Hope M. Queener

Adaptive optics scanning laser ophthalmoscopy.

We present the first scanning laser ophthalmoscope that uses adaptive optics to measure and correct the high order aberrations of the human eye. Adaptive optics increases both lateral and axial resolution, permitting axial sectioning of retinal tissue in vivo. The instrument is used to visualize photoreceptors, nerve fibers and flow of white blood cells in retinal capillaries.

Reproducibility of Measuring Lamina Cribrosa Pore Geometry in Human and Nonhuman Primates with In Vivo Adaptive Optics Imaging

PURPOSE The ability to consistently resolve lamina cribrosa pores in vivo has applications in the study of optic nerve head and retinal disease mechanisms. Repeatability was assessed in imaging laminar pores in normal living eyes with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). METHODS Reflectance images (840 nm) of the anterior lamina cribrosa were acquired using the AOSLO in four or more different sessions in two normal rhesus monkey eyes and three normal human eyes. Laminar pore areas, elongations (ratio of major to minor axes of the best-fit ellipse) and nearest neighbor distances were calculated for each session. Measurement repeatability was assessed across sessions. RESULTS Pore areas ranged from 90 to 4365 μm(2) in monkeys and 154 to 6637 μm(2) in humans. Mean variabilities in measuring pore area and elongation (i.e., mean of the standard deviation of measurements made across sessions for the same pores) were 50 μm(2) (6.1%) and 0.13 (6.7%), respectively, in monkeys and 113 μm(2) (8.3%) and 0.17 (7.7%), respectively, in humans. Mean variabilities in measuring nearest neighbor distances were 1.93 μm (5.2%) in monkeys and 2.79 μm (4.1%) in humans. There were no statistically significant differences in any pore parameters across sessions (ANOVA, P > 0.05). CONCLUSIONS The anterior lamina cribrosa was consistently imaged in vivo in normal monkey and human eyes. The small intersession variability in normal pore geometry suggests that AOSLO imaging could be used to measure and track changes in laminar pores in vivo during glaucomatous progression.

Wavefront sensorless adaptive optics ophthalmoscopy in the human eye

Wavefront sensor noise and fidelity place a fundamental limit on achievable image quality in current adaptive optics ophthalmoscopes. Additionally, the wavefront sensor ‘beacon’ can interfere with visual experiments. We demonstrate real-time (25 Hz), wavefront sensorless adaptive optics imaging in the living human eye with image quality rivaling that of wavefront sensor based control in the same system. A stochastic parallel gradient descent algorithm directly optimized the mean intensity in retinal image frames acquired with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). When imaging through natural, undilated pupils, both control methods resulted in comparable mean image intensities. However, when imaging through dilated pupils, image intensity was generally higher following wavefront sensor-based control. Despite the typically reduced intensity, image contrast was higher, on average, with sensorless control. Wavefront sensorless control is a viable option for imaging the living human eye and future refinements of this technique may result in even greater optical gains.

3D modeling to characterize lamina cribrosa surface and pore geometries using in vivo images from normal and glaucomatous eyes

En face adaptive optics scanning laser ophthalmoscope (AOSLO) images of the anterior lamina cribrosa surface (ALCS) represent a 2D projected view of a 3D laminar surface. Using spectral domain optical coherence tomography images acquired in living monkey eyes, a thin plate spline was used to model the ALCS in 3D. The 2D AOSLO images were registered and projected onto the 3D surface that was then tessellated into a triangular mesh to characterize differences in pore geometry between 2D and 3D images. Following 3D transformation of the anterior laminar surface in 11 normal eyes, mean pore area increased by 5.1 ± 2.0% with a minimal change in pore elongation (mean change = 0.0 ± 0.2%). These small changes were due to the relatively flat laminar surfaces inherent in normal eyes (mean radius of curvature = 3.0 ± 0.5 mm). The mean increase in pore area was larger following 3D transformation in 4 glaucomatous eyes (16.2 ± 6.0%) due to their more steeply curved laminar surfaces (mean radius of curvature = 1.3 ± 0.1 mm), while the change in pore elongation was comparable to that in normal eyes (−0.2 ± 2.0%). This 3D transformation and tessellation method can be used to better characterize and track 3D changes in laminar pore and surface geometries in glaucoma.

