions, allowing to collect several volumes from the same area. This system enables spatially targeted retinal imaging as well as volume averaging over multiple imaging sessions with minimal correction of motion in post processing.

Wide-vergence, multi-spectral adaptive optics scanning laser ophthalmoscope with diffraction-limited illumination and collection.

Visualizing and assessing the function of microscopic retinal structures in the human eye is a challenging task that has been greatly facilitated by ophthalmic adaptive optics (AO). Yet, as AO imaging systems advance in functionality by employing multiple spectral channels and larger vergence ranges, achieving optimal resolution and signal-to-noise ratios (SNR) becomes difficult and is often compromised. While current-generation AO retinal imaging systems have demonstrated excellent, near diffraction-limited imaging performance over wide vergence and spectral ranges, a full theoretical and experimental analysis of an AOSLO that includes both the light delivery and collection optics has not been done, and neither has the effects of extending wavefront correction from one wavelength to imaging performance in different spectral channels. Here, we report a methodology and system design for simultaneously achieving diffraction-limited performance in both the illumination and collection paths for a wide-vergence, multi-spectral AO scanning laser ophthalmoscope (SLO) over a 1.2 diopter vergence range while correcting the wavefront in a separate wavelength. To validate the design, an AOSLO was constructed to have three imaging channels spanning different wavelength ranges (543 ± 11 nm, 680 ± 11 nm, and 840 ± 6 nm, respectively) and one near-infrared wavefront sensing channel (940 ± 5 nm). The AOSLO optics and their alignment were determined via simulations in optical and optomechanical design software and then experimentally verified by measuring the AOSLO's illumination and collection point spread functions (PSF) for each channel using a phase retrieval technique. The collection efficiency was then measured for each channel as a function of confocal pinhole size when imaging a model eye achieving near-theoretical performance. Imaging results from healthy human adult volunteers demonstrate the system's ability to resolve the foveal cone mosaic in all three imaging channels despite a wide spectral separation between the wavefront sensing and imaging channels.

Human foveal cone photoreceptor topography and its dependence on eye length.

We provide the first measures of foveal cone density as a function of axial length in living eyes and discuss the physical and visual implications of our findings. We used a new generation Adaptive Optics Scanning Laser Ophthalmoscope to image cones at and near the fovea in 28 eyes of 16 subjects. Cone density and other metrics were computed in units of visual angle and linear retinal units. The foveal cone mosaic in longer eyes is expanded at the fovea, but not in proportion to eye length. Despite retinal stretching (decrease in cones/mm2), myopes generally have a higher angular sampling density (increase in cones/deg2) in and around the fovea compared to emmetropes, offering the potential for better visual acuity. Reports of deficits in best-corrected foveal vision in myopes compared to emmetropes cannot be explained by increased spacing between photoreceptors caused by retinal stretching during myopic progression.

Versatile multi-detector scheme for adaptive optics scanning laser ophthalmoscopy.

Adaptive optics scanning laser ophthalmoscopy (AOSLO) is a powerful tool for imaging the retina at high spatial and temporal resolution. In this paper, we present a multi-detector scheme for AOSLO which has two main configurations: pixel reassignment and offset aperture imaging. In this detection scheme, the single element detector of the standard AOSLO is replaced by a fiber bundle which couples the detected light into multiple detectors. The pixel reassignment configuration enables high resolution imaging with an increased light collection. The increase in signal-to-noise ratio (SNR) from this configuration can improve the accuracy of motion registration techniques. The offset aperture imaging configuration enhances the detection of multiply scattered light, which improves the contrast of retinal vasculature and inner retinal layers similar to methods such as nonconfocal split-detector imaging and multi-offset aperture imaging.

Spatial summation in the human fovea: Do normal optical aberrations and fixational eye movements have an effect?

Psychophysical inferences about the neural mechanisms supporting spatial vision can be undermined by uncertainties introduced by optical aberrations and fixational eye movements, particularly in fovea where the neuronal grain of the visual system is fine. We examined the effect of these preneural factors on photopic spatial summation in the human fovea using a custom adaptive optics scanning light ophthalmoscope that provided control over optical aberrations and retinal stimulus motion. Consistent with previous results, Ricco's area of complete summation encompassed multiple photoreceptors when measured with ordinary amounts of ocular aberrations and retinal stimulus motion. When both factors were minimized experimentally, summation areas were essentially unchanged, suggesting that foveal spatial summation is limited by postreceptoral neural pooling. We compared our behavioral data to predictions generated with a physiologically-inspired front-end model of the visual system, and were able to capture the shape of the summation curves obtained with and without pre-retinal factors using a single postreceptoral summing filter of fixed spatial extent. Given our data and modeling, neurons in the magnocellular visual pathway, such as parasol ganglion cells, provide a candidate neural correlate of Ricco's area in the central fovea.

Suboptimal eye movements for seeing fine details.

