Closed-loop experimental optimization of tunable lenses.

Tunable lenses (TLs) are optical devices that can change their optical power in response to an electrical signal. In many applications, they are often pushed to or beyond their temporal limits. Fast periodic and/or abrupt variations of the optical power induce undesired distortions in their transient response and produce a decrease in their performance. A low-cost focimetry system, along with a custom closed-loop iterative optimization algorithm, was developed to (1) characterize a TL's response at high speed and (2) optimize their performance in realistic TL working conditions. A significant lens performance improvement was found in about 23 iterations with a decrease in the area under the error curve and an improved effective time. Applying the closed-loop optimization algorithm in a depth scanning experiment enhanced the image quality. Quantitatively, the image quality was evaluated using the structural similarity index metric that improves in individual frames, on average, from 0.345 to 0.895.

VioBio lab adaptive optics: technology and applications by women vision scientists.

PURPOSE: Adaptive Optics allows measurement and manipulation of the optical aberrations of the eye. We review two Adaptive Optics set-ups implemented at the Visual Optics and Biophotonics Laboratory, and present examples of their use in better understanding of the role of optical aberrations on visual perception, in normal and treated eyes. RECENT FINDINGS: Two systems (AOI and AOII) are described that measure ocular aberrations with a Hartmann-Shack wavefront sensor, which operates in closed-loop with an electromagnetic deformable mirror, and visual stimuli are projected in a visual display for psychophysical measurements. AOI operates in infrared radiation (IR) light. AOII is provided with a supercontiniuum laser source (IR and visible wavelengths), additional elements for simulation (spatial light modulator, temporal multiplexing with optotunable lenses, phase plates, cuvette for intraocular lenses-IOLs), and a double-pass retinal camera. We review several studies undertaken with these AO systems, including the evaluation of the visual benefits of AO correction, vision with simulated multifocal IOLs (MIOLs), optical aberrations in pseudophakic eyes, chromatic aberrations and their visual impact, and neural adaptation to ocular aberrations. SUMMARY: Monochromatic and chromatic aberrations have been measured in normal and treated eyes. AO systems have allowed understanding the visual benefit of correcting aberrations in normal eyes and the adaptation of the visual system to the eye's native aberrations. Ocular corrections such as intraocular and contact lenses modify the wave aberrations. AO systems allow simulating vision with these corrections before they are implanted/fitted in the eye, or even before they are manufactured, revealing great potential for industry and the clinical practice. This review paper is part of a special issue of Ophthalmic & Physiological Optics on women in visual optics, and is co-authored by all women scientists of the research team.

Cones in ageing and harsh environments: the neural economy hypothesis.

PURPOSE: Cones are at great risk in a wide variety of retinal diseases, especially when there is a harsh microenvironment and retinal pigment epithelium is damaged. We provide established and new methods for assessing cones and retinal pigment epithelium, together with new results. We investigated conditions under which cones can be imaged and could guide light, despite the proximity of less than ideal retinal pigment epithelium. RECENT FINDINGS: We used a variety of imaging methods to detect and localise damage to the retinal pigment epithelium. As age-related macular degeneration is a particularly widespread disease, we imaged clinical hallmarks: drusen and hyperpigmentation. Using near infrared light provided improved imaging of the deeper fundus layers. We compared confocal and multiply scattered light images, using both the variation of detection apertures and polarisation analysis. We used optical coherence tomography to examine distances between structures and thickness of retinal layers, as well as identifying damage to the retinal pigment epithelium. We counted cones using adaptive optics scanning laser ophthalmoscopy. We compared the results of five subjects with geographic atrophy to data from a previous normative ageing study. Using near infrared imaging and layer analysis of optical coherence tomography, the widespread aspect of drusen became evident. Both multiply scattered light imaging and analysis of the volume in the retinal pigment epithelial layer from the optical coherence tomography were effective in localising drusen and hyperpigmentation beneath the photoreceptors. Cone photoreceptors in normal older eyes were shorter than in younger eyes. Cone photoreceptors survived in regions of atrophy, but with greatly reduced and highly variable density. Regular arrays of cones were found in some locations, despite abnormal retinal pigment epithelium. For some subjects, the cone density was significantly greater than normative values in some retinal locations outside the atrophy. SUMMARY: The survival of cones within atrophy is remarkable. The unusually dense packing of cones at some retinal locations outside the atrophy indicates more fluidity in cone distribution than typically thought. Together these findings suggest strategies for therapy that includes preserving cones.