A correction algorithm to simultaneously control dual deformable mirrors in a woofer-tweeter adaptive optics system

We present a direct slope-based correction algorithm to simultaneously control two deformable mirrors (DMs) in a woofer-tweeter adaptive optics system. A global response matrix was derived from the response matrices of each deformable mirror and the voltages for both deformable mirrors were calculated simultaneously. This control algorithm was tested and compared with a 2-step sequential control method in five normal human eyes using an adaptive optics scanning laser ophthalmoscope. The mean residual total root-mean-square (RMS) wavefront errors across subjects after adaptive optics (AO) correction were 0.128 ± 0.025 μm and 0.107 ± 0.033 μm for simultaneous and 2-step control, respectively (7.75-mm pupil). The mean intensity of reflectance images acquired after AO convergence was slightly higher for 2-step control. Radially-averaged power spectra calculated from registered reflectance images were nearly identical for all subjects using simultaneous or 2-step control. The correction performance of our new simultaneous dual DM control algorithm is comparable to 2-step control, but is more efficient. This method can be applied to any woofer-tweeter AO system.

Attenuation of short wavelengths alters sleep and the ipRGC pupil response

Exposure to increasing amounts of artificial light during the night may contribute to the high prevalence of reported sleep dysfunction. Release of the sleep hormone melatonin is mediated by the intrinsically photosensitive retinal ganglion cells (ipRGCs). This study sought to investigate whether melatonin level and sleep quality can be modulated by decreasing night‐time input to the ipRGCs.

Optimizing wavefront-guided corrections for highly aberrated eyes in the presence of registration uncertainty.

Dynamic registration uncertainty of a wavefront-guided correction with respect to underlying wavefront error (WFE) inevitably decreases retinal image quality. A partial correction may improve average retinal image quality and visual acuity in the presence of registration uncertainties. The purpose of this paper is to (a) develop an algorithm to optimize wavefront-guided correction that improves visual acuity given registration uncertainty and (b) test the hypothesis that these corrections provide improved visual performance in the presence of these uncertainties as compared to a full-magnitude correction or a correction by Guirao, Cox, and Williams (2002). A stochastic parallel gradient descent (SPGD) algorithm was used to optimize the partial-magnitude correction for three keratoconic eyes based on measured scleral contact lens movement. Given its high correlation with logMAR acuity, the retinal image quality metric log visual Strehl was used as a predictor of visual acuity. Predicted values of visual acuity with the optimized corrections were validated by regressing measured acuity loss against predicted loss. Measured loss was obtained from normal subjects viewing acuity charts that were degraded by the residual aberrations generated by the movement of the full-magnitude correction, the correction by Guirao, and optimized SPGD correction. Partial-magnitude corrections optimized with an SPGD algorithm provide at least one line improvement of average visual acuity over the full magnitude and the correction by Guirao given the registration uncertainty. This study demonstrates that it is possible to improve the average visual acuity by optimizing wavefront-guided correction in the presence of registration uncertainty.