Human eyes are never stable, even during attempts of maintaining gaze on a visual target. Considering transient response characteristics of retinal ganglion cells, a certain amount of motion of the eyes is required to efficiently encode information and to prevent neural adaptation. However, excessive motion of the eyes leads to insufficient exposure to the stimuli, which creates blur and reduces visual acuity. Normal miniature eye movements fall in between these extremes, but it is unclear if they are optimally tuned for seeing fine spatial details. We used a state-of-the-art retinal imaging technique with eye tracking to address this question. We sought to determine the optimal gain (stimulus/eye motion ratio) that corresponds to maximum performance in an orientation-discrimination task performed at the fovea. We found that miniature eye movements are tuned but may not be optimal for seeing fine spatial details.

Transverse chromatic aberration across the visual field of the human eye.

The purpose of this study was to measure the transverse chromatic aberration (TCA) across the visual field of the human eye objectively. TCA was measured at horizontal and vertical field angles out to ±15° from foveal fixation in the right eye of four subjects. Interleaved retinal images were taken at wavelengths 543 nm and 842 nm in an adaptive optics scanning laser ophthalmoscope (AOSLO). To obtain true measures of the human eye's TCA, the contributions of the AOSLO system's TCA were measured using an on-axis aligned model eye and subtracted from the ocular data. The increase in TCA was found to be linear with eccentricity, with an average slope of 0.21 arcmin/degree of visual field angle (corresponding to 0.41 arcmin/degree for 430 nm to 770 nm). The absolute magnitude of ocular TCA varied between subjects, but was similar to the resolution acuity at 10° in the nasal visual field, encompassing three to four cones. Therefore, TCA can be visually significant. Furthermore, for high-resolution imaging applications, whether visualizing or stimulating cellular features in the retina, it is important to consider the lateral displacements between wavelengths and the variation in blur over the visual field.

Eye-tracking technology for real-time monitoring of transverse chromatic aberration.

Objective measurements of transverse chromatic aberration (TCA) between two or more wavelengths with an adaptive optics scanning laser ophthalmoscope (AOSLO) are very accurate, but frequent measurements are impractical in many experimental settings. Here, we demonstrate a pupil tracker that can accurately measure relative changes in TCA that are caused by small shifts in the pupil relative to the AOSLO imaging beam. Corrections for TCA caused by these shifts improve the measurement of TCA as a function of eccentricity, revealing a strong linear relationship. We propose that pupil tracking be integrated into AOSLO systems, where robust and unobtrusive control of TCA is required.

Active eye-tracking for an adaptive optics scanning laser ophthalmoscope.

We demonstrate a system that combines a tracking scanning laser ophthalmoscope (TSLO) and an adaptive optics scanning laser ophthalmoscope (AOSLO) system resulting in both optical (hardware) and digital (software) eye-tracking capabilities. The hybrid system employs the TSLO for active eye-tracking at a rate up to 960 Hz for real-time stabilization of the AOSLO system. AOSLO videos with active eye-tracking signals showed, at most, an amplitude of motion of 0.20 arcminutes for horizontal motion and 0.14 arcminutes for vertical motion. Subsequent real-time digital stabilization limited residual motion to an average of only 0.06 arcminutes (a 95% reduction). By correcting for high amplitude, low frequency drifts of the eye, the active TSLO eye-tracking system enabled the AOSLO system to capture high-resolution retinal images over a larger range of motion than previously possible with just the AOSLO imaging system alone.

How the unstable eye sees a stable and moving world.

Eye motion, even during fixation, results in constant motion of the image of the world on our retinas. Vision scientists have long sought to understand the process by which we perceive the stable parts of the world as unmoving despite this instability and perceive the moving parts with realistic motion. We used an instrument capable of delivering visual stimuli with controlled motion relative to the retina at cone-level precision while capturing the subjects' percepts of stimulus motion with a matching task. We found that the percept of stimulus motion is more complex than conventionally thought. Retinal stimuli that move in a direction that is consistent with eye motion (i.e., opposite eye motion) appear stable even if the magnitude of that motion is amplified. The apparent stabilization diminishes for stimulus motions increasingly inconsistent with eye motion direction. Remarkably, we found that this perceived direction-contingent stabilization occurs separately for each separately moving pattern on the retina rather than for the image as a whole. One consequence is that multiple patterns that move at different rates relative to each other in the visual input are perceived as immobile with respect to each other, thereby disrupting our hyperacute sensitivity to target motion against a frame of reference. This illusion of relative stability has profound implications regarding the underlying visual mechanisms. Functionally, the system compensates retinal slip induced by eye motion without requiring an extremely precise optomotor signal and, at the same time, retains an exquisite sensitivity to an object's true motion in the world.

Real-time eye motion correction in phase-resolved OCT angiography with tracking SLO.