Tunable lenses: dynamic characterization and fine-tuned control for high-speed applications.

Tunable lenses are becoming ubiquitous, in applications including microscopy, optical coherence tomography, computer vision, quality control, and presbyopic corrections. Many applications require an accurate control of the optical power of the lens in response to a time-dependent input waveform. We present a fast focimeter (3.8 KHz) to characterize the dynamic response of tunable lenses, which was demonstrated on different lens models. We found that the temporal response is repetitive and linear, which allowed the development of a robust compensation strategy based on the optimization of the input wave, using a linear time-invariant model. To our knowledge, this work presents the first procedure for a direct characterization of the transient response of tunable lenses and for compensation of their temporal distortions, and broadens the potential of tunable lenses also in high-speed applications.

Adaptive optics retinal imaging with automatic detection of the pupil and its boundary in real time using Shack-Hartmann images.

Retinal imaging with an adaptive optics (AO) system usually requires that the eye be centered and stable relative to the exit pupil of the system. Aberrations are then typically corrected inside a fixed circular pupil. This approach can be restrictive when imaging some subjects, since the pupil may not be round and maintaining a stable head position can be difficult. In this paper, we present an automatic algorithm that relaxes these constraints. An image quality metric is computed for each spot of the Shack-Hartmann image to detect the pupil and its boundary, and the control algorithm is applied only to regions within the subject's pupil. Images on a model eye as well as for five subjects were obtained to show that a system exit pupil larger than the subject's eye pupil could be used for AO retinal imaging without a reduction in image quality. This algorithm automates the task of selecting pupil size. It also may relax constraints on centering the subject's pupil and on the shape of the pupil.

Rapid high resolution imaging with a dual-channel scanning technique.

A spatial shift between channels in a dual-beam raster-scan imaging system introduces a temporal separation between images from the two channels that can be much shorter than the frame rate of the system. The technique is demonstrated by measuring the velocity of erythrocytes in the retinal capillaries. We used an adaptive optics scanning laser ophthalmoscope and introduced a temporal separation between imaging channels of 4.7 ms. We imaged three subjects and measured changing capillary blood flow velocity at the pulse rate. Since the time shift between channels is easily and continuously adjustable, this method can be used to measure rapidly changing events in any raster scan system with little added complexity.

Single neural code for blur in subjects with different interocular optical blur orientation.

The ability of the visual system to compensate for differences in blur orientation between eyes is not well understood. We measured the orientation of the internal blur code in both eyes of the same subject monocularly by presenting pairs of images blurred with real ocular point spread functions (PSFs) of similar blur magnitude but varying in orientations. Subjects assigned a level of confidence to their selection of the best perceived image in each pair. Using a classification-images-inspired paradigm and applying a reverse correlation technique, a classification map was obtained from the weighted averages of the PSFs, representing the internal blur code. Positive and negative neural PSFs were obtained from the classification map, representing the neural blur for best and worse perceived blur, respectively. The neural PSF was found to be highly correlated in both eyes, even for eyes with different ocular PSF orientations (rPos = 0.95; rNeg = 0.99; p < 0.001). We found that in subjects with similar and with different ocular PSF orientations between eyes, the orientation of the positive neural PSF was closer to the orientation of the ocular PSF of the eye with the better optical quality (average difference was ∼10°), while the orientation of the positive and negative neural PSFs tended to be orthogonal. These results suggest a single internal code for blur with orientation driven by the orientation of the optical blur of the eye with better optical quality.

Impact of astigmatism and high-order aberrations on subjective best focus.

