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.

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.

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.

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.

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.

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.

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.].

High speed visual stimuli generator to estimate the minimum presentation time required for an orientation discrimination task.

How brief can a visual stimulus be and still be seen? To answer this question, we developed a digital micromirror device (DMD) based system operating at high speed (22.7 kHz) to control the rapid presentation of visual stimuli and estimated the minimum time required to identify the orientation of tumbling Snellen E letters. Time thresholds were measured in five subjects using a QUEST algorithm to vary the presentation time of the letters subtending either 0.75°, 1.5° and 4.5° on the retina, for two different effective pupil sizes (0.3 and 1 mm). Additionally, to evaluate the effect of defocus on time thresholds, the experiment was repeated with 1.5° letters and induced myopic defocus with 3, 6 and 9 D trial lenses placed in a conjugated pupil plane. We found that subjects were able to identify the orientation of the letters presented as briefly as 5 ms.

Enhanced retinal vasculature imaging with a rapidly configurable aperture.

In adaptive optics scanning laser ophthalmoscope (AOSLO) systems, capturing multiply scattered light can increase the contrast of the retinal microvasculature structure, cone inner segments, and retinal ganglion cells. Current systems generally use either a split detector or offset aperture approach to collect this light. We tested the ability of a spatial light modulator (SLM) as a rapidly configurable aperture to use more complex shapes to enhance the contrast of retinal structure. Particularly, we varied the orientation of a split detector aperture and explored the use of a more complex shape, the half annulus, to enhance the contrast of the retinal vasculature. We used the new approach to investigate the influence of scattering distance and orientation on vascular imaging.

Experimental validations of a tunable-lens-based visual demonstrator of multifocal corrections.

The Simultaneous Vision simulator (SimVis) is a visual demonstrator of multifocal lens designs for prospective intraocular lens replacement surgery patients and contact lens wearers. This programmable device employs a fast tunable lens and works on the principle of temporal multiplexing. The SimVis input signal is tailored to mimic the optical quality of the multifocal lens using the theoretical SimVis temporal profile, which is evaluated from the through-focus Visual Strehl ratio metric of the multifocal lens. In this paper, for the first time, focimeter-verified on-bench validations of multifocal simulations using SimVis are presented. Two steps are identified as being critical to accurate SimVis simulations. Firstly, a new iterative approach is presented that improves the accuracy of the theoretical SimVis temporal profile for three different multifocal intraocular lens designs - diffractive trifocal, refractive segmented bifocal, and refractive extended depth of focus, while retaining a low sampling. Secondly, a fast focimeter is used to measure the step response of the tunable lens, and the input signal is corrected to include the effects of the transient behavior of the tunable lens. It was found that the root-mean-square of the difference between the estimated through-focus Visual Strehl ratio of the multifocal lens and SimVis is not greater than 0.02 for all the tested multifocal designs.

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.

Alterations to the Foveal Cone Mosaic of Diabetic Patients.

Purpose: We measured localized changes occurring in the foveal cone photoreceptors and related defects in the cone mosaic to alterations in the nearby retinal vasculature. Methods: The central 4° of the retina of 54 diabetic (53.7 ± 12.5 years) and 85 control (35.8 ± 15.2 years) participants were imaged with the Indiana adaptive optics scanning laser ophthalmoscope. Foveal cones and overlying retinal capillaries were imaged and infrared scanning laser ophthalmoscopy (IR SLO) images and optical coherence tomography (OCT) B-scans were obtained. Follow-up imaging sessions were performed with intervals from 4 to 50 months for 22 of the 54 diabetic participants. Results: The foveal cone mosaics of 49 of 54 diabetic participants were of sufficient quality to assess the absence or presence of small localized defects in the cone mosaic. In 13 of these 49 diabetic participants we found localized defects, visualized as sharp-edged areas of cones with diminished reflectivity. These small, localized areas ranged in size from 10 × 10 µm to 75 × 30 µm. Of these 13 participants with cone defects, 11 were imaged over periods from 4 to 50 months and the defects remained relatively stable. These dark regions were not shadows of overlying retinal vessels, but all participants with these localized defects had alterations in the juxtafoveal capillary network. Conclusions: The foveal cone mosaic can show localized areas of dark cones that persist over time, that apparently correspond to either missing or nonreflecting cones, and may be related to local retinal ischemia.

The organization of the cone photoreceptor mosaic measured in the living human retina.

The cone photoreceptors represent the initial fundamental sampling step in the acquisition of visual information. While recent advances in adaptive optics have provided increasingly precise estimates of the packing density and spacing of the cone photoreceptors in the living human retina, little is known about the local cone geometric arrangement beyond a tendency towards hexagonal packing. We analyzed the cone mosaic in data from 10 normal subjects. A technique was applied to calculate the local average cone mosaic structure which allowed us to determine the hexagonality, spacing and orientation of local regions. Using cone spacing estimates, we find the expected decrease in cone density with retinal eccentricity and higher densities along the horizontal as opposed to the vertical meridians. Orientation analysis reveals an asymmetry in the local cone spacing of the hexagonal packing, with cones having a larger local spacing along the horizontal direction. This horizontal/vertical asymmetry is altered at eccentricities larger than 2 degrees in the superior meridian and 2.5 degrees in the inferior meridian. Analysis of hexagon orientations in the central 1.4° of the retina shows a tendency for orientation to be locally coherent, with orientation patches consisting of between 35 and 240 cones.

Perceived image quality with simulated segmented bifocal corrections.

Bifocal contact or intraocular lenses use the principle of simultaneous vision to correct for presbyopia. A modified two-channel simultaneous vision simulator provided with an amplitude transmission spatial light modulator was used to optically simulate 14 segmented bifocal patterns (+ 3 diopters addition) with different far/near pupillary distributions of equal energy. Five subjects with paralyzed accommodation evaluated image quality and subjective preference through the segmented bifocal corrections. There are strong and systematic perceptual differences across the patterns, subjects and observation distances: 48% of the conditions evaluated were significantly preferred or rejected. Optical simulations (in terms of through-focus Strehl ratio from Hartmann-Shack aberrometry) accurately predicted the pattern producing the highest perceived quality in 4 out of 5 patients, both for far and near vision. These perceptual differences found arise primarily from optical grounds, but have an important neural component.

Erratum: Perceived image quality with simulated segmented bifocal corrections: publisher's note.

[This corrects the article on p. 4388 in vol. 7.].

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.

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.

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.