In phase-resolved OCT angiography blood flow is detected from phase changes in between A-scans that are obtained from the same location. In ophthalmology, this technique is vulnerable to eye motion. We address this problem by combining inter-B-scan phase-resolved OCT angiography with real-time eye tracking. A tracking scanning laser ophthalmoscope (TSLO) at 840 nm provided eye tracking functionality and was combined with a phase-stabilized optical frequency domain imaging (OFDI) system at 1040 nm. Real-time eye tracking corrected eye drift and prevented discontinuity artifacts from (micro)saccadic eye motion in OCT angiograms. This improved the OCT spot stability on the retina and consequently reduced the phase-noise, thereby enabling the detection of slower blood flows by extending the inter-B-scan time interval. In addition, eye tracking enabled the easy compounding of multiple data sets from the fovea of a healthy volunteer to create high-quality eye motion artifact-free angiograms. High-quality images are presented of two distinct layers of vasculature in the retina and the dense vasculature of the choroid. Additionally we present, for the first time, a phase-resolved OCT angiogram of the mesh-like network of the choriocapillaris containing typical pore openings.

Real-time eye motion compensation for OCT imaging with tracking SLO.

Fixational eye movements remain a major cause of artifacts in optical coherence tomography (OCT) images despite the increases in acquisition speeds. One approach to eliminate the eye motion is to stabilize the ophthalmic imaging system in real-time. This paper describes and quantifies the performance of a tracking OCT system, which combines a phase-stabilized optical frequency domain imaging (OFDI) system and an eye tracking scanning laser ophthalmoscope (TSLO). We show that active eye tracking minimizes artifacts caused by eye drift and micro saccades. The remaining tracking lock failures caused by blinks and large saccades generate a trigger signal which signals the OCT system to rescan corrupted B-scans. Residual motion artifacts in the OCT B-scans are reduced to 0.32 minutes of arc (~1.6 µm) in an in vivo human eye enabling acquisition of high quality images from the optic nerve head and lamina cribrosa pore structure.

High-speed, image-based eye tracking with a scanning laser ophthalmoscope.

We demonstrate a high-speed, image-based tracking scanning laser ophthalmoscope (TSLO) that can provide high fidelity structural images, real-time eye tracking and targeted stimulus delivery. The system was designed for diffraction-limited performance over an 8° field of view (FOV) and operates with a flexible field of view of 1°-5.5°. Stabilized videos of the retina were generated showing an amplitude of motion after stabilization of 0.2 arcmin or less across all frequencies. In addition, the imaging laser can be modulated to place a stimulus on a targeted retinal location. We show a stimulus placement accuracy with a standard deviation less than 1 arcmin. With a smaller field size of 2°, individual cone photoreceptors were clearly visible at eccentricities outside of the fovea.

Comparison of spherical aberration and small-pupil profiles in improving depth of focus for presbyopic corrections.

PURPOSE: To compare the validity and effectiveness of 2 methods for expanding depth of focus to correct for presbyopia; that is, induction of spherical aberration and small-pupil apertures. SETTING: University of California, Berkeley, California, USA. DESIGN: Comparative case series. METHODS: A random 4-alternative forced-choice acuity task was performed on 13 subjects. Visual performance and depth of focus were compared using adaptive optics-corrected distance visual acuity (CDVA) values and mean visual acuity over a 3.0 diopter (D) range of defocus using the following 3 adaptive optics-corrected profiles: 2.0 mm pupil, 5.0 mm pupil, and 5.0 mm pupil with -0.274 µm of spherical aberration. RESULTS: The 5.0 mm pupil profile had a CDVA of -0.218 logMAR and a mean visual acuity through focus of 0.156 logMAR. The 2.0 mm pupil profile had a worse CDVA (0.012 logMAR) but an improved mean visual acuity (0.061 logMAR). The 5.0 mm pupil profile with -0.274 µm of spherical aberration measured a CDVA of -0.082 logMAR and a mean visual acuity of 0.103 logMAR. CONCLUSIONS: The spherical aberration and small-pupil profiles improved the mean visual acuity across a 3.0 D range of defocus but resulted in decreased CDVA at the plane of best focus in comparison to an adaptive optics-corrected 5.0 mm pupil. Small-pupil profiles are a better choice than spherical aberration profiles for presbyopic corrections due to expected accuracy, predictability, and patient satisfaction. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Measurement and correction of transverse chromatic offsets for multi-wavelength retinal microscopy in the living eye.

A special challenge arises when pursuing multi-wavelength imaging of retinal tissue in vivo, because the eye's optics must be used as the main focusing elements, and they introduce significant chromatic dispersion. Here we present an image-based method to measure and correct for the eye's transverse chromatic aberrations rapidly, non-invasively, and with high precision. We validate the technique against hyperacute psychophysical performance and the standard chromatic human eye model. In vivo correction of chromatic dispersion will enable confocal multi-wavelength images of the living retina to be aligned, and allow targeted chromatic stimulation of the photoreceptor mosaic to be performed accurately with sub-cellular resolution.