We studied the role of native astigmatism and ocular aberrations on best-focus setting and its shift upon induction of astigmatism in 42 subjects (emmetropes, myopes, hyperopes, with-the-rule [WTR] and against-the-rule [ATR] myopic astigmats). Stimuli were presented in a custom-developed adaptive optics simulator, allowing correction for native aberrations and astigmatism induction (+1 D; 6-mm pupil). Best-focus search consisted on randomized-step interleaved staircase method. Each subject searched best focus for four different images, and four different conditions (with/without aberration correction, with/without astigmatism induction). The presence of aberrations induced a significant shift in subjective best focus (0.4 D; p < 0.01), significantly correlated (p = 0.005) with the best-focus shift predicted from optical simulations. The induction of astigmatism produced a statistically significant shift of the best-focus setting in all groups under natural aberrations (p = 0.001), and in emmetropes and in WTR astigmats under corrected aberrations (p < 0.0001). Best-focus shift upon induced astigmatism was significantly different across groups, both for natural aberrations and AO-correction (p < 0.0001). Best focus shifted in opposite directions in WTR and ATR astigmats upon induction of astigmatism, symmetrically with respect to the best-focus shift in nonastigmatic myopes. The shifts are consistent with a bias towards vertical and horizontal retinal blur in WTR and ATR astigmats, respectively, indicating adaptation to native astigmatism.

Simulation of daily soft multifocal contact lenses using SimVis Gekko: from in-vitro and computational characterization to clinical validation.

Multifocal contact lenses (MCLs) are one of the solutions to correct presbyopia, but their adoption is not widespread. To address this situation, visual simulators can be used to refine the adaptation process. This study aims to obtain accurate simulations for a visual simulator (SimVis Gekko; 2EyesVision) of daily soft MCL designs from four manufacturers. In-vitro characterization of these MCLs-several powers and additions- was obtained using NIMO TR-1504. From the averaged relative power profiles across powers, phase maps were reconstructed and the Through-Focus Visual Strehl metric was calculated for each MCL design. The SimVis Gekko simulation corresponding to each MCL design was obtained computationally and bench-validated. Finally, the MCL simulations were clinically validated involving presbyopic patients. The clinical validation results show a good agreement between the SimVis Gekko simulations and the real MCLs for through-focus visual acuity (TF-VA) curves and VA at three real distances. All MCL designs showed a partial correlation higher than 0.90 and a Root Mean Square Error below 0.07 logMAR between the TF-VA of simulations and Real MCLs across subjects. The validity of the simulation approach using SimVis Gekko and in-vitro measurements was confirmed in this study, opening the possibility to accelerate the adaptation of MCLs.

Astigmatism impact on visual performance: meridional and adaptational effects.

PURPOSE: Astigmatic subjects are adapted to their astigmatism and perceptually recalibrate upon its correction. However, the extent to which prior adaptation to astigmatism affects visual performance, whether this effect is axis dependent, and the time scale of potential changes in visual performance after astigmatism correction are not known. Moreover, the effect of possible positive interactions of aberrations (astigmatism and coma) might be altered after recalibration to correction of astigmatism. METHODS: Visual acuity (VA) was measured in 25 subjects (astigmats and non-astigmats, corrected and uncorrected) under induction of astigmatism and combinations of astigmatism and coma while controlling subject aberrations. Astigmatism (1.00 diopter) was induced at three different orientations, the natural axis, the perpendicular orientation, and 45 degrees for astigmats and at 0, 90, and 45 degrees for non-astigmats. Experiments were also performed, adding coma (0.41 µm at a relative angle of 45 degrees) to the same mentioned astigmatism. Fourteen different conditions were measured using an 8-Alternative Forced Choice procedure with Tumbling E letters and a QUEST algorithm. Longitudinal measurements were performed up to 6 months. Uncorrected astigmats were provided with proper astigmatic correction after the first session. RESULTS: In non-astigmats, inducing astigmatism at 90 degrees, produced a statistically lower reduction in VA than at 0 or 45 degrees, whereas in astigmats, the lower decrease in VA occurred for astigmatism induced at the natural axis. Six months of astigmatic correction did not reduce the insensitivity to astigmatic induction along the natural axis. Differences after orientation of astigmatism were also found when adding coma to astigmatism. CONCLUSIONS: The impact of astigmatism on VA is greatly dependent on the orientation of the induced astigmatism, even in non-astigmats. Previous experience to astigmatism plays a significant role on VA, with a strong bias toward the natural axis. In contrast to perceived isotropy, the correction of astigmatism does not shift the bias in VA from the natural axis of astigmatism.

Adaptation to interocular differences in blur.