In Vivo Changes in Lamina Cribrosa Microarchitecture and Optic Nerve Head Structure in Early Experimental Glaucoma

The lamina cribrosa likely plays an important role in retinal ganglion cell axon injury in glaucoma. We sought to (1) better understand optic nerve head (ONH) structure and anterior lamina cribrosa surface (ALCS) microarchitecture between fellow eyes of living, normal non-human primates and (2) characterize the time-course of in vivo structural changes in the ONH, ALCS microarchitecture, and retinal nerve fiber layer thickness (RNFLT) in non-human primate eyes with early experimental glaucoma (EG). Spectral domain optical coherence tomography (SDOCT) images of the ONH were acquired cross-sectionally in six bilaterally normal rhesus monkeys, and before and approximately every two weeks after inducing unilateral EG in seven rhesus monkeys. ONH parameters and RNFLT were quantified from segmented SDOCT images. Mean ALCS pore area, elongation and nearest neighbor distance (NND) were quantified globally, in sectors and regionally from adaptive optics scanning laser ophthalmoscope images. In bilaterally normal monkeys, ONH parameters were similar between fellow eyes with few inter-eye differences in ALCS pore parameters. In EG monkeys, an increase in mean ALCS Depth (ALCSD) was the first structural change measured in 6 of 7 EG eyes. A decrease in mean minimum rim width (MRW) simultaneously accompanied this early change in 4 of 6 EG eyes and was the first structural change in the 7th EG eye. Mean ALCS pore parameters were among the first or second changes measured in 4 EG eyes. Mean ALCS pore area and NND increased in superotemporal and temporal sectors and in central and peripheral regions at the first time-point of change in ALCS pore geometry. RNFLT and/or mean ALCS radius of curvature were typically the last parameters to initially change. Survival analyses found mean ALCSD was the only parameter to significantly show an initial change prior to the first measured loss in RNFLT across EG eyes.

Impact of simulated micro-scotomas on reading performance in central and peripheral retina

Observers with central field loss typically fixate within a non-foveal region called the preferred retinal locus, which can include localized sensitivity losses, or micro-scotomas (Krishnan and Bedell, 2018). In this study, we simulated micro-scotomas at the fovea and in the peripheral retina to assess their impact on reading speed. Ten younger (<36 years old) and 8 older (>50 years old) naïve observers with normal vision monocularly read high and/or low contrast sentences, presented at or above the critical print size for young observers at the fovea and at 5 and 10 deg in the inferior visual field. Reading material comprised MNREAD sentences and sentences taken from novels that were presented in rapid serial visual presentation (RSVP) format. Randomly distributed 13 × 13 arc min blocks corresponding to 0-78% of the text area (corresponding to ∼0-17 micro-scotomas/deg2) were set to the background luminance to simulate micro-scotomas. A staircase algorithm estimated maximum reading speed from the threshold exposure duration for each combination of retinal eccentricity, contrast and micro-scotoma density in both age groups. Log10(RSVP reading speed) decreased significantly with simulated micro-scotoma density and eccentricity. Across conditions, reading speed was slower with low-compared to high-contrast text and was faster in younger than older normal observers. For a given eccentricity and contrast, a higher density of random element losses maximally affected older observers with normal vision. These outcomes may explain some of the reading deficits observed in older observers with central field loss.

Properties and performance of the adaptive optics scanning laser ophthalmoscope

The adaptive optics scanning laser ophthalmoscope (AOSLO) combines an ophthalmic adaptive optics system [1] with a confocal scanning laser ophthalmoscope [2]. Adaptive optics (AO) are used to overcome blur in retinal images that is caused by aberrations in the cornea and lens of the eye. By using adaptive optics, microscopic retinal features are visualized [3]. 30 frame-per-second imaging has revealed the flow of individual leukocytes in the smallest retinal capillaries. The increased optical sectioning ability allows for true optical sectioning of retinal layers. The AOSLO uses a 37-channel deformable mirror (Xinetics, Andover MA), combined with a Shack Hartmann wavefront sensor (400 µm lenslets, 24 mm focal length). 512 × 480 pixel images of a 1.5 × 1.4 degree field are captured at 30 frames per second. The imaging wavelength is 660 nm but other wavelength imaging is possible. The AOSLO measures and compensates for the wave aberrations at about 1 Hz simultaneously with image acquisition. Here we describe the latest advances in retinal imaging with the AOSLO instrument.