Adaptation to a blurred image causes a physically focused image to appear too sharp, and shifts the point of subjective focus toward the adapting blur, consistent with a renormalization of perceived focus. We examined whether and how this adaptation normalizes to differences in blur between the two eyes, which can routinely arise from differences in refractive errors. Observers adapted to images filtered to simulate optical defocus or different axes of astigmatism, as well as to images that were isotropically blurred or sharpened by varying the slope of the amplitude spectrum. Adaptation to the different types of blur produced strong aftereffects that showed strong transfer across the eyes, as assessed both in a monocular adaptation task and in a contingent adaptation task in which the two eyes were simultaneously exposed to different blur levels. Selectivity for the adapting eye was thus generally weak. When one eye was exposed to a sharper image than the other, the aftereffects also tended to be dominated by the sharper image. Our results suggest that while short-term adaptation can rapidly recalibrate the perception of blur, it cannot do so independently for the two eyes, and that the binocular adaptation of blur is biased by the sharper of the two eyes' retinal images.

Experimental characterization, modelling and compensation of temperature effects in optotunable lenses.

Most tunable lenses (TLs) are affected by deviations in optical power induced by external temperature changes or due to internal heating while in use. This study proposes: (1) An experimental characterization method to evaluate the magnitude of the optical power deviations due to internal temperature shifts; (2) three different mathematical models (experimental, polynomial, and optimized) to describe the response of the lens with temperature; (3) predictions of the internal temperature shifts while using the lens in time frames of minutes, seconds, and milliseconds and; (4) a real time optical power compensation tool based on the implementation of the models on a custom voltage electronic driver. The compensation methods were successfully applied to two TL samples in static and dynamic experiments and in hysteresis cycles. After 40 min at a static nominal power of 5 diopters (dpt), the internal temperature exponentially increased by 17 °C, producing an optical power deviation of 1.0 dpt (1.5 dpt when the lens cools down), representing a 20% distortion for heating and 30% for cooling. Modelling and compensation reduced the deviations to 0.2 dpt when heating (0.35 dpt when cooling) and the distortions to 4% and 7%. Similar levels of improvement were obtained in dynamic and hysteresis experiments. Compensation reduced temperature effects by more than 75%, representing a significant improvement in the performance of the lens.

Dependence of subjective image focus on the magnitude and pattern of high order aberrations.

The image formed by the eye's optics is inherently blurred by aberrations specific to the individual's eyes. We examined to what extent judgments of perceived focus depend on the total magnitude as opposed to the specific pattern of blur introduced by the eye's high order aberrations (HOA). An Adaptive Optics system was used to simultaneously correct each subject's wave aberrations and display natural images blurred by simulated aberrations. To isolate the effects of blur magnitude, images were blurred by pure symmetric defocus, and subjects judged the level of the defocus that subjectively appeared best focused (i.e., neither too blurred nor too sharp). These settings were strongly correlated with the native blur magnitude. To isolate the effect of the HOA pattern, retinal image blur was instead maintained at a constant blur (Strehl Ratio) equal to each subject's natural blur, and subjects judged the best-focused image from pairs of images blurred by different patterns of HOA, one selected from 100 patterns, the other blurred by a reference pattern which included the subject's natural HOA, rotated HOA, or nine other HOA patterns. The percentage of images judged as best focused was not systematically higher when filtered with the subject's own HOA pattern. However, all subjects preferred their own HOA to the rotated version significantly more often (57% versus 45% on average across subjects). The representation of subjective image focus thus appears to be driven primarily by the overall amount of blur and only weakly by HOA blur orientation.

Adapting to blur produced by ocular high-order aberrations.

The perceived focus of an image can be strongly biased by prior adaptation to a blurred or sharpened image. We examined whether these adaptation effects can occur for the natural patterns of retinal image blur produced by high-order aberrations (HOAs) in the optics of the eye. Focus judgments were measured for 4 subjects to estimate in a forced choice procedure (sharp/blurred) their neutral point after adaptation to different levels of blur produced by scaled increases or decreases in their HOAs. The optical blur was simulated by convolution of the PSFs from the 4 different HOA patterns, with Zernike coefficients (excluding tilt, defocus, and astigmatism) multiplied by a factor between 0 (diffraction limited) and 2 (double amount of natural blur). Observers viewed the images through an Adaptive Optics system that corrected their aberrations and made settings under neutral adaptation to a gray field or after adapting to 5 different blur levels. All subjects adapted to changes in the level of blur imposed by HOA regardless of which observer's HOA was used to generate the stimuli, with the perceived neutral point proportional to the amount of blur in the adapting image.

Visual performance with real-life tasks under adaptive-optics ocular aberration correction.

We measured the effect of the correction of the natural aberrations of the eye by means of adaptive optics on the subject's performance on three different visual tasks: subjective sharpness assessment of natural images, familiar face recognition, and facial expression recognition. Images were presented through a dedicated psychophysical channel and viewed through an electromagnetic deformable mirror. Experiments were performed on 17 normal subjects. Ocular aberrations (astigmatism and higher order aberrations) were reduced on average from 0.366 +/- 0.154 to 0.101 +/- 0.055 mum for a 5-mm pupil diameter. On average, subjects considered to be sharper 84 +/- 14% of the images viewed under AO correction, and there was a significant correlation between the amount of corrected aberrations and the percentage of images that the subject considered sharper when observed under AO-corrected aberrations. In all eyes (except one), AO correction improved familiar face recognition, by a factor of x1.13 +/- 0.12 on average. However, AO correction did not improve systematically facial expression recognition.

Adaptation to astigmatic blur.

Adapting to blurred or sharpened images alters the perceived focus of subsequently viewed images. We examined whether these adaptation effects could arise from actual sphero-cylindrical refractive errors, by testing aftereffects in images simulating second-order astigmatism. Image blur was varied from negative (vertical) through isotropic to positive (horizontal) astigmatism while maintaining constant blur strength. A 2AFC staircase was used to estimate the stimulus that appeared isotropically blurred before or after adapting to images with astigmatism. Adaptation to horizontal blur caused isotropically blurred images to appear vertically biased and vice versa, shifting the perceived isotropic point toward the adapting level. Aftereffects were similar for different types of images and showed partial selectivity so that strongest effects generally occurred when testing and adapting images were the same. Further experiments explored whether the adaptation depended more strongly on the blurring or "fuzziness" in the images vs. the apparent "figural" changes introduced by the blur, by comparing how the aftereffects transfer across changes in size or orientation. Our results suggest that strong selective adaptation can occur for different lower order aberrations of the eye and that these may be at least partly driven by the apparent figural changes that blurring introduces into the retinal image.

Full-field flicker evoked changes in parafoveal retinal blood flow.

When retinal activity is increased by exposure to dynamic visual stimuli, blood vessels dilate and the flow of blood within vessels increases to meet the oxygen and glucose demands of the neurons. This relationship is termed 'neurovascular coupling' and it is critical for regulating control of the human retinal vasculature. In this study, we used a recently developed technique based on a dual-beam adaptive optics scanning laser ophthalmoscope to measure changes in red blood cell velocities, vessel diameter, and flow in interconnected small parafoveal retinal vessels (< 50 µm) of nine healthy participants. A full-field flicker stimulus was presented onto the retina to induce a vascular response to neural activity. Flicker stimulation increased blood velocity, vessel diameter, and therefore flow in arterioles, capillaries, and venules in all nine subjects. ANOVA and post hoc t-test showed significant increases in velocity and flow in arterioles and venules. These measurements indicate that the mechanism of neurovascular coupling systematically affects the vascular response in small retinal vessels in order to maintain hemodynamic regulation in the retina when exposed to visual stimulation, in our case flicker. Our findings may provide insight into future investigations on the impairments of neurovascular coupling from vascular diseases such as diabetic mellitus.

Optical and Visual Quality With Physical and Visually Simulated Presbyopic Multifocal Contact Lenses.

Purpose: As multifocal contact lenses (MCLs) expand as a solution for presbyopia correction, a better understanding of their optical and visual performance becomes essential. Also, providing subjects with the experience of multifocal vision before contact lens fitting becomes critical, both to systematically test different multifocal designs and to optimize selection in the clinic. In this study, we evaluated the ability of a simultaneous vision visual simulator (SimVis) to represent MCLs. Methods: Through focus (TF) optical and visual quality with a center-near aspheric MCL (low, medium and high near adds) were measured using a multichannel polychromatic Adaptive Optics visual simulator equipped with double-pass, SimVis (temporal multiplexing), and psychophysical channels to allow measurements on-bench and in vivo. On bench TF optical quality of SimVis-simulated MCLs was obtained from double-pass (DP) images and images of an E-stimulus using artificial eyes. Ten presbyopic subjects were fitted with the MCL. Visual acuity (VA) and DP retinal images were measured TF in a 4.00 D range with the MCL on eye, and through SimVis simulations of the same MCLs on the same subjects. Results: TF optical (on bench and in vivo) and visual (in vivo) quality measurements captured the expected broadening of the curves with increasing add. Root mean square difference between real and SimVis-simulated lens was 0.031/0.025 (low add), 0.025/0.015 (medium add), 0.019/0.011 (high add), for TF DP and TF LogMAR VA, respectively. A shape similarity metric shows high statistical values (lag κ = 0), rho = 0.811/0.895 (low add), 0.792/0.944 (medium add), and 0.861/0.915 (high add) for TF DP/LogMAR VA, respectively. Conclusions: MCLs theoretically and effectively expand the depth of focus. A novel simulator, SimVis, captured the through-focus optical and visual performance of the MCL in most of the subjects. Visual simulators allow subjects to experience vision with multifocal lenses prior to testing them on-eye. Translational Relevance: Simultaneous visual simulators allow subjects to experience multifocal vision non-invasively. We demonstrated equivalency between real multifocal contact lenses and SimVis-simulated lenses. The results suggest that SimVis is a suitable technique to aid selection of presbyopic corrections in the contactology practice.

Accommodative lag and fluctuations when optical aberrations are manipulated.

We evaluated the accommodative response to a stimulus moving from 0 to 6 D following a staircase function under natural, corrected, and induced optical aberrations, using an adaptive-optics (AO) electromagnetic deformable mirror. The accommodative response of the eye (through the mirror) and the change of aberrations were measured on 5 subjects using a Hartmann-Shack wavefront sensor operating at 12.8 Hz. Five conditions were tested: (1) natural aberrations, (2) AO correction of the unaccommodated state and induction (over 6-mm pupils) of (3) +1 microm and (4) -1 microm of spherical aberration and (5) -2 microm of vertical coma. Four subjects showed a better accommodative response with AO correction than with their natural aberrations. The induction of negative spherical aberration also produced a better accommodative response in the same subjects. Accommodative lag increased in all subjects when positive spherical aberration and coma were induced. Fluctuations of the accommodative response (computed during each 1-D period of steady accommodation) increased with accommodative response when high-order aberrations were induced. The largest fluctuations occurred for induced negative spherical aberration and the smallest for natural and corrected aberrations. The study demonstrates that aberrations influence accommodative lag and fluctuations of accommodation and that correcting aberrations improves rather than compromises the accommodative response.

Effect of Crystalline Lens Aberrations on Adaptive Optics Simulation of Intraocular Lenses.

PURPOSE: To evaluate the impact of the lens aberrations on the adaptive optics visual simulation of pseudophakic intraocular lens (IOL) profiles. METHODS: In 20 right phakic eyes, lens higher order aberrations (HOAs) were calculated as the whole eye minus the corneal aberrations. Visual simulation using low and high contrast corrected distance visual acuity (CDVA) testing was carried out with the VAO instrument (Voptica, SL, Murcia, Spain), considering three optical conditions of the lens: removing HOA (no lens-HOA), removing spherical aberration (no lens-SA), and with lens HOA (natural condition). In addition, a through-focus visual simulation of a trifocal diffractive IOL profile with high contrast CDVA was also measured in two conditions: no lens-HOA and natural condition. Three different pupil sizes (3, 4.5, and 6 mm) were tested for all conditions. RESULTS: There were no significant intersubject differences between the three optical conditions and in the IOL simulation for all pupil sizes (P > .05). For 4.5- and 6-mm pupils, mean VA values of the no-lens SA and no lens-HOA conditions were similar and slightly worse than those of the natural condition. Individual differences between the no lens-HOA condition and the other two optical conditions, estimated as 95% limits of agreement, were acceptable for 3-mm pupil but worse as pupil diameter increased. CONCLUSIONS: The effect of lens aberrations on visual simulation is imperceptible for a small pupil diameter of 3 mm. Although the increment of pupil size increases the probability of patients with significant visual impact of lens HOAs, the mean intersubject VA differences are negligible. [J Refract Surg. 2019;35(2):126-131.].